ALBERT

Description: Background The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. Objective To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. Design In a cross-sectional design, long-term (n = 44, 〉 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC–MS/MS. Results Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P 

Description: Purpose Intermittent energy restriction (IER) is a popular weight loss (WL) strategy; however, its efficacy in clinical practice remains unknown. The present study compared the effects of IER compared to continuous energy restriction (CER) on WL and cardiometabolic risk factors in primary care. Methods A (self-selected) cohort study was conducted at the Rotherham Institute for Obesity (RIO), a primary care-based weight management service. 197(24% male) obese patients volunteered to participate and selected their diet group. IER participants (n = 99) consumed ~ 2600 kJ for two days/week. CER participants (n = 98) restricted their diet by ~ 2100 kJ/day below estimated requirements. Both interventions were delivered alongside RIO standard care. Changes in anthropometry and cardiometabolic disease risk markers (fasting biochemistry and blood pressure) were assessed after a 6-month intervention period and then participants were followed up again 6 months later (month 12). Results 27 IER patients (27%) and 39 CER patients (40%) completed the 6-month weight loss phase. Among completers, mean (SEM) WL was greater in the IER group at 6 months (5.4 ± 1.1% versus 2.8 ± 0.6%; p = 0.01), as were reductions in fat mass (p 

Description: Purpose Food-based dietary guidelines are proposed to not only improve diet quality, but to also reduce the environmental impact of diets. The aim of our study was to investigate whether food-related behavioral activation therapy (F-BA) applying Mediterranean-style dietary guidelines altered food intake and the environmental impact of the diet in overweight adults with subsyndromal symptoms of depression. Methods In total 744 adults who either received the F-BA intervention (F-BA group) or no intervention (control group) for 12 months were included in this analysis. Food intake data were collected through a food frequency questionnaire at baseline and after 6 and 12 months. Greenhouse gas emissions (GHGE), land use (LU), and fossil energy use (FEU) estimates from life-cycle assessments and a weighted score of the three (pReCiPe score) were used to estimate the environmental impact of each individual diet at each timepoint. Results The F-BA group reported increased intakes of vegetables (19.7 g/day; 95% CI 7.8–31.6), fruit (23.0 g/day; 9.4–36.6), fish (7.6 g/day; 4.6–10.6), pulses/legumes (4.0 g/day; 1.6–6.5) and whole grains (12.7 g/day; 8.0–17.5), and decreased intake of sweets/extras (− 6.8 g/day; − 10.9 to − 2.8) relative to control group. This effect on food intake resulted in no change in GHGE, LU, and pReCiPe score, but a relative increase in FEU by 1.6 MJ/day (0.8, 2.4). Conclusions A shift towards a healthier Mediterranean-style diet does not necessarily result in a diet with reduced environmental impact in a real-life setting. Trial registration ClinicalTrials.gov. Number of identification: NCT02529423. August 2015.

Description: Purpose Previously, the nutritional contribution, environmental and financial costs of dairy products have been examined independently. Our aim was to determine the nutritional adequacy, financial cost and environmental impact of UK diets according to dairy content. Methods In this cross-sectional study of adults (19–64 years) from the UK National Diet and Nutrition Survey years 1–4 (n = 1655), dietary intakes assessed from 4-day estimated food diaries were organized into quartiles (Q) total grams of dairy (milk, cheese, yogurt, dairy desserts) and analyzed using ANCOVA controlling for age, sex and energy intake with Bonferroni post hoc test for nutritional adequacy, Alternative Healthy Eating Index (AHEI-2010), environmental impact [greenhouse gas emissions (GHGE), eutrophication and acidification potentials], financial cost, markers of health and cardio-metabolic diseases. Results Nutritional adequacy, particularly for protein, calcium and iodine (+ 18 g, + 533 mg, + 95 g, respectively, all P 

Description: 〈h3〉Summary〈/h3〉 〈p〉〈em〉Background〈/em〉 It is well-known that long-chain non-coding RNA (LncRNA) plays an important role in the development of tumor. DANCR, which is one crucial part of the lncRNA family, has been shown to be involved in the invasion of various tumors. However, its molecular mechanism in pancreatic cancer remains unknown. 〈em〉Methods〈/em〉 qRT-PCR was used to detect the expression of DANCR, miR-135a mRNA in pancreatic cancer tissues or cells. E-cadherin and NLRP3 protein levels were measured by Western Blot. CCK-8, cell scratch, and transwell assays were applied to detect the proliferation and invasion of pancreatic cancer cells. Bioinformatical analysis and luciferase assay were performed to explore the relationship among DANCR, miR-135a and NLRP3. 〈em〉Results〈/em〉 In pancreatic cancer, DANCR was up-regulated while miR-135a was down-regulated. The over-expression of DANCR promoted the proliferation and invasion of pancreatic cancer cells. A negative relationship was found between DANCR and miR-135a expression. Moreover, we found that miR-135a reversed the effects of DANCR in the promoting of pancreatic cancer cells, which was achieved by regulating the downstream protein of NLRP3. The correlations among DANCR, miR-135a and NLRP3 were confirmed in animal experiments. 〈em〉Conclusion〈/em〉 DANCR promoted proliferation and invasion through the regulating of miR-135a / NLRP3 axis in pancreatic cancer cell. Our results suggest that DANCR may be a potential target for the therapy of pancreatic cancer.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉T cells are important effectors in anti-tumor immunity, and aberrant expression of B7 family members may contribute to tumor evasion. In this study, we analyzed expression of costimulatory molecules on human hematologic tumor cells and explored whether B7-H3, a member of the B7 superfamily, is an effective target for T cell mediated cytotoxicity toward hematologic malignancy. We investigated the bispecific antibody anti-CD3 × anti-B7-H3 (B7-H3Bi-Ab) for its ability to redirect T cells to target B7-H3 positive hematologic tumors, including Thp-1, K562, Daudi cells and a primary culture. The capacity of T cells armed with B7-H3Bi-Ab to kill hematologic tumors was evaluated by lactate dehydrogenase assay, flow cytometry, ELISA, and luciferase quantitative assay at an effector/target ratio of 5:1. Compared with unarmed T cells, B7-H3Bi-Ab-armed T cells exhibited significant cytotoxicity toward hematological tumor cells. Moreover, B7-H3Bi-Ab-armed T cells secreted more IFN-γ, TNF-α, IL-2, and Granzyme B and expressed higher levels of activating marker CD69 compared to unarmed T cells. In conclusion, B7-H3Bi-Ab enhances the ability of T cells to kill hematologic tumor cells, and B7-H3 may serve as a novel target for immunotherapy against hematologic malignancy.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Although there is documented evidence in the literature that 〈em〉Marinobacterium georgiense〈/em〉 González et al. 1997 and 〈em〉Pseudomonas iners〈/em〉 Iizuka and Komagata 1964 (Approved Lists 1980) should be treated as heterotypic synonyms, the nomenclatural consequences have not been implemented. Based on the rules of the International Code of Nomenclature of Prokaryotes when 〈em〉Marinobacterium georgiense〈/em〉 González et al. 1997 and 〈em〉Pseudomonas iners〈/em〉 Iizuka and Komagata 1964 (Approved Lists 1980) are considered to belong to the genus 〈em〉Marinobacterium〈/em〉 González et al. 1997, the earliest epithet (from the competing heterotypic synonyms) is to be used for the resulting taxon, i.e., the combination 〈em〉Marinobacterium iners〈/em〉 (Iizuka and Komagata 1964) must be created.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Coal-fired power stations are significant sources of soil contamination with heavy metals and a source of hazard to human health. The soil samples (〈em〉n〈/em〉 = 25) selected in the area around Novocherkassk Power Station (Rostov Region, Russia) within a radius of up to 20 km revealed the enrichment with Pb, Cu and Zn. The heavy metals (HM) content in soil is reduced in the following sequence: Mn 〉 Cr 〉 Zn 〉 Ni 〉 Cu 〉 Pb 〉 Co. The correlation diagrams of the HM total content in soils revealed a significant association between the following HM pairs: Cu–Pb, Ni–Cu, Cd–Ni, Cd–Cu (〈em〉r〈/em〉 ≥ 0.7, 〈em〉p〈/em〉 〈 0.001). The concentration coefficient (Kc) and the total pollution coefficient (Zc) were used to estimate anthropogenic pollution. The use of generalized additive model (GAM) to detect the dependence of HM distribution on factors revealed the significance of the source distance. The influence of wind rhumb on HM distribution has a complex nonlinear nature. A GAM shows a good performance for all data sets: 〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.71, 81% deviance explained for Zn, 〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.85, 91% deviance explained for Cd, 〈em〉R〈/em〉〈sup〉2〈/sup〉 = 0.63, 70% deviance explained for Ni. Thus, GAM model reveals significant factors (Dist_km, rhumb) in forming pollution by heavy metals in studied impact zone and proved a valuable approach to assess the degree and sources of pollution in soils on a large scale.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Ansamitocins are extraordinarily potent antitumor agents. Ansamitocin P-3 (AP-3), which is produced by 〈em〉Actinosynnema pretiosum〈/em〉, has been developed as a cytotoxic drug for breast cancer. Despite its importance, AP-3 is of limited applicability because of the low production yield. 〈em〉A. pretiosum〈/em〉 strain X47 was developed from 〈em〉A. pretiosum〈/em〉 ATCC 31565 by mutation breeding and shows a relatively high AP-3 yield. Here, we analyzed the 〈em〉A. pretiosum〈/em〉 X47 genome, which is ~8.13 Mb in length with 6693 coding sequences, 58 tRNA genes, and 15 rRNA genes. The DNA sequence of the ansamitocin biosynthetic gene cluster is highly similar to that of the corresponding cluster in 〈em〉A. pretiosum〈/em〉 ATCC 31565, with 99.9% identity. However, RT-qPCR analysis showed that the expression levels of ansamitocin biosynthetic genes were significantly increased in X47 compared with the levels in the wild-type strain, consistent with the higher yield of AP-3 in X47. The annotated complete genome sequence of this strain will facilitate understanding the molecular mechanisms of ansamitocin biosynthesis and regulation in 〈em〉A. pretiosum〈/em〉 and help further genetic engineering studies to enhance the production of AP-3.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The basidiomycete 〈em〉Ustilago maydis〈/em〉 is a biotrophic organism responsible for corn smut disease. In recent years, it has become one of the most promising models for biochemical and biotechnological research due to advantages, such as rapid growth, and easy genetic manipulation. In some aspects, this yeast is more similar to complex eukaryotes, such as humans, compared to standard laboratory yeast models. 〈em〉U. maydis〈/em〉 can be employed as a tool to explore physiological processes with more versatility than other fungi. Previously, 〈em〉U. maydis〈/em〉 was only considered as a phytopathogenic fungus, but different studies have shown its potential as a research model. Therefore, numerous promising studies have focused on deepening our understanding of the natural interactions, enzyme production, and biotechnological capacity. In this review, we explore general characteristics of 〈em〉U. maydis〈/em〉, both as pathogenic and “innocuous” basidiomycete. Additionally, a comparison with other yeast models focusing on genetic, biochemical, and biotechnological research are analyzed, to emphasize the versatility, dynamism, and novelty that 〈em〉U. maydis〈/em〉 has as a research model. In this review, we highlight the applications of the yeast form of the fungus; however, since the filamentous form is also of relevance, it is addressed in the present work, as well.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Avian virus infection remains one of the most important threats to the poultry industry. Pathogens such as avian influenza virus (AIV), avian infectious bronchitis virus (IBV), and infectious bursal disease virus (IBDV) are normally controlled by antibodies specific for surface proteins and cellular immune responses. However, standard vaccines aimed at inducing neutralizing antibodies must be administered annually and can be rendered ineffective because immune-selective pressure results in the continuous mutation of viral surface proteins of different strains circulating from year to year. Chicken T cells have been shown to play a crucial role in fighting virus infection, offering lasting and cross-strain protection, and offer the potential for developing universal vaccines. This review provides an overview of our current knowledge of chicken T cell immunity to viruses. More importantly, we point out the limitations and barriers of current research and a potential direction for future studies.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Recent high-throughput genome-wide sequencing studies have identified recurrent somatic mutations in myeloid neoplasms. An epigenetic regulator, 〈em〉Additional sex combs〈/em〉-〈em〉like 1〈/em〉 (〈em〉ASXL1〈/em〉), is one of the most frequently mutated genes in all subtypes of myeloid malignancies. 〈em〉ASXL1〈/em〉 mutations are also frequently detected in clonal hematopoiesis, which is associated with an increased risk of mortality. Therefore, it is important to understand how 〈em〉ASXL1〈/em〉 mutations contribute to clonal expansion and myeloid transformation in hematopoietic cells. Studies using 〈em〉ASXL1〈/em〉-depleted human hematopoietic cells and 〈em〉Asxl1〈/em〉 knockout mice have shown that deletion of wild-type ASXL1 protein leads to impaired hematopoiesis and accelerates myeloid malignancies via loss of interaction with polycomb repressive complex 2 proteins. On the other hand, 〈em〉ASXL1〈/em〉 mutations in myeloid neoplasms typically occur near the last exon and result in the expression of C-terminally truncated mutant ASXL1 protein. Biological studies and biochemical analyses of this variant have shed light on its dominant-negative and gain-of-function features in myeloid transformation via a variety of epigenetic changes. Based on these results, it would be possible to establish novel promising therapeutic strategies for myeloid malignancies harboring 〈em〉ASXL1〈/em〉 mutations by blocking interactions between ASXL1 and associating epigenetic regulators. Here, we summarize the clinical implications of 〈em〉ASXL1〈/em〉 mutations, the role of wild-type ASXL1 in normal hematopoiesis, and oncogenic functions of mutant ASXL1 in myeloid neoplasms.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉A Gram-negative, strictly aerobic, motile, rod-shaped bacterium with monopolar flagellum, designated as F51〈sup〉T〈/sup〉, was isolated from the skin ulcer of farmed Murray cod sampled from Zhejiang Province, China. Strain F51〈sup〉T〈/sup〉 grew at 4–37 °C (optimal temperature, 28 °C), pH 5.0–8.5 (optimal pH, 7.5) and NaCl concentration of 0–6.0% (w/v) (optimal concentration, 2.0%). Phylogenetic analysis based on average nucleotide identity (76.2–78.4%) and in silico DNA–DNA hybridization (22.3–23.2%) values revealed that strain F51〈sup〉T〈/sup〉 forms a distinct lineage in the clade of genus 〈em〉Pseudomonas〈/em〉 with less than 98.9% 16S rRNA gene sequence similarity to type strains of the genus and represents a novel species related most closely to 〈em〉Pseudomonas floridensis〈/em〉 LMG 30013〈sup〉T〈/sup〉. Three housekeeping genes (〈em〉rpoB〈/em〉, 〈em〉rpoD〈/em〉 and 〈em〉gyrB〈/em〉) of strain F51〈sup〉T〈/sup〉 were analysed to further confirm that the isolate is distinctly delineated from related 〈em〉Pseudomonas〈/em〉 species. Chemotaxonomic analysis indicated that the sole respiratory quinone of strain F51〈sup〉T〈/sup〉 is Q-9; its predominant cellular fatty acids are C〈sub〉16:0〈/sub〉, summed feature 3 (iso-C〈sub〉15:0〈/sub〉 2-OH and/or C〈sub〉16:1〈/sub〉〈em〉ω〈/em〉7〈em〉c〈/em〉), summed feature 8 (C〈sub〉18:1〈/sub〉〈em〉ω〈/em〉7〈em〉c〈/em〉 and/or C〈sub〉18:1〈/sub〉〈em〉ω〈/em〉6〈em〉c〈/em〉) and C〈sub〉10:0〈/sub〉 3-OH; and its major polar lipids consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified glycolipids, three unidentified phospholipids and an unidentified aminophosphoglycolipid. This composition is typical of the chemotaxonomic attributes of 〈em〉Pseudomonas〈/em〉. Based on its phenotypic, chemotaxonomic and phylogenetic features, strain F51〈sup〉T〈/sup〉 is considered to represent a novel species for which the name 〈em〉Pseudomonas ovata〈/em〉 sp. nov. is proposed. The type strain is F51〈sup〉T〈/sup〉 (= KCTC 62133〈sup〉T〈/sup〉 = MCCC 1K03458〈sup〉T〈/sup〉).〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Precise neuronal wiring is critical for the function of the nervous system and is ultimately determined at the level of individual synapses. Neurons integrate various intrinsic and extrinsic cues to form synapses onto their correct targets in a stereotyped manner. In the past decades, the nervous system of nematode (〈em〉Caenorhabditis elegans〈/em〉) has provided the genetic platform to reveal the genetic and molecular mechanisms of synapse formation and specificity. In this review, we will summarize the recent discoveries in synapse formation and specificity in 〈em〉C. elegans〈/em〉.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Purpose〈/h3〉 〈p〉The objective of this secondary analysis is to describe the types of commercial complementary foods (CCF) consumed by infants and young children enrolled in the European Childhood Obesity Project (CHOP), to describe the contribution of CCF to dietary energy intakes and to determine factors associated with CCF use over the first 2 years of life.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉The CHOP trial is a multicenter intervention trial in Germany, Belgium, Italy, Poland and Spain that tested the effect of varying levels of protein in infant formula on the risk for childhood obesity. Infants were recruited from October 2002 to June 2004. Dietary data on CCF use for this secondary analysis were taken from weighted, 3-day dietary records from 1088 infants at 9 time points over the first 2 years of life.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Reported energy intakes from CCF during infancy (4–9 months) was significantly higher (〈em〉p〈/em〉 ≤ 0.002) amongst formula-fed children compared to breastfed children. Sweetened CCF intakes were significantly higher (〈em〉p〈/em〉 ≤ 0.009) amongst formula-fed infants. Female infants were fed significantly less CCF and infant age was strongly associated with daily CCF intakes, peaking at 9 months of age. Infants from families with middle- and high-level of education were fed significantly less quantities of CCF compared to infants with parents with lower education. Sweetened CCF were very common in Spain, Italy and Poland, with over 95% of infants and children fed CCF at 9 and 12 months of age consuming at least one sweetened CCF. At 24 months of age, 68% of the CHOP cohort were still fed CCF.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉CCF comprised a substantial part of the diets of this cohort of European infants and young children. The proportion of infants being fed sweetened CCF is concerning. More studies on the quality of commercial complementary foods in Europe are warranted, including market surveys on the saturation of the Western European market with sweetened CCF products.〈/p〉 〈/span〉

Description: 〈p〉Authors of the original article have observed an inadvertent error in their manuscript post-publication.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉We determined mercury (Hg) concentrations in various tissues of Burmese pythons (〈em〉Python bivitattus〈/em〉; n = 227) caught in southwest Florida from 2012–2018 as part of a program to control this invasive species. Mercury ranged as high as 4.86 mg/kg in liver tissue from a snake that was 4.7 m long but overall averaged 0.12 ± 0.19 mg/kg in tail tips (n = 123). These levels were relatively low as compared to concentrations reported in pythons from Everglades National Park, a recognized Hg hotspot. These results show that snakes, particularly watersnakes, present another opportunity to biomonitor Hg at the aquatic-terrestrial interface. Although capturing snakes presents obvious challenges, which differ from sampling other taxa typically used in monitoring programs, taking advantage of this program to control an invasive species was cost effective and alleviated concerns about sampling and possibly reducing native snake populations.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Sirtuins are NAD〈sup〉+〈/sup〉-dependent protein deacylases and ADP-ribosyltransferases that are involved in a wide range of cellular processes including genome homeostasis and metabolism. Sirtuins are expressed in human and mouse oocytes yet their role during female gamete development are not fully understood. Here, we investigated the role of a mammalian sirtuin member, SIRT7, in oocytes using a mouse knockout (KO) model. 〈em〉Sirt7〈/em〉 KO females have compromised fecundity characterized by a rapid fertility decline with age, suggesting the existence of a diminished oocyte pool. Accordingly, 〈em〉Sirt7〈/em〉 KO females produced fewer oocytes and ovulated fewer eggs. Because of the documented role of SIRT7 in DNA repair, we investigated whether SIRT7 regulates prophase I when meiotic recombination occurs. 〈em〉Sirt7〈/em〉 KO pachynema-like staged oocytes had approximately twofold increased γH2AX signals associated with regions with unsynapsed chromosomes. Consistent with the presence of asynaptic chromosome regions, 〈em〉Sirt7〈/em〉 KO oocytes had fewer MLH1 foci (~one less), a mark of crossover-mediated repair, than WT oocytes. Moreover, this reduced level of crossing over is consistent with an observed twofold increased incidence of aneuploidy in Metaphase II eggs. In addition, we found that acetylated lysine 18 of histone H3 (H3K18ac), an established SIRT7 substrate, was increased at asynaptic chromosome regions suggesting a functional relationship between this epigenetic mark and chromosome synapsis. Taken together, our findings demonstrate a pivotal role for SIRT7 in oocyte meiosis by promoting chromosome synapsis and have unveiled the importance of SIRT7 as novel regulator of the reproductive lifespan.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Although a high number of wet compresses are prescribed daily in medical institutions in Japan, our understanding of the national burden of the cost of wet compresses and the details regarding their prescription is far from complete. We investigated the national burden of the annual pharmaceutical cost of wet compresses prescribed in Japan and estimated the predictors of this cost using nationwide health insurance claims data.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉We extracted the records on wet compress products from summary table files obtained from the second version of the “NDB Open Data Japan” website and calculated the annual pharmaceutical cost of wet compresses by patients’ 5-year age group, sex, and prefecture. We also conducted an ecological study treating each prefecture as an individual unit and multiple linear regression analyses using the age-standardized cost of wet compresses per resident as a dependent variable.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉The annual pharmaceutical cost of wet compresses prescribed in Japan in fiscal year 2015 was 149.0 billion Japanese yen (1.18 billion euros; 1.33 billion USD). Multiple linear regression analyses showed that the number of orthopedists and rehabilitation physicians per 100,000 residents were significantly positively associated with the annual pharmaceutical cost of wet compresses per resident (〈em〉P〈/em〉 = 0.042 and 〈em〉P〈/em〉 = 0.008, respectively).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉The annual pharmaceutical cost of wet compresses prescribed in Japan has a considerable impact on the nation’s limited healthcare resources. The number of orthopedists and rehabilitation physicians per 100,000 residents may be independent predictors of the wet compress cost in Japan.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉〈em〉Amynthas agrestis〈/em〉 and 〈em〉Metaphire hilgendorfi〈/em〉 are being distributed across North America with unknown ecosystem impacts. Forest soils in urban areas sequester trace elements and earthworms may be bioaccumulating them. This study examined Cd, Cr, Co, Cu, Mn, Ni, Pb, V, and Zn in soils and earthworm tissues at 28 urban forest sites in and surrounding Poughkeepsie, NY, USA. Megascolecidae were present at 22 sites with means of 12 to 27 individuals m〈sup〉−2〈/sup〉 and 4 to 12 dry weight g m〈sup〉−2〈/sup〉. Urban forest soils within commercial uses had Mn, Pb, and Zn concentrations higher than within residential and agricultural uses. Earthworm trace element concentrations were poorly predicted by their respective soil concentrations, except for Pb. Urban forests in commercial uses and land-preserves, earthworm Cd and Pb concentrations were at or above concentrations known to negatively impact small mammal and bird health ( 〉 10 mg kg〈sup〉−1〈/sup〉) with Co and V approaching toxic concentrations.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉Vitamin K〈sub〉3〈/sub〉, also known as menadione, is a synthetic lipid-soluble 2-methyl-1,4- naphthoquinone analogs of vitamin K. The vitamin K derivatives exhibit potent cytotoxicity against several cancer cell lines through ROS induction and mitochondrial dysfunction. We investigated vitamin K〈sub〉3〈/sub〉-inspired derivatives as potential apoptotic inducers and analyzed their mechanisms beyond apoptosis. The cytotoxicity of a panel of vitamin K〈sub〉3〈/sub〉 analogs was screened against 10 doxorubicin-sensitive and -resistant cancer cell lines overexpressing ATP-binding cassette transporters (P-glycoprotein, ABCB5, BCRP) or oncogenes (ΔEGFR) or with knockout of tumor suppressors (p53), Cell cycle arrest, apoptosis, cell migration, and microtubule formation were further investigated. The online tool SwissTargetPrediction was utilized for target prediction. Among the screened compounds, one vitamin K〈sub〉3〈/sub〉 thio-derivative (No. 45, VKT-1) exhibited the most potent cytotoxicity specifically against both drug-sensitive and -resistant cancer cell lines. In addition, VKT-1 arrested the cells at the G2/M phase and induced apoptosis as detected by flow cytometry. As predicted by SwissTargetPrediction, VKT-1 targeted microtubule-associated tau protein. Indeed, VKT-1 dramatically inhibited cell migration and microtubule formation 〈em〉in vitro〈/em〉. In conclusion, the synthetic vitamin K〈sub〉3〈/sub〉 thio-derivative (VKT-1〈strong〉)〈/strong〉 inhibited doxorubicin-sensitive and -resistant tumor cells by cell arrest, apoptosis induction, as well as, migration inhibition, and microtubule deterioration of U2OS-GFP-α-tubulin cells.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉Rucaparib, a poly(ADP-ribose) polymerase inhibitor, is licensed for use in recurrent ovarian, fallopian tube, or primary peritoneal cancer. We characterized the absorption, distribution, metabolism, and elimination of rucaparib in 6 patients with advanced solid tumors following a single oral dose of [〈sup〉14〈/sup〉C]-rucaparib 600 mg (≈140 μCi). Total radioactivity (TRA) in blood, plasma, urine, and feces was measured using liquid scintillation counting. Unchanged rucaparib concentrations in plasma were determined using validated liquid chromatography with tandem mass spectrometry. Maximum concentration (C〈sub〉max〈/sub〉) of TRA and unchanged rucaparib in plasma was 880 ng Eq/mL and 428 ng/mL, respectively, at approximately 4 h post dose; terminal half-life was 〉25 h for both TRA and rucaparib. The plasma TRA-time profile was parallel to yet higher than that of rucaparib, suggesting the presence of metabolites in plasma. Mean blood:plasma ratio of radioactivity was 1.0 for C〈sub〉max〈/sub〉 and 0.8 for area under the concentration-time curve from time zero to infinity. Mean postdose recovery of TRA was 89.3% over 12 days (71.9% in feces; 17.4% in urine). Unchanged rucaparib and M324 (oxidative metabolite) were the major components in plasma, contributing to 64.0% and 18.6% of plasma radioactivity, respectively. Rucaparib and M324 were the major rucaparib-related components (each ≈7.6% of dose) in urine, whereas rucaparib was the predominant component (63.9% of dose) in feces. The high fecal recovery of unchanged rucaparib could be attributed to hepatic excretion and/or incomplete oral absorption. Overall, these data suggest that rucaparib is eliminated through multiple pathways, including metabolism and renal and biliary excretion.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The main expression sites of HLA-G are human extravillous trophoblast cells. The interaction of HLA-G with uterine NK cells promotes their maturation and differentiation into decidual NK (dNK) cells. dNK cells secrete chemokines, cytokines, and proangiogenic factors in favor of a vascular remodeling and an immune suppressive microenvironment of the decidua. HLA-G is the most polymorphic member of the oligomorphic non-classical HLA molecule family; yet, the impact of polymorphic differences is not comprehensively understood. sHLA-G levels in embryo culture medium correlate with successful pregnancy; however, it remains questionable if HLA-G allelic diversity impacts on the outcome of dNK cell development. We utilized synthetic 〈em〉sHLA-G*01:01〈/em〉, 〈em〉01:03〈/em〉, and 〈em〉01:04〈/em〉 molecules and transduced 〈em〉K652/mHLA-G*01:01〈/em〉, 〈em〉01:03〈/em〉, and 〈em〉01:04〈/em〉 cells to study the biological interaction between HLA-G alleles and primary NK cells of human term placenta. Despite its low frequency, 〈em〉HLA-G*01:04〈/em〉 and not the most prevalent allele 〈em〉HLA-G*01:01〈/em〉 appear to be strong catalysts of dNK cell proliferation. Concluding, this study illustrates novel insights into the impact and binding efficiency of the three most common variants of HLA-G on primary placental NK cells.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉This study summarized existing adsorption technologies for the removal of elemental mercury in the flue gas. Both carriers (e.g., active carbon (AC), pyrolyzed char, inorganic adsorbents and fly ash) and various modification methods (pore structure improvement, oxygen-containing functional groups addition and new active reagents impregnation) were compared to shed light on the development of future adsorption technology. AC and char possibly performed more mercury adsorption capacity (MAC) compared with fly ash and inorganic adsorbents since carbon atom existence was easier to form the active halogen groups (C–X) and oxygen containing groups. Though both pore structure improvement and chemical group formation improved the MAC of adsorbents, the chemical modification methods (oxygen-containing functional groups addition and new active reagents impregnation) were more effective. The impregnation of halogen, sulfur and metal chloride could distinctly form lots of active sites on the adsorbents and developed high effective mercury adsorbents. In the future, the adsorption researches possibly focus on SO〈sub〉2〈/sub〉 and H〈sub〉2〈/sub〉O resistance of adsorbents, separable adsorbents, low-cost chemical modification methods, and utilization potential of fly ash.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Objective〈/h3〉 〈p〉Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, 〈em〉n〈/em〉 = 12; healthy control group,〈em〉 n〈/em〉 = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [V〈sub〉d〈/sub〉], maximum (or peak) serum concentration [〈em〉C〈/em〉〈sub〉max〈/sub〉], amount of time drug is present in serum at C〈sub〉max〈/sub〉 [T〈sub〉max〈/sub〉], area under the curve [AUC; total drug exposure across time], mean residence time [MRT] and elimination half-life [t〈sub〉1/2〈/sub〉]) were calculated.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉The demographic characteristics of the two groups were not significantly different, with the exception of renal function. The mean 〈em〉C〈/em〉〈sub〉max〈/sub〉 and AUC〈sub〉0-t〈/sub〉 (AUC from time 0 to the last measurable concentration) of imrecoxib in the renal insufficiency group were 59 and 70%, respectively, of those of the healthy control volunteers with normal renal function, indicating a significant decline in the former group (〈em〉P〈/em〉 〈 0. 05). The mean pharmacokinetic parameters of Ml in the renal insufficiency and healthy control groups did not significantly differ. In contrast, the mean 〈em〉C〈/em〉〈sub〉max〈/sub〉 and AUC〈sub〉0-t〈/sub〉 of M2 in the renal insufficiency group were 233 and 367%, respectively, of those of the normal renal function group, indicating a significant increase in the former group (〈em〉P〈/em〉 〈 0.05). The mean CL/F (clearance/bioavailability) of M2 of the renal insufficiency group was 37% of that of the normal renal function group, indicating a notable reduction in the former group (〈em〉P〈/em〉 〈 0.05).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.〈/p〉 〈/span〉

Description: 〈p〉Every author has erroneously been assigned to the affiliation “62”. The affiliation 62 belongs to the author Graham Casey.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉To determine the function of miR-206 in epilepsy. Epileptic rat model was established by intra-amygdala injection of kainic acid (KA). Expression levels of miR-206, C–C Motif Chemokine Ligand 2 (CCL2) and interleukin-1β (Il-1β) in hippocampus tissues was measured by reverse transcription-quantitative PCR (RT-qPCR) and western blot. Dual luciferase reporter assay was performed to determine the binding of miR-206 to 3′ untranslated region (UTR) of CCL2. Finally, brain waves were recorded and Hematoxylin and eosin (HE) staining and Nissl’s staining were performed on the epileptic rat injected with LPS, miR-206 agomir, adeno-associated virus (AAV) expressed CCL2 alone or in combination. Expression of miR-206 was specially decreased in hippocampus tissues compared to cortex in response to KA induced pathologic brain activity. Enforced expression of miR-206 by injection miR-206 agomir not only decreased seizure activity, but also protected KA-induced neuronal loss. And enforced expression of miR-206 suppressed increase of C–C Motif Chemokine Ligand 2 (CCL2) and interleukin-1β (Il-1β) which were induced by injection of KA or KA combined with lipopolysaccharide (LPS). Further more, results of dual luciferase reporter assay confirmed CCL2 was a target of miR-206. Finally, co-injection adeno-associated virus (AAV) expressed CCL2 with miR-206 agomir abolished the function of miR-206 agomir. Taken together, our results showed that expression of miR-206 could inhibit seizure-induced brain injury by targeting CCL2. Our results showed that expression of miR-206 could inhibit seizure-induced brain injury by targeting CCL2.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The Israeli population mainly includes Jews, Muslim and Christian Arabs, and Druze. Data on genetic diseases present in the population have been systematically collected and are available online in the Israeli national genetic database. Among the Israeli Arabs in December 31 2018, the database included molecular data on six diseases relatively frequent in the whole population: thalassemia, familial Mediterranean fever (FMF), cystic fibrosis, deafness, phenylketonuria or congenital adrenal hyperplasia as well as data on 632 autosomal recessive diseases among Muslim Israeli Arabs, 52 among the Christian Arabs and 79 among Druze. A single variant was characterized in 590 out of the 771 genes causing disorders in which the molecular basis was known. Many of the variants reported among Arabs in Israel are novels, most being found in one community only. Some variants are ancient and for instance, consistent with the migration history, several variants are found in the Bedouins from the Negev as well as from the Arab peninsula. In the 181 other disorders more than one variant was characterized either in the same gene or in more than one gene. While it is probable that most of these cases represent random events in some cases the reason may be a selective advantage to the heterozygotes.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Reservoir sediment can work as both sink and source for contaminants. Once released into the water column, contaminants can be toxic to biota and humans. We investigate potential ecological risk to benthic organisms by metals contamination in six reservoirs in Southeast Brazil. Results of the bioavailable fraction of copper (Cu), chromium (Cr), cadmium (Cd), lead (Pb), zinc (Zn), and iron (Fe) in sediment samples are presented. Considering Cu, Cd, and Zn concentrations, about 6% of the samples exceeded the threshold effect levels of sediment quality guidelines. The comparison to sediment quality guidelines is conservative because we used a moderate metal extraction. Control of contaminant sources in these reservoirs is key because they are sources of water and food. The mixture toxicity assessment showed an increased incidence of toxicity to aquatic organisms showing that mixture toxicity should be taken into account in sediment assessment criteria.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉〈em〉Purpose〈/em〉 Cancer therapy-associated paronychia (CAP) is a frequent adverse event associated with cytotoxic and targeted therapies that may impact dosing of anticancer therapies and patient quality of life (QoL). There are currently no evidence-based management strategies or approved treatments for CAP. 〈em〉Materials and Methods〈/em〉 This was a prospective, multicenter, randomized, double-blind, vehicle-controlled phase 2 study that evaluated the efficacy and safety of 6 to 8 weeks of 1% or 2% povidone-iodine (PVP-I) topical solution versus vehicle-control in adult patients with CAP. Patients were randomized to one of three treatment arms administered twice daily: 1% PVP-I (Cohort A), 2% PVP-I (Cohort B), or vehicle-control (Cohort C). The primary endpoint was a two-grade reduction (or reduction to grade 0 if involved nails were grade 1) on the six-point Paronychia Severity Grading (PSG) scale. Secondary endpoints included safety and the effect on QoL and microbiota. 〈em〉Results〈/em〉 A total of 102 patients with cancer were randomized to the study. In Cohort A, 83 of 205 (40.5%, 〈em〉P〈/em〉 = 0.6059) affected nails met the primary endpoint versus Cohort C. In Cohort B, 88 of 167 (52.7%, 〈em〉P〈/em〉 = 0.0063) affected nails met the primary endpoint versus 64 of 169 (37.9%) in Cohort C. Nineteen of 29 patients (65.5%) in Cohort B reported moderately or very painful nails at baseline that decreased to 15 patients (51.7%) at visit 2 and five patients (17.2%) at visit 3. 〈em〉Conclusions〈/em〉 Treatment with twice-daily topical 2% PVP-I was safe and resulted in improvement in CAP compared with control. Clinicaltrials.gov identifier: NCT03207906. 〈a href="https://clinicaltrials.gov/ct2/show/NCT03207906"〉https://clinicaltrials.gov/ct2/show/NCT03207906〈/a〉〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉It was assessed the efficiency of the electrocoagulation (EC) in slaughterhouse wastewater (SW) treatment by using antioxidant parameters of 〈em〉Gammarus pulex〈/em〉. The SW was treated by EC. Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities and malondialdehyde (MDA) levels in 〈em〉G. pulex〈/em〉 exposed to pre- and post-treated of the SW during 24 h and 96 h were analysed. Standard methods were applied during the analysing process of the physicochemical quality parameters for both untreated and treated SW. All measured physicochemical parameters were decreased following the treatment process via EC. After the treatment process, it was observed that while SOD activities and MDA levels were decreased, CAT activities were increased and GPx activities did not exhibit any change. In conclusion, the present study demonstrated the abilities of untreated SW to promote oxidative stress in model organism. The SOD, CAT activities and MDA levels in 〈em〉G. pulex〈/em〉 revealed that EC process were efficient in the SW treatment.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of 〈em〉L-〈/em〉mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the 〈em〉L-〈/em〉enantiomer of a methylated analogue of 〈em〉L-〈/em〉mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉Cutaneous melanoma, the most aggressive form of skin cancer, is characterized by activating BRAF mutations. Despite the initial success of selective BRAF inhibitors, only few patients exhibited complete responses, whereas many showed disease progression. Melanoma is one of the few types of cancer in which p53 is not frequently mutated, but p53 inactivation can be indirectly achieved by a stable activation of MDM2 induced by a deletion in CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) locus, encoding for p16〈sup〉INK4A〈/sup〉 and p14〈sup〉ARF〈/sup〉, two tumor suppressor genes. In this study, we tested the efficacy of the previously synthesized tetra-substituted pyrrole derivatives, 〈strong〉8 g〈/strong〉, 〈strong〉8 h〈/strong〉 and 〈strong〉8i〈/strong〉, in melanoma cell lines, and we compared the effects of the most active of these, the 〈strong〉8i〈/strong〉 compound, with that exerted by Nutlin 3, a well-known inhibitor of p53-MDM2 interaction. The obtained results showed that 〈strong〉8i〈/strong〉 potentiates the inhibitory effect of Nutlin 3 and the combined use of 〈strong〉8i〈/strong〉 and Nutlin 3 triggers apoptosis and significantly impairs melanoma viability. Finally, the 〈strong〉8i〈/strong〉 compound reduces p53-MDM2 interaction and induces p53-HSP90 complex formation, suggesting that the observed raise in p53 transcriptional activity could be mediated by HSP90. Because the main feature of melanoma is the resistance to most chemotherapeutics, our studies suggest that the 〈strong〉8i〈/strong〉 tetra-substituted pyrrole derivative, restoring p53 functions and its transcriptional activities, may have potential application, at least as adjuvant, in the treatment of human melanoma.〈/p〉

Description: 〈span〉 〈h3〉Abstract〈/h3〉 〈p〉Amphibians are constantly exposed to pollutants and the stress of agricultural activities. We selected three anuran amphibian species 〈em〉Dendropsophus minutus〈/em〉, 〈em〉Boana albopunctata〈/em〉, and 〈em〉Physalaemus cuvieri〈/em〉, totaling 309 individuals. We collected tadpoles in 15 permanent ponds: 5 soybean crops, 3 corn crops, and 7 nonagricultural lands. Our study provides the first comparative data on the genotoxicity and mutagenicity of three common amphibian anurans. 〈em〉Dendropsophus minutus〈/em〉 was the most vulnerable species compared with 〈em〉B. albopunctata〈/em〉 and 〈em〉P. cuvieri〈/em〉 for comet assay and micronuclei test. However, the more significant amount of DNA damage seen in 〈em〉D. minutus〈/em〉 does not mean that their populations are threatened once such species adapt well to anthropogenic disturbances. Despite, 〈em〉P. cuvieri〈/em〉 was less sensitive than the other two species; the DNA damage was significantly higher in soybean crops. 〈em〉Physalaemus cuvieri〈/em〉 is a leptodactylidae species that deposit their eggs in foam nests, which are essential to protect eggs from dehydration. Moreover, the foam reduces the contact of eggs with water; thus, 〈em〉P. cuvieri〈/em〉 eggs could be less exposed to contaminants present in pounds, compared with 〈em〉D. minutus〈/em〉 and 〈em〉B. albopunctata〈/em〉, which deposit their eggs directly in the water. Therefore, this study was sufficiently sensitive to detect genotoxic and mutagenic effects in tadpoles exposed to agroecosystems. We strongly suggest 〈em〉D. minutus〈/em〉 in future biomonitoring studies that involve the comparison of anthropized versus not anthropized environments. Overall, we recommend the comet assay and micronucleus test as effective methods for the detection of genotoxic damage in amphibian anurans to the environmental disturbance, especially in agricultural sites.〈/p〉 〈/span〉 〈span〉 〈h3〉Graphic Abstract〈/h3〉 〈p〉 〈span〉 〈span〉 〈img alt="" src="https://static-content.springer.com/image/MediaObjects/244_2019_647_Figa_HTML.png"〉 〈/span〉 〈/span〉 〈/p〉 〈/span〉

Description: 〈h3〉Summary〈/h3〉 〈p〉〈em〉Introduction〈/em〉 We conducted a multicenter, phase 2 trial using gemcitabine plus axitinib (GX) in patients with recurrent or metastatic sarcomatoid renal cell carcinoma (SRCC) to evaluate its efficacy and safety. 〈em〉Methods〈/em〉 Patients with advanced RCC and a sarcomatoid component of ≥25% on resected kidney or exclusive sarcomatoid carcinoma on needle biopsy were included. Patients received gemcitabine 1000 mg/m〈sup〉2〈/sup〉 intravenously on days 1 and 8 of a 3-week cycle and axitinib 5 mg twice daily. Primary endpoint was objective response rate (ORR) according to the response evaluation criteria in solid tumors version 1.1, and secondary end points were progression-free (PFS) and overall (OS) survivals and adverse events. 〈em〉Results〈/em〉 Twenty-five patients were enrolled. Median age was 61 (range: 33–80), and 84% were men. The Eastern Cooperative Oncology Group performance status was one in 23 patients (92%). Clear cell carcinoma was the most common histology of the carcinoma component (60%). ORR was 56%, and 28% patients achieved stable disease with a control rate of 84%. With a median follow-up duration of 24.8 months, the median PFS was 4.2 months (95% CI, 2.3–6.1) and median OS was 8.4 months (95% CI 3.3–13.4 months). The most common grade 3 or higher adverse events were neutropenia (36%), hypertension (12%), and anorexia (12%). Most adverse events were manageable, and no unexpected toxicities were found. 〈em〉Conclusion〈/em〉 GX showed promising efficacy in patients with SRCC. GX could be considered as a treatment option for patients with SRCC and should be confirmed in larger clinical trials.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉In order to investigate the influence of different lignin sources on humic substance formation during composting, this study selected two lignin sources, including wood sawdust and maize straw, to be co-composted with pig manure. Humic substances (HS) were characterized based on their fluorescence characteristics and complexing behaviors with heavy metals. The results showed that lignin sources, especially wood sawdust, were more conducive in promoting the formation of humic acids (HAs) than inorganic matter. The fluorescence excitation–emission matrix spectra also proved the positive effects of lignin on the formation of HAs during the humification process. The binding capacities of HAs isolated from mature composts for Cu and Cd followed the order of WS-90 〉 MS-90 〉 I-90, indicating that organic bulking agents are superior at increasing the complexing capacity of HAs. This finding suggests that the co-composting of pig manure with ligneous bulking agents is more advantageous at reducing the environmental risk of heavy metals.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉For decades, megakaryocytopoiesis is believed to occur following a classical binary hierarchical developmental model. This model is based on an analysis of predefined flow-sorted cell populations by using cell surface markers. However, this classical model has been challenged by increasing evidences obtained with new techniques which integrating flow cytometric, transcriptomic and functional data at single-cell level and with lineage tracing technique. These recent advances in megakaryocytopoiesis proposed that commitment of haematopoietic stem cells (HSCs) towards megakaryocytic lineage occurs in much earlier stage than that postulated in the classical model. There may exist multipotent but megakaryocyte (MK)/platelet-biased HSCs within HSC compartment and even HSCs can directly differentiate into MKs in steady state or in response to stress. In this review, we focus on recent findings about differentiation from commitment of HSCs to MK and its regulation, and discuss future directions in this research field.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (~ 45%) that manifests before 30 years of age. The genetic locus containing 〈em〉COL4A1〈/em〉 (13q33–34) has been implicated in vesicoureteral reflux (VUR), but mutations in 〈em〉COL4A1〈/em〉 have not been reported in CAKUT. We hypothesized that 〈em〉COL4A1〈/em〉 mutations cause CAKUT in humans. We performed whole exome sequencing (WES) in 550 families with CAKUT. As negative control cohorts we used WES sequencing data from patients with nephronophthisis (NPHP) with no genetic cause identified (〈em〉n〈/em〉 = 257) and with nephrotic syndrome (NS) due to monogenic causes (〈em〉n〈/em〉 = 100). We identified a not previously reported heterozygous missense variant in 〈em〉COL4A1〈/em〉 in three siblings with isolated VUR. When examining 549 families with CAKUT, we identified nine additional different heterozygous missense mutations in 〈em〉COL4A1〈/em〉 in 11 individuals from 11 unrelated families with CAKUT, while no 〈em〉COL4A1〈/em〉 mutations were identified in a control cohort with NPHP and only one in the cohort with NS. Most individuals (12/14) had isolated CAKUT with no extrarenal features. The predominant phenotype was VUR (9/14). There were no clinical features of the 〈em〉COL4A1〈/em〉-related disorders (e.g., HANAC syndrome, porencephaly, tortuosity of retinal arteries). Whereas 〈em〉COL4A1〈/em〉-related disorders are typically caused by glycine substitutions in the collagenous domain (84.4% of variants), only one variant in our cohort is a glycine substitution within the collagenous domain (1/10). We identified heterozygous 〈em〉COL4A1〈/em〉 mutations as a potential novel autosomal dominant cause of CAKUT that is allelic to the established 〈em〉COL4A1〈/em〉-related disorders and predominantly caused by non-glycine substitutions.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉We aimed to identify genetic variation in the response of reproductive behaviors to lead (Pb〈sup〉2+〈/sup〉) exposure. We reared a subset of the 〈em〉Drosophila〈/em〉 Genetic Reference Panel (DGRP) inbred lines on control or Pb-treated (500 μM PbAc) medium and tested for differences in copulation latency, copulation duration, and fecundity. Pb exposure decreased fecundity (〈em〉p〈/em〉 〈 0.05) and increased copulation duration (〈em〉p〈/em〉 〈 0.05) across DGRP lines. We found intraspecific genetic variation in latency, duration, and fecundity in both control and Pb-treated flies, with heritability ranging from 0.45 to 0.80. We found a significant genotype-by-environment interaction for copulation duration (〈em〉p〈/em〉 〈 0.05). Genetic correlation matrices revealed significant genetic variation in common between control and Pb-treated flies for each trait (〈em〉p〈/em〉 〈 0.05). Our results indicate that intraspecific genetic variation plays a role in Pb susceptibility and emphasize the importance of considering the impacts of variation in susceptibility to Pb pollution.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉The majority of patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) harbor a gain of function mutation V617F in Janus kinase (JAK) 2. Although JAK2 inhibitors such as ruxolitinib have been shown to be clinically efficacious, the hematological toxicity and eventual drug resistance limit its use as monotherapy. Other gene mutations or dysregulation correlated with the disease phenotype and prognosis have been found to contribute to the complexity and heterogeneity of MPNs, giving rise to an increasing demand for combination therapies. Here, we combine ruxolitinib and the histone deacetylase inhibitor vorinostat as a rational combination strategy for MPNs. We tested the combination of ruxolitinib and vorinostat in cells with the 〈em〉JAK2〈/em〉V617F mutation, such as HEL cells, c-Kit〈sup〉+〈/sup〉 cells from 〈em〉JAK2〈/em〉V617F transgenic mice and bone marrow mononuclear cells (BMMNCs) from patients with MPN. Our results showed significant synergistic effects of this combination strategy. Cotreatment with ruxolitinib and vorinostat synergistically induced apoptosis, cell cycle arrest and inhibition of the colony-forming capacity of HEL cells by attenuating the JAK/signal transducer and activator of transcription (STAT) and protein kinase-B (AKT) signaling pathways. In particular, cotreatment with ruxolitinib and vorinostat prevented the formation of large colonies of colony-forming unit-granulocyte/erythroid/macrophage/megakaryocytes (CFU-GEMMs) and colony-forming unit-granulocyte/macrophages (CFU-GMs) derived from the BMMNCs of patients with MPN. Taken together, these data provided preclinical evidence that the combination of ruxolitinib and vorinostat is a potential dual-target therapy for patients with MPN.〈/p〉

Description: 〈span〉 〈h3〉Abstract〈/h3〉 〈p〉Soils from the old Mortórios uranium mine area were studied to look for contamination, as they are close to two villages, up to 3 km away, and used for agriculture. They are mainly contaminated in U and As and constitute an ecological threat. This study attempts to outline the degree to which soils have been affected by the old mining activities through the computation of significant hot clusters, Traditional geostatistical approaches commonly use raw data (concentrations) accepting that the analyzed elements represent the soil’s entirety. However, in geochemical studies these elements are just a fraction of the total soil composition. Thus, considering compositional data is pivotal. The spatial characterization, considering raw and compositional data together, allowed a broad discussion about not only the concentrations’ spatial distribution, but also a better understanding on the possibility of trends of “relative enrichment” and, furthermore an insight in U and As fate. The highest proportions (compositional data) on U (up to 33%), As (up to 35%) and Th (up to 13%) are reached in the south-southeast segment. However, the highest concentrations (raw data) occur in north and northwest of the studied area, pointing out to a “relative enrichment” toward the south-southeast zone. The Mondego Sul area is mainly contaminated in U and As, but also in Co, Cu, Pb and Sb. The Mortórios area is less contaminated than the Mondego Sul area.〈/p〉 〈/span〉 〈span〉 〈h3〉Graphic abstract〈/h3〉 〈p〉 〈span〉 〈span〉 〈img alt="" src="https://static-content.springer.com/image/MediaObjects/10653_2019_347_Figa_HTML.png"〉 〈/span〉 〈/span〉 〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Insufficient information on the link between health data and geology in developing countries is a major barrier to identify sources of some emerging public health problems. A total of 2868 soil samples were collected from field sheet 0503B in Ghana to evaluate the concentrations and distributions of trace elements and their effects on human health. The samples were sieved to 〈 106 µm fraction and analysed for elements, As, Ba, K, Zn, Co, Cr, Cu, Mn, Ni, Pb, Mg and Fe by XRF technique and Au by fire assay method. The study identified disparities in averages of As, Cr, Fe and Mg, which resulted in enrichment and deficiencies when compared with the worldwide background average. The measured averages for As and Cr were 17.27 mg/kg and 89.25 mg/kg, respectively, for the entire area. Both averages exceeded the worldwide background values of 10 mg/kg and 8 mg/kg of As and Cr. The four traditional towns with varied activities recorded As concentrations ranging from 6.11 mg/kg at Samreboi, 16.29 mg/kg at Asankragwa, 17.42 mg/kg at Akropong and 25.99 mg/kg at Bogoso. Principal component analysis revealed a good association among Ba, Cr, Cu, Fe, K, Ni, Pb and Zn in Group 1, and their main source was interpreted as the underlying geology. Arsenic, Cr and Mg in Group 2 show a relatively weak correlation, and their sources were ascribed to a combination of geologic and anthropogenic sources. Gold had a good correlation with As, which was associated with the hydrothermal veins in the underlying rocks. The spatial plots generated from transformed soil data by Getis Ord Gi* treatments were visual methods to clearly identify geographically the hotspots and coldspots of elements that cause diseases.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Knowledge on the fraction of trace elements in the bottom sediments is a key to understand their mobility and ecotoxicological impact. The purpose of this study was to assess the influence of the content of organic matter fractions on the mobility and ecotoxicity of trace elements in sediments from the Rybnik reservoir. The most refractory fraction of organic matter—Cnh (non-hydrolysing carbon)—dominated in the sediments. The content of organic matter fractions are arranged in the following order: Cnh (non-hydrolysing carbon) 〉 Cfa (fulvic acid) 〉 Cha (humic acid) 〉 DOC (dissolved organic carbon). On the other hand, the highest value of correlation coefficients was found for different fractions of trace elements and DOC content in the bottom sediments. A higher content of TOC in the sediments significantly increased the share of elements in the potential mobile fraction and, at the same time, decreased the binding of elements in the mobile fractions. Moreover, in sediments that contain more than 100 g/kg d.m. TOC, no and medium risk of trace element release from sediments was observed. The Cu, Cd and Ni were potentially the most toxic elements for biota in the Rybnik reservoir. However, the correlation between the content of trace elements and the response of bacteria was insignificant. These results suggested that the complexation of trace elements with organic matter makes them less toxic for 〈em〉Vibrio fischeri〈/em〉. The transformation and sources of organic matter play an important role in the behaviour of trace elements in the bottom sediments of the Rybnik reservoir.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Purpose〈/h3〉 〈p〉Epidemiological studies directly investigating the association between different types of meat intake and cognitive impairment are limited. We, therefore, examined this association in the Singapore Chinese Health Study.〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉In total, 16,948 participants were included in analysis. Diet was measured by a 165-item semiquantitative food-frequency questionnaire at baseline (1993–1998) when participants were 45–74 years. Cognitive impairment was defined using a Singapore modified version of Mini-Mental State Examination during follow-up three visits (2014–2016) when participants were 61–96 years. Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI).〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Cognitive impairment was present in 2443 (14.4%) participants. Compared to the lowest quartile, the highest quartile of red meat intake was associated with increased risk of cognitive impairment (OR 1.16, 95% CI 1.01–1.32, 〈em〉P〈/em〉 for trend = 0.009), while the corresponding value for poultry intake was 0.89 (95% CI 0.78–1.02, 〈em〉P〈/em〉 for trend = 0.10). Higher fresh fish/shellfish was associated with a lower risk of cognitive impairment (OR 0.88, 95% CI 0.77–1.00, 〈em〉P〈/em〉 for trend = 0.03), while preserved fish/shellfish intake was associated with a higher risk (OR 1.19, 95% CI 1.04–1.36, 〈em〉P〈/em〉 for trend = 0.01).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉This study found that a higher intake of red meat in midlife was associated with increased likelihood of cognitive impairment in later life, while substitution of red meat intake with poultry or fresh fish/shellfish was associated with reduced risk.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Cell death is an essential physiological process required for the proper development and function of the human placenta. Although the mouse is a commonly used animal model for development studies, little is known about the extent and distribution of cell death in the mouse placenta throughout development and its physiological relevance. In the present study, we report the results of a systematic and quantitative assessment of cell death patterns in the placentae of two strains of laboratory mice commonly used for developmental studies—ICR and C57Bl/6. TUNEL staining revealed that ICR and C57Bl/6 placentae exhibited similar cell death patterns to those reported in human placentae during pregnancy, with comparatively infrequent death observed during early gestation, which increased and became more organized towards term. Interestingly, when comparing strain differences, increased cell death was observed in almost all regions of the inbred C57Bl/6 placentae compared to the outbred ICR strain. Finally, since Bcl-2 ovarian killer (Bok) has been reported to be a key player in human placental cell death, we examined its expression in murine placentae throughout gestation. Bok protein expression was observed in all placental regions and increased towards term in both strains. The results of this study indicate that although strain-specific differences in placental cell death exist, the overall rates and patterns of cell death during murine placentation parallel those previously described in humans. Thus, the murine placenta is a useful model to investigate molecular pathways involved in cell death signaling during human placentation.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The aim of this paper was to describe the outcome of therapeutic administration of mesenchymal stem cells (MSC) obtained from Wharton’s jelly (WJ-MSCs) in paediatric patients with spina bifida (SB) during a medical therapeutic experiment. We retrospectively analysed the records of twenty-eight patients aged 1–18 years (median age 4 years) recruited in daily clinical practice. Each patient received 0.9–5.0 × 10〈sup〉6〈/sup〉 WJ-MSCs/kg (median 2.6 × 10〈sup〉6〈/sup〉 WJ-MSCs/kg) administered in 1–5 injections as an experimental treatment for SB (allogenic administration). All the patients were examined by the same neurologist (study investigator, SI) on the day of each infusion. Based on the neurological examination, the SI used a six-point Likert scale to assess the quality of life and self-service of each patient. Twenty-six follow-up observations after MSC administration were analysed retrospectively. In addition, the assessments of the parents and other healthcare professionals were obtained for 5 patients and compared with the SI’s assessment. Twenty-one of 26 patients (81%) experienced some improvement in their health status. Twenty-one (81%) patients experienced increased quality of life (median 2.0) and 10 patients (38%) achieved a slight increase in their self-service level (median 1). Improvement was achieved in 12 out of 17 areas. Five were significant in low-power sign test: muscle tension, muscle strength, gross motor development, micturition/defecation control, and cognitive functions. Adverse events were mild and temporary. Age, body mass, single dose or poor response after the first administration were not significant predictors of later response to treatment in contrast to the total cell dose per one kg in the whole treatment course. WJ-MSC administration is a safe and effective procedure that improves motor functions, micturition/defecation control, and cognitive functions, and improves the quality of life in children with SB.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The widespread use of pharmaceutical and personal care products (PPCPs) has attracted much attention and the impact of PPCPs on indigenous microbial communities has become increasingly important in recent days. Five common PPCPs, including doxycycline (DOX), ciprofloxacin (CIP), triclocarban (TCC), carbamazepine (CBZ), and sulfadimidine (SMZ), were selected and their effects on soil microbial respiration were studied at concentrations of 0, 0.2, 1, 5, 25 and 50 mg/kg. The results of this study indicate that the effect of five common PPCPs on soil microbial respiration was dose- and time- dependent. At low concentrations (0.2 and 1 mg/kg), CBZ and SMZ exhibited an activation effect on microbial soil respiration at 1 day (58.02%, 26.39% and 1.54%, 1.76% at 0.2 and 1 mg/kg respectively), while DOX showed inhibition for all tested concentrations at 1 day of incubation. At high concentrations (25 and 50 mg/kg) CIP and SMZ showed an inhibitory effect (− 69.13%, − 80.86% for 25 and 50 mg/kg, respectively), while TCC and CBZ exhibited stimulatory effect (38.07%, 9.64% and 4.06%, 12.18% at 25 and 50 mg/kg, respectively) at 1 day of incubation. Our findings indicate that the effect of tested PPCPs on soil microbial respiration had an inhibitory or stimulatory effect based on the dose and extent of time.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉The cost of rural health continues to be high in the United States despite an overall improvement in national health insurance enrolment. Stakeholder’s perception of adverse selection remains a paramount culprit in the challenges of rural insurance markets. Risk attitude has been revealed as an alternative for measuring this phenomenon, given the 2014 prohibition law on pre-existing conditions and a subsequent repeal in 2018 accompanied by extensive debate among congress. We examine the existence of adverse selection in rural insurance markets by comparing the effects of pre-existing or chronic health conditions and risk attitudes in a Principal-Agent model.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉Using multinomial logit and complementary log-log binomial link models in a Principal-Agent framework, our results indicate that there is adverse selection in rural health insurance markets if pre-existing conditions are considered, but risk attitudes yield contrary effects.〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusions〈/h3〉 〈p〉The major policy implication from this study is that respondents who have pre-existing/chronic conditions tend to patronise health insurance with a higher probability than other counterparts and therefore insurers are likely to incur losses given the law on pre-existing conditions as private information. The 2018 law on the exclusion of individuals with pre-existing conditions may be beneficial to the insurance companies at the expense of the populace. Hence, we suggest that market incentive-based programs should be encouraged to minimize rural health uninsurance.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Composting is an efficient and cost-effective technology for sewage sludge treatment, and bulking agents are essential in sewage sludge composting. In this study, perlite was chosen as inorganic bulking agent to partially substitute for the organic bulking agent. Variations in the temperature, bulk density, moisture content, pH, electrical conductivity, organic carbon, nitrogen, phosphorus and potassium were detected during sewage sludge composting. The treatment with a mass ratio of spent mushroom substrate to perlite at 3:1 exhibited the highest pile temperature and the best effect on reducing bulk density and moisture content. In addition, Fourier transform infrared spectra showed that perlite promotes the degradation of organic matter during the composting process, and the germination index showed that the compost from all treatments was safe for agricultural application. When the mass ratios of spent mushroom substrate and perlite at 3:1 and 2:2 were chosen as bulking agents, the sewage sludge compost product could be used to produce plant cultivation substrate, and economic benefits could be obtained from sewage sludge composting according to comprehensive cost analysis.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Circular RNAs (circRNAs) are members of the non-coding transcriptome; however, some of them are translated into proteins. These transcripts have important roles in both physiological and pathological mechanisms due to their ability to directly influence cellular signaling pathways. Specifically, circRNAs are regulators of transcription, translation, protein interaction, and signal transduction. An increased knowledge within their area is observed over the last few years, concomitant with the development of next-generation sequencing techniques. circRNAs are mostly tissue and disease specific with the ability of specifically changing the biological behavior of cells. The altered expression profile is currently investigated as novel minimally invasive diagnosis/prognosis tool and also therapeutic target in human disease. The diagnosis approach is based on their level modification within pathological states, especially cancer, where circRNAs’ therapies are intensively explored in anti-aging strategies, diabetes, cardiovascular diseases, and malignant pathologies, and are relying on the restoration of homeostatic profiles.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Duchenne muscular dystrophy (DMD) represents one of the most devastating types of muscular dystrophies which affect boys already at early childhood. Despite the fact that the primary cause of the disease, namely the lack of functional dystrophin is known already for more than 30 years, DMD still remains an incurable disease. Thus, an enormous effort has been made during recent years to reveal novel mechanisms that could provide therapeutic targets for DMD, especially because glucocorticoids treatment acts mostly symptomatic and exerts many side effects, whereas the effectiveness of genetic approaches aiming at the restoration of functional dystrophin is under the constant debate. Taking into account that dystrophin expression is not restricted to muscle cells, but is present also in, e.g., endothelial cells, alterations in angiogenesis process have been proposed to have a significant impact on DMD progression. Indeed, already before the discovery of dystrophin, several abnormalities in blood vessels structure and function have been revealed, suggesting that targeting angiogenesis could be beneficial in DMD. In this review, we will summarize current knowledge about the angiogenesis status both in animal models of DMD as well as in DMD patients, focusing on different organs as well as age- and sex-dependent effects. Moreover, we will critically discuss some approaches such as modulation of vascular endothelial growth factor or nitric oxide related pathways, to enhance angiogenesis and attenuate the dystrophic phenotype. Additionally, we will suggest the potential role of other mediators, such as heme oxygenase-1 or statins in those processes.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉NAFLD is currently the main cause of chronic liver disease in developed countries, and the number of NAFLD patients is growing worldwide. NAFLD often has similar symptoms to other metabolic disorders, including type 2 diabetes and obesity. Recently, the role of the gut microbiota in the pathophysiology of many diseases has been revealed. Regarding NAFLD, experiments using gut microbiota transplants to germ-free animal models showed that fatty liver disease development is determined by gut bacteria. Moreover, the perturbation of the composition of the gut microbiota has been observed in patients suffering from NAFLD. Numerous mechanisms relating the gut microbiome to NAFLD have been proposed, including the dysbiosis-induced dysregulation of gut endothelial barrier function that allows for the translocation of bacterial components and leads to hepatic inflammation. In addition, the various metabolites produced by the gut microbiota may impact the liver and thus modulate NAFLD susceptibility. Therefore, the manipulation of the gut microbiome by probiotics, prebiotics or synbiotics was shown to improve liver phenotype in NAFLD patients as well as in rodent models. Hence, further knowledge about the interactions among dysbiosis, environmental factors, and diet and their impacts on the gut–liver axis can improve the treatment of this life-threatening liver disease and its related disorders.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉LncRNAs have recently emerged as new and fundamental transcriptional and post-transcriptional regulators acting at multiple levels of gene expression. Indeed, lncRNAs participate in a wide variety of stem cell and developmental processes, acting in 〈em〉cis〈/em〉 and/or in 〈em〉trans〈/em〉 in the nuclear and/or in the cytoplasmic compartments, and generating an intricate network of interactions with RNAs, enhancers, and chromatin-modifier complexes. Given the versatility of these molecules to operate in different subcellular compartments, via different modes of action and with different target specificity, the interest in this research field is rapidly growing. Here, we review recent progress in defining the functional role of lncRNAs in stem cell biology with a specific focus on the underlying mechanisms. We also discuss recent findings on a new family of evolutionary conserved lncRNAs transcribed from ultraconserved elements, which show perfect conservation between human, mouse, and rat genomes, and that are emerging as new player in this complex scenario.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Iodinated radiographic contrast media is used in cancer radiography for cancer diagnosis. The aim of this present study was to examine five iodinated radiographic contrast media (IRCM) (i.e., iohexol, iopamidol, iobitridol, ioxaglate, and iodixanol) in terms of their cytotoxicity, mitochondria membrane potential (ΔΨm), and P-glycoprotein function in multidrug resistant K562/Dox cancer cells and corresponding sensitive cancer cells. The cytotoxicity was determined by colorimetric resazurin reduction assay. The ΔΨm and P-glycoprotein function was measured using a noninvasive functional spectrofluorometry. Rhodamine B, fluorescence probe, was used to estimate ΔΨm. The kinetic of P-glycoprotein-mediated efflux pirarubicin was used to monitor P-glycoprotein function in multidrug resistant (MDR) cancer cells. The results showed that ioxaglate and iodixanol show similar efficacy in MDR cancer cells and for their corresponding sensitive cancer cells. Iopamidol, iohexol, and iobitridol showed higher efficacy in MDR cancer cells than for the corresponding sensitive cancer cells by approximately 2 fold. The results also showed no significant change in the |ΔΨm| values in treated K562 and K562/Dox cancer cells when compared to the non-treated K562 and K562/Dox cancer cells. However, there were notable changes detected for iobitridol and iodixanol at 50 mgI/mL. Similarly, the results showed significant differences in P-glycoprotein function of K562/Dox cancer cells after treatment with IRCM when compared to the non-treated K562/Dox cancer cells, with iohexol and iodixanol being the notable exceptions once again. In this present study, IRCM exhibited cytotoxicity on MDR cancer cells and their corresponding sensitive cancer cells. IRCM also showed potential as an anticancer agent in the future.〈/p〉

Description: 〈h3〉Summary〈/h3〉 〈p〉Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese medicines, has been proven to have a wide range of pharmacological effects, such as anti-inflammatory, antiviral, and antitumor activities. Previous studies have confirmed that emodin has inhibitory effects on various solid tumors, such as osteosarcoma, liver cancer, prostate cancer and glioma. This study aimed to investigate the effects and mechanisms of emodin-induced necroptosis in the glioma cell line U251 by targeting the TNF-α/RIP1/RIP3 signaling pathway. We found that emodin could significantly inhibit U251 cell proliferation, and the viability of U251 cells treated with emodin was reduced in a dose- and time-dependent manner. Flow cytometry assays and Hoechst-PI staining assays showed that emodin induced apoptosis and necroptosis. Real-time PCR and western blot analysis showed that emodin upregulated the levels of TNF-α, RIP1, RIP3 and MLKL. Furthermore, the RIP1 inhibitor Nec-1 and the RIP3 inhibitor GSK872 attenuated the killing effect of emodin on U251 cells. In addition, emodin could increase the levels of TNF-α, RIP1, RIP3 and MLKL in vivo. The results demonstrate that emodin could induce necroptosis in glioma possibly through the activation of the TNF-α/RIP1/RIP3 axis. These studies provide novel insight into the induction of necroptosis by emodin and indicate that emodin might be a potential candidate for treating glioma through the necroptosis pathway.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉This study aimed to select rivers of priority management through the assessment of heavy metal pollution of sediments. We investigated the distribution characteristics of heavy metals in surface sediments of the Nakdong River in South Korea and used various pollution indices to assess pollution risk and identify factors influencing pollution. The kriging method was used to determine heavy metal distribution. The pollution load index, potential ecological risk index, mean PEL quotient, and the Canada Council of Ministers of the Environment sediment quality index were used as sediment pollution assessment methods. The toxicity evaluation was performed on sites that appeared to be contaminated, by applying existing methods for assessing sediment pollution level and the national standards for evaluating the pollution level. The toxicity test was performed on 〈em〉Hyalella azteca,〈/em〉 and a methodology for assessing sediment pollution level was proposed. Ecotoxicity was assessed at seven sites that were found to have heavy metal contaminants. The results showed that sites N1, N8, T28, and T29 were not toxic, while T8, T19, and T21 were. Thus, this study shows that high heavy metal pollution does not necessarily lead to a toxic environment. To assess sediment pollution, an additional assessment of toxicity should be made, along with assessments of existing sediment pollution. Our results demonstrate that streams showing high sediment pollution levels should be granted priority in management. The efforts should particularly focus on Cu at T8, Cr at T19, and Hg at T21.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Eutherian mammals have an extremely conserved sex-determining system controlled by highly differentiated sex chromosomes. Females are XX and males XY, and any deviation generally leads to infertility, mainly due to meiosis disruption. The African pygmy mouse (〈em〉Mus minutoides〈/em〉) presents an atypical sex determination system with three sex chromosomes: the classical X and Y chromosomes and a feminizing X chromosome variant, called X*. Thus, three types of females coexist (XX, XX*, and X*Y) that all show normal fertility. Moreover, the three chromosomes (X and Y on one side and X* on the other side) are fused to different autosomes, which results in the inclusion of the sex chromosomes in a quadrivalent in XX* and X*Y females at meiotic prophase. Here, we characterized the configurations adopted by these sex chromosome quadrivalents during meiotic prophase. The XX* quadrivalent displayed a closed structure in which all homologous chromosome arms were fully synapsed and with sufficient crossovers to ensure the reductional segregation of all chromosomes at the first meiotic division. Conversely, the X*Y quadrivalents adopted either a closed configuration with non-homologous synapsis of the X* and Y chromosomes or an open chain configuration in which X* and Y remained asynapsed and possibly transcriptionally silenced. Moreover, the number of crossovers was insufficient to ensure chromosome segregation in a significant fraction of nuclei. Together, these findings raise questions about the mechanisms allowing X*Y females to have a level of fertility as good as that of XX and XX* females, if not higher.〈/p〉

Description: 〈p〉In the original publication, the funding and conflict of interest statements were not correct.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈span〉 〈h3〉Background〈/h3〉 〈p〉Enterolignans are important biomarkers of microbiota diversity, with higher levels indicating greater diversity. Diet and inflammation have been shown to play a role in maintaining microbiota diversity. This study examined whether inflammatory potential of diet, as measured by the Dietary Inflammatory Index (DII〈sup〉®〈/sup〉) has an impact on levels of urinary enterolignans in the National Health and Nutrition Examination Survey (NHANES) 2003–2008. We also carried out construct validation of the DII with C-reactive protein (CRP).〈/p〉 〈/span〉 〈span〉 〈h3〉Methods〈/h3〉 〈p〉Data came from NHANES 2003–2008. Enterolignans [enterodiol (END) and enterolactone (ENL)] and CRP were assayed from urine and serum specimens, respectively. Energy-adjusted DII (E-DII) scores were calculated from food intakes assessed using 24-h dietary recalls and expressed per 1000 calories consumed. Associations were examined using survey-based multivariable linear and logistic regression for enterolignans, and logistic regression for CRP.〈/p〉 〈/span〉 〈span〉 〈h3〉Results〈/h3〉 〈p〉After multivariable adjustment, higher E-DII scores (i.e., indicating a relatively more pro-inflammatory diet) were associated with lower levels of creatinine-normalized END [beta coefficient (〈em〉b〈/em〉)〈sub〉DIIquartile4vs1〈/sub〉 = − 1.22; 95% CI = − 0.69, − 1.74; 〈em〉P〈/em〉〈sub〉trend〈/sub〉 ≤ 0.001] and ENL (〈em〉b〈/em〉〈sub〉DIIquartile4vs1〈/sub〉 = − 7.80; 95% CI = − 5.33, − 10.26; 〈em〉P〈/em〉〈sub〉trend〈/sub〉 ≤ 0.001). A positive association was also observed when enterolignans were dichotomized based on the cut-off of the 75th percentile value. In this same sample, the E-DII also was associated with CRP ≥ 3 mg/l (OR〈sub〉DIIcontinuous〈/sub〉 = 1.12; 95% CI 1.05, 1.19).〈/p〉 〈/span〉 〈span〉 〈h3〉Conclusion〈/h3〉 〈p〉In these NHANES data, there was an association between E-DII score and enterolignans. This study also provided construct validation of the E-DII using CRP in a nationally representative sample. The results indicate that dietary inflammatory potential is associated with urinary enterolignans, a potential marker for microbiota diversity. However, studies are required to understand the direct association between DII and microbiota.〈/p〉 〈/span〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The aim of the study was to assess heavy metals (Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn) air pollution in Bosnia and Herzegovina by using a lichen, 〈em〉Hypogymnia physodes〈/em〉. Metal content was determined by flame atomic absorption spectrometry (FAAS) and was between very high naturality or alteration to middle naturality or alteration. Strong correlations between Cr and Ni confirmed mainly anthropogenic sources. The scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM/EDS) analysis of C, O, Na, Mg, Al, Si, P, S, Cl, K, Ca, V, Co, As, Sn, Sb, Hg and Bi were performed on the lichen surface and hyphae of the transplanted samples. Despite significant damage to tissue and cell integrity, the recurrent presence of particulate matter in lichen indicates the considerable presence of dust in the urban atmosphere which, according to chemical composition, may be due to anthropogenic and natural sources such as soil.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The objective of this study was to investigate the transport dynamics of total mercury (THg) and methylmercury (MeHg) in the first rainfall-runoff event after summer drought, to understand flushing effects (FFEs) and to quantificationally estimate contributions to the annual outputs of Hg. The results showed that both THg and MeHg in rainfall-runoff predominated by particulate fraction peaked at the beginning of the monitoring period. On average, more than 80% of THg and MeHg loadings were transported during the initial runoff (≤ 6 h). Simultaneously, significant FFEs were observed for both THg and MeHg, with a larger effect for MeHg. More importantly, the estimated output fluxes of THg and MeHg in runoff produced by this rainfall event contributed 3.0% (THg) and 7.8% (MeHg) to the annual output fluxes, respectively, suggesting the importance of the first-rainfall on the Hg loss (especially for MeHg).〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The biosynthesis of the pimelate moiety of biotin in 〈em〉Escherichia coli〈/em〉 requires two specialized proteins, BioC and BioH. However, the enzymes that have BioC- or BioH-like activities show remarkable sequence diversity among biotin-producing bacteria. Here, we report that the intracellular rickettsial pathogen 〈em〉Ehrlichia chaffeensis〈/em〉 encodes two novel proteins, BioT and BioU, which functionally replace the 〈em〉E. coli〈/em〉 BioC and BioH proteins, respectively. The desthiobiotin assays demonstrated that these two proteins make pimeloyl-acyl carrier protein (ACP) from the substrate malonyl-ACP with the aid of the FAS II pathway, through the expected pimeloyl-ACP methyl ester intermediate. BioT and BioU homologues seem restricted to the species of 〈em〉Ehrlichia〈/em〉 and its close relative, 〈em〉Anaplasma〈/em〉. Taken together, the synthesis of the biotin precursor in 〈em〉E. chaffeensis〈/em〉 appears to be catalyzed by two novel BioC- and BioH-like proteins.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Endogenous protease tissue-type plasminogen activator (tPA) has highly efficient fibrinolytic activity and its recombinant variants alteplase and tenecteplase are established as highly effective thrombolytic drugs for ischemic stroke. Endogenous tPA is constituted of five functional domains through which it interacts with a variety of substrates, binding proteins and receptors, thus having enzymatic and cytokine-like effects to act on all cell types of the brain. In the past 2 decades, numerous studies have explored the clinical relevance of endogenous tPA in neurological diseases, especially in ischemic stroke. tPA is released from many cells within the brain parenchyma exposed to ischemia conditions in vitro and in vivo, which is believed to control neuronal fate. Some studies proved that tPA could induce blood–brain barrier disruption, neural excitotoxicity and inflammation, while others indicated that tPA also has anti-excitotoxic, neurotrophic and anti-apoptotic effects on neurons. Therefore, more work is needed to elucidate how tPA mediates such opposing functions that may amplify tPA from a therapeutic means into a key therapeutic target in endogenous neuroprotection after stroke. In this review, we summarize the biological characteristics and pleiotropic functions of tPA in the brain. Then we focus on possible hypotheses about why and how endogenous tPA mediates ischemic neuronal death and survival. Finally, we analyze how endogenous tPA affects neuron fate in ischemic stroke in a comprehensive view.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Adipose stem cells (ASCs) are a great promise in wound healing due to their potential in differentiating into various cell lineages and secreting growth factors. The purpose of this study is to evaluate the in vivo effects of 〈em〉Aloe vera〈/em〉 hydrogel loaded by allogeneic ASCs on a rat burn wound model. The ASCs were isolated, cultured and mixed with 50% 〈em〉Aloe vera〈/em〉 hydrogel and injected intradermally around the wound. Demineralized bone matrix (DBM) was used as dressing in the experiment. The burn wound-healing properties of different experimental groups were investigated by histopathological, molecular, scanning electron microscopic and biochemical analysis at the 7th, 14th and 28th days post-wounding. The 〈em〉Aloe vera〈/em〉 and DBM-〈em〉Aloe vera〈/em〉 groups showed almost similar healing properties, while treatment by DBM-〈em〉Aloe vera〈/em〉/ASCs significantly enhanced wound healing. The levels of transforming growth factor-β1 (TGF-β1) and interleukin-1β markedly decreased at the 7th day post-injury, in the DBM-〈em〉Aloe vera〈/em〉/ASC-treated group, suggesting that this treatment regime subsided the inflammatory responses. Angiogenesis, re-epithelialization and the level of TGF-β1 in the wounds treated with DBM-〈em〉Aloe vera〈/em〉/ASCs were also remarkably higher than those of other groups, at the 14th day post-injury. Besides, scar formation significantly decreased in the DBM-〈em〉Aloe vera〈/em〉/ASC-treated wounds when compared with other groups. Our biochemical results were in agreement with the molecular and histopathological findings and strongly demonstrated that a DBM-〈em〉Aloe vera〈/em〉/ASC composite can stimulate burn wound healing. These results suggest that the DBM-〈em〉Aloe vera〈/em〉/ASC composite can be considered as a promising therapeutic strategy in the treatment of burn wounds.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Fungicidal effect of 2-amino-4-nitrophenol and its derivates, prepared by replacing the hydrogen atom in its amino group by different organic radicals was studied. Evaluation of the biological activity of studied substances by сomputational chemistry methods was performed. Toxicity of 2-amino-4-nitrophenol and synthesized N-(2-hydroxy-5-nitrophenyl)formamide and N-(2-hydroxy-5-nitrophenyl)acetamide to six species of phytophatogen fungi were tested in the experiment. The results of the study demonstrate that replacement of the hydrogen atom in the amino group by a aldehyde group leads to an increase in fungicidal activity with respect to 〈em〉Rhizoctonia solani〈/em〉 and 〈em〉Bipolaris sorokiniana〈/em〉. A replacement of the hydrogen atom by a ketone group increases the inhibitory effect on 〈em〉Sclerotinia sclerotiorum〈/em〉 and 〈em〉Venturia inaequalis〈/em〉. The paper contains comparative data on the fungicide effect of commercial preparation for studied fungi also.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Mouse mutants are a long-lasting, valuable tool to identify genes underlying eye diseases, because the absence of eyes, very small eyes and severely affected, cataractous eyes are easily to detect without major technical equipment. In mice, actually 145 genes or loci are known for anophthalmia, 269 for microphthalmia, and 180 for cataracts. Approximately, 25% of the loci are not yet characterized; however, some of the ancient lines are extinct and not available for future research. The phenotypes of the mutants represent a continuous spectrum either in anophthalmia and microphthalmia, or in microphthalmia and cataracts. On the other side, mouse models are still missing for some genes, which have been identified in human families to be causative for anophthalmia, microphthalmia, or cataracts. Finally, the mouse offers the possibility to genetically test the roles of modifiers and the role of SNPs; these aspects open new avenues for ophthalmogenetics in the mouse.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Despite extensive investigation focused on both the molecular characteristics and the expression level of Toll-like receptors (TLRs) during the inflammatory response in vertebrates, few data are available in the literature on the role of these proteins in invertebrate’s immune response. Here, we propose the medicinal leech as a valuable model to better elucidate the role of TLR4 and its related products, such as tumor necrosis factor (TNF-α), after activation of the leech peripheral immune system with the endogenous medicinal leech recombinant allograft inflammatory factor-1 (r〈em〉Hm〈/em〉AIF-1) or with an exogenous stimulus, such as lipopolysaccharide (LPS). Our results indicate that activated macrophages (〈em〉Hm〈/em〉AIF-1〈sup〉+〈/sup〉) and granulocytes (CD11b〈sup〉+〈/sup〉) express both TLR4 and its coreceptor CD14. Moreover, functional studies performed by injecting a cyanobacterium selective TLR4 antagonist CyP demonstrated that only the TLR4 pathway was blocked, while the immune response caused by lipoteichoic acid (LTA) treatment is not affected. These results are consistent with literature on vertebrates, indicating that TLR4 functions as a LPS receptor while the recognition of LTA may involve other pathways.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Mercury (Hg) contamination in environmental matrices and associated human exposure has been recognized as a critical long-lasting issue worldwide. However, studies are still elusive that summarized the overall status of Hg pollution and its impacts on public health in Pakistan. Hence, this review encompasses the environmental prevalence, potential sources, and human exposure tendencies to Hg contamination in Pakistan. Reviewed literature revealed jolting levels of Hg in various environmental samples, such as dust, soil, water, and air collected from the residential and industrial areas. Inhalation of Hg via dust particle was identified as the primary pathway for human exposure, while atmospheric deposition and gold mining are identified as the two primary sources of Hg contamination in the environment. Considering human exposure, the highest bioaccumulation of Hg was ranged from 5885 to 8698 µg/kg in hair samples collected from the residents of the Kashmir Valley, Pakistan. However, in the lower Himalayan regions, including Islamabad and Swabi, the concentration of Hg in hair samples was reported at 1085 µg/kg, slightly beyond WHO devised reference dose (RfD) of Hg (1000 µg/kg). This review revealed the worst scenario of Hg contamination in human biomatrices and environmental compartments in Pakistan, which needed immediate rehabilitation measures.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Statistical methods for genome-wide association studies (GWAS) continue to improve. However, the increasing volume and variety of genetic and genomic data make computational speed and ease of data manipulation mandatory in future software. In our view, a collaborative effort of statistical geneticists is required to develop open source software targeted to genetic epidemiology. Our attempt to meet this need is called the 〈span〉OpenMendel〈/span〉 project (〈a href="https://openmendel.github.io/"〉https://openmendel.github.io〈/a〉). It aims to (1) enable interactive and reproducible analyses with informative intermediate results, (2) scale to big data analytics, (3) embrace parallel and distributed computing, (4) adapt to rapid hardware evolution, (5) allow cloud computing, (6) allow integration of varied genetic data types, and (7) foster easy communication between clinicians, geneticists, statisticians, and computer scientists. This article reviews and makes recommendations to the genetic epidemiology community in the context of the 〈span〉OpenMendel〈/span〉 project.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Glutamate is the major excitatory neurotransmitter in the central nervous system. Beyond this function, glutamate also plays a key role in intermediary metabolism in all organs and tissues, linking carbohydrate and amino acid metabolism via the tricarboxylic acid cycle. Under both physiological and pathological conditions, we have recently found that the ability of glutamate to fuel cell metabolism selectively relies on the activity of two main transporters: the sodium–calcium exchanger (NCX) and the sodium-dependent excitatory amino-acid transporters (EAATs). In ischemic settings, when glutamate is administered at the onset of the reoxygenation phase, the coordinate activity of EAAT and NCX allows glutamate to improve cell viability by stimulating ATP production. So far, this phenomenon has been observed in both cardiac and neuronal models. In this review, we focus on the most recent findings exploring the unusual activity of glutamate as a potential survival factor in different settings.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Tetraspanin protein CD151 has typically been studied as binding partner and functional regulator of laminin-binding integrins. However, we show here that CD151 supports anti-cancer drug resistance independent of integrins. CD151 ablation sensitized multiple tumor cell types to several anti-cancer drugs (e.g., gefitinib and camptothecin), thus increasing apoptosis, as seen using cleaved caspase-3, cleaved PARP (poly (ADP-ribose) polymerase), annexin V, and propidium iodide staining assays. Drug sensitization due to CD151 ablation is integrin-independent, because, (1) effects occurred in cells when integrins were unengaged with ligand, (2) integrin ablation (α3 and α6 subunits) did not mimic effects of CD151 ablation, (3) the CD151〈sup〉QRD〈/sup〉 mutant, with diminished integrin association, and CD151〈sup〉WT〈/sup〉 (unmutated CD151) similarly reconstituted drug protection, and (4) treatment with anti-cancer drugs selectively upregulated intracellular nonintegrin-associated CD151 (NIA-CD151), consistent with its role in drug resistance. Together, these results suggest that upregulated CD151 expression may support not only typical integrin-dependent functions, but also integrin-independent survival of circulating (and possibly metastatic) cancer cells during anti-cancer drug therapy.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Macrophages play an important role in tissue development and homeostasis. They serve as a nexus between adaptive and innate immunity, and employ considerable plasticity. In cancer, they play a pivotal role in chronic inflammation and tumor growth either by directly stimulating the proliferation of cancer cells or by producing angiogenic and lymphangiogenic factors. Although numerous immune cells play an important role in the tumor microenvironment, tumor-associated macrophages (TAMs) are by far the most extensively studied. A better understanding of the role of TAMs in mediating chemo- and radiotherapy resistance and suppressing immunosurveillance has led to numerous strategies targeting TAMs as an anticancer therapy either by targeting them directly or by polarizing TAMs toward a tumoricidal phenotype.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The proteostasis network (PN) comprises a plethora of proteins that are dedicated to aid in protein folding and maintenance; some with overlapping functions. Despite this, there are multiple pathophysiological states associated with depletion of chaperones. This is counter-intuitive, assuming cells have the ability to re-program transcriptional outputs in accordance with its proteostasic limitations. Here, we have used 〈em〉S. cerevisiae〈/em〉 to understand how cells respond to different types of proteostasis impairments. We monitored the proteostasis status and transcriptome of single deletions of fourteen different Protein Quality Control (PQC) genes. In most cases, cellular response did not activate proteostasis components or pathways that could either complement the function of the missing PQC gene or restore proteostasis. Over-expression of alternate machineries could restore part of the proteostasis defect in two representative PQC gene deletion strains. We posit that 〈em〉S. cerevisiae〈/em〉 inherently lacks the ability to sense and respond optimally to defects in proteostasis caused due to deletion of specific PQC components.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉HMG box protein 1 (HBP1) is a transcription factor and a potent cell cycle inhibitor in normal and cancer cells. HBP1 activates or represses the expression of different cell cycle genes (such as 〈em〉CDKN2A, CDKN1A,〈/em〉 and 〈em〉CCND1〈/em〉) through direct DNA binding, cofactor recruitment, chromatin remodeling, or neutralization of other transcription factors. Among these are LEF1, TCF4, and MYC in the WNT/beta-catenin pathway. HBP1 also contributes to oncogenic RAS-induced senescence and terminal cell differentiation. Collectively, these activities suggest a tumor suppressor function. However, HBP1 is not listed among frequently mutated cancer driver genes. Nevertheless, HBP1 expression is lower in several tumor types relative to matched normal tissues. Several micro-RNAs, such as miR-155, miR-17-92, and miR-29a, dampen HBP1 expression in cancer cells of various origins. The phosphatidylinositol-3 kinase (PI3K)/AKT pathway also inhibits HBP1 transcription by preventing FOXO binding to the HBP1 promoter. In addition, AKT directly phosphorylates HBP1, thereby inhibiting its transcriptional activity. Taken together, these findings place HBP1 at the center of a network of micro-RNAs and oncoproteins that control cell proliferation. In this review, we discuss our current understanding of HBP1 function in human physiology and diseases.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Quorum sensing is a system of stimuli and response correlated to population density and involves in pathogen infection, colonization, and pathogenesis. Quorum quenching enzymes as quorum sensing inhibitors have been identified in a number of bacteria and been used to control by triggering the pathogenic phenotype. The marine bacteria of 〈em〉Pseudoalteromonas〈/em〉 had wide activity of degrading AHLs as a type of signal molecule associated with quorum sensing. We screened many 〈em〉Pseudoalteromonas〈/em〉 strains in large scale to explore genes of quorum quenching enzymes from the China seas by whole-genome sequencing rather than genomic library construction. Nine target strains were obtained and an acylases gene APTM01 from the strain MQS005 belonging to PvdQ type on sub-branch in phylogenetic tree. And the heterogenous host containing the vector with target gene could degrade C10-HSL, C12-HSL and OC12-HSL. The obtained AHL acylase gene would be a candidate quorum quenching gene to apply in some fields. We identified that the strains of 〈em〉Pseudoalteromonas〈/em〉 have wide AHL-degrading ability depending on quorum quenching. The strains would be a resource to explore new quorum quenching enzymes.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Iturin A is a very important cyclic lipopeptide produced by several 〈em〉B. subtilis〈/em〉 strains and has large commercial and therapeutic application potentials but its production on industrial scale has not been realized yet. In the present study, we have observed that the strain ET-1 of 〈em〉Bacillus subtilis〈/em〉, a producer of Iturin A, can present at least three different colony morphologies, which we arbitrarily called Rough, Smooth, and Mucoid morphotypes (R-, S-, and M-form). Performing HPLC analysis, a significant difference between the amounts of Iturin A produced by the three morphotypes was found. The morphotype R-form showed the highest productivity with yields about 10 and 100 times higher than morphotypes S and M, respectively. The results show that the production of Iturin A by 〈em〉B. subtilis〈/em〉 could be strongly influenced by the phenotypic heterogeneity of cells within the inoculum. Indeed, we have observed that, pasteurizing the inoculum before seeding in order to improve the homogeneity removing the phenotypes less able to synthesize the Iturin A, its yields in a bench-scale production could be significantly improved. This can represent an important control factor also at industrial scale to improve the Iturin A yields, the robustness, the replicability, and consequently the cost-effectiveness of fermentation processes.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Imidacloprid (C〈sub〉9〈/sub〉H〈sub〉10〈/sub〉ClN〈sub〉5〈/sub〉O〈sub〉2〈/sub〉) is used as the most recommended type of insecticide in vegetable farming worldwide. Two types of bacteria (〈em〉Methylobacterium radiotolerans〈/em〉 and 〈em〉Microbacterium arthrosphaerae〈/em〉) were isolated from a corn farming field in the Thrace region of Turkey, and then consortia of these bacteria were prepared from equal volumes of 10〈sup〉7〈/sup〉 CFU/ml for each bacterium type. Imidacloprid remediation studies were carried out during 18 days in soil test units. The water filtered from these soil test units was determined for chemical oxygen demand (COD) and biochemical oxygen demand (BOD〈sub〉5〈/sub〉) to determine the optimum concentration of microorganisms to ascertain the best removal efficiency of Imidacloprid. COD removal rates were 98.7%, 96.4% and 51.6% with 80, 40, and 20 ml volumes of the consortia of bacteria, respectively, at the end of 18 days. The BOD〈sub〉5〈/sub〉 removal rates were 88.4%, 78.6% and 49.9% in the same volumes of bacteria, respectively. As a result of this study, we have found that this bacterial consortium is very effective for the bioremediation of this insecticide at the two volumes of 40 and 80 ml, both being better than 20 ml.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉The diversity and community composition of archaea in soil samples from three wetlands (SP1, SP2, and SP3) of Ebinur Lake were studied by constructing 16S rDNA cloning library. The correlation between the diversity of archaea and soil environmental factors was analyzed by CANOCO software. The aim of this study was to reveal the differences of community structures of archaea in different sample sites, to provide a theoretical basis for further study on degradation and restoration of Ebinur Lake wetland. The results showed that 〈em〉Euryarchaeota〈/em〉 accounted for 57.1% was the most dominant phylum observed, followed by 〈em〉Thaumarchaeota〈/em〉 and 〈em〉Crenarchaeota〈/em〉 for the three wetland soil analyzed. Compared with SP3 site, the proportions of 〈em〉Euryarchaeota〈/em〉 were decreased by 16.70% and 31.78%, while 〈em〉Thaumarchaeota〈/em〉 increased by 7.26% and 17.64% in the SP1 and SP2, respectively. 〈em〉Crenarchaeota〈/em〉 was found only in SP3. Shannon–wiener diversity indices in SP1, SP2, and SP3 sites were 3.44, 3.87, and 3.94, respectively, indicating that the diversity of archaea in three plots was: SP3 〉 SP2 〉 SP1. Redundancy analysis (RDA) showed that electrical conductivity (EC), soil moisture (SM), hydrogen potential (pH), and soil organic matter content (SOM) may affect archaeal communities. Compared to EC and pH, SM and SOM may have a greater impact on the community composition of archaea.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉As an emerging food-borne pathogen, 〈em〉Cronobacter〈/em〉 species are ubiquitous in the food and environment. In order to know the characteristics of 〈em〉Cronobacter〈/em〉 spp. from the environment, we isolated 〈em〉Cronobacter〈/em〉 spp. from soil and water, and then studied the molecular typing and antibiotic resistance characteristics of these isolates. In 2016, 141 soil and water samples were collected from farms and Riverside Park in Beijing. Isolates were identified by real-time PCR, 16s rRNA sequencing, and whole-genome sequencing. Molecular subtyping of these isolates was characterized by pulsed-field gel electrophoresis, multilocus sequence typing (MLST), and antibiotic susceptibility tests. 〈em〉Cronobacter〈/em〉 species were classified based on 〈em〉fusA〈/em〉 sequencing. Twenty-two samples (15.60%) contained 〈em〉Cronobacter〈/em〉 spp., and four species were detected, i.e., 〈em〉C. dubliniensis〈/em〉 (〈em〉n〈/em〉 = 10), 〈em〉C. sakazakii〈/em〉 (〈em〉n〈/em〉 = 6), 〈em〉C. turicensis〈/em〉 (〈em〉n〈/em〉 = 4), and 〈em〉C. malonaticus〈/em〉 (〈em〉n〈/em〉 = 2). For MLST, 12 types (ST519–ST525, ST533–ST537) were newly identified, indicating high diversity. Most isolates (68.18%) showed resistance to cefazolin. 〈em〉Siccibacter turicensis〈/em〉 and 〈em〉Cronobacter〈/em〉 both with blue-green colonies on selective media should be respectively identified. Apparently, major 〈em〉Cronobacter〈/em〉 species in soil and water samples differed from those in food. Molecular subtyping showed that the environment could not be excluded as a source of 〈em〉Cronobacter〈/em〉 infection. The resistance to cefazolin of most isolates indicated natural resistance.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉U6 RNA polymerase III promoter (PU6), which is a key element in controlling the generation of single-guide RNA (sgRNA) for gene editing through CRISPR-Cas9 system, was investigated in this work. Using bioinformatics approach, two novel U6 ribonucleic acid (U6 RNA) sequences of 〈em〉Aspergillus niger〈/em〉 were identified, showing that they had conserved motifs similar to other U6 RNAs. The putative PU6 located at the upstream sequence of 〈em〉A. niger〈/em〉 U6 RNA exhibited the consensus motif, CCAATYA, and the TATA box which shared highly conserved characteristics across Aspergilli, whereas the A- and B-boxes were found at the intragenic and downstream of the structural genes, respectively. Using 〈em〉Aspergillus oryzae〈/em〉 as a workhorse system, the function of 〈em〉A. niger〈/em〉 PU6s for controlling the transcripts of sgRNA was verified, in which the orotidine-5′-phosphate decarboxylase (〈em〉pyr〈/em〉G) sequence was used as a target for gene disruption through CRISPR-Cas9 system. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis of the selected 〈em〉pyr〈/em〉G auxotrophic strains showed the expression of sgRNA, indicating that the non-native promoters could efficiently drive sgRNA expression in 〈em〉A. oryzae〈/em〉. These identified promoters are useful genetic tools for precise engineering of metabolic pathways in the industrially important fungus through the empowered CRISPR-Cas9-associated gene-editing system.〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉One novel ascomycetous yeast strain TF5-16-2 was isolated from water samples of Tuofengling crater lake located in Da Hinggan Ling Mountain, in the Inner Mongolia province of China. Morphological, physiological characteristics, as well as phylogenetic analyses of D1/D2 domains of the large subunit rRNA (LSU), ITS region, small subunit rRNA (SSU), and elongation factor-1〈em〉α〈/em〉 (EF-1〈em〉α〈/em〉) were performed and finally confirmed the phylogenetic placement of strain TF5-16-2 in the genus 〈em〉Wickerhamomyces〈/em〉. Sequences analysis revealed that strain TF5-16-2 differed from its most closely related phylogenetic neighbors 〈em〉‘Candida’ silvicultrix〈/em〉 CBS 6269〈sup〉T〈/sup〉 and 〈em〉Wickerhamomyces anomalus〈/em〉 CBS 5759〈sup〉T〈/sup〉 by 8.0% (including 2.3% gaps), 8.5% (including 2.4% gaps) divergences in D1/D2 domains of LSU, and 11% (including 4.3% gaps) and 13% (including 4.4% gaps) divergences in ITS region, respectively. As the considerable sequence divergence and distinguishable physiological characteristics, strain TF5-16-2 was proposed as a new species of the genus 〈em〉Wickerhamomyces〈/em〉, with the name 〈em〉Wickerhamomyces kurtzmanii〈/em〉 sp. nov. (holotype = CGMCC 2.5597, Mycobank number is MB829959).〈/p〉

Description: 〈h3〉Abstract〈/h3〉 〈p〉Conventional glycoconjugates are prepared with polysaccharides (PS) isolated from bacterial sources by fermentation technique. This approach has some major challenges like lower yield of PS, impurities and usage of hazardous chemicals. Reports on efficient and enhanced production of PS from 〈em〉Shigella flexneri〈/em〉 is meager in literature. Hence, in the current study, three different types of media namely Yeast extract medium, 〈em〉Shigella sonnei〈/em〉-defined medium and synthetic medium were utilized for the culture of 〈em〉S. flexneri〈/em〉. Among the selected media it was recognized that the culture of 〈em〉S. flexneri〈/em〉 harvested in synthetic media produced significant quantity of PS in less time when compared to the other two media. Different purification techniques such as phenol chloroform extraction, acid precipitation, detergent method, chromatographic purification and a novel silicate method were carried out to refine the harvested PS from impurities. It was observed that large impurities such as bacterial protein, debris and media components were eliminated significantly by using chromatographic and silicate methods. The final yield of purified PS was approximately 20–35% higher in silicate method which is reported for the first time in this study for purification of PS. Further, the characterization of the purified PS was done using high-performance liquid chromatography and high-performance anion-exchange chromatography with pulsed amperometric detection. Hence, the robust process developed in the present study using synthetic media and chromatographic filtration technique along with the novel silicate treatment produced significant quantities of PS from 〈em〉S. flexneri〈/em〉 in reduced cost and time, which could be further conjugated to a suitable carrier to generate a potential 〈em〉Shigella〈/em〉 conjugate antigen.〈/p〉