Environmentally relevant concentrations of benzophenones exposure disrupt intestinal homeostasis, impair the intestinal barrier, and induce inflammation in mice.

The aim of this study is to investigate the adverse effects of benzophenones (BPs) on the intestinal tract of mice and the potential mechanism. F1-generation ICR mice were exposed to BPs (benzophenone-1, benzophenone-2, and benzophenone-3) by breastfeeding from birth until weaning, and by drinking water after weaning until maturity. The offspring mice were executed on postnatal day 56, then their distal colons were sampled. AB-PAS staining, HE staining, immunofluorescence, Transmission Electron Microscope, immunohistochemistry, Western Blot and RT-qPCR were used to study the effects of BPs exposure on the colonic tissues of offspring mice. The results showed that colonic microvilli appeared significantly deficient in the high-dose group, and the expression of tight junction markers Zo-1 and Occludin was significantly down-regulated and the number of goblet cells and secretions were reduced in all dose groups, and the expression of secretory cell markers MUC2 and KI67 were decreased, as well as the expression of intestinal stem cell markers Lgr5 and Bmi1, suggesting that BPs exposure caused disruption of intestinal barrier and imbalance in the composition of the intestinal stem cell pool. Besides, the expression of cellular inflammatory factors such as macrophage marker F4/80 and tumor necrosis factor TNF-α was elevated in the colonic tissues of all dose groups, and the inflammatory infiltration was observed, which means the exposure of BPs caused inflammatory effects in the intestinal tract of F1-generation mice. In addition, the contents of Notch/Wnt signaling pathway-related genes, such as Dll-4, Notch1, Hes1, Ctnnb1and Sfrp2 were significantly decreased in each high-dose group (P < 0.05), suggesting that BPs may inhibit the regulation of Notch/Wnt signaling pathway. In conclusion, exposure to BPs was able to imbalance colonic homeostasis, disrupt the intestinal barrier, and trigger inflammation in the offspring mice, which might be realized through interfering with the Notch/Wnt signaling pathway.

Comparative and functional analysis unveils the contribution of photoperiod to DNA methylation, sRNA accumulation, and gene expression variations in short-day and long-day grasses.

Photoperiod employs complicated networks to regulate various developmental processes in plants, including flowering transition. However, the specific mechanisms by which photoperiod affects epigenetic modifications and gene expression variations in plants remain elusive. In this study, we conducted a comprehensive analysis of DNA methylation, small RNA (sRNA) accumulation, and gene expressions under different daylengths in facultative long-day (LD) grass Brachypodium distachyon and short-day (SD) grass rice. Our results showed that while overall DNA methylation levels were minimally affected by different photoperiods, CHH methylation levels were repressed under their favorable light conditions, particularly in rice. We identified numerous differentially methylated regions (DMRs) that were influenced by photoperiod in both plant species. Apart from differential sRNA clusters, we observed alterations in the expression of key components of the RNA-directed DNA methylation pathway, DNA methyltransferases, and demethylases, which may contribute to the identified photoperiod-influenced CHH DMRs. Furthermore, we identified many differentially expressed genes in response to different daylengths, some of which were associated with the DMRs. Notably, we discovered a photoperiod-responsive gene MYB11 in the transcriptome of B. distachyon, and further demonstrated its role as a flowering inhibitor by repressing FT1 transcription. Together, our comparative and functional analysis sheds light on the effects of daylength on DNA methylation, sRNA accumulation, and gene expression variations in LD and SD plants, thereby facilitating better designing breeding programs aimed at developing high-yield crops that can adapt to local growing seasons.

Wemics: A Single-Base Resolution Methylation Quantification Method for Enhanced Prediction of Epigenetic Regulation.

DNA methylation, an epigenetic mechanism that alters gene expression without changing DNA sequence, is essential for organism development and key biological processes like genomic imprinting and X-chromosome inactivation. Despite tremendous efforts in DNA methylation research, accurate quantification of cytosine methylation remains a challenge. Here, a single-base methylation quantification approach is introduced by weighting methylation of consecutive CpG sites (Wemics) in genomic regions. Wemics quantification of DNA methylation better predicts its regulatory impact on gene transcription and identifies differentially methylated regions (DMRs) with more biological relevance. Most Wemics-quantified DMRs in lung cancer are epigenetically conserved and recurrently occurred in other primary cancers from The Cancer Genome Atlas (TCGA), and their aberrant alterations can serve as promising pan-cancer diagnostic markers. It is further revealed that these detected DMRs are enriched in transcription factor (TF) binding motifs, and methylation of these TF binding motifs and TF expression synergistically regulate target gene expression. Using Wemics on epigenomic-transcriptomic data from the large lung cancer cohort, a dozen novel genes with oncogenic potential are discovered that are upregulated by hypomethylation but overlooked by other quantification methods. These findings increase the understanding of the epigenetic mechanism by which DNA methylation regulates gene expression.

Identification of reliable QTLs and designed QTL breeding for grain shape and milling quality in the reciprocal introgression lines in rice.

Milling quality (MQ) and grain shape (GS) of rice (Oryza sativa L.) are correlated traits, both determine farmers' final profit. More than one population under multiple environments may provide valuable information for breeding selection on these MQ-GS correlations. However, suitable analytical methods for reciprocal introgression lines with linkage map for this kind of correlation remains unclear. In this study, our major tasks were (1) to provide a set of reciprocal introgression lines (composed of two BC2RIL populations) suitable for mapping by linkage mapping using markers/bins with physical positions; (2) to test the mapping effects of different methods by using MQ-GS correlation dissection as sample case; (3) to perform genetic and breeding simulation on pyramiding favorite alleles of QTLs for representative MQ-GS traits. Finally, with four analysis methods and data collected under five environments, we identified about 28.4 loci on average for MQ-GS traits. Notably, 52.3% of these loci were commonly detected by different methods and eight loci were novel. There were also nine regions harboring loci for different MQ-GS traits which may be underlying the MQ-GS correlations. Background independent (BI) loci were also found for each MQ and GS trait. All these information may provide useful resources for rice molecular breeding.

Searching across-cohort relatives in 54,092 GWAS samples via encrypted genotype regression.

Explicitly sharing individual level data in genomics studies has many merits comparing to sharing summary statistics, including more strict QCs, common statistical analyses, relative identification and improved statistical power in GWAS, but it is hampered by privacy or ethical constraints. In this study, we developed encG-reg, a regression approach that can detect relatives of various degrees based on encrypted genomic data, which is immune of ethical constraints. The encryption properties of encG-reg are based on the random matrix theory by masking the original genotypic matrix without sacrificing precision of individual-level genotype data. We established a connection between the dimension of a random matrix, which masked genotype matrices, and the required precision of a study for encrypted genotype data. encG-reg has false positive and false negative rates equivalent to sharing original individual level data, and is computationally efficient when searching relatives. We split the UK Biobank into their respective centers, and then encrypted the genotype data. We observed that the relatives estimated using encG-reg was equivalently accurate with the estimation by KING, which is a widely used software but requires original genotype data. In a more complex application, we launched a finely devised multi-center collaboration across 5 research institutes in China, covering 9 cohorts of 54,092 GWAS samples. encG-reg again identified true relatives existing across the cohorts with even different ethnic backgrounds and genotypic qualities. Our study clearly demonstrates that encrypted genomic data can be used for data sharing without loss of information or data sharing barrier.

The role of macrophage polarization and related key molecules in pulmonary inflammation and fibrosis induced by coal dust dynamic inhalation exposure in Sprague-Dawley rats.

Coal dust is the main occupational hazard factor during coal mining operations. This study aimed to investigate the role of macrophage polarization and its molecular regulatory network in lung inflammation and fibrosis in Sprague-Dawley rats caused by coal dust exposure. Based on the key exposure parameters (exposure route, dose and duration) of the real working environment of coal miners, the dynamic inhalation exposure method was employed, and a control group and three coal dust groups (4, 10 and 25 mg/m3) were set up. Lung function was measured after 30, 60 and 90 days of coal dust exposure. Meanwhile, the serum, lung tissue and bronchoalveolar lavage fluid were collected after anesthesia for downstream experiments (histopathological analysis, RT-qPCR, ELISA, etc.). The results showed that coal dust exposure caused stunted growth, increased lung organ coefficient and decreased lung function in rats. The expression level of the M1 macrophage marker iNOS was significantly upregulated in the early stage of exposure and was accompanied by higher expression of the inflammatory cytokines TNF-α, IL-1ß, IL-6 and the chemokines IL-8, CCL2 and CCL5, with the most significant trend of CCL5 mRNA in lung tissues. Expression of the M2 macrophage marker Arg1 was significantly upregulated in the mid to late stages of coal dust exposure and was accompanied by higher expression of the anti-inflammatory cytokines IL-10 and TGF-ß. In conclusion, macrophage polarization and its molecular regulatory network (especially CCL5) play an important role in lung inflammation and fibrosis in SD rats exposed to coal dust by dynamic inhalation.

Ferroptosis-associated lncRNA prognostic signature predicts prognosis and immune response in laryngeal squamous carcinoma.

In order to construct a prognostic model of ferroptosis-related lncRNA associated with laryngeal carcinoma and to investigate its prognostic value, RNA sequencing, genomic mutation, and clinical data of laryngeal squamous carcinoma patients were collected from the TCGA database. Patients were randomly divided into train and test groups. Cox regression analysis and lasso regression analysis were performed on the data of patients in the training group, and their independent prognostic effect was validated in the test group and the whole cohort. Data from 123 laryngeal squamous carcinoma patients in the TCGA database were collected. According to previous literature, 484 ferroptosis-related genes were collected, and 912 ferroptosis-related lncRNAs were obtained by co-expression. Cox models suggested six lncRNAs involved in ferroptosis (AC083862.2, CYTOR, AC114296.1, LINC02768, GATA2-AS1, CTB-178M22.2). Patients were divided into high-risk and low-risk groups based on median risk scores. Kapkan-Meier survival curve results showed a statistical difference in survival between the high- and low-risk groups. Receiver operating characteristic curves and principal component analysis demonstrated the high accuracy of the model. Univariate and multifactorial Cox regression analyses and column plots demonstrated risk scores as independent prognostic factors. The distribution of prognostic marker risk scores was correlated with clinical staging. Immune infiltration studies suggested the model was associated with immune checkpoints and multiple immune functions. GATA2-AS1 was able to promote cell proliferation, cell migration, and cell invasion. This study identified six lncRNAs associated with ferroptosis in laryngeal squamous carcinoma as prognostic predictors, which may be promising biomarkers involved in the treatment of laryngeal squamous carcinoma.

Wavefield imaging of nonlinear ultrasonic Lamb waves for visualizing fatigue micro-cracks.

The traditional nonlinear ultrasonic technique, as typified by the second-harmonic generation and the frequency mixing response, can be employed to identify and characterize the micro-damage. However, the research on micro-damage characterization using nonlinear Lamb wave imaging technique remains an ongoing challenge and is rarely reported. A method called standardized amplitude difference is proposed for nonlinear feature enhancement, and further for fatigue crack imaging based on the wavefield data. Wavefield data contain abundant information on the spatial and temporal variation of propagating waves in the damaged structure. The nonlinearity index ß' of the signal difference under the high and low incident wave amplitudes is calculated for fatigue crack imaging. Two scanning methods, including local scanning and global scanning, are introduced to image the fatigue crack tip and visualize the wave field of the harmonics respectively. The experimental validation, based on the imaging results of an aluminum alloy plate specimen with a barely visible fatigue crack and a steel plate with a blind hole, manifests that the proposed method can be used to enhance and extract the nonlinear features and suppress the fundamental frequency, so as to improve the signal-to-noise ratio (SNR) of the micro-damage imaging results.

Exploration of the Pathogenesis of Chronic Obstructive Pulmonary Disease Caused by Smoking-Based on Bioinformatics Analysis and In Vitro Experimental Evidence.

This study was aimed at investigating the pathogenesis of chronic obstructive pulmonary disease (COPD) caused by smoking-based on bioinformatics analysis and in vitro experimental evidence. The GEO, GEO2R, TargetScan, miRDB, miRWalk, DAVID, and STRING databases were used for bioinformatics analysis. The mRNA expression and the protein levels were determined by real-time PCR and ELISA. After taking the intersection of the diversified results of the databases, four differentially expressed miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) were screened out. Subsequently, a total of 57 target genes of the selected miRNAs were obtained. The results of DAVID analysis showed that the selected miRNAs participated in COPD pathogenesis through long-term potentiation, the TGF-ß signaling pathway, the PI3K-Akt signaling pathway, etc. The results of STRING prediction showed that TP53, EP300, and MAPK1 were the key nodes of the PPI network. The results of the confirmatory experiment showed that, compared with the control group, the mRNA expression of ZEB1, MAPK1, EP300, and SP1 were up-regulated, while the expression of MYB was down-regulated and the protein levels of ZEB1, MAPK1, and EP300 were increased. Taken together, miRNAs (hsa-miR-146a, hsa-miR-708, hsa-miR-150, and hsa-miR-454) and their regulated target genes and downstream protein molecules (ZEB1, EP300, and MAPK1) may be closely related to the pathological process of COPD.

Preliminary Study on the Effect and Molecular Mechanism of Tetrandrine in Alleviating Pulmonary Inflammation and Fibrosis Induced by Silicon Dioxide.

This study aims to explore the molecular mechanism of tetrandrine (Tet) in alleviating pulmonary inflammation and fibrosis induced by silica (SiO2) from the perspective of autophagy. C57BL/6J mice were selected as experimental animals, and SiO2 was exposed by intranasal instillation. Tet was intervened by oral gavage. The mice were euthanized on the 7th and 42nd day of SiO2 exposure, and lung tissues were collected for histopathological, molecular biological, immunological, and transmission electron microscopy analysis. The results showed that SiO2 exposure could lead to significant lung inflammation and fibrosis, while Tet could significantly reduce SiO2 exposure-induced lung inflammation and fibrosis. Molecular mechanism research indicated that, compared with SiO2 expose group, Tet intervention could significantly reduce the expression levels of inflammatory cytokines and fibrosis markers (TNF-α, IL-1ß, MCP-1, TGF-ß1, HYP, Col-I, and Fn), and regulate the expression of key molecules ATG7, microtubule-associated protein 1 light chain 3B (LC3B), and P62 in the autophagy pathway to improve the blocking of autophagic flux, promote the recovery of autophagic lysosomal system function, and inhibit apoptosis. In summary, Tet can alleviate silica-induced lung inflammation and fibrosis, which may be achieved by regulating the expression of key molecules in the autophagy process and associated apoptotic pathway.

Inflammation biomarkers are associated with the incidence of cardiovascular disease: a meta-analysis.

Background: Inflammation is a risk factor for cardiovascular disease (CVD), and particular inflammatory parameters can be used to predict the incidence of CVD. The aim of this study was to assess the association between fibrinogen (FIB), interleukin-6 (IL-6), C-reactive protein (CRP) and galectin-3 (Gal-3) and the risk of cardiovascular disease using meta-analysis. Methods: PubMed, Embase, Scopus, and Web of Science databases were searched with the appropriate strategies to identify observational studies relevant to this meta-analysis. A random-effects model was used to combine inflammation factor-associated outcomes and cardiovascular disease outcomes, except in the case of galectin-3, where a fixed-effects model was used because of less heterogeneity. Location, age, type of cardiovascular disease, and sample size factors were used to explore heterogeneity in stratification and metaregression for subgroup analysis. A case-by-case literature exclusion approach was used for sensitivity analysis. The funnel plot and Begg's test were combined to assess publication bias. Results: Thirty-three papers out of 11,456 were screened for inclusion in the analysis. Four inflammation biomarkers were significantly associated with the development of CVD: FIB (OR: 1.21, 95% CI: 1.15-1.27, P < 0.001; HR: 1.04, 95% CI: 1.00-1.07, P < 0.05), IL-6 (HR: 1.16, 95% CI: 1.10-1.22, P < 0.001), CRP (OR: 1.25, 95% CI: 1.15-1.35, P < 0.001; HR: 1.20, 95% CI: 1.14-1.25, P < 0.001) and Gal-3 (HR: 1.09, 95% CI: 1.05-1.14, P < 0.001). Location factors help explain the source of heterogeneity, and there is publication bias in the Gal-3 related literature. Conclusion: Taken together, the current research evidence suggests that high levels of fibrinogen, interleukin-6, C-reactive protein and galectin-3 are risk factors for cardiovascular disease and can be used as biomarkers to predict the development of cardiovascular disease to some extent. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023391844.

Preliminary study on the role of aryl hydrocarbon receptor in the neurotoxicity of three typical bisphenol compounds (BPA, BPS and TBBPA) at environmentally relevant concentrations to adult zebrafish (Danio rerio).

Objective: This study was aimed to explore the role of AhR in the neurotoxicity of adult zebrafish induced by three typical bisphenol compounds (BPA, BPS, TBBPA) at environmentally relevant doses. Methods: The adult zebrafish were randomly divided into solvent control group (DMSO) and AhR inhibitor CH223191 (CH) group (0.05 µmol/L), bisphenol exposure groups (10, 100, 1000 nmol/L) and combined exposure groups (0.05 µmol/L CH and 1000 nmol/L bisphenol compounds). Each tank contained 8 fish (4 male and 4 female), and two parallel tanks were set synchronously. After 30 days of exposure, zebrafish were put on ice plate for anesthesia, weighed and measured for body length, and dissected for brain tissue. The gene expression was detected by RT-qPCR, and the activities of antioxidant enzymes were detected by commercial kits. SPSS 26.0 was used to analyze the data. Additionally, GO, KEGG and principal component analysis (PCA) were carried out. Results: Compared with the solvent control group, there were no significant differences in body weight and length among the exposed groups. In general, exposure to bisphenol compounds could affect the expression of Ahr2 and AhR target genes (cyp1a1, cyp1a2, and cyp1c1), key genes of neural function (elavl3, gfap, mbp, syn2a, gap43, Zn5, shha, and ache), oxidative stress related genes (nrf2, gpx1a, gstp1/gstp1.2, gstp2/gstp1.1, sod1, sod2, and cat), and the activities of antioxidant enzymes (SOD, CAT and GSH-Px/GPX) in zebrafish brain tissue to some extent. Compared with the groups exposed to bisphenols alone, CH could antagonize the above interference effects caused by bisphenols to some extent. Therefore, the toxic effects of BPA, BPS and TBBPA might be produced through similar mechanisms. Conclusion: Environmentally related doses of bisphenols (BPA, BPS, TBBPA) could disturb the expression of key molecules of oxidative stress and neural function through activating the AhR signaling pathway, and ultimately lead to neurotoxicity.

Hsa-miR-379 down-regulates Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction by targeting connective tissue growth factor in human alveolar basal epithelial A549 cells.

OBJECTIVE: This study was aimed to screen and identify miRNAs that could regulate human CTGF gene and downstream cascade reaction Rac1/MLK3/JNK/AP-1/Collagen I by bioinformatics and experimental means. METHODS: TargetScan and Tarbase were used to predict miRNAs that may have regulatory effects on human CTGF gene. The dual-luciferase reporter gene assay was employed to verify the results obtained in bioinformatics. Human alveolar basal epithelial A549 cells were exposed to silica (SiO2) culture medium for 24 h to establish an in vitro model of pulmonary fibrosis, and bleomycin (BLM) of 100 ng/mL was used as a positive control. The miRNA and mRNA expression levels were determined by RT-qPCR, and the protein levels were measured by western blot in hsa-miR-379-3p overexpression group or not. RESULTS: A total of 9 differentially expressed miRNAs that might regulate the human CTGF gene were predicted. Hsa-miR-379-3p and hsa-miR-411-3p were selected for the subsequent experiments. The results of the dual-luciferase reporter assay showed that hsa-miR-379-3p could bind to CTGF, but hsa-miR-411-3p could not. Compared with the control group, SiO2 exposure (25 and 50 µg/mL) could significantly reduce the expression level of hsa-miR-379-3p in A549 cells. SiO2 exposure (50 µg/mL) could significantly increase the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM in A549 cells, while CDH1 level was significantly decreased. Compared with SiO2 + NC group, the mRNA expression levels of CTGF, Collagen I, Rac1, MLK3, JNK, AP1, and VIM were significantly decreased, and CDH1 level was significantly higher when hsa-miR-379-3p was overexpressed. At the same time, overexpression of hsa-miR-379-3p improved the protein levels of CTGF, Collagen I, c-Jun and phospho-c-Jun, JNK1 and phospho-JNK1 significantly compared with SiO2 + NC group. CONCLUSION: Hsa-miR-379-3p was demonstrated for the first time that could directly target and down-regulate human CTGF gene, and further affect the expression levels of key genes and proteins in Rac1/MLK3/JNK/AP-1/Collagen I cascade reaction.

Unique regulatory roles of ncRNAs changed by PM2.5 in human diseases.

PM2.5 is a type of particulate matter with an aerodynamic diameter smaller than 2.5 µm, and exposure to PM2.5 can adversely damage human health. PM2.5 may impair health through oxidative stress, inflammatory reactions, immune function alterations and chromosome or DNA damage. Through increasing in-depth studies, researchers have found that noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), circular RNAs (circRNAs) as well as long noncoding RNAs (lncRNAs), might play significant roles in PM2.5-related human diseases via some of the abovementioned mechanisms. Therefore, in this review, we mainly discuss the regulatory function of ncRNAs altered by PM2.5 in human diseases and summarize the potential molecular mechanisms. The findings reveal that these ncRNAs might induce or promote diseases via inflammation, the oxidative stress response, cell autophagy, apoptosis, cell junction damage, altered cell proliferation, malignant cell transformation, disruption of synaptic function and abnormalities in the differentiation and status of immune cells. Moreover, according to a bioinformatics analysis, the altered expression of potential genes caused by these ncRNAs might be related to the development of some human diseases. Furthermore, some ncRNAs, including lncRNAs, miRNAs and circRNAs, or processes in which they are involved may be used as biomarkers for relevant diseases and potential targets to prevent these diseases. Additionally, we performed a meta-analysis to identify more promising diagnostic ncRNAs as biomarkers for related diseases.

Construction of a high-density genetic map and dissection of genetic architecture of six agronomic traits in tobacco (Nicotiana tabacum L.).

Tobacco (Nicotiana tabacum L.) is an economic crop and a model organism for studies on plant biology and genetics. A population of 271 recombinant inbred lines (RIL) derived from K326 and Y3, two elite flue-cured tobacco parents, has been constructed to investigate the genetic basis of agronomic traits in tobacco. Six agronomic traits including natural plant height (nPH), natural leaf number (nLN), stem girth (SG), inter-node length (IL), length of the largest leaf (LL) and width of the largest leaf (LW) were measured in seven environments, spanning the period between 2018 and 2021. We firstly developed an integrated SNP-indel-SSR linkage map with 43,301 SNPs, 2,086 indels and 937 SSRs, which contained 7,107 bin markers mapped on 24 LGs and covered 3334.88 cM with an average genetic distance of 0.469cM. Based on this high-density genetic map, a total of 70 novel QTLs were detected for six agronomic traits by a full QTL model using the software QTLNetwork, of which 32 QTLs showed significant additive effects, 18 QTLs showed significant additive-by-environment interaction effects, 17 pairs showed significant additive-by-additive epistatic effects and 13 pairs showed significant epistasis-by-environment interaction effects. In addition to additive effect as a major contributor to genetic variation, both epistasis effects and genotype-by-environment interaction effects played an important role in explaining phenotypic variation for each trait. In particular, qnLN6-1 was detected with considerably large main effect and high heritability ( h a 2 =34.80%). Finally, four genes including Nt16g00284.1, Nt16g00767.1, Nt16g00853.1, Nt16g00877.1 were predicted as pleiotropic candidate genes for five traits.

Combined application of multiple biomarkers for early auxiliary diagnosis of silicosis.

Silicosis is an important industrial health problem for those workers exposed to silica. The present study aimed to investigate the sensitivity and specificity of combined detection of biomarkers in early auxiliary diagnosis of silicosis, the risk factors of silicosis were also studied. The study sample comprised 65 workers who had clinical silicosis and 70 matched control subjects who were exposed to silica but did not have clinical silicosis. The levels of superoxide dismutase, malondialdehyde, interleukin 6 (IL-6), tumor necrosis factor-alpha, and cholinesterases in the serum of 135 subjects were measured. After completing the biochemical assays, a logistic regression model based on the above biochemical determination results was established, and the receiver operating characteristic curve was used for judging the discrimination ability of different statistical indexes. The expression levels of MDA, IL-6, and TNF-alpha in serum samples of patients with stage I silicosis and MDA and IL-6 in serum samples of patients with stage II silicosis were all significantly higher. Results from logistic regression analysis showed that ChEs were protective factors for silicosis, while age, chronic respiratory symptoms, IL-6, and MDA were risk factors. The areas under the ROC curve (AUC) were 0.86 (IL-6), 0.81 (MDA), and 0.65 (TNF-alpha or ChEs). AUC-ROC = 0.90 (95%CI:0.84-0.95). The diagnostic efficiency of IL-6 combined with MDA and TNF-alpha was better than that of any single biomarker.

WMDS.net: a network control framework for identifying key players in transcriptome programs.

MOTIVATION: Mammalian cells can be transcriptionally reprogramed to other cellular phenotypes. Controllability of such complex transitions in transcriptional networks underlying cellular phenotypes is an inherent biological characteristic. This network controllability can be interpreted by operating a few key regulators to guide the transcriptional program from one state to another. Finding the key regulators in the transcriptional program can provide key insights into the network state transition underlying cellular phenotypes. RESULTS: To address this challenge, here, we proposed to identify the key regulators in the transcriptional co-expression network as a minimum dominating set (MDS) of driver nodes that can fully control the network state transition. Based on the theory of structural controllability, we developed a weighted MDS network model (WMDS.net) to find the driver nodes of differential gene co-expression networks. The weight of WMDS.net integrates the degree of nodes in the network and the significance of gene co-expression difference between two physiological states into the measurement of node controllability of the transcriptional network. To confirm its validity, we applied WMDS.net to the discovery of cancer driver genes in RNA-seq datasets from The Cancer Genome Atlas. WMDS.net is powerful among various cancer datasets and outperformed the other top-tier tools with a better balance between precision and recall. AVAILABILITY AND IMPLEMENTATION: https://github.com/chaofen123/WMDS.net. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Preliminary Study on the Protective Effects and Molecular Mechanism of Procyanidins against PFOS-Induced Glucose-Stimulated Insulin Secretion Impairment in INS-1 Cells.

This study aimed to investigate the effects of perfluorooctanesulfonic acid (PFOS) exposure on glucose-stimulated insulin secretion (GSIS) of rat insulinoma (INS-1) cells and the potential protective effects of procyanidins (PC). The effects of PFOS and/or PC on GSIS of INS-1 cells were investigated after 48 h of exposure (protein level: insulin; gene level: glucose transporter 2 (Glut2), glucokinase (Gck), and insulin). Subsequently, the effects of exposure on the intracellular reactive oxygen species (ROS) activity were measured. Compared to the control group, PFOS exposure (12.5, 25, and 50 µM) for 48 h had no significant effect on the viability of INS-1 cells. PFOS exposure (50 µM) could reduce the level of insulin secretion and reduce the relative mRNA expression levels of Glut2, Gck, and insulin. It is worth noting that PC could partially reverse the damaging effect caused by PFOS. Significantly, there was an increase in ROS after exposure to PFOS and a decline after PC intervention. PFOS could affect the normal physiological function of GSIS in INS-1 cells. PC, a plant natural product, could effectively alleviate the damage caused by PFOS by inhibiting ROS activity.

Low concentrations of benzophenone-type UV-filters impair testis development in the amphibian Xenopus laevis.

Benzophenone-type UV filters (BPs) are ubiquitous contaminants in aquatic environments, possibly posing ecological risks to aquatic populations. So far, little is known about the potential adverse effects of BPs on amphibians. Given their potential estrogenic property, we investigated the detrimental effects of the commonly used BPs, BP-3, BP-2, and BP-1, on testis development in amphibians using Xenopus laevis as a model species. Following exposure to 10, 100, 1000 nM BP-3, BP-2, or BP-1 from stages 45/46 to 52, tadpoles presented morphological abnormal testes, characterized by reduced gonomere size and testis area, coupled with suppressed cell proliferation. Meanwhile, the downregulation of testis-biased gene expression and the upregulation of ovary-biased gene expression were observed in BPs-treated testes. Moreover, the estrogen receptor (ER) antagonist ICI 182780 significantly antagonized ovary-biased gene upregulation caused by BPs, suggesting that the effects of BPs on testis differentiation could be mediated by ER, at least partially. Of note, the effects of BPs were not concentration-dependent, but the lowest concentration generally exerted significant effects. Altogether, these observations indicate that the three BPs inhibited testis differentiation and exerted feminizing effects. Importantly, when BP-2 exposure was extended to two months post-metamorphosis, testes of froglets were generally less-developed, with relatively fewer spermatocytes, more spermatogonia, and poorly formed seminiferous tubules. Considering the fact that the lowest concentration (10 nM) of BPs in this study are detectable in aquatic environments, we conclude that BP-3, BP-2, and BP-1, even at environmentally relevant concentrations, can retard testis differentiation at pre-metamorphic stages and cause testis dysgenesis after metamorphosis in the amphibian X. laevis. Our findings suggest that ubiquitous BPs in aquatic environments could pose a potential risk to amphibians.

Role of non-neuronal cholinergic system in the early stage response of epithelial-mesenchymal transformation related markers in A549 cells induced by coal particles.

Objective: This study was aimed to investigate the role of non-neuronal cholinergic system (NNCS) in the early stage response of epithelial-mesenchymal transformation (EMT) related markers in human lung adenocarcinoma A549 cells induced by coal particles. Methods: A549 cells were exposed to different concentrations of GBW11110K, GBW11126D and exogenous acetylcholinesterase (AChE) (the exposure doses were determined according to the results of CCK-8 experiment, and the doses that had no significant effects on cell viability were selected) for 24 h. After exposure, the indexes of oxidative stress (SOD and MDA), inflammatory factors (IL-6 and TNF-α), EMT marker proteins (E-cadherin and vimentin), AChE enzymatic activity and mRNA expression levels of different types of acetylcholine receptors (CHRM3, CHRM5, CHRNA5, CHRNA7, CHRNA9 and CHRNB2) were determined. Results: GBW11110K and GBW11126D exposure could lead to the following injury effects: the levels of oxidative stress and inflammatory factors changed to a certain extent (SOD decreased gradually, while MDA, IL-6 and TNF-α increased). The protein level of E-cadherin decreased while the vimentin level increased (P < 0.05), suggesting the occurrence of EMT. The AChE enzymatic activity decreased gradually. The expression of acetylcholine receptor mRNA changed as follows (GBW11110K/GBW11126D: CHRM3 (↑↑), CHRM5 (↓↓), CHRNA5 (↓↓), CHRNA7 (↓↓), CHRNA9 (- ↑), CHRNB2 (- -). The addition of exogenous AChE recombinant protein could antagonize the damage effects caused by the coal particles to a certain extent. Conclusion: The coal particle exposure could induce the change of oxidative stress response, inflammatory response and EMT related markers, down-regulate the AChE enzymatic activity, and interfere the mRNA expression levels of AChRs in A549 cells. The addition of exogenous AChE recombinant protein could reverse the above effects to a certain extent.