Background Benzophenones (BPs), widely used UV filters and endocrine disruptors globally known for their estrogenic effects, are raising growing concerns about chronic reproductive toxicity in males due to their increasing environmental concentrations. This study aims to reveal the effects and mechanisms of male reproductive injury induced by environmentally relevant concentrations of BPs exposure. Methods The study employed NHANES analysis, animal experiments, cell experiments, network toxicology, and molecular docking, and used transcriptome sequencing along with various biochemical and molecular experimental methods to measure downstream indicators. Results Analysis of the NHANES database indicates that BP-3 exposure showed dose-dependent associations with reduced total testosterone (TT)/estradiol (E2)/sex hormone-binding globulin (SHBG) and elevated testosterone deficiency (TD) risk. Effects attenuated but held direction after multi-pollutant adjustment. The results of animal experiments indicate that chronic exposure to BPs (PND1-PND240) impaired fertility and offspring development, reduced body weight, anogenital distance, and testis coefficient, and altered histopathology, sperm quantity, and quality. Differentially expressed genes were predominantly enriched in energy metabolism and integrity of actin cytoskeleton, and disulfidptosis-related metabolic/redox indicators were dysregulated in the testis. Notably, even short-term exposure to BP-3 disturbs the levels of disulfidptosis-associated metabolic drivers (PND1-PND56). In GC-2 cells, BP-3 reduced cell viability and antioxidant capacity, induced morphological alterations, elevated ROS level, and upregulated disulfidptosis markers. The involvement of disulfidptosis was confirmed by the addition of the antagonist TCEP and agonist KL-11743. Notably, estrogen receptor (ER) directly regulates disulfidptosis. Zeaxanthin dipalmitate (ZD) alleviates BPs-induced male reproductive injury by modulating disulfidptosis. Co-culture assays further confirmed BP-3 disrupts testicular metabolic coupling and triggers disulfidptosis. Conclusion BPs exposure induces male reproductive dysfunction via ER-mediated disulfidptosis. ZD can alleviate this dysfunction.

Cardiac fibrosis is a key pathological driver of heart failure and cardiovascular mortality, with environmental pollutants being increasingly implicated. Tetrabromobisphenol A (TBBPA), a dominant brominated flame retardant (BFR), is environmentally pervasive and poses potential cardiotoxic risks. However, direct evidence for TBBPA-induced cardiac fibrosis in mammals is lacking. Additionally, its ability to adsorb onto nanoplastics, such as polystyrene (PS-NPs), raises concerns about combined toxicity, especially cardiotoxicity. To addressed this, we systematically evaluated the cardiotoxicity of TBBPA and PS-NPs in vivo and in vitro. In mice, environmentally relevant TBBPA exposure impaired cardiac function and induced inflammation and fibrosis, leading to cardiac remodeling, whereas co-exposure with PS-NPs only induced fibrosis. In H9C2 cells, TBBPA and PS-NPs individually promoted the expression of inflammatory, fibrotic, and hypertrophic markers, with co-exposure resulting in a synergistic exacerbation and a remodeling phenotype. Furthermore, transcriptomic and mechanistic data showed that ESR inhibitors blocked the H19/Wnt pathway activation induced by TBBPA or PS-NPs. Through gain- and loss-of-function experiments, we further confirmed that H19 mediates pollutant-induced Wnt/β-catenin activation and fibrotic responses, positioning H19 as a critical downstream mediator of the ESR/H19/Wnt axis. Overall, for the first time, this study elucidates the cardiotoxic profiles of TBBPA and PS-NPs and identifies the ESR/H19/Wnt axis as a key pro-fibrotic mechanism, highlighting a cardiovascular risk and a potential therapeutic target.

The long-term inhalation of free silica dust causes silicosis-a prevalent occupational hazard-yet its systemic effect on male reproductive toxicity remains underexplored. Tetrandrine (Tet) is the only plant-derived anti-silicosis drug approved in China. This study investigates silica (SiO2) -induced male reproductive damage and evaluates Tet's protective effects. Sixty male C57BL/6 mice (6-8 weeks) were divided into control, SiO2 exposure, and SiO2 + Tet groups. SiO2 was administered via intranasal infusion and Tet via gavage. Mice were sacrificed at day 7 (male reproductive injury model corresponding to the pulmonary inflammation stage) and day 42 (male reproductive injury model corresponding to the pulmonary fibrosis stage). Analyses included sperm morphology, testicular transcriptome sequencing, RT-qPCR, and immunofluorescence. At day 7, SiO2 exposure upregulated testicular inflammatory markers, which were partially mitigated by Tet. At day 42, SiO2 increased sperm deformity and testicular fibrosis markers (fibronectin and vimentin); Tet intervention reduced these abnormalities. Transcriptome analysis revealed distinct gene expression patterns at day 7 versus day 42, indicating time-dependent injury mechanisms. Tetrandrine alleviates silica-induced reproductive damage in male mice, suggesting potential therapeutic applications for occupational silica exposure and expanding the understanding of silica toxicity beyond the respiratory system.

Benzophenone-3 (BP-3), a widely used ultraviolet absorber in various scenarios, exhibits estrogenic toxicity at environmental concentrations—as demonstrated in our prior work. Given the importance of hepatic metabolism and the limitations of previous hepatotoxicity research (high-dose models, lack of mammalian data, etc.), we evaluated BP-3’s hepatic effects on postpartum mice at environmentally relevant levels. Postpartum mice were exposed to BP-3 via drinking water from postpartum day 1 (PPD1) to PPD35. Groups solvent control (0.001% DMSO), 10–1000 nM BP-3, and diethylstilbestrol (DES) were established. Basic growth performance, histopathological changes, and a range of molecular indicators were assessed. The results showed that BP-3 exposure induced dose-dependent increases in liver weight, histopathological alterations (sinusoidal dilation, hepatocyte edema, and necrosis), and significant upregulation of oxidative stress markers (Ros, Mda), chemokines (Ccl27a/b), and inflammatory factors (Tnf-α, Il-6, Nf-κb) at the mRNA level (all p < 0.05). Conversely, levels of antioxidant enzymes (Cat, Sod1/2) and anti-inflammatory factor Ho-1 were markedly decreased (p < 0.05). A clear dose-effect relationship was confirmed using the Integrated Biomarker Response (IBR) framework. This pioneering study establishes the hepatotoxicity of environmentally relevant BP-3 levels in mammals and offers methodological insights for endocrine disruptor assessment.

Exploring the health damage caused by joint exposure in the real world is one of the hotspots in modern environmental toxicology. Recent studies indicate that environmental chemicals can heighten sensitivity to future stress or damage, potentially leading to various diseases. Benzophenone-type (BPs) chemicals, which are commonly used UV filters with estrogenic properties, have been shown to affect the development of male reproductive systems in aquatic animals, rodents, and humans. This study aims to determine whether BPs exposure during development increases the testes' susceptibility to stress in adulthood. Newborn male ICR mice were exposed to the three most common BPs (BP-1, BP-2, and BP-3) in the environment at concentrations of 10 nM (equivalent to 2.14, 2.46, and 2.28 μg/L, respectively) and 1000 nM (equivalent to 214, 246, and 228 μg/L, respectively) via breast milk and drinking water for 56 days (from postnatal day 1 to postnatal day 56), using diethylstilbestrol (DES) as a positive control. The results showed that BPs affected the integrity of the blood-testis barrier (BTB) and resulted in reduced mRNA levels of genes associated with reproduction, apoptosis and cytoskeleton in testicular tissue of mice at PND 56. Subsequently, intrapitoneal injection of 3 mg/kg cyclophosphamide (CTX) for 4 weeks was conducted to induce spermatogenic stress. It was found that the testes in the BPs pre-treated groups showed significant changes in decreased testicular organ coefficient, damaged seminiferous tubules, delayed spermatogenesis, reduced sperm quality, pro-apoptotic effect, and disrupted microfilament structure, but not in untreated ones. The study indicates that mice with historical low-dose BPs exposure are more susceptible to CTX-induced spermatogenic stress, resulting in severe reproductive issues, and suggests that chemical-induced reproductive harm should be taken seriously. It's the first study to examine BPs-induced reproductive risks from testicular stress susceptibility, offering a novel approach to identify environmental chemicals that may cause male reduced fertility and infertility.

The fungicide carbendazim (CBZ), widely present in aquatic environments, has been reported to disrupt testicular development in rodents, yet its impacts on amphibians remain poorly understood. Here, we investigated the effects of environmentally-relevant concentrations of CBZ (1, 10, 100 μg/L) on early testicular development in Xenopus laevis following exposure from Nieuwkoop-Faber (NF) stages 45/46 to 52 in Experiment I. While all the concentrations of CBZ inhibited tadpole development, 10 and 100 μg/L CBZ caused retarded testicular development, which was characterized by morphological abnormality, suppressed cell proliferation and reduced germ cells, along with downregulation of testis-biased genes and upregulation of ovary-biased genes in certain concentration groups. Although 1 μg/L CBZ did not lead to significant changes in these testicular parameters, their declining trends are of concern, especially when considering its combined exposure with other contaminants. Thus, we conducted Experiment II to address the combined effects of 1 μg/L CBZ with the UV filter benzophenone-3 (BP-3), which was reported to affect testicular development in X. laevis, on testicular development from stages 45/46 to 66. As expected, we found that co-exposure to 1 μg/L CBZ and 2.28 μg/L BP-3 produced smaller testis size accompanied with fewer germ cells compared to the control, while alone exposure had no significant effects on the two parameters, exhibiting a synergistic effect on testicular development. Besides, their combined exposure also exerted synergistic effects with regard to metamorphic delay, increased liver weight and hepatic histological changes. Our findings emphasize the impacts of environmentally relevant concentrations of CBZ alone or in combination with UV-filters on testicular development, highlighting the ecological risk of these contaminants especially their mixtures for amphibians, which warrants continued attention.

Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was evaluated, especially focusing on its alteration on the key molecules in FAM171A2-GRN-NF-κB signaling pathway. The results showed that TBBPA exposure could lead to an increase in the production of inflammation-related genes IL-6, iNOS, TGF-β1, COX2, and TNF-α in both HT22 cells and HT22-AD-model, intensifying the inflammatory response; it inhibits the mRNA expression of antioxidative enzymes genes Sod1, Cat, Gpx1, and Gsta1, resulting in reduced antioxidant enzyme activities of SOD, CAT, and GSH-Px/GPX. Mechanistically, TBBPA caused the upregulation of FAM171A2 expression level, alongside increased GRN, IκBα and p65 levels; whereas the expression of GRN, IκBα and p65 was decreased after FAM171A2 knockdown, demonstrating TBBPA-induced upregulation of FAM171A2 should be responsible for the increased GRN, IκBα and p65 expression. Therefore, for the first time, our data indicate that TBBPA-induced oxidative stress and inflammatory response is closely related to the FAM171A2-GRN-NF-κB pathway.

Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly utilized to produce epoxy resins, polycarbonate plastics, and other products. Mounting evidence has shown that BPs, especially BPA, may enter into the human body and participate in the development of human diseases mediated by nuclear hormone receptors. Moreover, BPA may negatively affect human health at the epigenetic level through processes such as DNA methylation and histone acetylation. Recent studies have demonstrated that, as part of epigenetics, noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs), have vital impacts on BP-related diseases, such as reproductive system diseases, nervous system diseases, digestive system diseases, endocrine system diseases, and other diseases. Moreover, based on the bioinformatic analysis, changes in ncRNAs may be relevant to normal activities and functions and BP-induced diseases. Thus, we conducted a meta-analysis to identify more promising ncRNAs as biomarkers and therapeutic targets for BP exposure and relevant human diseases. In this review, we summarize the regulatory functions of ncRNAs induced by BPs in human diseases and latent molecular mechanisms, as well as identify prospective biomarkers and therapeutic targets for BP exposure and upper diseases.

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.

Atherosclerosis (AS) and its related cardiovascular diseases (CVDs) remain the most frequent cause of morbidity and mortality worldwide. Researches showed that bisphenol A (BPA) exposure might exacerbate AS progression. However, as an analogue of BPA, little is known about the cardiovascular toxicity of bisphenol S (BPS), especially whether BPS exposure has the pro-atherogenic effects in mammals is still unknown. Here, we firstly constructed an apolipoprotein E knockout (ApoE-/-) mouse model and cultured cells to investigate the risk of BPS on AS and explore the underlying mechanisms. Results showed that prolonged exposure to 50 μg/kg body weight (bw)/day BPS indeed aggravated AS lesions both in the en face aortas and aortic sinuses of ApoE-/- mice. Moreover, BPS were found to be implicated in the AS pathological process: 1) stimulates adhesion molecule expression to promote monocyte-endothelial cells (ECs) adhesion with 3.6 times more than the control group in vivo; 2) increases the distribution of vascular smooth muscle cells (VSMCs) with 9.3 times more than the control group in vivo, possibly through the migration of VSMCs; and 3) induces an inflammatory response by increasing the number of macrophages (MACs), with 3.7 times more than the control group in vivo, and the release of inflammatory mediators. Furthermore, we have identified eight significant AS-related genes induced by BPS, including angiopoietin-like protein 7 (Angptl17) and lipocalin-2 (Lcn2) in ECs; matrix metalloproteinase 9 (Mmp13), secreted phosphoprotein 1 (Spp1), and collagen type II alpha 1 (Col2a1) in VSMCs; and kininogen 1 (Kng1), integrin alpha X (Itgax), and MAC-expressed gene 1 (Mpeg1) in MACs. Overall, this study firstly found BPS exposure could exacerbate mammalian AS and might also provide a theoretical basis for elucidating BPS and its analogues induced AS and related CVDs.

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-alpha, IL-1 beta, 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 antiinflammatory cytokines IL-10 and TGF-beta. 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.

Nanoplastics (NPs) cause serious contamination of drinking water and potential damage to human health. This study aimed to investigate the effects of NPs with different particle sizes and concentrations on the reproductive function of male mice. In this study, free drinking water exposure was used to expose male BALB/C mice to PS-NPs (20 nm, 200 nm, and 1000 nm) at 0.1 mg/L, 1 mg/L, and 5 mg/L for 4 months. The male reproductive function of the mice was assessed after NPs exposure, and fecal and blood samples were collected for macrogenomics and metabolomics. The results showed that PS-NPs resulted in mice with reduced testicular organ coefficients, decreased sperm quality, altered testicular tissue structure, disturbed sex hormone levels, and abnormal levels of inflammatory factors and oxidative stress. Furthermore, this study found that NP exposure affected the alteration of gut communities and metabolic pathways related to male reproduction, such as Clostridium and glutathione metabolism. Importantly, we found an effect of NP particle size on reproductive function. In the future, more attention should be paid to the smaller particle sizes of NPs.

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.

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-β 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.

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.

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.

尘肺病是由于吸入一定的粉尘以及肺组织对粉尘的反应而引起的一类间质性肺病.其主要病理特征为慢性肺部炎症和进行性肺纤维化,最终可因呼吸衰竭或心力衰竭而死亡.microRNAs(miRNAs)是一类内生的、长度约22个核苷酸的非编码RNA,主要参与转录后调控.近年来研究发现,miRNAs与尘肺病的病理过程密切相关,有望为尘肺的诊疗提供新的生物标志物及潜在的药物靶点.本文综述了特异性差异表达的miRNAs在尘肺发生发展中的分子机制和生物学功能,对以miRNAs为中心的调控网络在尘肺病理进程中发挥的作用进行了总结,以更好地理解表观遗传学和基因表达之间的相互作用.

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.

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 & mu;mol/L), bisphenol exposure groups (10, 100, 1000 nmol/ L) and combined exposure groups (0.05 & mu;mol/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

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.