ALBERT

Description: Among industrially important pyridoxal-5’-phosphate (PLP)-dependent transaminases of fold type IV D-amino acid transaminases are the least studied. However, the development of cascade enzymatic processes, including the synthesis of D-amino acids, renewed interest in their study. Here, we describe the identification, biochemical and structural characterization of a new D-amino acid transaminase from Haliscomenobacter hydrossis (Halhy). The new enzyme is strictly specific towards D-amino acids and their keto analogs; it demonstrates one of the highest rates of transamination between D-glutamate and pyruvate. We obtained the crystal structure of the Halhy in the holo form with the protonated Schiff base formed by the K143 and the PLP. Structural analysis revealed a novel set of the active site residues that differ from the key residues forming the active sites of the previously studied D-amino acids transaminases. The active site of Halhy includes three arginine residues, one of which is unique among studied transaminases. We identified critical residues for the Halhy catalytic activity and suggested functions of the arginine residues based on the comparative structural analysis, mutagenesis, and molecular modeling simulations. We suggested a strong positive charge in the O-pocket and the unshaped P-pocket as a structural code for the D-amino acid specificity among transaminases of PLP fold type IV. Characteristics of Halhy complement our knowledge of the structural basis of substrate specificity of D-amino acid transaminases and the sequence-structure-function relationships in these enzymes.

Description: Non-persistent viruses classically cause transient, acute infections triggering immune responses aimed at the elimination of the pathogen. Successful viruses evolved strategies to manipulate and evade these anti-viral defenses. Symptoms during the acute phase are often linked to dysregulated immune responses that disappear once the patient recovers. In some patients, however, symptoms persist or new symptoms emerge beyond the acute phase. Conditions resulting from previous transient infection are termed post-acute sequelae (PAS) and were reported for a wide range of non-persistent viruses such as rota-, influenza- or polioviruses. Here we provide an overview of non-persistent viral pathogens reported to be associated with diverse PAS, among them chronic fatigue, auto-immune disorders, or neurological complications and highlight known mechanistic details. Recently, the emergence of post-acute sequelae of COVID-19 (PASC) or long COVID highlighted the impact of PAS. Notably, PAS of non-persistent infections often resemble symptoms of persistent viral infections, defined by chronic inflammation. Inflammation maintained after the acute phase may be a key driver of PAS of non-persistent viruses. Therefore, we explore current insights into aberrant activation of innate immune signaling pathways in the post-acute phase of non-persistent viruses. Finally, conclusions are drawn and future perspectives for treatment and prevention of PAS are discussed.

Description: The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland). We observed a robust Ctrp3 expression in primary endothelial cells and a transient upregulation in murine endothelial (MyEND) cells by LPS (50 ng/mL). In MyEND cells, CTRP3 inhibited the LPS-induced expression of interleukin (Il)-6 and the tumor necrosis factor (Tnf)-α, and suppressed the LPS-dependent expression of the major endothelial adhesion molecules Vcam-1 and Icam-1. The LPS-induced adhesion of monocytic cells to an endothelial monolayer was antagonized by CTRP3. In C57BL/6J mice with an LPS-induced systemic inflammation, exogenous CTRP3 did not affect circulating levels of TNF-α, ICAM-1, and VCAM-1. In conclusion, we characterized CTRP3 beyond its function as an adipokine in a setting of vascular inflammation. CTRP3 inhibited LPS-induced endothelial expression of adhesion molecules and monocyte cell adhesion, indicating an important vascular anti-inflammatory role for CTRP3 in endotoxemia.

Description: The development of an efficient pretreatment, prior to enzymatic hydrolysis, is a good strategy for the sustainable use of refractory fish byproducts. This study compared hydrothermal pretreatments at 159 °C for 2 min, followed by water extraction (steam explosion-assisted extraction, SE) and 121 °C for 70 min (hot-pressure extraction, HPE), for the recovery of proteins from fish backbones. The effect of enzymatic hydrolysis on the properties of the obtained fish bone protein (FBP) was also evaluated. The results demonstrated that FBP had high contents of protein (81.09–84.88 g/100 g) and hydroxyproline (70–82 residues/1000 residues). After hydrolysis with Flavourzyme, for 3 h, the FBP hydrolysates that were pretreated with SE (SFBP-H) exhibited a better degree of hydrolysis (DH) and nitrogen recovery (NR), and a higher level of umami taste free amino acids (151.50 mg/100 mL), compared with the HPE-treated samples. The obtained SFBP-H mainly distributed below 3000 Da and had strong scavenging effects on 1,1-diphenyl-2-picrylhydrazy (DPPH) (IC50 = 4.24 mg/mL) and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) (IC50 = 1.93 mg/mL) radicals. Steam explosion-assisted extraction is a promising route for recovering proteins from native fish bone materials, and improving the flavor and antioxidant activity of the hydrolysates.

Description: Since mineral supplements for horses commonly contain macro minerals, although the requirement for such is usually covered by roughage-based diets, the aim of this study was to investigate the effects of different dietary calcium levels on mineral serum concentrations and bone metabolism. The trial was conducted in 30 young warmblood stallions (2–3 years) that were divided into two groups for a five-month feeding trial. The groups were fed a hay- and oat-based diet and were either supplied with high (Ca-High) or moderate (Ca-Moderate) calcium excess. While in Ca-High calcium supply was about 2–2.5-fold of the requirement, in Ca-Moderate calcium requirements were slightly surpassed (1.5–1.6-fold). In order to monitor the effects of the different calcium supply, blood samples were taken during the trial and analysed for levels of macro and trace elements as well as concentrations of two bone markers. In Ca-Moderate a trend towards higher phosphorus serum levels compared to Ca-High was observed which was significant at the end of the trial (p = 0.0002). Furthermore, results showed no influence of the diet on bone markers. Results support the idea that forage-based rations for horses do not necessarily have to be supplemented with macro minerals but with trace elements.

Description: Retinal dystrophies (RD) are clinically and genetically heterogenous disorders showing mutations in over 270 disease-associated genes. Several millions of people worldwide are affected with different types of RD. Studying the relevance of disease-associated sequence alterations will assist in understanding disorders and may lead to the development of therapeutic approaches. Here, we established a whole exome sequencing (WES) pipeline to rapidly identify disease-associated mutations in patients. Sanger sequencing was applied to identify deep-intronic variants and to verify the co-segregation of WES results within families. We analyzed 26 unrelated patients with different syndromic and non-syndromic clinical manifestations of RD. All patients underwent ophthalmic examinations. We identified nine novel disease-associated sequence variants among 37 variants identified in total. The sequence variants located to 17 different genes. Interestingly, two cases presenting with Stargardt disease carried deep-intronic variants in ABCA4. We have classified 21 variants as pathogenic variants, 4 as benign/likely benign variants, and 12 as variants of uncertain significance. This study highlights the importance of WES-based mutation analyses in RD patients supporting clinical decisions, broadly based genetic diagnosis and support genetic counselling. It is essential for any genetic therapy to expand the mutation spectrum, understand the genes’ function, and correlate phenotypes with genotypes.

Description: Exploring differences in clinical outcomes based on race and origin among patients hospitalized for COVID-19 is a controversial issue. The ALC COVID-19 Registry includes all confirmed COVID-19 patients admitted to hospital from 3 March 2020 to 17 December 2020. The data were obtained from electronic health records in order to evaluate the differences in the clinical features and outcomes among European and Latin American patients. The follow-ups occurred after 156 days. A propensity score weighting (PSW) logistic regression model was used to estimate the odds ratio (OR, 95% CI) for Latin American origin and outcome associations. Of the 696 patients included, 46.7% were women, with a median age of 65 (IQR 53–67) years, 614 (88.2%) were European, and 82 (11.8%) were Latin American. Latin American patients were younger, with fewer comorbidities, and a higher incidence of extensive pneumonia. After adjusting for residual confounders, Latin American origin was not associated with an increased risk of death (PSW OR 0.85 (0.23–3.14)) or with the need for invasive mechanical ventilation (PSW OR 0.35 (0.12–1.03)). Latin American origin was associated with a shorter hospital stay, but without differences in how long the patient remained on mechanical ventilation. In a public healthcare system, the rates of death or mechanical ventilation in severe COVID-19 cases were found to be comparable between patients of European and Latin American origins.

Description: Black soldier fly (Hermetia illucens) larvae (BSFL) are a promising, sustainable source of nutrients, however, there is limited knowledge regarding the food safety of consuming BSFL. This study determined the safety of consuming BSFL for direct human consumption in terms of microbial, heavy metal and allergen content. Microbial counts were determined using ISO (International Organization for Standardization) methods, heavy metals were determined using inductively coupled plasma mass spectrometry and allergens were determined via Orbitrap mass spectrometry and ELISA (enzyme-linked immunosorbent assay) kits. Feed and killing method influenced the presence of Bacillus cereus (p = 0.011), and only the killing method influenced Escherichia coli (p 〈 0.00) and total viable count (TVC) (p 〈 0.00). Blanching resulted in a 3-log reduction in E. coli and a 3.4 log reduction in the TVC counts. Salmonella spp. and Listeria spp. were not detected in the BSFL samples. Heavy metals were detected although they were below maximum legal limits. Cross-reactive allergens, tropomyosin and arginine kinase, were detected in the BSFL samples, although the clinical significance requires research. The feed fed to the BSFL and blanching were found to influence the safety of consuming BSFL, highlighting the importance of incorporating sufficient decontamination steps, such as blanching, to ensure food safety.

Description: This case series study aimed to evaluate the safety, feasibility, and positive outcome of the neurorehabilitation multimodal protocol (NRMP) in 16 chronic post-surgical IVDD Hansen type I dogs, with OFS 0/DPP− (n = 9) and OFS 1/DPP+ (n = 7). All were enrolled in the NRMP for a maximum of 90 days and were clinically discharged after achieving ambulation. The NRMP was based on locomotor training, functional electrical stimulation, transcutaneous electrical spinal cord stimulation, and 4-aminopyridine (4-AP) pharmacological management. In the Deep Pain Perception (DPP)+ dogs, 100% recovered ambulation within a mean period of 47 days, reaching OFS ≥11, which suggests that a longer period of time is needed for recovery. At follow-up, all dogs presented a positive evolution with voluntary micturition. Of the DPP− dogs admitted, all achieved a flexion/extension locomotor pattern within 30 days, and after starting the 4-AP, two dogs were discharged at outcome day 45, with 78% obtaining Spinal Reflex Locomotion (SRL) and automatic micturition within a mean period of 62 days. At follow-up, all dogs maintained their neurological status. After the NRMP, ambulatory status was achieved in 88% (14/16) of dogs, without concurrent events. Thus, an NRMP may be an important therapeutic option to reduce the need for euthanasia in the clinical setting.

Description: Prophylactic antibiotic usage during delivery is a common practice worldwide, especially in low- to middle-income countries. Guidelines have been published to reduce antibiotic overuse; however, data describing the use of prophylactic antibiotics and clinician adherence to guidelines in low- to middle-income countries remain limited. This study aimed to describe the prevalence of prophylactic antibiotic use, factors associated with its use, and clinician adherence to guidelines. A retrospective review was conducted for all deliveries from 1 January 2016 to 31 December 2018 at a tertiary level hospital in Indonesia. The prevalence of prophylactic antibiotic use during delivery was 47.1%. Maternal education level, Ob/Gyn specialist-led delivery, a history of multiple abortions, C-section, premature membrane rupture, and antepartum hemorrhage were independently associated with prophylactic antibiotic use. Clinician adherence to the guidelines was 68.9%. Adherence to guidelines was the lowest in conditions where the patient had only one indication for prophylactic antibiotics (aOR 0.36, 95% CI 0.24–0.54). The findings showed that the prevalence of prophylactic antibiotic use during delivery was moderate to high. Adherence to local guidelines was moderate. Updating the local prescribing guidelines may improve clinician adherence.

Description: Phenolic compounds have long been of great importance in the pharmaceutical, food, and cosmetic industries. Unfortunately, conventional extraction procedures have a high cost and are time consuming, and the solvents used can represent a safety risk for operators, consumers, and the environment. Deep eutectic solvents (DESs) are green alternatives for extraction processes, given their low or non-toxicity, biodegradability, and reusability. This review discusses the latest research (in the last two years) employing DESs for phenolic extraction, solvent components, extraction yields, extraction method characteristics, and reviewing the phenolic sources (natural products, by-products, wastes, etc.). This work also analyzes and discusses the most relevant DES-based studies for phenolic extraction from natural sources, their extraction strategies using DESs, their molecular mechanisms, and potential applications.

Description: Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them.. Due to the low effectiveness of classic antimycotics against Candida biofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination against Candida strains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy.

Description: The muskrat is a neozoon species that has occupied many countries of continental North Europe after its introduction from north America as fur animals. Due to its burrowing activity it damages river and canal banks and structures of flood control. For this reason, the eradication of this alien species is recommended. Muskrats are also of parasitological interest since they can act as suitable intermediate hosts for Echinococcus multilocularis. On the other hand, little is known on the other helminths that infect muskrats. A total of 130 muskrats of different age groups trapped in different habitats in the Barnim district of the Brandenburg state by a professional hunter were examined for parasites and seven trematodes (Echinostoma sp., Notocotylus noyeri, Plagiorchis elegans, Plagiorchis arvicolae, Psilosostoma simillimum, P. spiculigerum, Opisthorchis felineus and four larval cestode species (Hydatigera taeniaeformis, Taenia martis, Taenia polyacantha, Taenia crassiceps) were detected. Larval stages of E. multilocularis were not found. O. felineus was found for the first time in muskrats in Germany. All the named parasites were present in Europe prior to the introduction of muskrats. With a prevalence of 48.9%, Strobilocercus fasciolaris, the larval stage of the cat tapeworm, H. taeniaeformis, was the most frequent parasite found in adult muskrats.

Description: C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.

Description: Small nucleolar RNA (snoRNA) were one of our earliest recognised classes of non-coding RNA, but were largely ignored by cancer investigators due to an assumption that their activities were confined to the nucleolus. However, as full genome sequences have become available, many new snoRNA genes have been identified, and multiple studies have shown their functions to be diverse. The consensus now is that many snoRNA are dysregulated in cancers, are differentially expressed between cancer types, stages and metastases, and they can actively modify disease progression. In addition, the regulation of the snoRNA class is dominated by the cancer-supporting mTOR signalling pathway, and they may have particular significance to immune cell function and anti-tumour immune responses. Given the recent advent of therapeutics that can target RNA molecules, snoRNA have robust potential as drug targets, either solely or in the context of immunotherapies.

Description: High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated anion channels (VRACs) in breast cell lines using an ATP luminescence imaging system. We detected a slowly rising diffuse pattern of ATP release that was only observed in undifferentiated cells, not in differentiated primary cultured cells. This was confirmed by suppression with DCPIB, a blocker of VRACs, and shRNA for LRRC8A, an indispensable subunit of VRACs. We herein demonstrated that the inflammatory mediator sphingosine-1-phosphate (S1P), which exists abundantly in the cancer microenvironment, induced a diffuse pattern of ATP release isovolumetrically. The response was dose-dependent and suppressed by the knock-down of LRRC8A. It was also suppressed by blockers of S1P receptor 1 and 2 (W146 and JTE013, respectively). RTqPCR demonstrated the prominent presence of S1PR1 and S1PR2 mRNAs. We discussed the roles of S1P-induced ATP release in the cancer microenvironment.

Description: Seaweeds are an important ingredient of functional foods recommended for daily food, due to their unique compositions and nutritional value. Padina tetrastromatica is a brown edible seaweed that is commonly found along the coastal regions of Peninsular Malaysia and consumed as food by some coastal communities. This study investigates the nutritional and antihyperglycaemic potential of P. tetrastromatica extracts, which is generally accepted as an important functional food. In our methodology, we induced diabetes intraperitoneally in experimental animals with a dose of 65 mg kg−1 body weight of streptozotocin. Oral treatment with 200 and 400 mg kg−1 of P. tetrastromatica ethanolic and ethyl acetate extracts were initiated, respectively, to experimental rats once daily for 18 days. Metformin was used as the positive control. Biochemical estimations and histopathological analysis were included in this study. Treatment with P. tetrastromatica extracts significantly lowered the plasma glucose levels in Streptozotocin-induced diabetic rats. In addition, P. tetrastromatica extract treatment also showed a significant reduction in serum alanine transaminase levels. However, no significant changes were observed in serum aspartate transaminase levels. The ethyl acetate extract of P. tetrastromatica at 400 mg kg−1 dose shows some nephroprotective effect, which is observed from the significant increase in the plasma albumin levels. Histopathological evaluation revealed no marked morphological changes in tissues of the isolated organs of the ethyl acetate extract-treated group, revealing the safe nature of P. tetrastromatica.

Description: The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated with their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic, and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure.

Description: Black garlic (BG) is a form of aged garlic obtained from raw garlic (Allium sativum) via Millard reaction under high temperature (60–90 °C) and humidity (70–90%) for a period of time. Several studies reported higher contents of water-soluble antioxidants compounds (S-allyl cysteine, S-allyl-mercapto cysteine), 5-hydroxymethylfurfural, organosulfur compounds, polyphenol, volatile compounds, and products of other Millard reactions compared to fresh garlic after the thermal processing. Recent studies have demonstrated that BG and its bioactive compounds possess a wide range of biological activities and pharmacological properties that preserve and show better efficacy in preventing different types of diseases. Most of these benefits can be attributed to its anti-oxidation, anti-inflammation, anti-obesity, hepatoprotection, hypolipidemia, anti-cancer, anti-allergy, immunomodulation, nephroprotection, cardiovascular protection, and neuroprotection. Substantial studies have been conducted on BG and its components against different common human diseases in the last few decades. Still, a lot of research is ongoing to find out the therapeutic effects of BG. Thus, in this review, we summarized the pre-clinical and clinical studies of BG and its bioactive compounds on human health along with diverse bioactivity, a related mode of action, and also future challenges.

Description: In mammalian cells, two cellular organelles, mitochondria and peroxisomes, share the ability to degrade fatty acid chains. Although each organelle harbors its own fatty acid β-oxidation pathway, a distinct mitochondrial system feeds the oxidative phosphorylation pathway for ATP synthesis. At the same time, the peroxisomal β-oxidation pathway participates in cellular thermogenesis. A scientific milestone in 1965 helped discover the hepatomegaly effect in rat liver by clofibrate, subsequently identified as a peroxisome proliferator in rodents and an activator of the peroxisomal fatty acid β-oxidation pathway. These peroxisome proliferators were later identified as activating ligands of Peroxisome Proliferator-Activated Receptor α (PPARα), cloned in 1990. The ligand-activated heterodimer PPARα/RXRα recognizes a DNA sequence, called PPRE (Peroxisome Proliferator Response Element), corresponding to two half-consensus hexanucleotide motifs, AGGTCA, separated by one nucleotide. Accordingly, the assembled complex containing PPRE/PPARα/RXRα/ligands/Coregulators controls the expression of the genes involved in liver peroxisomal fatty acid β-oxidation. This review mobilizes a considerable number of findings that discuss miscellaneous axes, covering the detailed expression pattern of PPARα in species and tissues, the lessons from several PPARα KO mouse models and the modulation of PPARα function by dietary micronutrients.

Description: Euphorbia species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, Euphorbia diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from Euphorbia species, their structures, classification, biosynthetic pathways, and their structure–activity relationships for the period covering 2013–2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most Euphorbia species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC50) values ranging from 10–50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure–activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, Euphorbia diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.

Description: Rotifers are the most diverse group in freshwater zooplankton and play an important role in food webs and ecosystems. DNA barcoding has become a useful approach to investigate species diversity at local and regional scales, but its application is still limited by efficient primers for the group. To test a pair of primers 30F/885R recently designed for rotifers, we applied them to investigating regional species diversity in the freshwater of South China. We sequenced the cytochrome c oxidase subunit I (COI) gene of rotifers collected from the investigated 23 reservoirs in a large river basin and obtained 145 COI sequences from 33 species in 14 genera. The mean PCR success rate for all tested species was 50%. The 145 sequenced mtCOI in this study covered 33 of 64 identified morphological taxa, including most of the common species in the basin. The intraspecific genetic distance was calculated with a K2P model for 24 rotifer species occurring in the quantitative samples, in which 15 rotifers, such as Keratella cochlearis and Brachionus calyciflorus, had a genetic distance higher than 5%. The high intraspecific genetic differentiation indicates that cryptic species are probably common in (sub)tropical China.

Description: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a significant impact on people’s daily lives. The rapidly spreading B.1.617 lineage harbors two key mutations—L452R and E484Q—in the receptor binding domain (RBD) of its spike (S) protein. To understand the impact and structural dynamics of the variations in the interface of S protein and its host factor, the human angiotensin-converting enzyme 2 (hACE2), triplicate 500 ns molecular dynamics simulations were performed using single (E484Q or L452R) and double (E484Q + L452R) mutant structures and compared to wild type simulations. Our results indicate that the E484Q mutation disrupts the conserved salt bridge formed between Lys31 of hACE2 and Glu484 of S protein. Additionally, E484Q, which could favor the up conformation of the RBD, may help in enhanced hACE2 binding and immune escape. L452R introduces a charged patch near the binding surface that permits increased electrostatic attraction between the proteins. An improved network of intramolecular interactions observed is likely to increase the stability of the S protein and conformational changes may prevent the binding of neutralizing antibodies. The results obtained from the molecular dynamics simulations suggest that structural and dynamic changes introduced by these variations enhance the affinity of the viral S protein to hACE2 and could form the basis for further studies.

Description: Mycobacterium avium subspecies paratuberculosis (MAP) are detectable viable in milk and other dairy products. The molecular mechanisms allowing the adaptation of MAP in these products are still poorly understood. To obtain information about respective adaptation of MAP in milk, we differentially analyzed the proteomes of MAP cultivated for 48 h in either milk at 37 °C or 4 °C or Middlebrook 7H9 broth as a control. From a total of 2197 MAP proteins identified, 242 proteins were at least fivefold higher in abundance in milk. MAP responded to the nutritional shortage in milk with upregulation of 32% of proteins with function in metabolism and 17% in fatty acid metabolism/synthesis. Additionally, MAP upregulated clusters of 19% proteins with roles in stress responses and immune evasion, 19% in transcription/translation, and 13% in bacterial cell wall synthesis. Dut, MmpL4_1, and RecA were only detected in MAP incubated in milk, pointing to very important roles of these proteins for MAP coping with a stressful environment. Dut is essential and plays an exclusive role for growth, MmpL4_1 for virulence through secretion of specific lipids, and RecA for SOS response of mycobacteria. Further, 35 candidates with stable expression in all conditions were detected, which could serve as targets for detection. Data are available via ProteomeXchange with identifier PXD027444.

Description: The industrial use of enzymes generally necessitates their immobilization onto solid supports. The well-known high affinity of enzymes for metal-organic framework (MOF) materials, together with the great versatility of MOFs in terms of structure, composition, functionalization and synthetic approaches, has led the scientific community to develop very different strategies for the immobilization of enzymes in/on MOFs. This review focuses on one of these strategies, namely, the one-pot enzyme immobilization within sustainable MOFs, which is particularly enticing as the resultant biocomposite Enzyme@MOFs have the potential to be: (i) prepared in situ, that is, in just one step; (ii) may be synthesized under sustainable conditions: with water as the sole solvent at room temperature with moderate pHs, etc.; (iii) are able to retain high enzyme loading; (iv) have negligible protein leaching; and (v) give enzymatic activities approaching that given by the corresponding free enzymes. Moreover, this methodology seems to be near-universal, as success has been achieved with different MOFs, with different enzymes and for different applications. So far, the metal ions forming the MOF materials have been chosen according to their low price, low toxicity and, of course, their possibility for generating MOFs at room temperature in water, in order to close the cycle of economic, environmental and energy sustainability in the synthesis, application and disposal life cycle.

Description: The nature of the chemical bond is important in all natural sciences, ranging from biology to chemistry, physics and materials science. The atomic force microscope (AFM) allows to put a single chemical bond on the test bench, probing its strength and angular dependence. We review experimental AFM data, covering precise studies of van-der-Waals-, covalent-, ionic-, metallic- and hydrogen bonds as well as bonds between artificial and natural atoms. Further, we discuss some of the density functional theory calculations that are related to the experimental studies of the chemical bonds. A description of frequency modulation AFM, the most precise AFM method, discusses some of the experimental challenges in measuring bonding forces. In frequency modulation AFM, forces between the tip of an oscillating cantilever change its frequency. Initially, cantilevers were made mainly from silicon. Most of the high precision measurements of bonding strengths by AFM became possible with a technology transfer from the quartz watch technology to AFM by using quartz-based cantilevers (“qPlus force sensors”), briefly described here.

Description: The purpose of our study was to evaluate the role of macrophage migration inhibitory factor (MIF) in the differentiation of tendon-derived stem cells (TdSCs) under hyperglycemic conditions. In the in vivo experiment, rats were classified into diabetic (DM) and non-DM groups depending on the intraperitoneal streptozotocin (STZ) or saline injection. Twelve-week after STZ injection, the supraspinatus tendon was harvested and prepared for histological evaluation and real-time reverse transcription polymerase chain reaction for osteochondrogenic (aggrecan, BMP-2, and Sox9) and tenogenic (Egr1, Mkx, scleraxis, type 1 collagen, and Tnmd) markers. For the in vitro experiment, TdSCs were isolated from healthy rat Achilles tendons. Cultured TdSCs were treated with methylglyoxal and recombinant MIF or MIF gene knockdown to determine the effect of hyperglycemic conditions and MIF on the differentiation function of TdSCs. These conditions were classified into four groups: hyperglycemic-control group, hyperglycemic-recombinant-MIF group, hyperglycemic-knockdown-MIF group, and normal-control group. The mRNA expression of osteochondrogenic and tenogenic markers was compared among the groups. In the in vivo experiment, the mRNA expression of all osteochondrogenic and tenogenic differentiation markers in the DM group was significantly higher and lower than that in the non-DM group, respectively. Similarly, in the in vitro experiments, the expression of all osteochondrogenic and tenogenic differentiation markers was significantly upregulated and downregulated, respectively, in the hyperglycemic-control group compared to that in the normal-control group. The hyperglycemic-knockdown-MIF group demonstrated significantly decreased expression of all osteochondrogenic differentiation markers and increased expression of only some tenogenic differentiation markers compared with the hyperglycemic-control group. In contrast, the hyperglycemic-recombinant-MIF group showed significantly increased expression of all osteochondrogenic differentiation markers, but no significant difference in any tenogenic marker level, compared to the hyperglycemic-control group. These results suggest that tendon homeostasis could be affected by hyperglycemic conditions, and MIF appears to alter the differentiation of TdSCs via enhancement of the osteochondrogenic differentiation in hyperglycemic conditions. These are preliminary findings, and must be confirmed in a further study.

Description: WD is caused by ATP7B variants disrupting copper efflux resulting in excessive copper accumulation mainly in liver and brain. The diagnosis of WD is challenged by its variable clinical course, onset, morbidity, and ATP7B variant type. Currently it is diagnosed by a combination of clinical symptoms/signs, aberrant copper metabolism parameters (e.g., low ceruloplasmin serum levels and high urinary and hepatic copper concentrations), and genetic evidence of ATP7B mutations when available. As early diagnosis and treatment are key to favorable outcomes, it is critical to identify subjects before the onset of overtly detrimental clinical manifestations. To this end, we sought to improve WD diagnosis using artificial neural network algorithms (part of artificial intelligence) by integrating available clinical and molecular parameters. Surprisingly, WD diagnosis was based on plasma levels of glutamate, asparagine, taurine, and Fischer’s ratio. As these amino acids are linked to the urea–Krebs’ cycles, our study not only underscores the central role of hepatic mitochondria in WD pathology but also that most WD patients have underlying hepatic dysfunction. Our study provides novel evidence that artificial intelligence utilized for integrated analysis for WD may result in earlier diagnosis and mechanistically relevant treatments for patients with WD.

Description: A major advantage of the use of passive sonar in the tracking multiple underwater targets is that they can be kept covert, which reduces the risk of being attacked. However, the nonlinearity of the passive Doppler and bearing measurements, the range unobservability problem, and the complexity of data association between measurements and targets make the problem of underwater passive multiple target tracking challenging. To deal with these problems, the cardinalized probability hypothesis density (CPHD) recursion, which is based on Bayesian information theory, is developed to handle the data association uncertainty, and to acquire existing targets’ numbers and states (e.g., position and velocity). The key idea of the CPHD recursion is to simultaneously estimate the targets’ intensity and the probability distribution of the number of targets. The CPHD recursion is the first moment approximation of the Bayesian multiple targets filter, which avoids the data association procedure between the targets and measurements including clutter. The Bayesian-filter-based extended Kalman filter (EKF) is applied to deal with the nonlinear bearing and Doppler measurements. The experimental results show that the EKF-based CPHD recursion works well in the underwater passive multiple target tracking system in cluttered and noisy environments.

Description: Microwave-absorbing materials have attracted increased research interest in recent years because of their core roles in the fields of electromagnetic (EM) pollution precaution and information security. In this paper, microwave-absorbing material NiFe-layered double hydroxide (NiFe-LDH) was synthesized by a simple co-precipitation method and calcined for the fabrication of NiFe-mixed metal oxide (NiFe-MMO). The phase structure and micromorphology of the NiFe-LDH and NiFe-MMO were analyzed, and their microwave-absorbing properties were investigated with a vector network analyzer in 2–18 GHz. Both NiFe-LDH and NiFe-MMO possessed abundant interfaces and a low dielectric constant, which were beneficial to electromagnetic wave absorption, owing to the synergistic effect of multi-relaxation and impedance matching. The optimum reflection loss (RL) of NiFe-LDH and NiFe-MMO was −58.8 dB and −64.4 dB, respectively, with the thickness of 4.0 mm in the C band. This work demonstrates that LDH-based materials have a potential application in electromagnetic wave absorption.

Description: Al2O3 and Al2O3-ZrO2 coatings were deposited on stainless steel using atmospheric plasma spraying. The influence of arc current and zirconia addition on the surface morphology of the coating, phase composition and tribological properties under dry sliding conditions were investigated. The addition of zirconia reduced the surface roughness of the coatings. The X-ray diffraction measurements indicated that the Al2O3 coatings were composed of β-Al2O3, α-Al2O3, and γ-Al2O3 phases. The addition of zirconia led to the formation of tetragonal and monoclinic phases of zirconia in the as-sprayed coatings. The friction coefficients of Al2O3 and Al2O3-ZrO2 coatings were similar and varied in the range of 0.72–0.75. The specific wear rates of the as-sprayed coatings were reduced with the increase of arc current. It was obtained that the wear rates of the Al2O3-ZrO2 coatings were at least three times lower compared to Al2O3 coatings.

Description: This study evaluated the effects of the duration of ZH supplementation and days on feed (DOF) on performance, carcass characteristics, and saleable meat yield of Nellore young bulls. The fixed effects included the duration (0, 20, 30, or 40 d before slaughter plus a 3 d ZH withdrawal period—8.33 mg of ZH/kg of DM) and DOF (90 and 117 d). Feed efficiency (G:F) linearly increased when the duration of ZH supplementation increased (p 〈 0.01). Nellore bulls fed ZH had greater HCW (p 〈 0.01), dressing percentage (p 〈 0.01) and Longissimus muscle area (LMA) (p 〈 0.01), but less 12th-rib fat (p = 0.04) than the control group. The hot carcass weight (HCW) (p 〈 0.01), and dressing percentage increased linearly (p 〈 0.01) with the increase of duration of ZH supplementation. The HCW, ossification, and 12th-rib fat increased with DOF (p 〈 0.01). The ZH supplemented group had most of the individual cuts of hindquarters and total saleable meat increased compared with the control. Zilpaterol hydrochloride was effective in improving hot carcass weight, hindquarter, and saleable meat yields of Nellore bulls when fed for at least 20 d before slaughter, independently of days on feed.

Description: Healthy, weaned, coccidial-free male rabbits from two breeds (New Zealand white (NZ) and V-line (VL)) were divided into 10 equal groups (5 groups each for NZ and VL) (3 replicates/group, 6 rabbits/replicate, 18 rabbits/group). All rabbits were inoculated with 5 × 104 Eimeria spp. oocysts (E. intestinalis (67%), E. magna (22%), and E. media (11%)) except for the rabbits in the first group (G1), which were inoculated with a sterile solution and served as a negative control. The remaining four groups were treated as follows: G2, no treatment/positive control, G3, treated with neem leaf extract, G4, treated with pomegranate peel extract (PPE), and G5, treated with a combination of neem leaf extract and PPE. For both breeds, our results showed that the use of neem leaf and/or pomegranate peel extract resulted in improved growth performance, with a significant improvement in relative feed conversion ratio (FCR) compared to the positive control groups, which recorded the worst values, as well as a significant (p ≤ 0.05) reduction in mean oocyst count compared to the positive control groups. We also observed downregulation of mRNA levels of IL-1βα, IL6, and TNF-α in the herbal treatment groups compared with the mRNA levels of these genes in the positive control groups. Herbal treatment with neem leaf and/or pomegranate peel extracts had positive effects on the NZ and VL rabbits experimentally infected with mixed Eimeria species, as evidenced by their healthy appearance, good appetite, no mortalities, an anticoccidial index 〉 120, and a significantly higher total return and net profit when compared to the positive control groups of both breeds. In NZ rabbits, the treatment with neem leaf extract alone (G3) or in combination with PPE (G5) recorded the most efficient economic anticoccidial activity.

Description: The factors of brine time, concentration, and temperature, affect the high-quality production of brined cabbage used in Kimchi. Although changes in Kimchi cabbage quality depending on brine time and concentration have been reported, changes in brine temperature have not been explored. Here, we optimized the brine process considering specific conditions of temperature (15–25 °C), concentration (10–14%), and osmosis duration (14–18 h) affecting the characteristics such as pH, titratable acidity, soluble solid content, glucose, fructose, and lactic acid bacteria and mass transport (salt gain, water loss, and weight reduction). The optimal parameters were determined using multivariate statistical analysis using the Box–Behnken design combined with response surface methodology. For each response as qualitative characteristics, second order polynomial models were developed using multiple regression analysis. Analysis of variance was performed to check the adequacy and accuracy of the fitted models. The brine temperature and concentration affected salt gain and water loss; the optimal brining temperature, concentration, and time were 19.17 °C, 10.53%, and 15.38 h, respectively. Statistical regression analysis indicated that standardized brined cabbage can be produced efficiently using a brining tank at controllable temperature.

Description: The microcirculation includes an invisible network of micro-vessels that are up to a few hundred microns in diameter [...]

Description: The short form of the leptin receptor (LRa) plays a key role in the transport of leptin to the central nervous system (CNS). Here, the resistin (RSTN)-mediated expression of LRa in the preoptic area (POA), ventromedial and dorsomedial nuclei (VMH/DMH),arcuate nucleus (ARC) and the anterior pituitary gland (AP)was analyzed considering the photoperiodic (experiment 1) and nutritional status (experiment 2) of ewes. In experiment 1, 30 sheep were fed normally and received one injection of saline or two doses of RSTN one hour prior to euthanasia. RSTN increased LRa expression mainly in the ARC and AP during long days (LD) and only in the AP during short days (SD). In experiment 2, an altered diet for 5 months created lean or fat sheep. Twenty sheep were divided into four groups: the lean and fat groups were given saline, while the lean-R and fat-R groups received RSTN one hour prior to euthanasia. Changes in adiposity influenced the effect of RSTN on LRa mRNA transcript levels in the POA, ARC and AP and without detection of LRa in the VMH/DMH. Overall, both photoperiodic and nutritional signals influence the effects of RSTN on leptin transport to the CNS and are involved in the adaptive/pathological phenomenon of leptin resistance in sheep.

Description: We evaluated the association of VEGFA rs3025039 polymorphism with clinical co-variates and outcomes in 849 subjects with primary myelofibrosis (PMF) and 250 healthy controls. Minor T-allele frequency was higher in subjects with JAK2V617F compared with those without JAK2V617F (18% vs. 13%; p = 0.014). In subjects with JAK2V617F, the TT genotype was associated at diagnosis with lower platelet concentrations (p = 0.033), higher plasma LDH concentration (p = 0.005), higher blood CD34-positive cells (p = 0.027), lower plasma cholesterol concentration (p = 0.046), and higher concentration of high-sensitivity C-reactive protein (p = 0.018). These associations were not found in subjects with PMF without JAK2V617F. In subjects with the TT genotype, risk of death was higher compared with subjects with CC/CT genotypes (HR = 2.12 [1.03, 4.35], p = 0.041). Finally, the TT genotype was associated with higher frequency of deep vein thrombosis in typical sites (12.5% vs. 2.5%; OR = 5.46 [1.51, 19.7], p = 0.009). In conclusion, in subjects with PMF, the VEGFA rs3025039 CT or TT genotypes are more common in those with JAK2V617F than in those without JAK2V67F mutation and are associated with disease severity, poor prognosis, and risk of deep vein thrombosis.

Description: Alternative pre-mRNA splicing plays a very important role in expanding protein diversity as it generates numerous transcripts from a single protein-coding gene. Therefore, alterations lead this process to neurological human disorders, including Alzheimer’s and Parkinson’s diseases. Moreover, accumulating evidence indicates that the splicing machinery highly contributes to the cells’ ability to adapt to different altered cellular microenvironments, such as hypoxia. Hypoxia is known to have an effect on the expression of proteins involved in a multiple of biological processes, such as erythropoiesis, angiogenesis, and neurogenesis, and is one of the important risk factors in neuropathogenesis. In this review, we discuss the current knowledge of alternatively spliced genes, which, as it is reported, are associated with Alzheimer’s and Parkinson’s diseases. Additionally, we highlight the possible influence of cellular hypoxic microenvironment for the formation of mRNA isoforms contributing to the development of these neurodegenerative diseases.

Description: The importance of yeast old yellow enzymes is increasingly recognized for direct asymmetric reduction of (E/Z)-citral to (R)-citronellal. As one of the most performing old yellow enzymes, the enzyme OYE3 from Saccharomyces cerevisiae S288C exhibited complementary enantioselectivity for the reduction of (E)-citral and (Z)-citral, resulting in lower e.e. value of (R)-citronellal in the reduction of (E/Z)-citral. To develop a novel approach for the direct synthesis of enantio-pure (R)-citronellal from the reduction of (E/Z)-citral, the enzyme OYE3 was firstly modified by semi-rational design to improve its (R)-enantioselectivity. The OYE3 variants W116A and S296F showed strict (R)-enantioselectivity in the reduction of (E)-citral, and significantly reversed the (S)-enantioselectivity in the reduction of (Z)-citral. Next, the double substitution of OYE3 led to the unique variant S296F/W116G, which exhibited strict (R)-enantioselectivity in the reduction of (E)-citral and (E/Z)-citral, but was not active on (Z)-citral. Relying on its capability discriminating (E)-citral and (Z)-citral, a new cascade reaction catalyzed by the OYE3 variant S296F/W116G and glucose dehydrogenase was developed, providing the enantio-pure (R)-citronellal and the retained (Z)-citral after complete reduction of (E)-citral.

Description: Tuberculosis remains the most afflicting infectious disease known by humankind, with one quarter of the population estimated to have it in the latent state. Discovering antituberculosis drugs is a challenging, complex, expensive, and time-consuming task. To overcome the substantial costs and accelerate drug discovery and development, drug repurposing has emerged as an attractive alternative to find new applications for “old” drugs and where computational approaches play an essential role by filtering the chemical space. This work reports the first multi-condition model based on quantitative structure–activity relationships and an ensemble of neural networks (mtc-QSAR-EL) for the virtual screening of potential antituberculosis agents able to act as multi-strain inhibitors. The mtc-QSAR-EL model exhibited an accuracy higher than 85%. A physicochemical and fragment-based structural interpretation of this model was provided, and a large dataset of agency-regulated chemicals was virtually screened, with the mtc-QSAR-EL model identifying already proven antituberculosis drugs while proposing chemicals with great potential to be experimentally repurposed as antituberculosis (multi-strain inhibitors) agents. Some of the most promising molecules identified by the mtc-QSAR-EL model as antituberculosis agents were also confirmed by another computational approach, supporting the capabilities of the mtc-QSAR-EL model as an efficient tool for computational drug repurposing.

Description: The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative functional roles for OTX2 in adult choroid plexus function, including cell signaling and adhesion, and show that OTX2 regulates the expression of factors that are secreted into the cerebrospinal fluid, notably transthyretin. We also show that Otx2 expression impacts choroid plexus immune and stress responses, and affects splicing, leading to changes in the mRNA isoforms of proteins that are implicated in the oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell-autonomous target regions, such as the visual cortex and subventricular zone, we identify putative targets that are involved in cell adhesion, chromatin structure, and RNA processing. Thus, OTX2 retains important roles for regulating choroid plexus function and brain homeostasis throughout life.

Description: Mast cell disease is an epigenetically and genetically determined disease entity with very diverse clinical manifestations in potentially every system and tissue due to inap pro priate release of variable subsets of mast cell mediators together with accumulation of either morphologically normal or altered mast cells. Easy bruising, excessive bleeding, and aberrancies of erythropoiesis can frequently be observed in patients with mast cell disease. A thorough history, including a family history, will guide the appropriate work-up, and laboratory evaluations may provide clues to diagnosis. In recent years, our understanding of the involvement of coagulation and anticoagulant pathways, the fibrinolytic system, and erythropoiesis in the pathophysiology of mast cell disease has increased considerably. This review summarizes current knowledge of the impact of the disturbed hemostatic and erythropoietic balance in patients with mast cell disease and describes options of treatment.

Description: A nested structure is a structural feature that is conducive to system stability formed by the coevolution of biological species in mutualistic ecosystems The coopetition relationship and value flow between industrial sectors in the global value chain are similar to the mutualistic ecosystem in nature. That is, the global economic system is always changing to form one dynamic equilibrium after another. In this paper, a nestedness-based analytical framework is used to define the generalist and specialist sectors for the purpose of analyzing the changes in the global supply pattern. We study why the global economic system can reach a stable equilibrium, what the role of different sectors play in the steady status, and how to enhance the stability of the global economic system. In detail, the domestic trade network, export trade network and import trade network of each country are extracted. Then, an econometric model is designed to analyze how the microstructure of the production system affects a country’s macroeconomic performance.

Description: Skin fibrotic diseases, such as keloids, are mainly caused by pathologic scarring of wounds during healing and characterized by benign cutaneous overgrowths of dermal fibroblasts. Current surgical and therapeutic modalities of skin fibrosis are unsatisfactory. Pinocembrin, a natural flavonoid, has been shown to possess a vast range of pharmacological activities including antimicrobial, antioxidant, anti-inflammatory, and anti-tumor activities. In this study we explored the potential effect and mechanisms of pinocembrin on skin fibrosis in vitro and in vivo. In vitro studies indicated that pinocembrin dose-dependently suppressed proliferation, migration, and invasion of keloid fibroblasts and mouse primary dermal fibroblasts. The in vivo studies showed that pinocembrin could effectively alleviate bleomycin (BLM)-induced skin fibrosis and reduce the gross weight and fibrosis-related protein expression of keloid tissues in xenograft mice. Further mechanism studies indicated that pinocembrin could suppress TGF-β1/Smad signaling and attenuate TGF-β1-induced activation of skin fibroblasts. In conclusion, our results demonstrate the therapeutic potential of pinocembrin for skin fibrosis.

Description: “What is heat?” was the title of a 1954 article by Freeman J. Dyson, published in Scientific American. Apparently, it was appropriate to ask this question at that time. The answer is given in the very first sentence of the article: heat is disordered energy. We will ask the same question again, but with a different expectation for its answer. Let us imagine that all the thermodynamic knowledge is already available: both the theory of phenomenological thermodynamics and that of statistical thermodynamics, including quantum statistics, but that the term “heat” has not yet been attributed to any of the variables of the theory. With the question “What is heat?” we now mean: which of the physical quantities deserves this name? There are several candidates: the quantities Q, H, Etherm and S. We can then formulate a desideratum, or a profile: What properties should such a measure of the quantity or amount of heat ideally have? Then, we evaluate all the candidates for their suitability. It turns out that the winner is the quantity S, which we know by the name of entropy. In the second part of the paper, we examine why entropy has not succeeded in establishing itself as a measure for the amount of heat, and we show that there is a real chance today to make up for what was missed.

Description: Starch is the most abundant storage carbohydrate and a major component in pea seeds, accounting for about 50% of dry seed weight. As a by-product of pea protein processing, current uses for pea starch are limited to low-value, commodity markets. The globally growing demand for pea protein poses a great challenge for the pea fractionation industry to develop new markets for starch valorization. However, there exist gaps in our understanding of the genetic mechanism underlying starch metabolism, and its relationship with physicochemical and functional properties, which is a prerequisite for targeted tailoring functionality and innovative applications of starch. This review outlines the understanding of starch metabolism with a particular focus on peas and highlights the knowledge of pea starch granule structure and its relationship with functional properties, and industrial applications. Using the currently available pea genetics and genomics knowledge and breakthroughs in omics technologies, we discuss the perspectives and possible avenues to advance our understanding of starch metabolism in peas at an unprecedented level, to ultimately enable the molecular design of multi-functional native pea starch and to create value-added utilization.

Description: Acute myocardial infarction (MI) is associated with an intense inflammatory response that is critical for cardiac repair but is also involved in the pathogenesis of adverse cardiac remodeling, i.e., the set of size, geometry, and structure changes that represent the structural substrate for the development of post-MI heart failure. Deciphering the pathophysiological mechanisms underlying cardiac repair after MI is, therefore, critical to favorably regulate cardiac wound repair and to prevent development of heart failure. Catecholamines and estrogen play an active role in regulating the inflammatory response in the infarcted area. For example, stress-induced catecholamines alter recruitment and trafficking of leukocytes to the heart. Additionally, estrogen affects rate of cardiac rupture during the acute phase of MI, as well as infarct size and survival in animal models of MI. In this review, we will summarize the role of β-adrenergic receptors and estrogen in cardiac repair after infarction in preclinical studies.

Description: Bacteriophages are viruses infecting bacterial cells. Since there is a lack of specific receptors for bacteriophages on eukaryotic cells, these viruses were for a long time considered to be neutral to animals and humans. However, studies of recent years provided clear evidence that bacteriophages can interact with eukaryotic cells, significantly influencing the functions of tissues, organs, and systems of mammals, including humans. In this review article, we summarize and discuss recent discoveries in the field of interactions of phages with animal and human organisms. Possibilities of penetration of bacteriophages into eukaryotic cells, tissues, and organs are discussed, and evidence of the effects of phages on functions of the immune system, respiratory system, central nervous system, gastrointestinal system, urinary tract, and reproductive system are presented and discussed. Modulations of cancer cells by bacteriophages are indicated. Direct and indirect effects of virulent and temperate phages are discussed. We conclude that interactions of bacteriophages with animal and human organisms are robust, and they must be taken under consideration when using these viruses in medicine, especially in phage therapy, and in biotechnological applications.

Description: Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3+, CD8+, and FoxP3+ T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3+, CD8+, or FoxP3+ T lymphocytes were associated with TNM stages I-II (p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases (p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3+ T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3+, CD8+, or FoxP3+T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3+ T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.

Description: Microalgal biomass is a sustainable source of bioactive lipids with omega-3 fatty acids. The efficient extraction of neutral and polar lipids from microalgae requires alternative extraction methods, frequently combined with biomass pretreatment. In this work, a combined ultrasound and enzymatic process using commercial enzymes Viscozyme, Celluclast, and Alcalase was optimized as a pretreatment method for Nannochloropsis gaditana, where the Folch method was used for lipid extraction. Significant differences were observed among the used enzymatic pretreatments, combined with ultrasound bath or probe-type sonication. To further optimize this method, ranges of temperatures (35, 45, and 55 °C) and pH (4, 5, and 8) were tested, and enzymes were combined at the best conditions. Subsequently, simultaneous use of three hydrolytic enzymes rendered oil yields of nearly 29%, showing a synergic effect. To compare enzymatic pretreatments, neutral and polar lipids distribution of Nannochloropsis was determined by HPLC–ELSD. The highest polar lipids content was achieved employing ultrasound-assisted enzymatic pretreatment (55 °C and 6 h), whereas the highest glycolipid (44.54%) and PE (2.91%) contents were achieved using Viscozyme versus other enzymes. The method was applied to other microalgae showing the potential of the optimized process as a practical alternative to produce valuable lipids for nutraceutical applications.

Description: This study applies relative entropy in naturalistic large-scale corpus to calculate the difference among L2 (second language) learners at different levels. We chose lemma, token, POS-trigram, conjunction to represent lexicon and grammar to detect the difference among different L2 groups using relative entropy. The results show that information distribution discrimination regarding lexical and grammatical differences continues to increase from L2 learners at a lower level to those at a higher level. This result is consistent with the assumption that in the course of second language acquisition, L2 learners develop towards a more complex and diverse use of language. Meanwhile, this study uses the statistics method of time series to process the data on L2 differences yielded by traditional frequency-based methods processing the same L2 corpus to compare with the results of relative entropy. However, the results from the traditional methods rarely show regularity. As compared to the algorithms in traditional approaches, relative entropy performs much better in detecting L2 proficiency development. In this sense, we have developed an effective and practical algorithm for stably detecting and predicting the developments in L2 learners’ language proficiency.

Description: One important type of animal welfare concern is “natural living” (i.e., that animals are able to express natural behaviours that are important to them, and to engage with aspects of the natural world that they find important). The aims of this narrative review were to describe the behavioural development of calves (Bos taurus) in natural settings and use this to identify characteristics of natural systems that may be important to consider relative to this natural living conception of animal welfare. At birth, calves are licked by their mothers and soon stand to suckle for colostrum, and during the milk-feeding period, calves spend much of their time lying down. In natural systems, calves perform a variety of social behaviours with herd-mates, and slowly transition from their mother’s milk to eating solid food, by gradually increasing time spent grazing and ruminating. In contrast, on most commercial dairy systems, dairy calves are removed from their mothers at birth, housed individually, fed restricted amounts of milk and weaned abruptly at a young age. The results of this review suggest that accommodating key natural behaviours, for example through the use of teat feeding of milk, social housing, and gradual weaning, can help address welfare concerns.

Description: Background: DNA methylation is an epigenetic control mechanism that may be altered by environmental exposures. We have previously reported that in utero exposure to the mycotoxin and liver carcinogen aflatoxin B1 from the maternal diet, as measured using biomarkers in the mothers’ blood, was associated with differential DNA methylation in white blood cells of 6-month-old infants from The Gambia. Methods: Here we examined aflatoxin B1-associated differential DNA methylation in white blood cells of 24-month-old children from the same population (n = 244), in relation to the child’s dietary exposure assessed using aflatoxin albumin biomarkers in blood samples collected at 6, 12 and 18 months of age. HM450 BeadChip arrays were used to assess DNA methylation, with data compared to aflatoxin albumin adduct levels using two approaches; a continuous model comparing aflatoxin adducts measured in samples collected at 18 months to DNA methylation at 24 months, and a categorical time-dose model that took into account aflatoxin adduct levels at 6, 12 and 18 months, for comparison to DNA methylation at 24 months. Results: Geometric mean (95% confidence intervals) for aflatoxin albumin levels were 3.78 (3.29, 4.34) at 6 months, 25.1 (21.67, 29.13) at 12 months and 49.48 (43.34, 56.49) at 18 months of age. A number of differentially methylated CpG positions and regions were associated with aflatoxin exposure, some of which affected gene expression. Pathway analysis highlighted effects on genes involved with with inflammatory, signalling and growth pathways. Conclusions: This study provides further evidence that exposure to aflatoxin in early childhood may impact on DNA methylation.

Description: The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogenic components of primary BMS for a better understanding of the disease. This systematic review (SR) was registered in PROSPERO (CRD42021224160). The search was limited to articles in English or French from 1990 to 01 December 2020. A total of 113 articles were considered for data extraction. We divided them into four subgroups: pharmacological and nonpharmacological management studies (n = 23); neurophysiological studies (n = 35); biohistopathological studies (n = 25); and questionnaire-based studies (n = 30). Several of these studies have shown neuropathic involvement at various levels of the neuraxis in BMS with the contribution of quantitative sensory testing (QST), functional brain imaging, and biohistopathological or pharmacologic studies. On the other hand, the role of psychological factors in BMS has also been the focus of several studies and has shown a link with psychiatric disorders such as anxiety and/or depression symptoms. Depending on the patient, the neuropathic and psychogenic components may exist simultaneously, with a preponderance of one or the other, or exist individually. These two components cannot be dissociated to define BMS. Consequently, BMS may be considered nociplastic pain.

Description: Demographics and psychographics are used to study the influence of different consumers on product effects in food development and testing. Demographics have a longer history and are routinely used in most research; psychographics are more recent, raising the question of whether they add to research on food products. The research presented here represents extensive exploratory data that demonstrate that both demographic measures and psychographic measures add to our understanding of consumer’s liking ratings for nutrient supplements. The results are discussed in the context of broader research on a range of food products. In addition, the research reported here was conducted in four different countries, demonstrating many country effects. Finally, tests were conducted with users of the products, lapsed users of the product, and users of other nutrient supplements (non-users), and this led to many differences in product testing. These results further suggest that age and gender are not the only demographic variables to be studied, along with psychographic variables. The psychographic variables should be selected for a particular product category under investigation, as effects of specific psychographic measures vary for product categories. Specific variables do not fit all products for both demographics and psychographics.

Description: Plant-derived antioxidants are a large group of natural products with the capacity to reduce radical-scavenging. Due to their potent therapeutic and preventive actions, these compounds receive a lot of attention from scientists, particularly pharmacologists. The pharmacological activities of the Azima tetracantha Lam. (AT) plant, belonging to the Salvadoraceae family, reported here justifies its traditional use in treating several diseases or disorders. This study aims to look at the propensity of certain plant compounds found in natural AT plant extracts that might play a critical role as a secondary metabolite in cervical cancer treatment. There is a shortage of information on the plant’s phytochemical and biological characteristics. Methanol (MeOH) solvent extracts of the dried AT plant were screened phytochemically. Its aqueous extract was tested for antioxidant, antiseptic, anti-inflammatory, and anticancerous properties. Absorption Distribution Metabolism and Excretion (ADME/T), Docking, and HPLC were also performed. In clinical treatment, the plant shown no adverse effects. The antioxidant activity was evaluated and showed the highest concentration at 150 µg/mL (63.50%). MeOH leaf extract of AT exhibited the highest and best inhibitory activity against Staphylococcus aureus (15.3 mm/1000) and displayed a high antiseptic potential. At a 200 µg/mL concentration, MeOH leaves-extract inhibited red blood cells (RBC) hemolysis by 66.56 ± 0.40, compared with 62.33 ± 0.40 from the standard. Albumin’s ability to suppress protein denaturation ranged from 16.75 ± 0.65 to 62.35 ± 0.20 inhibitions in this test, providing even more support for its favorable anti-inflammatory properties. The ADME/T studies were considered for a potential cancer drug molecule, and one of our compounds from MeOH extract fills the ADME and toxicity parameters. The forms of compound 4 showed a strong hydrogen-bonding interaction with the vital amino acids (ASN923, THR410, LEU840TRY927, PHE921, and GLY922). A total of 90% of cell inhibition was observed when HeLa cell lines were treated with 300 µg/mL of compound 4 (7-acetyl-3a1-methyl- 4,14-dioxo-1,2,3a,3a1,4,5,5a,6,8a,9b,10,11,11a-tetradecahydro-2,5a epoxy5,6a (methanooxymethano)phenaleno[1′,9′:5,6,7]indeno[1,7a-b]oxiren-2-yl acetate). The polyphenol compounds demonstrated significant advances in anticancer drug properties, and it could lead to activation of cancer cell apoptosis.

Description: Silicon (Si) is considered a non-essential element similar to cadmium, arsenic, lead, etc., for plants, yet Si is beneficial to plant growth, so it is also referred to as a quasi-essential element (similar to aluminum, cobalt, sodium and selenium). An element is considered quasi-essential if it is not required by plants but its absence results in significant negative consequences or anomalies in plant growth, reproduction and development. Si is reported to reduce the negative impacts of different stresses in plants. The significant accumulation of Si on the plant tissue surface is primarily responsible for these positive influences in plants, such as increasing antioxidant activity while reducing soil pollutant absorption. Because of these advantageous properties, the application of Si-based nanoparticles (Si-NPs) in agricultural and food production has received a great deal of interest. Furthermore, conventional Si fertilizers are reported to have low bioavailability; therefore, the development and implementation of nano-Si fertilizers with high bioavailability could be crucial for viable agricultural production. Thus, in this context, the objectives of this review are to summarize the effects of both Si and Si-NPs on soil microbes, soil properties, plant growth and various plant pathogens and diseases. Si-NPs and Si are reported to change the microbial colonies and biomass, could influence rhizospheric microbes and biomass content and are able to improve soil fertility.

Description: Arthropod antimicrobial peptides (AMPs) offer a promising source of new leads to address the declining number of novel antibiotics and the increasing prevalence of multidrug-resistant bacterial pathogens. AMPs with potent activity against Gram-negative bacteria and distinct modes of action have been identified in insects and scorpions, allowing the discovery of AMP combinations with additive and/or synergistic effects. Here, we tested the synergistic activity of two AMPs, from the dung beetle Copris tripartitus (CopA3) and the scorpion Heterometrus petersii (Hp1090), against two strains of Escherichia coli. We also tested the antibacterial activity of two hybrid peptides generated by joining CopA3 and Hp1090 with linkers comprising two (InSco2) or six (InSco6) glycine residues. We found that CopA3 and Hp1090 acted synergistically against both bacterial strains, and the hybrid peptide InSco2 showed more potent bactericidal activity than the parental AMPs or InSco6. Molecular dynamics simulations revealed that the short linker stabilizes an N-terminal 310-helix in the hybrid peptide InSco2. This secondary structure forms from a coil region that interacts with phosphatidylethanolamine in the membrane bilayer model. The highest concentration of the hybrid peptides used in this study was associated with stronger hemolytic activity than equivalent concentrations of the parental AMPs. As observed for CopA3, the increasing concentration of InSco2 was also cytotoxic to BHK-21 cells. We conclude that AMP hybrids linked by glycine spacers display potent antibacterial activity and that the cytotoxic activity can be modulated by adjusting the nature of the linker peptide, thus offering a strategy to produce hybrid peptides as safe replacements or adjuncts for conventional antibiotic therapy.

Description: In machine learning and data science, feature selection is considered as a crucial step of data preprocessing. When we directly apply the raw data for classification or clustering purposes, sometimes we observe that the learning algorithms do not perform well. One possible reason for this is the presence of redundant, noisy, and non-informative features or attributes in the datasets. Hence, feature selection methods are used to identify the subset of relevant features that can maximize the model performance. Moreover, due to reduction in feature dimension, both training time and storage required by the model can be reduced as well. In this paper, we present a tri-stage wrapper-filter-based feature selection framework for the purpose of medical report-based disease detection. In the first stage, an ensemble was formed by four filter methods—Mutual Information, ReliefF, Chi Square, and Xvariance—and then each feature from the union set was assessed by three classification algorithms—support vector machine, naïve Bayes, and k-nearest neighbors—and an average accuracy was calculated. The features with higher accuracy were selected to obtain a preliminary subset of optimal features. In the second stage, Pearson correlation was used to discard highly correlated features. In these two stages, XGBoost classification algorithm was applied to obtain the most contributing features that, in turn, provide the best optimal subset. Then, in the final stage, we fed the obtained feature subset to a meta-heuristic algorithm, called whale optimization algorithm, in order to further reduce the feature set and to achieve higher accuracy. We evaluated the proposed feature selection framework on four publicly available disease datasets taken from the UCI machine learning repository, namely, arrhythmia, leukemia, DLBCL, and prostate cancer. Our obtained results confirm that the proposed method can perform better than many state-of-the-art methods and can detect important features as well. Less features ensure less medical tests for correct diagnosis, thus saving both time and cost.

Description: Broccoli sprouts contain 10–100 times higher levels of sulforaphane than mature plants, something that has been well known since 1997. Sulforaphane has a whole range of unique biological properties, and it is especially an inducer of phase 2 detoxication enzymes. Therefore, its use has been intensively studied in the field of health and nutrition. The formation of sulforaphane is controlled by the epithiospecifier protein, a myrosinase co-factor, which is temperature-specific. This paper studies the influence of temperature, heating time, the addition of myrosinase in the form of Raphanus sativus sprouts in constant ratio to broccoli sprouts, and other technological steps on the final sulforaphane content in broccoli sprout homogenates. These technological steps are very important for preserving sulforaphane in broccoli sprouts, but there are some limitations concerning the amount of sulforaphane. We focused, therefore, on the extraction process, using suitable β-cyclodextrin, hexane and ethanol, with the goal of increasing the amount of sulforaphane in the final extract, thus stabilizing it and reducing the required amount sulforaphane needed, e.g., as a dietary supplement.

Description: Inhibition of pyruvate dehydrogenase kinase (PDK) emerged as a potential strategy for treatment of cancer and metabolic disorders. Dichloroacetate (DCA), a prototypical PDK inhibitor, reduces the abundance of some PDK isoenzymes. However, the underlying mechanisms are not fully characterized and may differ across cell types. We determined that DCA reduced the abundance of PDK1 in breast (MDA-MB-231) and prostate (PC-3) cancer cells, while it suppressed both PDK1 and PDK2 in skeletal muscle cells (L6 myotubes). The DCA-induced PDK1 suppression was partially dependent on hypoxia-inducible factor-1α (HIF-1α), a transcriptional regulator of PDK1, in cancer cells but not in L6 myotubes. However, the DCA-induced alterations in the mRNA and the protein levels of PDK1 and/or PDK2 did not always occur in parallel, implicating a role for post-transcriptional mechanisms. DCA did not inhibit the mTOR signaling, while inhibitors of the proteasome or gene silencing of mitochondrial proteases CLPP and AFG3L2 did not prevent the DCA-induced reduction of the PDK1 protein levels. Collectively, our results suggest that DCA reduces the abundance of PDK in an isoform-dependent manner via transcriptional and post-transcriptional mechanisms. Differential response of PDK isoenzymes to DCA might be important for its pharmacological effects in different types of cells.

Description: The development and spread of antibiotics and biocides resistance is a significant global challenge. To find a solution for this emerging problem, the discovery of novel bacterial cellular targets and the critical pathways associated with antimicrobial resistance is needed. In the present study, we investigated the role of the two most critical envelope stress response regulators, RpoE and CpxR, on the physiology and susceptibility of growing Salmonella enterica serovar enteritidis cells using the polycationic antimicrobial agent, chlorhexidine (CHX). It was shown that deletion of the cpxR gene significantly increased the susceptibility of this organism, whereas deletion of the rpoE gene had no effect on the pathogen’s susceptibility to this antiseptic. It has been shown that a lack of the CpxR regulator induces multifaceted stress responses not only in the envelope but also in the cytosol, further affecting the key biomolecules, including DNA, RNA, and proteins. We showed that alterations in cellular trafficking and most of the stress responses are associated with a dysfunctional CpxR regulator during exponential growth phase, indicating that these physiological changes are intrinsically associated with the lack of the CpxR regulator. In contrast, induction of type II toxin-antitoxin systems and decrease of abundances of enzymes and proteins associated with the recycling of muropeptides and resistance to polymixin and cationic antimicrobial peptides were specific responses of the ∆cpxR mutant to the CHX treatment. Overall, our study provides insight into the effects of CpxR on the physiology of S. Enteritidis cells during the exponential growth phase and CHX treatment, which may point to potential cellular targets for the development of an effective antimicrobial agent.

Description: The accurate analysis of circulating tumor cells (CTCs) holds great promise in early diagnosis and prognosis of cancers. However, the extremely low abundance of CTCs in peripheral blood samples limits the practical utility of the traditional methods for CTCs detection. Thus, novel and powerful strategies have been proposed for sensitive detection of CTCs. In particular, nanomaterials with exceptional physical and chemical properties have been used to fabricate cytosensors for amplifying the signal and enhancing the sensitivity. In this review, we summarize the recent development of nanomaterials-based optical and electrochemical analytical techniques for CTCs detection, including fluorescence, colorimetry, surface-enhanced Raman scattering, chemiluminescence, electrochemistry, electrochemiluminescence, photoelectrochemistry and so on.

Description: Wildland fire management decision-makers need to quickly understand large amounts of quantitative information under stressful conditions. Categorization and visualization “schemes” have long been used to help, but how they are done affects the speed and accuracy of interpretation. Using traditional fire management schemes can unduly restrict the design of new products. Our design process for Ontario’s fine-scale, spatially explicit, daily fire occurrence prediction (FOP) models led us to develop guidance for designing new schemes. We show selected historical fire management schemes and describe our method. It includes specifying goals and requirements, exploring design options and making trade-offs. The design options include gradient continuity, hue selection, range completeness and scale linearity. We apply our method to a case study on designing the scheme for Ontario’s FOP models. We arrived at a smooth, nonlinear scale that accommodates data spanning many orders of magnitude. The colouring draws attention according to levels of concern, reveals meaningful spatial patterns and accommodates some colour vision deficiencies. Our method seems simple now but reconciles complex considerations and is useful for mapping many other datasets. Our method improved the clarity and ease of interpretation of several information products used by fire management decision-makers.

Description: With the rapid development of deep learning, computer vision has assisted in solving a variety of problems in engineering construction. However, very few computer vision-based approaches have been proposed on work productivity’s evaluation. Therefore, taking a super high-rise project as a research case, using the detected object information obtained by a deep learning algorithm, a computer vision-based method for evaluating the productivity of assembling reinforcement is proposed. Firstly, a detector that can accurately distinguish various entities related to assembling reinforcement based on CenterNet is established. DLA34 is selected as the backbone. The mAP reaches 0.9682, and the speed of detecting a single image can be as low as 0.076 s. Secondly, the trained detector is used to detect the video frames, and images with detected boxes and documents with coordinates can be obtained. The position relationship between the detected work objects and detected workers is used to determine how many workers (N) have participated in the task. The time (T) to perform the process can be obtained from the change of coordinates of the work object. Finally, the productivity is evaluated according to N and T. The authors use four actual construction videos for validation, and the results show that the productivity evaluation is generally consistent with the actual conditions. The contribution of this research to construction management is twofold: On the one hand, without affecting the normal behavior of workers, a connection between construction individuals and work object is established, and the work productivity evaluation is realized. On the other hand, the proposed method has a positive effect on improving the efficiency of construction management.

Description: In addition to increasing the complexity of the transcriptional output, alternative RNA splicing can lead to the reduction of mRNA translation or the production of non-functional or malfunctional proteins, thus representing a vital component of the gene regulation process. Herein, we set out to detect and characterize alternative splicing events that occur in whole-blood samples of patients with Systemic Lupus Erythematosus (SLE) as compared to healthy counterparts. Through the implementation of a computational pipeline on published RNA-sequencing data, we identified extensive changes in the transcription dynamics affecting a large number of genes. We found a predominance of intron retention events, with the majority introducing premature stop codons, suggestive of gene repression, in both inactive and active SLE patient samples. Alternative splicing affected a distinct set of genes from the ones detected as differentially expressed in the same comparisons, while alternatively spliced genes tended to reside in genome areas associated with increased gene co-expression. Functional analysis of genes affected by alternative splicing pointed towards particular functions related to metabolism and histone acetylation as of potential interest. Together, our findings underline the importance of incorporating alternative splicing analyses in the context of molecular characterization of complex diseases such as SLE.

Description: The anorexigenic neuropeptide prolactin-releasing peptide (PrRP) is involved in the regulation of food intake and energy expenditure. Lipidization of PrRP stabilizes the peptide, facilitates central effect after peripheral administration and increases its affinity for its receptor, GPR10, and for the neuropeptide FF (NPFF) receptor NPFF-R2. The two most potent palmitoylated analogs with anorectic effects in mice, palm11-PrRP31 and palm-PrRP31, were studied in vitro to determine their agonist/antagonist properties and mechanism of action on GPR10, NPFF-R2 and other potential off-target receptors related to energy homeostasis. Palmitoylation of both PrRP31 analogs increased the binding properties of PrRP31 to anorexigenic receptors GPR10 and NPFF-R2 and resulted in a high affinity for another NPFF receptor, NPFF-R1. Moreover, in CHO-K1 cells expressing GPR10, NPFF-R2 or NPFF-R1, palm11-PrRP and palm-PrRP significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and cAMP-responsive element-binding protein (CREB). Palm11-PrRP31, unlike palm-PrRP31, did not activate either c-Jun N-terminal kinase (JNK), p38, c-Jun, c-Fos or CREB pathways in cells expressing NPFF-1R. Palm-PrRP31 also has higher binding affinities for off-target receptors, namely, the ghrelin, opioid (KOR, MOR, DOR and OPR-L1) and neuropeptide Y (Y1, Y2 and Y5) receptors. Palm11-PrRP31 exhibited fewer off-target activities; therefore, it has a higher potential to be used as an anti-obesity drug with anorectic effects.

Description: Membrane proteins responsible for transporting magnetic resonance (MR) and fluorescent contrast agents are of particular importance because they are potential reporter proteins in noninvasive molecular imaging. Gadobenate dimeglumine (Gd-BOPTA), a liver-specific MR contrast agent, has been used globally for more than 10 years. However, the corresponding molecular transportation mechanism has not been validated. We previously reported that the organic anion transporting polypeptide (OATP) 1B3 has an uptake capability for both MR agents (Gd-EOB-DTPA) and indocyanine green (ICG), a clinically available near-infrared (NIR) fluorescent dye. This study further evaluated OATP1B1, another polypeptide of the OATP family, to determine its reporter capability. In the OATP1B1 transfected 293T transient expression model, both Gd-BOPTA and Gd-EOB-DTPA uptake were confirmed through 1.5 T MR imaging. In the constant OAPT1B1 and OATP1B3 expression model in the HT-1080 cell line, both HT-1080-OAPT1B1 and HT-1080-OATP1B3 were observed to ingest Gd-BOPTA and Gd-EOB-DTPA. Lastly, we validated the ICG uptake capability of both OATP1B1 and OATP1B3. OAPT1B3 exhibited a superior ICG uptake capability to that of OAPT1B1. We conclude that OATP1B1 is a potential reporter for dual MR and NIR fluorescent molecular imaging, especially in conjunction with Gd-BOPTA.

Description: In this work, a single-layer TiO2–ZrO2 thin film is deposited on the AISI 316L austenitic stainless steel by the sol–gel process and the dip coating method to improve its corrosion resistance properties. For the sol preparation, titanium isopropoxide and zirconium butoxide are used as the precursors, yttrium acetate hydrate is used for the ZrO2 stabilization, i-propanol as the solvent, nitric acid as the catalyst, acetylacetone as the chelating agent, and the distilled water for the hydrolysis. The deposited films are annealed at 400 °C or 600 °C. Morphology and phase composition of the sol–gel TiO2–ZrO2 films and powders are analyzed by scanning electron microscopy (SEM) equipped with EDX detector and X-ray diffraction (XRD), respectively. The thickness of the sol–gel TiO2–ZrO2 films deposited on the stainless steel is determined by glow discharge optical emission spectrometry (GD-OES). The corrosion behavior of the stainless steel, coated by amorphous films, is evaluated in 3 wt% NaCl and 0.5 mol dm−3 HCl by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. It is found that the sol–gel TiO2–ZrO2 films with the amorphous structure, deposited by the sol–gel process, and calcined at 400 °C significantly enhance the corrosion properties of AISI 316L in both chloride media.

Description: Physical inactivity increases the risk of many adverse health conditions, including the world’s major non-communicable diseases, such as coronary heart disease, type 2 diabetes, and breast and colon cancers, shortening life expectancy. There are minimal medical care and personal trainers’ methods to monitor a patient’s actual physical activity types. To improve activity monitoring, we propose an artificial-intelligence-based approach to classify physical movement activity patterns. In more detail, we employ two deep learning (DL) methods, namely a deep feed-forward neural network (DNN) and a deep recurrent neural network (RNN) for this purpose. We evaluate the two models on two physical movement datasets collected from several volunteers who carried tri-axial accelerometer sensors. The first dataset is from the UCI machine learning repository, which contains 14 different activities-of-daily-life (ADL) and is collected from 16 volunteers who carried a single wrist-worn tri-axial accelerometer. The second dataset includes ten other ADLs and is gathered from eight volunteers who placed the sensors on their hips. Our experiment results show that the RNN model provides accurate performance compared to the state-of-the-art methods in classifying the fundamental movement patterns with an overall accuracy of 84.89% and an overall F1-score of 82.56%. The results indicate that our method provides the medical doctors and trainers a promising way to track and understand a patient’s physical activities precisely for better treatment.

Description: Antimicrobial peptides of mastatopara-S (M-S), thanatin, and ponericin W1(P W1) were able to disrupt the membrane integrity and alter the morphology of the hyphae of Geotrichum citri-aurantii and then reduced the sour rot of citrus fruit. In order to understand the mechanisms of thanatin, P W1 and M-S other than membrane disruption, the interaction betwixt the peptides and G. citri-aurantii DNA were investigated in this research. The laser confocal microscopy found that P W1, thanatin, and M-S could penetrate the cell membrane. Gel retardation assay demonstrated that P W1, thanatin, and M-S could bind to the G. citri-aurantii genomic DNA in vitro. UV-visible spectra and fluorescence spectra analysis further confirmed that the peptides can bind to the DNA, and then insert into the base pairs in the DNA helix, followed by wrecking the double-helix structure. In addition, M-S, thanatin, and P W1 can suppress the synthesis of DNA and RNA of G. citri-aurantii.

Description: We present a data-driven approach to unveil the pharmaceutical technologies of cyclodextrins (CDs) by analyzing a dataset of CD pharmaceutical patents. First, we implemented network science techniques to represent CD patents as a single structure and provide a framework for unsupervised detection of keywords in the patent dataset. Guided by those keywords, we further mined the dataset to examine the patenting trends according to CD-based dosage forms. CD patents formed complex networks, evidencing the supremacy of CDs for solubility enhancement and how this has triggered cutting-edge applications based on or beyond the solubility improvement. The networks exposed the significance of CDs to formulate aqueous solutions, tablets, and powders. Additionally, they highlighted the role of CDs in formulations of anti-inflammatory drugs, cancer therapies, and antiviral strategies. Text-mining showed that the trends in CDs for aqueous solutions, tablets, and powders are going upward. Gels seem to be promising, while patches and fibers are emerging. Cyclodextrins’ potential in suspensions and emulsions is yet to be recognized and can become an opportunity area. This is the first unsupervised/supervised data-mining approach aimed at depicting a landscape of CDs to identify trending and emerging technologies and uncover opportunity areas in CD pharmaceutical research.

Description: Milk is commonly exposed to processing including homogenization and thermal treatment before consumption, and this processing could have an impact on its digestion behavior in the stomach. In this study, we investigated the in vitro gastric digestion behavior of differently processed sheep milks. The samples were raw, pasteurized (75 °C/15 s), homogenized (200/20 bar at 65 °C)–pasteurized, and homogenized–heated (95 °C/5 min) milks. The digestion was performed using a dynamic in vitro gastric digestion system, the human gastric simulator with simulated gastric fluid without gastric lipase. The pH, structure, and composition of the milks in the stomach and the emptied digesta, and the rate of protein hydrolysis were examined. Curds formed from homogenized and heated milk had much looser and more fragmented structures than those formed from unhomogenized milk; this accelerated the curd breakdown, protein digestion and promoted the release of protein, fat, and calcium from the curds into the digesta. Coalescence and flocculation of fat globules were observed during gastric digestion, and most of the fat globules were incorporated into the emptied protein/peptide particles in the homogenized milks. The study provides a better understanding of the gastric emptying and digestion of processed sheep milk under in vitro gastric conditions.

Description: This study aimed to evaluate the sensory and physical characteristics of zingibain-injected meat combined with sous vide cooking. M. biceps femoris (BF; n = 12) acquired from 6–7 year old Angus cows were cooked using the sous vide method at 65 °C, for 8 h or 12 h, either with ginger powder (GP) injected in a 2 g/L solution in water (treatment) or un-injected (control). The sensory attributes included flavour, juiciness, tenderness, and physicochemical characteristics were Warner-Bratzler shear (WBSF), hardness, total water content (TWC), cooking loss (CL) and collagen content. A significant improvement in tenderness with injection treatment and cooking time was observed, as evaluated through trained sensory panellists, and reduced WBSF and hardness (p 〈 0.05 for all). The flavour of the meat was not affected by injection treatment or cooking time (p 〉 0.05), but juiciness and TWC were reduced with longer cooking times (p 〈 0.01 for both). Soluble collagen increased with injection treatment and cooking time (both p 〈 0.05). Moderate to high correlations were found between sensory and physical measurements for tenderness and juiciness. The longer cooking time (12 h) with GP injection treatment caused over tenderization of the meat. The soft texture associated with over-tenderization may be suitable for some specialised consumer markets, for instance, the elderly population with chewing difficulties. Improving the eating quality of low-quality meat from old animals through sous vide cooking and the use of ginger proteases may increase the acceptability of lower value beef, potentially enhancing the commercial value of carcasses typically produced in the beef industry.

Description: Plant-derived compounds have recently been gaining popularity as skincare factors due to their ability to absorb ultraviolet radiations and their anti-inflammatory, and antioxidant properties. In this light, this work aimed to evaluate in vitro the pharmacological activities of the butanolic extract prepared from the aerial parts of Astragalus gombiformis Pomel, an endemic species to southern Algeria. The sun protection factor was used to assess the photoprotective effect (SPF), the protein denaturation method to determine the anti-inflammatory activity, and brine shrimp nauplii and OxHLIA assay, respectively, to assess the cytotoxicity and antioxidant capacity of A. gombiformis. In addition, LC–ESI–MS analysis was employed for the characterization of the phenolic constituents of A. gombiformis. The results showed that A. gombiformis had high capacity for absorbing UV radiations with an SPF of 37.78 ± 0.85 and significant anti-inflammatory activity with a percentage inhibition of 75.38% which is close to that of diclofenac and ketoprofen. In addition, A. gombiformis was found to have effective cytotoxicity against Artemia nauplii with a DC50 value of about 44.7 µg/mL, but a weak hemolytic effect against human erythrocytes. LC–ESI–MS results detected the presence of 17 phenolic compounds with a predominance of cirsiliol, silymarin, quercitrin (quercetin-3-O-rhamnoside), and kaempferol. Taken together, these results suggest that A. gombiformis extract could be used as a skincare agent in cosmetic formulations, providing excellent antioxidant and anti-inflammatory protection, allowing the treatment of skin conditions, as well as a pharmaceutical agent with multidimensional applications.

Description: While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body’s adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.

Description: Amyotrophic Lateral Sclerosis (ALS) is the most common degenerative motor neuron disease in adults. About 97% of ALS patients present TDP-43 aggregates with post-translational modifications, such as hyperphosphorylation, in the cytoplasm of affected cells. GSK-3β is one of the protein kinases involved in TDP-43 phosphorylation. Up-regulation of its expression and activity is reported on spinal cord and cortex tissues of ALS patients. Here, we propose the repurposing of Tideglusib, an in-house non-ATP competitive GSK-3β inhibitor that is currently in clinical trials for autism and myotonic dystrophy, as a promising therapeutic strategy for ALS. With this aim we have evaluated the efficacy of Tideglusib in different experimental ALS models both in vitro and in vivo. Moreover, we observed that GSK-3β activity is increased in lymphoblasts from sporadic ALS patients, with a simultaneous increase in TDP-43 phosphorylation and cytosolic TDP-43 accumulation. Treatment with Tideglusib decreased not only phospho-TDP-43 levels but also recovered its nuclear localization in ALS lymphoblasts and in a human TDP-43 neuroblastoma model. Additionally, we found that chronic oral treatment with Tideglusib is able to reduce the increased TDP-43 phosphorylation in the spinal cord of Prp-hTDP-43A315T mouse model. Therefore, we consider Tideglusib as a promising drug candidate for ALS, being proposed to start a clinical trial phase II by the end of the year.

Description: This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1β (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1β significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1β. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1β than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.

Description: Malignant melanoma is the most aggressive form of skin cancer, which originates from the malignant transformation of melanocytes, the melanin-producing cells of the skin. Melanoma progression is typically described as a stepwise process in which metastasis formation ensues late during disease. A large body of evidence has shown that the accumulation of genetic and epigenetic alterations drives melanoma progression through the different steps. Mortality in melanoma is associated with metastatic disease. Accordingly, early-stage melanoma can be cured in the majority of cases by surgical excision, while late-stage melanoma is a highly lethal disease. Glycosylation is a post-translational modification that involves the transfer of glycosyl moieties to specific amino acid residues of proteins to form glycosidic bonds through the activity of glycosyltransferases. Aberrant glycosylation is considered a hallmark of cancer as it occurs in the majority of tumor types, including melanoma. The most widely occurring glycosylation changes in melanoma are represented by sialylation, fucosylation, and N- and I-glycan branching. In this review, we discuss the role of glycosylation in melanoma and provide insights on the mechanisms by which aberrant glycosylation promotes melanoma progression through activation of invasion and metastasis, immune evasion and cell proliferation.

Description: During acute infections, CD8+ T cells form various memory subpopulations to provide long-lasting protection against reinfection. T central memory (TCM), T effector memory (TEM), and long-lived effector (LLE) cells are circulating memory populations with distinct plasticity, migration patterns, and effector functions. Tissue-resident memory (TRM) cells permanently reside in the frontline sites of pathogen entry and provide tissue-specific protection upon reinfection. Here, using single-cell RNA-sequencing (scRNA-seq) and bulk RNA-seq, we examined the different and shared transcriptomes and regulators of TRM cells with other circulating memory populations. Furthermore, we identified heterogeneity within the TRM pool from small intestine and novel transcriptional regulators that may control the phenotypic and functional heterogeneity of TRM cells during acute infection. Our findings provide a resource for future studies to identify novel pathways for enhancing vaccination and immunotherapeutic approaches.

Description: TiAlN coatings with different Al ratios were deposited by the cathodic arc ion plating (AIP) method, and the relationship between solid particle erosion resistance and structural, mechanical properties was investigated by a micro slurry-jet erosion (MSE) test. The crystal structure of TiAlN coating changes depending on the Al ratio. The coating shows a B1 single cubic phase between the Al ratio of 0 and 0.58; above this ratio, formation of a B4 hexagonal phase is observed. The mechanical properties such as hardness and Young’s modulus of the TiAlN coating also depend on the Al ratio and the crystal structure. The erosion rate decreases by increasing the Al ratio up to 0.58, as the coating is a cubic single phase. The TiAlN coating shows the lowest erosion rate at an Al ratio of 0.58. The erosion rate increases drastically as the crystalline phase changes from the B1 cubic to B4 hexagonal phase at the Al ratio of more than 0.58. The change in erosion rate is also discussed in connection with mechanical properties such as erodent particle hardness to coating hardness ratio and coating hardness to Young’s modulus ratio.

Description: Contagious agalactia is associated with mastitis, keratoconjunctivitis, arthritis, pneumonia, and septicemia in small ruminants in countries with large dairy industries worldwide. The causative agents belong to four (sub)species of the Mycoplasma genus that have remained essentially susceptible to antimicrobials, including to the widely-used tetracycline family. However, some clinical isolates have been detected that show increased minimum inhibitory concentrations of tetracyclines, although they do not harbor the mutation in the 16SrRNA gene usually associated with resistance. The present work aimed to assess whether efflux pumps, infrequently described in mycoplasmas, could participate in the observed moderate loss of susceptibility. General efflux mechanisms were measured (i) using the fluorescence property of ethidium bromide when accumulated intracellularly and intercalated in the mycoplasma genomes, its active extrusion resulting in a temperature-dependent decrease in fluorescence and (ii) monitoring the growth inhibition of mycoplasmas by subinhibitory concentrations of tetracycline with or without reserpine, a known inhibitor of efflux in other bacteria. Both methods revealed non-specific efflux phenomena in most of the isolates tested, although their efficacy was difficult to quantify. This property could contribute to the acquisition of mutations conferring resistance by maintaining intracellular concentrations of tetracyclines at subinhibitory levels.

Description: The target of rapamycin (TOR) protein kinase is an atypical Ser/Thr protein kinase and evolutionally conserved among yeasts, plants, and mammals. TOR has been established as a central hub for integrating nutrient, energy, hormone, and environmental signals in all the eukaryotes. Despite the conserved functions across eukaryotes, recent research has shed light on the multifaceted roles of TOR signaling in plant-specific functional and mechanistic features. One of the most specific features is the involvement of TOR in plant photosynthesis. The recent development of tools for the functional analysis of plant TOR has helped to uncover the involvement of TOR signaling in several steps preceding photoautotrophy and maintenance of photosynthesis. Here, we present recent novel findings relating to TOR signaling and its roles in regulating plant photosynthesis, including carbon nutrient sense, light absorptions, and leaf and chloroplast development. We also provide some gaps in our understanding of TOR function in photosynthesis that need to be addressed in the future.

Description: The prediction of drug–target affinity (DTA) is a crucial step for drug screening and discovery. In this study, a new graph-based prediction model named SAG-DTA (self-attention graph drug–target affinity) was implemented. Unlike previous graph-based methods, the proposed model utilized self-attention mechanisms on the drug molecular graph to obtain effective representations of drugs for DTA prediction. Features of each atom node in the molecular graph were weighted using an attention score before being aggregated as molecule representation. Various self-attention scoring methods were compared in this study. In addition, two pooing architectures, namely, global and hierarchical architectures, were presented and evaluated on benchmark datasets. Results of comparative experiments on both regression and binary classification tasks showed that SAG-DTA was superior to previous sequence-based or other graph-based methods and exhibited good generalization ability.

Description: Multiple sclerosis (MS) and Devic’s disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.

Description: Tau is a highly soluble protein mainly localized at a cytoplasmic level in the neuronal cells, which plays a crucial role in the regulation of microtubule dynamic stability. Recent studies have demonstrated that several factors, such as hyperphosphorylation or alterations of Tau metabolism, may contribute to the pathological accumulation of protein aggregates, which can result in neuronal death and the onset of a number of neurological disorders called Tauopathies. At present, there are no available therapeutic remedies able to reduce Tau aggregation, nor are there any structural clues or guidelines for the rational identification of compounds preventing the accumulation of protein aggregates. To help identify the structural properties required for anti-Tau aggregation activity, we performed extensive chemoinformatics analyses on a dataset of Tau ligands reported in ChEMBL. The performed analyses allowed us to identify a set of molecular properties that are in common between known active ligands. Moreover, extensive analyses of the fragment composition of reported ligands led to the identification of chemical moieties and fragment combinations prevalent in the more active compounds. Interestingly, many of these fragments were arranged in recurring frameworks, some of which were clearly present in compounds currently under clinical investigation. This work represents the first in-depth chemoinformatics study of the molecular properties, constituting fragments and similarity profiles, of known Tau aggregation inhibitors. The datasets of compounds employed for the analyses, the identified molecular fragments and their combinations are made publicly available as supplementary material.

Description: An immunized mouse phage display scFv library with a capacity of 3.34 × 109 CFU/mL was constructed and used for screening of recombinant anti-ciprofloxacin single-chain antibody for the detection of ciprofloxacin (CIP) in animal-derived food. After four rounds of bio-panning, 25 positives were isolated and identified successfully. The highest positive scFv-22 was expressed in E. coli BL21. Then, its recognition mechanisms were studied using the molecular docking method. The result showed the amino acid residue Val160 was the key residue for the binding of scFv to CIP. Based on the results of virtual mutation, the scFv antibody was evolved by directional mutagenesis of contact amino acid residue Val160 to Ser. After the expression and purification, an indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) based on the parental and mutant scFv was established for CIP, respectively. The IC50 value of the assay established with the ScFv mutant was 1.58 ng/mL, while the parental scFv was 26.23 ng/mL; this result showed highly increased affinity, with up to 16.6-fold improved sensitivity. The mean recovery for CIP ranged from 73.80% to 123.35%, with 10.46% relative standard deviation between the intra-assay and the inter-assay. The RSD values ranged between 1.49% and 9.81%. The results indicate that we obtained a highly sensitive anti-CIP scFv by the phage library construction and directional evolution, and the scFv-based IC-ELISA is suitable for the detection of CIP residue in animal-derived edible tissues.

Description: Since 2013, Xylella fastidiosa Wells et al. has been reported to infect several hosts and to be present in different areas of Europe. The main damage has been inflicted on the olive orchards of southern Apulia (Italy), where a severe disease associated with X. fastidiosa subspecies pauca strain De Donno has led to the death of millions of trees. This dramatic and continuously evolving situation has led to European and national (Italian and Spanish) measures being implemented to reduce the spread of the pathogen and the associated olive quick decline syndrome (OQDS). Research has been also carried out to find solutions to better and directly fight the bacterium and its main insect vector, Philaenus spumarius L. In the course of this frantic effort, several treatments based on chemical or biological substances have been tested, in addition to plant breeding techniques and integrated pest management approaches. This review aims to summarize the attempts made so far and describe the prospects for better management of this serious threat, which poses alarming questions for the future of olive cultivation in the Mediterranean basin and beyond.

Description: The current knowledge about the mechanisms of action of light-based treatments (chiefly photodynamic therapy and phototherapy) in skin diseases leans to the possible involvement of epigenetic and oxidative stress mechanisms. To better understand and exploit, to the fullest, these relatively safe and reproducible treatments, several studies have focused on miRNAs, small non-encoding RNAs (22–24 nucleotides), after light-based treatments. The current narrative review focused on 25 articles. A meta-analysis was not deemed appropriate. The results gather the most recurrent skin-related miRNAs up- or downregulated after light treatment. Five of these, miR-21, -29, -125, -145 and -155, are either the most consistently related to efficacy/resistance to treatment or identified as helpful diagnostic tools. A specific class of miRNAs (angioMIRs) requires further studies. Future treatments and imaging techniques could benefit greatly from the use of antagomirs as a possible co-adjuvant therapy along with light-based treatments.

Description: Magnetic-field-induced dispersion of magnetic fillers has been proven to improve the gas separation performance of mixed matrix membranes (MMMs). However, the magnetic field induced is usually in a horizontal or vertical direction. Limited study has been conducted on the effects of alternating magnetic field (AMF) direction towards the dispersion of particles. Thus, this work focuses on the incorporation and dispersion of ferromagnetic iron oxide–titanium (IV) dioxide (αFe2O3/TiO2) particles in a poly (2,6-dimethyl-1,4-phenylene) oxide (PPOdm) membrane via an AMF to investigate its effect on the magnetic filler dispersion and correlation towards gas separation performance. The fillers were incorporated into PPOdm polymer via a spin-coating method at a 1, 3, and 5 wt% filler loading. The MMM with the 3 wt% loading showed the best performance in terms of particle dispersion and gas separation performance. The three MMMs were refabricated in an alternating magnetic field, and the MMM with the 3 wt% loading presented the best performance. The results display an increment in selectivity by 100% and a decrement in CO2 permeability by 97% to an unmagnetized MMM for the 3 wt% loading. The degree of filler dispersion was quantified and measured using Area Disorder of Delaunay Triangulation mapped onto the filler on binarized MMM images. The results indicate that the magnetized MMM presents a greater degree of dispersion than the unmagnetized MMM.

Description: Sex differences in a variety of cognitive traits have long been reported in various species, including dogs. However, only a few canine studies have taken the possible effect of reproductive hormones into account. The aim of this study was to investigate the effects of sex and reproductive status of pet dogs (N = 1032) on two cognitive traits: inhibitory control and social cognition. Inhibitory control was assessed using the cylinder test, and the dogs’ tendency to initiate social contact with a human during a problem-solving situation was assessed using the unsolvable task. Female dogs had a significantly higher success rate in the cylinder test compared to males, and they spent significantly more time in human-directed behavior during the unsolvable task. In contrast, males spent significantly more time in independent behavior during the unsolvable task. Reproductive status had no significant effect on the results of the cylinder test or the unsolvable task. Our results showed that female dogs asked for more help/used a more cooperative strategy during a problem-solving situation and had greater inhibitory control compared to males. According to our results, it seems likely that these sex differences were not influenced to a large extent by reproductive hormones.

Description: Leaf coloration changes evoke different photosynthetic responses among different poplar cultivars. The aim of this study is to investigate the photosynthetic difference between a red leaf cultivar (ZHP) and a green leaf (L2025) cultivar of Populus deltoides. In this study, ‘ZHP’ exhibited wide ranges and huge potential for absorption and utilization of light energy and CO2 concentration which were similar to those in ‘L2025’ and even showed a stronger absorption for weak light. However, with the increasing light intensity and CO2 concentration, the photosynthetic capacity in both ‘L2025’ and ‘ZHP’ was gradually restricted, and the net photosynthetic rate (Pn) in ‘ZHP’ was significantly lower than that in ‘L2025’ under high light or high CO2 conditions, which was mainly attributed to stomatal regulation and different photosynthetic efficiency (including the light energy utilization efficiency and photosynthetic CO2 assimilation efficiency) in these two poplars. Moreover, the higher anthocyanin content in ‘ZHP’ than that in ‘L2025’ was considered to be closely related to the decreased photosynthetic efficiency in ‘ZHP’. According to the results from the JIP-test, the capture efficiency of the reaction center for light energy in ‘L2025’ was significantly higher than that in ‘ZHP’. Interestingly, the higher levels of light quantum caused relatively higher accumulation of QA- in ‘L2025’, which blocked the electron transport and weakened the photosystem II (PSII) performance as compared with ‘ZHP’; however, the decreased capture of light quantum also could not promote the utilization of light energy, which was the key to the low photosynthetic efficiency in ‘ZHP’. The differential expressions of a series of photosynthesis-related genes further promoted these specific photosynthetic processes between ‘L2025’ and ‘ZHP’.

Description: It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to “safely” store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.

Description: Phytoestrogens are plant-produced bioactive secondary metabolites known to play an integral role in plant defense that frequently accumulate in times of stress and/or microbial infection. Phytoestrogens typically belong to two distinct chemical classes; flavonoids (isoflavones) and non-flavonoids (lignans and coumestans). Upon consumption by livestock, high concentrations of phytoestrogens can cause long-term disruption in reproduction due to structural similarities with mammalian estrogens and their tendency to bind estrogen receptors. Wide variation in phytoestrogen concentration has been reported in pasture legumes and corresponding silage or hay. Lucerne is a common perennial pasture legume in temperate climates, but information on phytoestrogen production or accumulation in grazing livestock is currently limited. Therefore, metabolic profiling using UHPLC-MS-QToF was performed to identify and quantitate key phytoestrogens in both fresh and dried lucerne fodder from replicated field or controlled glasshouse environments. Phytoestrogens were also profiled in the blood plasma of Angus cattle grazing field-grown lucerne. Results revealed that phytoestrogens varied quantitatively and qualitatively among selected lucerne cultivars grown under glasshouse conditions. Fresh lucerne samples contained higher concentrations of coumestans and other phytoestrogenic isoflavones than did dried samples for all cultivars profiled, with several exceeding desirable threshold levels for grazing cattle. Coumestans and isoflavones profiled in plasma of Angus heifers grazing lucerne increased significantly over a 21-day sampling period following experimental initiation. Currently, threshold concentrations for phytoestrogens in plasma are unreported. However, total phytoestrogen concentration exceeded 300 mg·kg−1 in fresh and 180 mg·kg−1 in dried samples of selected cultivars, suggesting that certain genotypes may upregulate phytoestrogen production, while others may prove suitable sources of fodder for grazing livestock.