AdaLiftOver: high-resolution identification of orthologous regulatory elements with Adaptive liftOver.

MOTIVATION: Elucidating functionally similar orthologous regulatory regions for human and model organism genomes is critical for exploiting model organism research and advancing our understanding of results from genome-wide association studies (GWAS). Sequence conservation is the de facto approach for finding orthologous non-coding regions between human and model organism genomes. However, existing methods for mapping non-coding genomic regions across species are challenged by the multi-mapping, low precision, and low mapping rate issues. RESULTS: We develop Adaptive liftOver (AdaLiftOver), a large-scale computational tool for identifying functionally similar orthologous non-coding regions across species. AdaLiftOver builds on the UCSC liftOver framework to extend the query regions and prioritizes the resulting candidate target regions based on the conservation of the epigenomic and the sequence grammar features. Evaluations of AdaLiftOver with multiple case studies, spanning both genomic intervals from epigenome datasets across a wide range of model organisms and GWAS SNPs, yield AdaLiftOver as a versatile method for deriving hard-to-obtain human epigenome datasets as well as reliably identifying orthologous loci for GWAS SNPs. AVAILABILITY AND IMPLEMENTATION: The R package and the data for AdaLiftOver is available from https://github.com/keleslab/AdaLiftOver.

Lactobacillus paracasei M11-4 isolated from fermented rice demonstrates good antioxidant properties in vitro and in vivo.

BACKGROUND: Probiotics are defined as microorganisms that can exert health benefits for the host. Among the recognized probiotics, Lactobacillus paracasei are one of the most frequently used probiotics in humans. The L. paracasei strain M11-4, isolated from fermented rice (which could ferment soymilk within a short curd time) and fermented soymilk presented high viability, acceptable flavor, and antioxidant activity, which revealed that the strain maybe have a potential antioxidant value. Therefore, it is necessary to further explore the antioxidant activity of L. paracasei strain M11-4. RESULTS: The radical scavenging activities, lipid peroxidation inhibition, and reducing power of L. paracasei M11-4 were the highest in the fermentation culture without cells, whereas the activities of other antioxidant enzymes of L. paracasei M11-4 were high in the cell-free extract and bacterial suspension. Moreover, L. paracasei M11-4 exerted its antioxidant effect by upregulating the gene expression of its antioxidant enzymes - the thioredoxin and glutathione systems - when hydrogen peroxide existed. Supplementation of rats with L. paracasei M11-4 effectively alleviated d-galactose-induced oxidative damage in the liver and serum and prevented d-galactose-induced changes to intestinal microbiota. Supplementation with L. paracasei M11-4 also reduced the elevated expression of thioredoxin and glutathione system genes induced by d-galactose. CONCLUSION: L. paracasei M11-4 has good antioxidant properties both in vitro and in vivo, and its antioxidant mechanism was studied at the molecular level. © 2021 Society of Chemical Industry.

TNFAIP8 regulates gastric cancer growth via mTOR-Akt-ULK1 pathway and autophagy signals.

In this study, the purpose of this study was to investigate the role of TNFAIP8 in gastric cancer (GC). The expression of TNFAIP8 was detected by RT-PCR or western blot . TNFAIP8 was silenced or overexpressed in two cell lines. CCK-8 assay, transwell assay and flow cytometry were used to analyse cell viability, cell invasion capability and apoptosis, respectively. Nude mice were inoculated with TNFAIP8 silencing or overexpressing cells to form transplanted tumours. HE staining and immunohistochemistry assay were performed to assess histopathological changes in tumours. We found that the mRNA and protein expression of TNFAIP8 were significantly up-regulated in GC tumour tissues and cells compared with the normal counterparts. Overexpression of TNFAIP8 in GC cells increased cell viability, decreased apoptosis and promoted the cell migration ability. Meanwhile, increased expression of TNFAIP8 promoted autophagy, while inhibiting mTOR-Akt-ULK1 signal pathway. In conclusions, this study presents data that TNFAIP8 inhibits GC cells presumably by down-regulating mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

Dexamethasone on postoperative gastrointestinal motility: A placebo-controlled, double-blinded, randomized controlled trial.

BACKGROUND AND AIM: Following abdominal surgery, patients usually experience a transient episode of impaired gastrointestinal motility. This study aimed to determine whether a single preoperative dose of dexamethasone can promote the recovery of gastrointestinal function in patients following elective gastrointestinal surgery. METHODS: In this single-center, two-arm, parallel, randomized controlled trial, we studied 126 patients (aged 18-80 years) who underwent elective open or laparoscopic bowel surgery for malignant or benign pathology. At the induction of anesthesia, a treatment group (n = 64) received a single dose of 8-mg intravenous dexamethasone, and a control group (n = 62) received normal saline. RESULTS: Intravenous administration of 8-mg dexamethasone significantly decreased the time to return of flatus by an average of approximately 8 h (P < 0.05). Abdominal distension was significantly reduced on the third day after surgery in the dexamethasone group (P < 0.05), and the time to tolerance of a liquid diet was shorter in the dexamethasone group (P < 0.01). There were no significant differences in other secondary outcomes, including postoperative pain, complication rates, length of hospital stay, or time to first defecation, between the two groups. CONCLUSIONS: A single intravenous dose of 8-mg dexamethasone at induction of anesthesia significantly decreases the time to return of flatus, improves abdominal distension at 72 h, and promotes tolerance of a liquid diet. Although further studies are required to confirm our results, we recommend that dexamethasone should be used more widely in gastrointestinal surgery.

Label-free electrochemical aptasensor for detection of alpha-fetoprotein based on AFP-aptamer and thionin/reduced graphene oxide/gold nanoparticles.

Sensitive and accurate detection of tumor markers is critical to early diagnosis, point-of-care and portable medical supervision. Alpha fetoprotein (AFP) is an important clinical tumor marker for hepatocellular carcinoma (HCC), and the concentration of AFP in human serum is related to the stage of HCC. In this paper, a label-free electrochemical aptasensor for AFP detection was fabricated using AFP-aptamer as the recognition molecule and thionin/reduced graphene oxide/gold nanoparticles (TH/RGO/Au NPs) as the sensor platform. With high electrocatalytic property and large specific surface area, RGO and Au NPs were employed on the screen-printed carbon electrode to load TH molecules. The TH not only acted as a bridging molecule to effectively capture and immobilize AFP-aptamer, but as the electron transfer mediator to provide the electrochemical signal. The AFP detection was based on the monitoring of the electrochemical current response change of TH by the differential pulse voltammetry. Under optimal conditions, the electrochemical responses were proportional to the AFP concentration in the range of 0.1-100.0 µg/mL. The limit of detection was 0.050 µg/mL at a signal-to-noise ratio of 3. The proposed method may provide a promising application of aptamer with the properties of facile procedure, low cost, high selectivity in clinic.

Effects of Traditional Chinese Exercises on Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Currently, most studies on the health benefits of traditional Chinese exercises on type 2 diabetes mellitus have explored the effects of a single type of traditional Chinese exercise on type 2 diabetes. Although a previous study evaluated the combined clinical effects of traditional Chinese exercises on type 2 diabetes, the studies included in that review were deficient in their study design. In addition, previous studies have not explored the ideal exercise dose that should be taken by patients with type 2 diabetes when performing traditional Chinese exercises. OBJECTIVE: To understand whether the findings of previous systematic reviews and meta-analyses are still applicable and to try to address the deficiencies in the previous review, this review conducted a meta-analysis of existing randomized controlled trials to investigate the impact of traditional Chinese exercises on glycemic control with type 2 diabetes. METHODS: The literature was searched in seven Chinese and English databases. Randomized controlled trials published in English and Chinese, from database inception to March 2023, were included in this review. Two reviewers independently reviewed the search results, extracted the data, and assessed the risk of bias. A meta-analysis of the included studies was conducted using Rev Man 5.4 and Stata 15.1 software. Heterogeneity was investigated using a sensitivity analysis, a subgroup analysis, and a meta-regression analysis. Pre-determined subgroups included the duration of the intervention, frequency of exercise, and duration of the single exercise session. RESULTS: A total of 31 randomized controlled trials (2077 subjects) were selected in this review. The meta-analysis revealed that traditional Chinese exercises were more effective than control groups in lowering glycated hemoglobin (Z = 6.06; mean difference [MD] = - 0.64, 95% confidence interval [CI] - 0.85, - 0.44; P < 0.00001), fasting blood glucose (Z = 7.81; MD = - 0.82, 95% CI - 1.03, - 0.62; P < 0.00001), 2-h plasma glucose (Z = 5.61; MD = - 1.03, 95% CI - 1.39, - 0.67; P < 0.00001), total cholesterol (Z = 4.23; MD = - 0.37, 95% CI - 0.54, - 0.20; P < 0.0001), high-density lipoprotein cholesterol (Z = 5.94; MD = 0.12, 95% CI 0.08, 0.16; P < 0.00001), low-density lipoprotein cholesterol (Z = 6.20; MD = - 0.34, 95% CI - 0.44, - 0.23; P < 0.00001), and triglyceride levels (Z = 3.74; MD = - 0.44, 95% CI - 0.67, - 0.21; P = 0.0002) among patients with type 2 diabetes. CONCLUSIONS: Traditional Chinese exercises can significantly improve blood glucose and lipid levels in patients with type 2 diabetes. When performing traditional Chinese exercise interventions for type 2 diabetes, it is recommended that exercise programs are designed for 30-50 min/session, 4-5 sessions/week for at least 3 months.

Joint extraction of wheat germplasm information entity relationship based on deep character and word fusion.

The verified text data of wheat varieties is an important component of wheat germplasm information. To automatically obtain a structured description of the phenotypic and genetic characteristics of wheat varieties, the aim at solve the issues of fuzzy entity boundaries and overlapping relationships in unstructured wheat variety approval data, WGIE-DCWF (joint extraction model of wheat germplasm information entity relationship based on deep character and word fusion) was proposed. The encoding layer of the model deeply fused word semantic information and character information using the Transformer encoder of BERT. This allowed for the cascading fusion of contextual semantic feature information to achieve rich character vector representation and improve the recognition ability of entity features. The triple extraction layer of the model established a cascading pointer network, extracted the head entity, extracted the tail entity according to the relationship category, and decoded the output triplet. This approach improved the model's capability to extract overlapping relationships. The experimental results demonstrated that the WGIE-DCWF model performed exceptionally well on both the WGD (wheat germplasm dataset) and the public dataset DuIE. The WGIE-DCWF model not only achieved high performance on the evaluation datasets but also demonstrated good generalization. This provided valuable technical support for the construction of a wheat germplasm information knowledge base and is of great significance for wheat breeding, genetic research, cultivation management, and agricultural production.

Effects of nanoselenium on the performance, blood indices, and milk metabolites of dairy cows during the peak lactation period.

To compare the impact of nanoselenium and sodium selenite on the performance, blood indices, and milk metabolites of dairy cows during the peak lactation period, two groups of dairy cows under the same conditions were selected as the control group (CON group) and treatment group (NSe group) for a 38-day (10 days for adaptation and 28 days for sampling) experiment. The control group (CON) was provided a basal diet +3.3 g/d of sodium selenite (purity1%), whereas the nanoselenium group (NSe) was offered the same diet +10 mL/d of nanoselenium (selenium concentration 1,500 mg/L). The results showed that NSe significantly increased the milk yield, milk selenium content, and feed efficiency (p < 0.05), but had no significant effect on other milk components (p > 0.05). NSe significantly increased blood urea nitrogen (BUN) and alkaline phosphatase (ALP) (p < 0.05), but had no significant effects on malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), blood total antioxidant capacity (T-AOC), or blood selenium (p > 0.05). In addition, the nontargeted metabolomics of the milk was determined by LC-MS technology, and the differentially abundant metabolites and their enrichment pathways were screened. According to these findings, NSe considerably increased the contents of cetylmannoside, undecylenoic acid, 3-hydroxypentadecanoic acid, 16-hydroxypentadecanoic acid, threonic acid, etc., but decreased the contents of galactaric acid, mesaconic acid, CDP-glucose etc. Furthermore, the enriched metabolic pathways that were screened with an impact value greater than 0.1 included metabolism of niacin and niacinamide, pyruvate, citrate cycle, riboflavin, glycerophospholipid, butanoate and tyrosine. Pearson correlation analysis also revealed a relationship between different milk metabolites and blood selenium, as well as between milk selenium and blood biochemical indices. In conclusion, compared with sodium selenite, nanoselenium improves the milk yield, feed efficiency, and milk selenium content of dairy cows and regulates milk metabolites and related metabolic pathways in Holstein dairy cows during the peak lactation period, which has certain application prospects in dairy production.

Harnessing the regenerative potential of interleukin11 to enhance heart repair.

Balancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. While Interleukin11 (IL11) is known as a fibrotic factor, its contribution to heart regeneration is poorly understood. We uncovered that il11a, an Il11 homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury. However, prolonged il11a induction in uninjured hearts causes persistent fibroblast emergence, resulting in fibrosis. While deciphering the regenerative and fibrotic effects of il11a, we found that il11-dependent fibrosis, but not regeneration, is mediated through ERK activity, suggesting to potentially uncouple il11a dual effects on regeneration and fibrosis. To harness the il11a's regenerative ability, we devised a combinatorial treatment through il11a induction with ERK inhibition. This approach enhances cardiomyocyte proliferation with mitigated fibrosis, achieving a balance between regenerative processes and fibrosis. Thus, we unveil the mechanistic insights into regenerative il11 roles, offering therapeutic avenues to foster cardiac repair without exacerbating fibrosis.

Effects of organic trace minerals chelated with oligosaccharides on growth performance, blood parameters, slaughter performance and meat quality in sheep.

The present study assessed the effects of oligosaccharide-chelated organic trace minerals (OTM) on the growth performance, digestive enzyme activity, blood parameters, slaughter performance, and meat quality indexes of mutton sheep. A total of 60 East Ujumuqin × small-tailed Han crossbred mutton sheep were assigned to two groups (10 duplicates per group) by body weight (26.12 ± 3.22 kg) according to a completely randomized design. Compared to the CON group, the results of the OTM group showed: (1) no significant changes in the initial body weight, final body weight, dry matter intake, average daily gain, and feed conversion ratio (p > 0.05); (2) the activities of trypsin, lipase, and amylase in the jejunum were significantly increased (p < 0.05); (3) serum total protein, albumin, and globulin of the blood were significantly increased (p < 0.05), and the growth factor interleukin IL-10 was significantly higher (p < 0.05), while IL-2, IL-6, and γ-interferon were significantly lower (p < 0.05). Immunoglobulins A, M, and G were significantly higher (p < 0.05); (4) the live weight before slaughter, carcass weights, dressing percentage, eye muscle areas, and GR values did not differ significantly (p > 0.05); (5) shear force of mutton was significantly lower (p < 0.05), while the pH45min, pH24h, drip loss, and cooking loss did not show a significant difference (p > 0.05). The content of crude protein was significantly higher (p < 0.05), while the ether extract content was significantly reduced (p < 0.05), but no significant difference was detected between moisture and ash content; (6) the total amino acids, essential amino acids, semi-essential amino acids, and umami amino acids were significantly increased (p < 0.05). Although umami amino acids were not significant, the total volume increased (p > 0.05). Among these, the essential amino acids, threonine, valine, leucine, lysine in essential amino acids and arginine were significantly increased (p < 0.05). Also, non-essential amino acids, glycine, serine, proline, tyrosine, cysteine, and aspartic acid, were significantly higher (p < 0.05). The content of alanine, aspartate, glutamic acid, phenylalanine, and tyrosine in umami amino acids was significantly higher (p < 0.05).

Effects of Lactobacillus plantarum (L) and molasses (M) on nutrient composition, aerobic stability, and microflora of alfalfa silage in sandy grasslands.

The objective of this experiment was to investigate the effects of Lactobacillus plantarum and molasses on the nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora of alfalfa silage in sandy grasslands. The experimental treatments included control (CK), 106 CFU/g Lactobacillus plantarum (L), 5% molasses (M), and 106 CFU/g Lactobacillus plantarum + 5% molasses (LM). The nutrient composition, fermentation quality, bacterial count, aerobic stability, and microflora were determined after 14 days and 56 days of ensiling, respectively. The results showed that the addition of L, M, and LM reduced dry matter loss (DM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) content, and increased water-soluble carbohydrates (WSC) and ether extract (EE) content, compared to the CK group. Meanwhile, more lactic acid (LA) and accelerated fermentation were observed, causing the pH value to drop below 4.5 in the L, M, and LM groups after 56 days of ensiling. The addition of L, M, and LM promoted lactic acid bacteria (LAB), and inhibited yeast. The addition of L significantly increased the content of acetic acid (AA). In terms of microflora, the addition of L, M, and LM made Firmicutes become the dominant bacterial phylum earlier, while Lactobacillus, Weissella, and Pediococcus had a higher abundance. According to the result of Pearson's correlation, there is a very significant negative correlation between pH value and Lactobacillus (P < 0.01) and a very significant positive correlation between pH value and Lactococcus, Enterobacter, Enterococcus, and Leuconostoc (P < 0.01), which may be inhibited by Lactobacillus under the decreased pH value. The results of the prediction of microbial genes indicated that the addition of M could enhance the carbohydrate metabolism and membrane transport metabolism, which may contribute to LA production by LAB metabolism. In general, L, M and LM all improved the fermentation quality and reduced the loss of nutrients to varying degrees, but considering the fermentation quality, the overall effects of M and LM were better than L. M and LM are recommended to be used as silage additives in the process of alfalfa silage in sandy grasslands to improve the quality.

Effect of exercise interventions based on family management or self-management on glycaemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Most studies about exercise interventions for patients with type 2 diabetes mellitus (T2DM) have been conducted in hospitals or labs, but it is unclear whether study findings from this specific condition can be generalised to real-life T2DM communities. If patients with T2DM can exercise on their own or with family members, it may also reduce the need for patient supervision by medical staff, thereby reducing the burden of medical treatment and improving condition management's cost-effectiveness and practicability. Much of the current research on exercise interventions for T2DM was focused on the type of exercise and less on the mode of management, so we aimed to examine the effect of exercise interventions based on family management or self-management on glycaemic control in patients with T2DM. METHODS: Articles were searched from eight Chinese and English databases. Randomized control trials (RCTs) published in English and Chinese, from inception to October 17, 2022, were included in this review. The methodological quality of the included studies was assessed using the RCT risk of bias assessment tool provided by the Cochrane Collaboration's tool. Meta-analysis was performed using Rev Man 5.4 and Stata 15.0 software. Heterogeneity was investigated using sensitivity analysis and subgroup analyses. Publication bias was tested by funnel plot and Egger's asymmetry tests. RESULTS: A total of 10 studies with a total of 913 subjects were finally included in this review. The Meta-analysis showed that exercise interventions based on family management or self-management were more effective than control groups in reducing HbA1c (Z = 3.90; 95% CI MD = - 0.81; - 1.21 to - 0.40; P < 0.0001), fasting glucose (Z = 4.63; 95% CI MD = - 1.17; - 1.67 to - 0.68; P < 0.00001), 2-h plasma glucose (Z = 5.53; 95% CI MD = - 1.84; - 2.50 to - 1.19; P < 0.00001), and Low-density lipoproteins levels (Z = 3.73; 95% CI MD = - 0.38; - 0.58 to - 0.18; P = 0.0002). CONCLUSIONS: Exercise interventions based on family management or self-management can significantly reduce glycosylated haemoglobin, fasting glucose, 2-h plasma glucose, and Low-density lipoproteins levels in patients with T2DM, which can effectively delay disease progression and reduce the risk of developing complications. In the future, for exercise interventions based on family or self-management, this review recommended that exercise intervention programmes should be formulated according to 30-60 min per session, more than three times per week, for more than six months of aerobic exercise or aerobic combined with resistance exercise.

Effects of guanidinoacetic acid on in vitro rumen fermentation and microflora structure and predicted gene function.

The fermentation substrate was supplemented with 0% guanidinoacetic acid (GAA) (control group, CON), 0.2% GAA (GAA02), 0.4% GAA (GAA04), 0.6% GAA (GAA06) and 0.8% GAA (GAA08) for 48 h of in vitro fermentation. Gas production was recorded at 2, 4, 6, 8, 12, 24, 36, and 48 h of fermentation. The gas was collected, and the proportions (%, v/v) of H2, CH4 and CO2 were determined. The rumen fermentation parameters, including pH, ammonia nitrogen (NH3-N), microbial protein (MCP) and volatile fatty acids (VFAs), were also determined. Furthermore, the bacterial community structure was analyzed through 16S rRNA high-throughput sequencing. The gene functions were predicted using PICRUSt1 according to the Kyoto Encyclopedia of Genes and Genomes (KEGG). The results showed that with the increase in GAA supplementation levels, the MCP and the concentration of rumen propionate were significantly increased, while the concentration of isovalerate was significantly decreased (p < 0.05). The results of microbial diversity and composition showed that the Shannon index was significantly decreased by supplementation with GAA at different levels (p < 0.05), but the relative abundance of norank_f_F082 and Papillibacter in the GAA06 group was significantly increased (p < 0.05). Especially in group GAA08, the relative abundances of Bacteroidota, Prevotella and Prevotellaceae_UCG-001 were significantly increased (p < 0.05). The results of gene function prediction showed that the relative abundances of the functions of flagellar assembly, bacterial chemotaxis, plant-pathogen interaction, mismatch repair and nucleotide excision repair were significantly decreased (p < 0.05), but the relative abundances of bile secretion and protein digestion and absorption were significantly increased (p < 0.05). In conclusion, supplementation with 0.8% GAA enhanced in vitro rumen fermentation parameters, increased the relative abundance of Prevotella and Prevotellaceae_UCG-001 in the rumen, and increased the metabolic pathways of bile secretion and protein digestion and absorption.

Nickel bioaccumulation by a marine bacterium Brevibacterium sp. (X6) isolated from Shenzhen Bay, China.

Nickel bioaccumulation capacity of a marine Brevibacterium sp., designated as X6, was evaluated to explore its potential application in the bioremediation of Ni2+ pollutants in marine environments. The minimum Ni2+ inhibitory concentration and maximum Ni2+ bioaccumulation of X6 were 1000 mg/L and 100.95 mg/g, respectively, higher than most reported strains. Among the co-existing metal ions in seawater, K+ caused a slight adverse impact on Ni2+ uptake, followed by Na+ and Ca2+, whereas Mg2+ drastically inhibited Ni2+ bioaccumulation. Other heavy metals such as Co2+, Zn2+ and Cd2+ moderately affected Ni2+ binding, but the adverse effect of Cu2+ was severe. The investigation of the mechanism of Ni2+ bioaccumulation revealed that 66.34% of the accumulated Ni2+ was bound to the cell surface. Carboxylic, hydroxyl, amino and thiol groups participated in Ni2+ binding, while carboxylic group contributed the most, while thiol group may be more involved in Ni2+ binding at low Ni2+ concentrations.

The SWI/SNF-Related, Matrix Associated, Actin-Dependent Regulator of Chromatin A4 Core Complex Represses Respiratory Syncytial Virus-Induced Syncytia Formation and Subepithelial Myofibroblast Transition.

Epigenetics plays an important role in the priming the dynamic response of airway epithelial cells to infectious and environmental stressors. Here, we examine the epigenetic role of the SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin A4 (SMARCA4) in the epithelial response to RSV infection. Depletion of SMARCA4 destabilized the abundance of the SMARCE1/ARID1A SWI/SNF subunits, disrupting the innate response and triggering a hybrid epithelial/mesenchymal (E/M) state. Assaying SMARCA4 complex-regulated open chromatin domains by transposase cleavage -next generation sequencing (ATAC-Seq), we observed that the majority of cleavage sites in uninfected cells have reduced chromatin accessibility. Paradoxically, SMARCA4 complex-depleted cells showed enhanced RSV-inducible chromatin opening and gene expression in the EMT pathway genes, MMP9, SNAI1/2, VIM, and CDH2. Focusing on the key MMP9, we observed that SMARCA4 complex depletion reduced basal BRD4 and RNA Polymerase II binding, but enhanced BRD4/Pol II binding in response to RSV infection. In addition, we observed that MMP9 secretion in SMARCA4 complex deficient cells contributes to mesenchymal transition, cellular fusion (syncytia) and subepithelial myofibroblast transition. We conclude the SMARCA4 complex is a transcriptional repressor of epithelial plasticity, whose depletion triggers a hybrid E/M state that affects the dynamic response of the small airway epithelial cell in mucosal remodeling via paracrine MMP9 activity.

INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants.

Genome-wide association studies reveal many non-coding variants associated with complex traits. However, model organism studies largely remain as an untapped resource for unveiling the effector genes of non-coding variants. We develop INFIMA, Integrative Fine-Mapping, to pinpoint causal SNPs for diversity outbred (DO) mice eQTL by integrating founder mice multi-omics data including ATAC-seq, RNA-seq, footprinting, and in silico mutation analysis. We demonstrate INFIMA's superior performance compared to alternatives with human and mouse chromatin conformation capture datasets. We apply INFIMA to identify novel effector genes for GWAS variants associated with diabetes. The results of the application are available at http://www.statlab.wisc.edu/shiny/INFIMA/ .

Identification of direct transcriptional targets of NFATC2 that promote ß cell proliferation.

The transcription factor NFATC2 induces ß cell proliferation in mouse and human islets. However, the genomic targets that mediate these effects have not been identified. We expressed active forms of Nfatc2 and Nfatc1 in human islets. By integrating changes in gene expression with genomic binding sites for NFATC2, we identified approximately 2200 transcriptional targets of NFATC2. Genes induced by NFATC2 were enriched for transcripts that regulate the cell cycle and for DNA motifs associated with the transcription factor FOXP. Islets from an endocrine-specific Foxp1, Foxp2, and Foxp4 triple-knockout mouse were less responsive to NFATC2-induced ß cell proliferation, suggesting the FOXP family works to regulate ß cell proliferation in concert with NFATC2. NFATC2 induced ß cell proliferation in both mouse and human islets, whereas NFATC1 did so only in human islets. Exploiting this species difference, we identified approximately 250 direct transcriptional targets of NFAT in human islets. This gene set enriches for cell cycle-associated transcripts and includes Nr4a1. Deletion of Nr4a1 reduced the capacity of NFATC2 to induce ß cell proliferation, suggesting that much of the effect of NFATC2 occurs through its induction of Nr4a1. Integration of noncoding RNA expression, chromatin accessibility, and NFATC2 binding sites enabled us to identify NFATC2-dependent enhancer loci that mediate ß cell proliferation.

Non-enzymatic electrochemical hydrogen peroxide biosensor based on reduction graphene oxide-persimmon tannin­platinum nanocomposite.

Hydrogen peroxide (H2O2) is one of the most universal and essential ingredients in distinct biological tissues. Herein, a novel non-enzymatic sensor based on reduction graphene oxide-persimmon tannin­platinum nanocomposite (RGO-PT-Pt) was exploited for H2O2 detection. RGO-PT-Pt nanocomposite was prepared by reduction procedure with ascorbic acid as reducing agent and characterized by Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), ultraviolet visible spectroscopy (UV-vis) and Fourier infrared spectroscopy (FT-IR). Taking advantage of high electro-catalytic efficiency of Pt nanoparticles, high electronic conductivity and large surface area of RGO, and significant adsorption ability of PT on metal ions and its prevention of agglomeration to promote RGO dispersion, RGO-PT-Pt nanocomposite revealed better catalytic ability towards H2O2 via a synergistic effect. Under the optimal conditions, the RGO-PT-Pt non-enzymatic biosensor exhibited outstanding electrocatalytic activity towards H2O2 reduction. The amperometric response demonstrated a linear relationship with H2O2 concentration from 1.0 to100 µM with the correlation coefficient of 0.9931. The limit of detection was 0.26 µM (S/N = 3) and the response time was 3 s. Furthermore, the fabricated sensor exhibited a practical applicability in the quantification of H2O2 in human serum samples with an excellent recovery rate. Due to excellent performance such as fast response time, low detection limit, high stability and selectivity, the RGO-PT-Pt non-enzymatic biosensor has potential application in clinical diagnostics.