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ABSTRACT: Zearalenone (ZEN), a mycotoxin produced by Fusarium species, is known for its reproductive toxicity as an estrogen analogue. However, there are limited knowledge about its hepatointestinal toxicity, as well as the role that gut microbiota and metabolites play in this process. In this study, a total of 24 thirty-week-old hens were fed to investigate the hepatointestinal toxicity subjected to long-term ZEN consumption at 2.0 mg/kg for 90 d. And we employed uncultured 16S rRNA sequencing for gut microbiota and untargeted metabolomics for fecal metabolites assessment. Notably, ZEN induced significant hepatic damage, as evidenced by hepatocyte necrosis, inflammatory cell infiltrate, increased liver lipopolysaccharide (LPS) and blood aspartate aminotransferase (AST) levels (P < 0.05). The decreased villus height, disruption of simple columnar epithelial cells, and exposure of the mucosal intrinsic layer were observed in the intestine. The gut microbial community composition and metabolites differed between ZEN group and control group. ZEN group exhibited higher gut microbial diversity (P < 0.05), lower Firmicutes/Bacteroidetes ratio and Lactobacillus abundance, and higher abundance in the genus such as Bacteroidetes, Parabacteroidetes and Desulfovibrio. Metabolomic analysis showed that ZEN treatment altered biosynthesis of siderophore group nonribosomal peptides and phenylpropanoids, metabolism of amino acid, digestion and absorption of vitamin and ABC transporters. Differential metabolites suggested that ZEN increase the risk of estrogen disorder, nucleic acid degradation, intestinal oxidative stress and inflammation. Neural network analysis showed that Ruminococcus was positively correlated with glyceric acid, and Prevotella was positively correlated with phenylacetylglycine. Both metabolites were positively correlated with blood AST level (P < 0.05), suggesting that intestinal microbe Ruminococcus and Prevotella might exacerbate liver damage by producing these harmful metabolites. Overall, we conclude that ZEN has damaged hepatointestinal system and the altered gut microbiota with resultant metabolite changes contribute to the adverse hepatointestinal effects of ZEN on laying hens. This study underscores the need for monitoring and mitigating ZEN exposure in poultry diets, highlighting its broader implications for animal health and food safety.

Abstract Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.

Urban reservoirs contribute significantly to human survival and ecological balance. Machine learning-based remote sensing techniques for monitoring water quality parameters (WQPs) have gained increasing prominence in recent years. However, these techniques still face challenges such as inadequate band selection, weak machine learning model performance, and the limited retrieval of non-optical active parameters (NOAPs). This study focuses on an urban reservoir, utilizing unmanned aerial vehicle (UAV) multispectral remote sensing and ensemble machine learning (EML) methods to monitor optically active parameters (OAPs, including Chla and SD) and non-optically active parameters (including CODMn, TN, and TP), exploring spatial and temporal variations of WQPs. A framework of Feature Combination and Genetic Algorithm (FC-GA) is developed for feature band selection, along with two frameworks of EML models for WQP estimation. Results indicate FC-GA’s superiority over popular methods such as the Pearson correlation coefficient and recursive feature elimination, achieving higher performance with no multicollinearity between bands. The EML model demonstrates superior estimation capabilities for WQPs like Chla, SD, CODMn, and TP, with an R2 of 0.72–0.86 and an MRE of 7.57–42.06%. Notably, the EML model exhibits greater accuracy in estimating OAPs (MRE ≤ 19.35%) compared to NOAPs (MRE ≤ 42.06%). Furthermore, spatial and temporal distributions of WQPs reveal nitrogen and phosphorus nutrient pollution in the upstream head and downstream tail of the reservoir due to human activities. TP, TN, and Chla are lower in the dry season than in the rainy season, while clarity and CODMn are higher in the dry season than in the rainy season. This study proposes a novel approach to water quality monitoring, aiding in the identification of potential pollution sources and ecological management.

Rainfall and wind speed are two important meteorological variables that have a significant impact on agriculture, human health, and socio-economic development. While individual rainfall or wind events have been widely studied, little attention has been devoted to studying the lead–lag relationship between rainfall and wind speed, particularly in coastal regions where strong dependence between rainfall and wind speed is expected. Taking China's coastline as the case study, this paper aims to explore the variation trends of wind speed and rainfall and reveal the relationships between rainfall events and wind speeds on days before and after rainfall occurrence, by using meteorological station data from 1960 to 2018. The results show that wind speed tended to decrease while rainfall showed a slight increase for most stations. The daily wind speed increased 2 days before rainfall occurrence and decreased after then, with the highest wind speed observed during rainfall onset regardless of rainfall amount. Moreover, heavier rainfall events are more likely to occur with higher wind speeds. The findings of this study potentially improve the understanding of the dependence of rainfall and wind speed, which could help rainfall or wind-related disaster mitigation. HIGHLIGHTS Dependence of daily rainfall and wind speed over China's coastline is investigated.; Daily wind speed increased 2 days before rainfall occurrence and decreased after then.; Heavier rainfall events are more likely to occur with higher wind speeds.;

Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have an increased risk of developing colorectal neoplasia (CRN) in the proximal colon. Objectives: To evaluate whether duration and severity of inflammation are linked to the development of CRN in this population. Design: Retrospective, case–control chart review of patients with PSC and IBD at a tertiary care center. Methods: Disease activity was scored per colonic segment at each colonoscopy prior to the first instance of observed CRN using a modified Mayo endoscopic sub-score and histologic assessment. Patients in the CRN-positive group were compared to controls that did not. Results: In all, 72 PSC-IBD patients with no history of CRN were identified, 13 of whom developed CRN after at least one colonoscopy at our institution. Patients in the CRN-positive group had significantly more endoscopic ( p

Because ADAM17 promotes colonic tumorigenesis, we investigated potential miRNAs regulating ADAM17; and examined effects of diet and tumorigenesis on these miRNAs. We also examined pre-miRNA processing and tumour suppressor roles of several of these miRNAs in experimental colon cancer. Using TargetScan, miR-145, miR-148a, and miR-152 were predicted to regulate ADAM17. miR-143 was also investigated as miR-143 and miR-145 are co-transcribed and associated with decreased tumour growth. HCT116 colon cancer cells (CCC) were co-transfected with predicted ADAM17-regulating miRNAs and luciferase reporters controlled by ADAM17-3’UTR. Separately, pre-miR-143 processing by colonic cells was measured. miRNAs were quantified by RT-PCR. Tumours were induced with AOM/DSS in WT and transgenic mice (Tg) expressing pre-miR-143/miR-145 under villin promoter. HCT116 transfection with miR-145, −148a or −152, but not scrambled miRNA inhibited ADAM17 expression and luciferase activity. The latter was suppressed by mutations in ADAM17-3’UTR. Lysates from colonocytes, but not CCC, processed pre-miR-143 and mixing experiments suggested CCC lacked a competency factor. Colonic miR-143, miR-145, miR-148a, and miR-152 were downregulated in tumours and more moderately by feeding mice a Western diet. Tg mice were resistant to DSS colitis and had significantly lower cancer incidence and tumour multiplicity. Tg expression blocked up-regulation of putative targets of miR-143 and miR-145, including ADAM17, K-Ras, XPO5, and SET. miR-145, miR-148a, and miR-152 directly suppress colonocyte ADAM17 and are down-regulated in colon cancer. This is the first direct demonstration of tumour suppressor roles for miR-143 and miR-145 in an in vivo model of colonic tumorigenesis.

Pseudomonas aeruginosa (P. aeruginosa), an opportunistic pathogen, is often associated with difficulties in treating hospital-acquired infections. Biofilms formed by P. aeruginosa significantly improve its resistance to antimicrobial agents, thereby, posing a great challenge to the combat of P. aeruginosa infection. Antimicrobial peptides (AMPs) have recently emerged as promising antibiofilm agents and increasingly attracting the attention of scientists worldwide. However, current knowledge of their antibiofilm behavior is limited and their underlying mechanism remains unclear. In this study, a novel AMP, named PEW300, with three-point mutations (E9H, D17K, and T33A) from Cecropin A was used to investigate its antibiofilm property and antibiofilm pathway against P. aeruginosa. PEW300 displayed strong antibacterial and antibiofilm activity against P. aeruginosa with no significant hemolysis or cytotoxicity to mouse erythrocyte and human embryonic kidney 293 cells. Besides, the antibiofilm pathway results showed that PEW300 preferentially dispersed the mature biofilm, leading to the biofilm-encapsulated bacteria exposure and death. Meanwhile, we also found that the extracellular DNA was a critical target of PEW300 against the mature biofilm of P. aeruginosa. In addition, multiple actions of PEW300 including destroying the cell membrane integrity, inducing high levels of intracellular reactive oxygen species, and interacting with genomic DNA were adopted to exert its antibacterial activity. Moreover, PEW300 could dramatically reduce the virulence of P. aeruginosa. Taken together, PEW300 might be served as a promising antibiofilm candidate to combat P. aeruginosa biofilms.

Background: Congenital cataract is one of the most common causes of blindness in children. A rapid and accurate genetic diagnosis benefit the patients in the pediatric department. The current study aims to identify the genetic defects in a congenital cataract patient without a family history.Case presentation: A congenital cataract patient with microphthalmia and nystagmus was recruited for this study. Trio-based whole-exome sequencing revealed a de novo variant (c.394delG, p.V132Sfs*15) in CRYGC gene. According to the American College of Medical Genetics and Genomics (ACMG) criteria, the variant could be annontated as pathogenic.Conclusion: Our findings provide new knowledge of the variant spectrum of CRYGC gene and are essential for understanding the heterogeneity of cataracts in the Chinese population.

DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

Abstract Background This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration.

To investigate the protective effect of quercetin on the lipopolysaccharide-induced inflammatory response of retinal ganglion cell line 5 cells and to explore its possible molecular mechanism. Retinal ganglion cell line 5 cells were cultured in vitro and assigned into blank control group, lipopolysaccharide (1.0 μg/ml) induction group, lipopolysaccharide+low dose (0.25 μg/ml) quercetin group, lipopolysaccharide+medium dose (0.5 μg/ml) quercetin group and lipopolysaccharide+high dose (1.0 μg/ml) quercetin group. The relative survival rate of retinal ganglion cell line 5 cells was determined by cell counting kit-8 assay and the levels of inflammatory factors interleukin-6 and tumor necrosis factor-alpha were detected using enzymelinked immunosorbent assay kits. In addition, the levels of tumor necrosis factor receptor-associated factor 6, phosphorylation-transforming growth factor-beta-activated kinase 1 and transforming growth factorbeta-activated kinase 1 were measured by western blotting. The results of cell counting kit-8 assay revealed that quercetin could dramatically elevate the relative survival rate of retinal ganglion cell line 5 cells. The levels of inflammatory factors interleukin-6 and tumor necrosis factor-alpha in different quercetin groups were significantly lower than those in lipopolysaccharide induction group and the levels of interleukin-6 and tumor necrosis factor-alpha in cell supernatant declined with the increase of quercetin concentration in a concentration-dependent manner. In addition, the expression levels of tumor necrosis factor receptorassociated factor 6 and phosphorylation-transforming growth factor-beta-activated kinase 1 in different quercetin groups were remarkably lower than those in lipopolysaccharide induction group and they also declined with the increase of quercetin concentration in a concentration-dependent manner. Quercetin displays a protective effect against the lipopolysaccharide-induced inflammatory response of retinal ganglion cell line 5 cells and its mechanism is related to suppression of the activation of the tumor necrosis factor receptor-associated factor 6/transforming growth factor-beta-activated kinase 1 signaling pathway. [ABSTRACT FROM AUTHOR]

Here, we report on a novel superoxide anion (O2•-) biosensor based on direct electron transfer of copper, zinc-superoxide dismutase (Cu, Zn-SOD) at zinc oxide nanodisks surface for in vivo tracking of O2•- in bean sprouts. Direct electron transfer of SOD is achieved at ZnO nanodisks film prepared by a one-step electrodeposited method, with a high heterogeneous electron rate constant of 17 ± 2 s-1. Spectroscopic data demonstrate that SOD strongly immobilized onto the nanostructured ZnO surfaces processes its inherent activity toward O2•- dismutation. A combination of the facilitated direct electron transfer and the bifunctional enzymatic catalytic activities of the SOD substantially provides a dual elecIrochemical approach to determination of O2•- with high selectivity, wide linear range, long stability, and good reproducibility. In particular, SOD adsorbed on the ZnO nanodisks film is capable of sensing O2•- cathodically at a very positive potential, 0 mV (vs Ag∣AgCl), where the common interfering species such as hydrogen peroxide, uric acid, ascorbic acid, and 3,4-dihydroxyphenylacetic acid were effectively avoided. The excellent analytical performance of the present O2•- biosensor, combined with the remarkable characteristics of nanostructured ZnO films, such as biocompatibility, ease of preparation, and facile to miniaturize, paves an electrochemical way for reliable and durable in vivo determination of O2•- in bean sprouts. [ABSTRACT FROM AUTHOR]