The 2023 MDPI Annual Report has
been released!
 
7 pages, 2333 KiB  
Case Report
HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases
by María Carmen Martínez-Romero, María Encarnación Hernández-Contreras, Juan Antonio Bafalliu-Vidal, María Barreda-Sánchez, Teresa Martínez-Menchón, Virginia Cabello-Chaves and Encarna Guillén-Navarro
Genes 2024, 15(6), 687; https://doi.org/10.3390/genes15060687 (registering DOI) - 26 May 2024
Abstract
HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, [...] Read more.
HELIX syndrome (Hypohidrosis–Electrolyte disturbances–hypoLacrimia–Ichthyosis–Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling. Full article
(This article belongs to the Special Issue Genetic Research on Monogenic Skin Disorders)
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13 pages, 3534 KiB  
Article
ATP Hydrolases Superfamily Protein 1 (ASP1) Maintains Root Stem Cell Niche Identity through Regulating Reactive Oxygen Species Signaling in Arabidopsis
by Qianqian Yu, Hongyu Li, Bing Zhang, Yun Song, Yueying Sun and Zhaojun Ding
Plants 2024, 13(11), 1469; https://doi.org/10.3390/plants13111469 (registering DOI) - 26 May 2024
Abstract
The maintenance of the root stem cell niche identity in Arabidopsis relies on the delicate balance of reactive oxygen species (ROS) levels in root tips; however, the intricate molecular mechanisms governing ROS homeostasis within the root stem cell niche remain unclear. In this [...] Read more.
The maintenance of the root stem cell niche identity in Arabidopsis relies on the delicate balance of reactive oxygen species (ROS) levels in root tips; however, the intricate molecular mechanisms governing ROS homeostasis within the root stem cell niche remain unclear. In this study, we unveil the role of ATP hydrolase superfamily protein 1 (ASP1) in orchestrating root stem cell niche maintenance through its interaction with the redox regulator cystathionine β-synthase domain-containing protein 3 (CBSX3). ASP1 is exclusively expressed in the quiescent center (QC) cells and governs the integrity of the root stem cell niche. Loss of ASP1 function leads to enhanced QC cell division and distal stem cell differentiation, attributable to reduced ROS levels and diminished expression of SCARECROW and SHORT ROOT in root tips. Our findings illuminate the pivotal role of ASP1 in regulating ROS signaling to maintain root stem cell niche homeostasis, achieved through direct interaction with CBSX3. Full article
(This article belongs to the Special Issue Plant Root: Anatomy, Structure and Development)
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12 pages, 2042 KiB  
Article
FLT3-TKD Measurable Residual Disease Detection Using Droplet Digital PCR and Clinical Applications in Acute Myeloid Leukemia
by Eric Wenlong Li, Ngoc Yen Kim Tran, Derek McCulloch, Michael Krigstein, Alberto Catalano, Jad Othman, Edward Abadir, Cheryl Smith and Harry Iland
Int. J. Mol. Sci. 2024, 25(11), 5771; https://doi.org/10.3390/ijms25115771 (registering DOI) - 26 May 2024
Abstract
The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This [...] Read more.
The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common FLT3-TKD mutations (D835Y, D835H, D835V, D835E). Twenty-two diagnostic samples, six donor controls, and a commercial D835Y positive control were tested using a commercial Bio-rad® ddPCR assay. All known variants were identified, and no false positives were detected in the wild-type control (100% specificity and sensitivity). The assays achieved a limit of detection suitable for MRD testing at 0.01% variant allelic fraction. Serial samples from seven intensively-treated patients with FLT3-TKD variants at diagnosis were tested. Five patients demonstrated clearance of FLT3-TKD clones, but two patients had FLT3-TKD persistence in the context of primary refractory disease. In conclusion, ddPCR is suitable for the detection and quantification of FLT3-TKD mutations in the MRD setting; however, the clinical significance and optimal management of MRD positivity require further exploration. Full article
(This article belongs to the Special Issue Leukemia: Present and Future)
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13 pages, 1981 KiB  
Article
N-Acetylcysteine Alleviates Impaired Muscular Function Resulting from Sphingosine Phosphate Lyase Functional Deficiency-Induced Sphingoid Base and Ceramide Accumulation in Caenorhabditis elegans
by Min Liu, Yunfei You, Huaiyi Zhu, Yu Chen, Zhenying Hu and Jingjing Duan
Nutrients 2024, 16(11), 1623; https://doi.org/10.3390/nu16111623 (registering DOI) - 26 May 2024
Abstract
Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency [...] Read more.
Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency in Caenorhabditis elegans using spl-1 RNA interference. Within these SPL-deficient nematodes, we observed diminished motility and perturbed muscle fiber organization, correlated with the accumulation of sphingoid bases, their phosphorylated forms, and ceramides (collectively referred to as the “sphingolipid rheostat”). The disturbance in mitochondrial morphology was also notable, as SPL functional loss resulted in heightened levels of reactive oxygen species. Remarkably, the administration of the antioxidant N-acetylcysteine (NAC) ameliorates locomotor impairment and rectifies muscle fiber disarray, underscoring its therapeutic promise for ceramide-accumulation-related muscle disorders. Our findings emphasize the pivotal role of SPL in preserving muscle integrity and advocate for exploring antioxidant interventions, such as NAC supplementation, as prospective therapeutic strategies for addressing muscle function decline associated with sphingolipid/ceramide metabolism disruption. Full article
(This article belongs to the Special Issue Dietary Lipid and Human Health)
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13 pages, 2747 KiB  
Article
Effect of CRISPR/Cas9 Targets Associated with Iron Metabolism and Its Variation on Transcriptional Regulation of SHK-1 Cell Line as a Model for Iron Metabolism
by Phillip Dettleff, Yehwa Jin, Carolina Peñaloza, Rodrigo Pulgar, Alejandro Sáez, Diego Robledo and Sebastian Escobar-Aguirre
Fishes 2024, 9(6), 198; https://doi.org/10.3390/fishes9060198 (registering DOI) - 26 May 2024
Abstract
In this study, we investigated the function of a gene associated with iron metabolism using CRISPR-Cas9 and RNA sequencing in SHK-1 salmon cells. Our objective was to understand how different guide RNA (gRNA) sequences against the transferrin gene tf could influence gene expression [...] Read more.
In this study, we investigated the function of a gene associated with iron metabolism using CRISPR-Cas9 and RNA sequencing in SHK-1 salmon cells. Our objective was to understand how different guide RNA (gRNA) sequences against the transferrin gene tf could influence gene expression and cellular processes related to iron uptake. RNA-Seq analysis was performed to evaluate the transcriptomic effects of two distinct gRNA targets with high knock-out (KO) efficiencies for the targeted tf gene in the SHK-1 genome. Our results showed no significant differential expression in transferrin-related transcripts between wild-type and CRISPR-edited cells; however, there were major differences between their transcriptomes, indicating complex transcriptional regulation changes. Enrichment analysis highlighted specific processes and molecular functions, including those related to the nucleus, cytoplasm, and protein binding. Notably, different sgRNAs targeting tf might result in different mutations at DNA levels in SHK-1 salmon cells. Full article
(This article belongs to the Special Issue Aquatic Animal Transgene and Gene Editing Technology)
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12 pages, 3661 KiB  
Article
An Enhanced Mask R-CNN Approach for Pulmonary Embolism Detection and Segmentation
by Kâmil Doğan, Turab Selçuk and Ahmet Alkan
Diagnostics 2024, 14(11), 1102; https://doi.org/10.3390/diagnostics14111102 (registering DOI) - 26 May 2024
Abstract
Pulmonary embolism (PE) refers to the occlusion of pulmonary arteries by blood clots, posing a mortality risk of approximately 30%. The detection of pulmonary embolism within segmental arteries presents greater challenges compared with larger arteries and is frequently overlooked. In this study, we [...] Read more.
Pulmonary embolism (PE) refers to the occlusion of pulmonary arteries by blood clots, posing a mortality risk of approximately 30%. The detection of pulmonary embolism within segmental arteries presents greater challenges compared with larger arteries and is frequently overlooked. In this study, we developed a computational method to automatically identify pulmonary embolism within segmental arteries using computed tomography (CT) images. The system architecture incorporates an enhanced Mask R-CNN deep neural network trained on PE-containing images. This network accurately localizes pulmonary embolisms in CT images and effectively delineates their boundaries. This study involved creating a local data set and evaluating the model predictions against pulmonary embolisms manually identified by expert radiologists. The sensitivity, specificity, accuracy, Dice coefficient, and Jaccard index values were obtained as 96.2%, 93.4%, 96.%, 0.95, and 0.89, respectively. The enhanced Mask R-CNN model outperformed the traditional Mask R-CNN and U-Net models. This study underscores the influence of Mask R-CNN’s loss function on model performance, providing a basis for the potential improvement of Mask R-CNN models for object detection and segmentation tasks in CT images. Full article
(This article belongs to the Special Issue Classification of Diseases Using Machine Learning Algorithms)
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13 pages, 1369 KiB  
Article
Piezoelectric Bone Conduction Hearing Implant: A Case Series of Audiological, Surgical and Patient-Reported Outcomes
by Mai Vagle, Michael Bille and Ramon Gordon Jensen
J. Clin. Med. 2024, 13(11), 3111; https://doi.org/10.3390/jcm13113111 (registering DOI) - 26 May 2024
Abstract
Objective: To examine the surgical, audiological and patient-reported outcomes of the Osia 2 implant. Methods: Data from 14 consecutive subjects undergoing implantation between April 2022 and November 2023 were reviewed. Ten subjects had conductive hearing loss, three had mixed hearing loss [...] Read more.
Objective: To examine the surgical, audiological and patient-reported outcomes of the Osia 2 implant. Methods: Data from 14 consecutive subjects undergoing implantation between April 2022 and November 2023 were reviewed. Ten subjects had conductive hearing loss, three had mixed hearing loss and one had single-sided deafness (SSD). Warble tone thresholds, Pure Tone Average (PTA4) and Speech Discrimination Score (SDS) in quiet and in noise were determined unaided and aided. The subjective outcome was determined from two standardized questionnaires: (1) International Outcome Inventory for Hearing Aids (IOI-HA) and (2) Speech, Spatial and Qualities of Hearing Scale 12 (SSQ12b). Results: Unexpected postoperative pain was found in four cases. The warble tone thresholds exhibited a consistent reduction across all frequencies, contributing to a mean decrease of 27 dB in the aided PTA4. SDS demonstrated notable improvements, with a 57.3% increase at 50 dB and a 55.6% increase at 65 dB. In noise, SDS exhibited a 43.9% improvement. The mean IOI-HA Score was 3.8, and the mean overall score for SSQ12b was 6.6, with consistent findings across the subgroups. Conclusions: The Osia device emerges as a promising recommendation for individuals with conductive or mixed hearing loss, possibly also for those with SSD. Its safety and efficacy profile aligns with the broader category of active transcutaneous devices, demonstrating a reduced risk of wound infection compared to percutaneous alternatives. Both audiological assessments and subjective evaluations revealed positive outcomes. Full article
(This article belongs to the Special Issue Advances in the Diagnosis, Treatment, and Prognosis of Hearing Loss)
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8 pages, 412 KiB  
Brief Report
Effect of Acute Dietary Nitrate Supplementation on the Changes in Calf Venous Volume during Postural Change and Skeletal Muscle Pump Activity in Healthy Young Adults
by Anna Oue, Yasuhiro Iimura, Yuichi Miyakoshi and Masako Ota
Nutrients 2024, 16(11), 1621; https://doi.org/10.3390/nu16111621 (registering DOI) - 26 May 2024
Abstract
Dietary nitrate (NO3) supplementation is known to enhance nitric oxide (NO) activity and acts as a vasodilator. In this randomized crossover study, we investigated the effect of inorganic NO3 supplementation on the changes in calf venous volume during [...] Read more.
Dietary nitrate (NO3) supplementation is known to enhance nitric oxide (NO) activity and acts as a vasodilator. In this randomized crossover study, we investigated the effect of inorganic NO3 supplementation on the changes in calf venous volume during postural change and subsequent skeletal muscle pump activity. Fifteen healthy young adults were assigned to receive beetroot juice (BRJ) or a NO3-depleted control beverage (prune juice: CON). Two hours after beverage consumption, the changes in the right calf volume during postural change from supine to upright and a subsequent right tiptoe maneuver were measured using venous occlusion plethysmography. The increase in calf volume from the supine to upright position (total venous volume [VV]) and the decrease in calf volume during the right tiptoe maneuver (venous ejection volume [Ve]) were calculated. Plasma NO3 concentration was higher in the BRJ group than in the CON group 2 h after beverage intake (p < 0.05). However, VV and Ve did not differ between CON and BRJ. These results suggest that acute intake of BRJ may enhance NO activity via the NO3 → nitrite → NO pathway but does not change calf venous pooling due to a postural change or the calf venous return due to skeletal muscle pump activity in healthy young adults. Full article
(This article belongs to the Special Issue Effects of Phytochemicals on Human Health)
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15 pages, 1753 KiB  
Article
Odour Fingerprints of Black (Tuber mesentericum) and Bianchetto (Tuber borchii) Truffles from Different Areas of the Campania Region
by Andrea Balivo, Enrica De Falco, Luca Branca, Michele Caputo, Raffaele Sacchi and Alessandro Genovese
Horticulturae 2024, 10(6), 557; https://doi.org/10.3390/horticulturae10060557 (registering DOI) - 25 May 2024
Abstract
In this study, E-nose and SPME-GC/MS were applied to compare the odour patterns and volatile compounds of two truffle species harvested in different areas of Campania (Southern Italy). In total, 107 Tuber mesentericum (black truffle) and 60 Tuber borchii (bianchetto truffle) truffles were [...] Read more.
In this study, E-nose and SPME-GC/MS were applied to compare the odour patterns and volatile compounds of two truffle species harvested in different areas of Campania (Southern Italy). In total, 107 Tuber mesentericum (black truffle) and 60 Tuber borchii (bianchetto truffle) truffles were sampled in areas of Avellino, Salerno, Benevento, and Caserta. The E-nose correctly discriminated between Tuber mesentericum and Tuber borchii truffles. The GC/MS analysis revealed qualitative-quantitative differences between Tuber mesentericum and Tuber borchii, with a prevalence of volatile phenols and aromatic compounds for the black truffle, which are responsible for smoky and floral aromas, and ketones, alcohols, aldehydes, and thiophene derivatives for the bianchetto truffle, mostly responsible for earthy mushroom- and garlic-like aromas. The discriminant analysis performed on the E-nose data pattern provided an average correct classification between 55 and 60% for the same species collected in different sites. Tuber borchii truffles were better discriminated based on the harvesting altitude (hilly and coastal areas). GC/MS revealed quantitative differences in the volatile compounds of truffles of the same species collected in different areas, with variations in abundance based on the harvesting site. The distinctive profile of volatile compounds could represent a useful chemical marker to be investigated to authenticate the truffle harvesting area. Full article
(This article belongs to the Section Postharvest Biology, Quality, Safety, and Technology)
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16 pages, 3797 KiB  
Article
Non-Targeted Detection of Synthetic Oligonucleotides in Equine Serum Using Liquid Chromatography–High-Resolution Mass Spectrometry
by Emily Helmes, Jacob Montgomery, Gwendolyne Alarcio, Herra G. Mendoza, Jeffrey A. Blea, Peter A. Beal and Benjamin C. Moeller
Int. J. Mol. Sci. 2024, 25(11), 5752; https://doi.org/10.3390/ijms25115752 (registering DOI) - 25 May 2024
Abstract
There is great concern in equine sport over the potential use of pharmaceutical agents capable of editing the genome or modifying the expression of gene products. Synthetic oligonucleotides are short, single-stranded polynucleotides that represent a class of agents capable of modifying gene expression [...] Read more.
There is great concern in equine sport over the potential use of pharmaceutical agents capable of editing the genome or modifying the expression of gene products. Synthetic oligonucleotides are short, single-stranded polynucleotides that represent a class of agents capable of modifying gene expression products with a high potential for abuse in horseracing. As these substances are not covered by most routine anti-doping analytical approaches, they represent an entire class of compounds that are not readily detectable. The nucleotide sequence for each oligonucleotide is highly specific, which makes targeted analysis for these agents problematic. Accordingly, we have developed a non-targeted approach to detect the presence of specific product ions that are not naturally present in ribonucleic acids. Briefly, serum samples were extracted using solid-phase extraction with a mixed-mode cartridge following the disruption of protein interactions to isolate the oligonucleotides. Following the elution and concentration steps, chromatographic separation was achieved utilizing reversed-phase liquid chromatography. Following an introduction to a Thermo Q Exactive HF mass spectrometer using electrospray ionization, analytes were detected utilizing a combination of full-scan, parallel reaction monitoring and all ion fragmentation scan modes. The limits of detection were determined along with the accuracy, precision, stability, recovery, and matrix effects using a representative 13mer oligonucleotide. Following method optimization using the 13mer oligonucleotide, the method was applied to successfully detect the presence of specific product ions in three unique oligonucleotide sequences targeting equine-specific transcripts. Full article
(This article belongs to the Special Issue Gene Doping Control in Human and Animal Sports)
18 pages, 1393 KiB  
Article
Investigating the Effectiveness of a Carb-Free Oloproteic Diet in Fibromyalgia Treatment
by Giuseppe Castaldo, Carmen Marino, Mariangela Atteno, Maria D’Elia, Imma Pagano, Manuela Grimaldi, Aurelio Conte, Paola Molettieri, Angelo Santoro, Enza Napolitano, Ilaria Puca, Mariangela Raimondo, Chiara Parisella, Anna Maria D’Ursi and Luca Rastrelli
Nutrients 2024, 16(11), 1620; https://doi.org/10.3390/nu16111620 (registering DOI) - 25 May 2024
Abstract
Fibromyalgia (FM), a chronic disease with a high incidence in women, poses a significant challenge for diagnosis and treatment, especially due to the absence of specific biomarkers and the multifaceted nature of its symptoms, which range from neuromuscular pain to mood disorders and [...] Read more.
Fibromyalgia (FM), a chronic disease with a high incidence in women, poses a significant challenge for diagnosis and treatment, especially due to the absence of specific biomarkers and the multifaceted nature of its symptoms, which range from neuromuscular pain to mood disorders and intestinal dysbiosis. While diagnosis currently relies on rheumatological clinical evaluations and treatment options mainly focus on symptom management, FM seems to have possible links with systemic metabolic dysfunctions with a common inflammatory root. In this context, a new therapeutic avenue emerges: could a therapeutic nutritional approach be the missing piece of the puzzle? Indeed, diet therapies employed particularly for metabolic syndromes proved recently to be efficacious for correcting systemic dysmetabolism and a high number of chronic inflammation conditions. In particular, the very-low-calorie ketogenic diet (VLCKD) demonstrated therapeutic benefits in many disorders. In the present study, we aimed to investigate the specific effects of two dietary interventions, namely the oloproteic VLCKD and the low-glycemic insulinemic (LOGI) diet, on two groups of female FM patients (FM1 and FM2) over a 45-day period. Utilizing clinical and laboratory tests, as well as non-invasive NMR metabolomic analysis of serum, urine, and saliva samples, we sought to uncover how these dietary regimens impact the metabolic dysfunctions associated with FM. Full article
(This article belongs to the Section Carbohydrates)
30 pages, 17809 KiB  
Article
Enhancing Gene Co-expression Network Inference for the Malaria Parasite Plasmodium falciparum
by Qi Li, Katrina A. Button-Simons, Mackenzie A. C. Sievert, Elias Chahoud, Gabriel F. Foster, Kaitlynn Meis, Michael T. Ferdig and Tijana Milenković
Genes 2024, 15(6), 685; https://doi.org/10.3390/genes15060685 (registering DOI) - 25 May 2024
Abstract
Background: Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal Plasmodium (P.) species P. falciparum. A full P. falciparum genome was published in 2002, yet 44.6% of its genes have unknown functions. [...] Read more.
Background: Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal Plasmodium (P.) species P. falciparum. A full P. falciparum genome was published in 2002, yet 44.6% of its genes have unknown functions. Improving the functional annotation of genes is important for identifying drug targets and understanding the evolution of drug resistance. Results: Genes function by interacting with one another. So, analyzing gene co-expression networks can enhance functional annotations and prioritize genes for wet lab validation. Earlier efforts to build gene co-expression networks in P. falciparum have been limited to a single network inference method or gaining biological understanding for only a single gene and its interacting partners. Here, we explore multiple inference methods and aim to systematically predict functional annotations for all P. falciparum genes. We evaluate each inferred network based on how well it predicts existing gene–Gene Ontology (GO) term annotations using network clustering and leave-one-out crossvalidation. We assess overlaps of the different networks’ edges (gene co-expression relationships), as well as predicted functional knowledge. The networks’ edges are overall complementary: 47–85% of all edges are unique to each network. In terms of the accuracy of predicting gene functional annotations, all networks yielded relatively high precision (as high as 87% for the network inferred using mutual information), but the highest recall reached was below 15%. All networks having low recall means that none of them capture a large amount of all existing gene–GO term annotations. In fact, their annotation predictions are highly complementary, with the largest pairwise overlap of only 27%. We provide ranked lists of inferred gene–gene interactions and predicted gene–GO term annotations for future use and wet lab validation by the malaria community. Conclusions: The different networks seem to capture different aspects of the P. falciparum biology in terms of both inferred interactions and predicted gene functional annotations. Thus, relying on a single network inference method should be avoided when possible. Supplementary data: Attached. Full article
22 pages, 3523 KiB  
Article
Design and Experiment of Toggle Lever-Type Potato Picker
by Kailiang Lu, Shengshi Xie, Xiuzhi Gai and Xinjie Ji
Agriculture 2024, 14(6), 826; https://doi.org/10.3390/agriculture14060826 (registering DOI) - 25 May 2024
Abstract
To address the issues of significant soil blockage and high potato damage rates in current potato picking machines, this study developed a toggle lever-type potato picker designed to minimize potato damage and improve operational efficiency. Design calculations were performed for the picker components, [...] Read more.
To address the issues of significant soil blockage and high potato damage rates in current potato picking machines, this study developed a toggle lever-type potato picker designed to minimize potato damage and improve operational efficiency. Design calculations were performed for the picker components, and kinematic analyses were conducted for the toggle lever. Single-factor experiments were carried out to determine the variation in performance parameters of the potato picker under different experimental conditions. Discrete element simulations were performed to measure the peak soil height before the pick-up shovel and the peak force on potatoes during the pick-up process. A Box–Behnken response surface experiment was conducted using toggle lever speed, machine forward speed, and shovel angle as experiments factors. Subsequently, an analysis of variance was performed, and a mathematical regression model was established based on the experiments results. The findings revealed that at a toggle lever speed of 50 r/min, machine forward speed of 0.9 m/s, and shovel angle of 19°; the potato leakage rate was 2.32%, and the potato damage rate was 2.72%, thereby meeting the requirements stipulated by potato mechanized picking technology regulations. Full article
(This article belongs to the Section Agricultural Technology)
25 pages, 536 KiB  
Article
Risk Evaluation of Radioactive Concrete Structure Decommissioning in Nuclear Power Plants Using Fuzzy-AHP
by Hyosoo Moon, Seyedali Mirmotalebi, Youjin Jang, Yonghan Ahn and Nahyun Kwon
Buildings 2024, 14(6), 1536; https://doi.org/10.3390/buildings14061536 (registering DOI) - 25 May 2024
Abstract
Over 50% of nuclear power plants (NPPs) worldwide have operated for over three decades, leading to a surge in decommissioning projects. This study addresses the gap in current guidelines by analyzing risks in nuclear decommissioning. Using the fuzzy-AHP technique, tasks within dismantling radioactive [...] Read more.
Over 50% of nuclear power plants (NPPs) worldwide have operated for over three decades, leading to a surge in decommissioning projects. This study addresses the gap in current guidelines by analyzing risks in nuclear decommissioning. Using the fuzzy-AHP technique, tasks within dismantling radioactive concrete structures are prioritized. Findings reveal structural and human-related risks across five main cutting tasks. Collision emerges as a significant concern, particularly during wire saw installation and concrete block hoisting hole creation. Subcategory risk priorities highlight variations in risk across tasks, with jamming, falling, and falling objects identified as top concerns during wire saw transportation. This study emphasizes the importance of comprehensive risk assessment in enhancing safety during decommissioning. It underscores the need to consider both physical risks and risks to personnel throughout the process. By prioritizing safety, stakeholders can ensure worker safety and operational efficiency while minimizing hazards. This research contributes to standardized safety protocols for nuclear decommissioning worldwide, aligning with sustainable energy practices. The outcomes offer practical insights for safety manual development and decision-making processes. This study represents progress in ensuring safety during nuclear decommissioning, paving the way for further refinement of safety protocols and guidelines tailored to decommissioning sites. Full article
(This article belongs to the Special Issue Advanced Technologies for Urban and Architectural Design)
19 pages, 4378 KiB  
Article
Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing
by João P. N. Silva, Bárbara Pinto, Luís Monteiro, Patrícia M. A. Silva and Hassan Bousbaa
Cancers 2024, 16(11), 2014; https://doi.org/10.3390/cancers16112014 (registering DOI) - 25 May 2024
Abstract
Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting [...] Read more.
Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting KSP and AurB selectively affect dividing cells and have shown significant activity in vitro. However, these drugs, despite advancing to clinical trials, often yield unsatisfactory outcomes as monotherapy, likely due to variable responses driven by cyclin B degradation and apoptosis signal accumulation networks. Accumulated data suggest that combining emerging antimitotics with various cytostatic drugs can enhance tumor-killing effects compared to monotherapy. Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. The combination of BH3-mimetics with both KSP and AurB inhibitors synergistically induced substantial cell death, primarily through apoptosis. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness. Full article
(This article belongs to the Topic Recent Advances in Anticancer Strategies)
19 pages, 483 KiB  
Article
Interpersonal and Intrapersonal Skills for Sustainability in the Educational Robotics Classroom
by David Llanos-Ruiz, Vanesa Ausin-Villaverde and Victor Abella-Garcia
Sustainability 2024, 16(11), 4503; https://doi.org/10.3390/su16114503 (registering DOI) - 25 May 2024
Abstract
Education is an indispensable tool for improving social sustainability. In the school context, a wide variety of methodologies are being considered to achieve this goal by promoting cultural and experiential sustainability through educational and technological innovation. Educational robotics is an educational–formative context that [...] Read more.
Education is an indispensable tool for improving social sustainability. In the school context, a wide variety of methodologies are being considered to achieve this goal by promoting cultural and experiential sustainability through educational and technological innovation. Educational robotics is an educational–formative context that makes it possible to develop new learning environments, enhance sustainable curriculum development, and promote active student participation. The general objective of this research is to analyze the perceptions of teachers of technology, robotics, and/or programming and to study the social benefits of interpersonal, intrapersonal, and/or academic skills of students to improve curricular sustainability during the teaching–learning process from the perspective of robotics and programming in students in early childhood education, primary education, compulsory secondary education, and other educational levels in formal and non-formal education. The study sample included 115 teachers of technology, programming, and/or robotics (50.4% male, 49.6% female). The research was carried out using a quantitative, retrospective, and cohort methodology through a cross-sectional, non-experimental, and non-longitudinal study over time. A questionnaire specifically designed to collect data from the participating teachers was used. According to the results obtained, educational robotics is a multidisciplinary learning tool that enhances the development of skills such as personal autonomy, collaborative work, and emotional management, motivates the acquisition of knowledge based on practice, promotes curricular sustainability, and creates a new learning context where the teacher is the formative guide of the students and the students are engaged in their own learning. Full article
(This article belongs to the Special Issue Assessing Sustainability in Higher Education)
22 pages, 8295 KiB  
Article
Deletion of Glyoxalase 1 Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice
by Prakashkumar Dobariya, Wei Xie, Swetha Pavani Rao, Jiashu Xie, Davis M. Seelig, Robert Vince, Michael K. Lee and Swati S. More
Antioxidants 2024, 13(6), 648; https://doi.org/10.3390/antiox13060648 (registering DOI) - 25 May 2024
Abstract
Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can [...] Read more.
Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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18 pages, 1408 KiB  
Review
Adenosine A3 Receptor: From Molecular Signaling to Therapeutic Strategies for Heart Diseases
by Ratchanee Duangrat, Warisara Parichatikanond, Wisinee Chanmahasathien and Supachoke Mangmool
Int. J. Mol. Sci. 2024, 25(11), 5763; https://doi.org/10.3390/ijms25115763 (registering DOI) - 25 May 2024
Abstract
Cardiovascular diseases (CVDs), particularly heart failure, are major contributors to early mortality globally. Heart failure poses a significant public health problem, with persistently poor long-term outcomes and an overall unsatisfactory prognosis for patients. Conventionally, treatments for heart failure have focused on lowering blood [...] Read more.
Cardiovascular diseases (CVDs), particularly heart failure, are major contributors to early mortality globally. Heart failure poses a significant public health problem, with persistently poor long-term outcomes and an overall unsatisfactory prognosis for patients. Conventionally, treatments for heart failure have focused on lowering blood pressure; however, the development of more potent therapies targeting hemodynamic parameters presents challenges, including tolerability and safety risks, which could potentially restrict their clinical effectiveness. Adenosine has emerged as a key mediator in CVDs, acting as a retaliatory metabolite produced during cellular stress via ATP metabolism, and works as a signaling molecule regulating various physiological processes. Adenosine functions by interacting with different adenosine receptor (AR) subtypes expressed in cardiac cells , including A1AR, A2AAR, A2BAR, and A3AR. In addition to A1AR, A3AR has a multifaceted role in the cardiovascular system, since its activation contributes to reducing the damage to the heart in various pathological states, particularly ischemic heart disease, heart failure, and hypertension, although its role is not as well documented compared to other AR subtypes. Research on A3AR signaling has focused on identifying the intricate molecular mechanisms involved in CVDs through various pathways, including Gi or Gq protein-dependent signaling, ATP-sensitive potassium channels, MAPKs, and G protein-independent signaling. Several A3AR-specific agonists, such as piclidenoson and namodenoson, exert cardioprotective impacts during ischemia in the diverse animal models of heart disease. Thus, modulating A3ARs serves as a potential therapeutic approach, fueling considerable interest in developing compounds that target A3ARs as potential treatments for heart diseases. Full article
(This article belongs to the Special Issue Adenosine Receptors in Health and Disease)
21 pages, 7362 KiB  
Article
Numerical Study on the Mechanical Behavior of Sand–Rubber Mixtures under True Triaxial Tests
by Yiming Liu, Xiang Gao, Huiru Dou, Liu Yang and Zhangshuaihang Cao
Appl. Sci. 2024, 14(11), 4560; https://doi.org/10.3390/app14114560 (registering DOI) - 25 May 2024
Abstract
A series of numerical true triaxial compression tests were carried out on rubber–sand mixtures (RSMs) by means of the 3D discrete element method to study the effect of the intermediate principal stress ratio b on the failure properties of RSMs with different rubber [...] Read more.
A series of numerical true triaxial compression tests were carried out on rubber–sand mixtures (RSMs) by means of the 3D discrete element method to study the effect of the intermediate principal stress ratio b on the failure properties of RSMs with different rubber contents (RCs), and to explore the effect mechanism from a microscopic point of view. The numerical simulation results show that as the intermediate principal stress ratio b increases and the peak deviator stress qpeak gradually increases, while the peak internal friction angle φb first increases and then decreases. The numerical simulation results were compared with four common strength criteria, including the modified Lade–Duncan criterion, the SMP criterion, the FKZ criterion and the DP criterion. The comparative analysis showed that the existing common criteria cannot accurately predict the damage state of RSMs, suggesting the necessity for further research. At the micro level, the combined effects of the intermediate principal stress ratio b values and RC on the micro-parameters, such as the coordination number, average normal stress between particles, probability density and anisotropy, were investigated. Full article
(This article belongs to the Section Additive Manufacturing Technologies)
19 pages, 2817 KiB  
Article
Hydrogen Gas Compression for Efficient Storage: Balancing Energy and Increasing Density
by Alessandro Franco and Caterina Giovannini
Hydrogen 2024, 5(2), 293-311; https://doi.org/10.3390/hydrogen5020017 (registering DOI) - 25 May 2024
Abstract
This article analyzes the processes of compressing hydrogen in the gaseous state, an aspect considered important due to its contribution to the greater diffusion of hydrogen in both the civil and industrial sectors. This article begins by providing a concise overview and comparison [...] Read more.
This article analyzes the processes of compressing hydrogen in the gaseous state, an aspect considered important due to its contribution to the greater diffusion of hydrogen in both the civil and industrial sectors. This article begins by providing a concise overview and comparison of diverse hydrogen-storage methodologies, laying the groundwork with an in-depth analysis of hydrogen’s thermophysical properties. It scrutinizes plausible configurations for hydrogen compression, aiming to strike a delicate balance between energy consumption, derived from the fuel itself, and the requisite number of compression stages. Notably, to render hydrogen storage competitive in terms of volume, pressures of at least 350 bar are deemed essential, albeit at an energy cost amounting to approximately 10% of the fuel’s calorific value. Multi-stage compression emerges as a crucial strategy, not solely for energy efficiency, but also to curtail temperature rises, with an upper limit set at 200 °C. This nuanced approach is underlined by the exploration of compression levels commonly cited in the literature, particularly 350 bar and 700 bar. The study advocates for a three-stage compression system as a pragmatic compromise, capable of achieving high-pressure solutions while keeping compression work below 10 MJ/kg, a threshold indicative of sustainable energy utilization. Full article
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16 pages, 1706 KiB  
Review
The Role of Plant Ubiquitin-like Modifiers in the Formation of Salt Stress Tolerance
by Siarhei A. Dabravolski and Stanislav V. Isayenkov
Plants 2024, 13(11), 1468; https://doi.org/10.3390/plants13111468 (registering DOI) - 25 May 2024
Abstract
The climate-driven challenges facing Earth necessitate a comprehensive understanding of the mechanisms facilitating plant resilience to environmental stressors. This review delves into the crucial role of ubiquitin-like modifiers, particularly focusing on ATG8-mediated autophagy, in bolstering plant tolerance to salt stress. Synthesising recent research, [...] Read more.
The climate-driven challenges facing Earth necessitate a comprehensive understanding of the mechanisms facilitating plant resilience to environmental stressors. This review delves into the crucial role of ubiquitin-like modifiers, particularly focusing on ATG8-mediated autophagy, in bolstering plant tolerance to salt stress. Synthesising recent research, we unveil the multifaceted contributions of ATG8 to plant adaptation mechanisms amidst salt stress conditions, including stomatal regulation, photosynthetic efficiency, osmotic adjustment, and antioxidant defence. Furthermore, we elucidate the interconnectedness of autophagy with key phytohormone signalling pathways, advocating for further exploration into their molecular mechanisms. Our findings underscore the significance of understanding molecular mechanisms underlying ubiquitin-based protein degradation systems and autophagy in salt stress tolerance, offering valuable insights for designing innovative strategies to improve crop productivity and ensure global food security amidst increasing soil salinisation. By harnessing the potential of autophagy and other molecular mechanisms, we can foster sustainable agricultural practices and develop stress-tolerant crops resilient to salt stress. Full article
(This article belongs to the Special Issue Mitigation Strategies and Tolerance of Plants to Abiotic Stresses)
15 pages, 1866 KiB  
Article
Amelioration of Insulin Resistance by Whey Protein in a High-Fat Diet-Induced Pediatric Obesity Male Mouse Model
by Kengo Matsuda, Nobuhiko Nagano, Kimitaka Nakazaki, Daichi Katayama, Wataru Tokunaga, Koh Okuda, Shoichi Shimizu, Ryoji Aoki, Kazumasa Fuwa, Keisuke Shirai, Kazumichi Fujioka and Ichiro Morioka
Nutrients 2024, 16(11), 1622; https://doi.org/10.3390/nu16111622 (registering DOI) - 25 May 2024
Abstract
This study examined whey protein’s impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. [...] Read more.
This study examined whey protein’s impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Full article
21 pages, 550 KiB  
Article
Digital Wallet, Happy Heart: An Analysis Based on the Economic–Social–Environmental Perspective
by Xiaomei Gong, Huirong Zhang and Jiaping Zhang
J. Theor. Appl. Electron. Commer. Res. 2024, 19(2), 1222-1242; https://doi.org/10.3390/jtaer19020063 (registering DOI) - 25 May 2024
Abstract
While the prior mobile payment−subjective well-being (SWB) literature has mainly discussed its economic and social impacts, the present study supplements this body of research by introducing an economic–social–environmental perspective. Using two waves of representative Chinese national surveys, the instrumental variable (IV) estimator suggests [...] Read more.
While the prior mobile payment−subjective well-being (SWB) literature has mainly discussed its economic and social impacts, the present study supplements this body of research by introducing an economic–social–environmental perspective. Using two waves of representative Chinese national surveys, the instrumental variable (IV) estimator suggests that mobile payment is positively and statistically significantly correlated with SWB. Furthermore, the results reveal that the positive correlation comes from the compound influence of economic, social, and environmental channels. Specifically, it shows that mobile payment not only affects people’s economic and social performance but also mitigates the adverse effects of poor environmental conditions on SWB. Additionally, a further disaggregated analysis shows that mobile payment exerts a stronger positive influence on SWB for people from underdeveloped areas within the economic–social–environmental framework. These findings shed light on the role of financial technology in facilitating sustainable development. Full article
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