Wenqian Huo

Given the potential of organochlorine pesticides (OCPs) to disrupt metabolic health, we aimed to explore their association with obesity and to explore the potential bidirectional mediating relationships involving metabolic health indicators among 894 rural Chinese adults with prediabetes. A total of 894 individuals were included in this cross-sectional study. The associations of plasma OCPs on obesity and obese anthropometric measurements were assessed by generalized linear regression models for single exposure, and quantile g-computation (QGC) and LASSO regression for mixed exposure. The potential contributions of multiple health indicators to observed associations were assessed through mediation analysis. Exploratory bidirectional mediation analysis was employed to assess two potential pathways: (1) whether metabolic health indicators mediate the association between OCP exposure and obesity, and (2) whether obesity mediates the relationship between OCP exposure and metabolic health indicators. We discovered that β-Benzene hexachloride (β-BHC) and p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE) were related to obesity for single exposure. QGC and LASSO demonstrated that OCPs were positively correlated with a higher likelihood of obesity for mixed exposure, with β-BHC being the primary contributor. Exploratory mediation analysis found that obesity and metabolic-related indicators play a bidirectional mediating role in the association with OCPs, mainly involving systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-Cholesterol (HDL-C), low-density lipoprotein-Cholesterol (LDL-C), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase/alanine aminotransferase (AST/ALT). In this cross-sectional study, we found that OCPs exposure may increase obesity risk both directly and by disrupting metabolism, while obesity itself can worsen OCP-related metabolic damage, revealing a bidirectional environment-body interaction.

The Chinese famine occurred between 1959 and 1961. Findings on early exposure to famine on obesity have been inconsistent. Therefore, this study aimed to assess the effect of early exposure to famine on obesity and the mediating role of testosterone. The design enrolled 2667 participants from the Henan Rural Cohort Study. The associations between early famine exposure and indicators of obesity and obesity were explored using generalized linear models and logistic regression models, respectively. Stratified analyses by sex were performed to account for potential sex-specific effects. Mediation analyses were applied to address the contribution of testosterone in mediating the impact of early-life famines on obesity and its indicators. The median age of the study participants was 54 (range: 48-64) years old. Fetal famine exposure was positively associated with central obesity (waist circumference (WC) and waist-to-hip ratio (WHR)) in both sexes. Nevertheless, childhood famine exposure (3-9 years old after 3-year famine) was negatively associated with general obesity (body mass index (BMI)), and central obesity (WC) in males. In contrast, childhood famine exposure in females was positively associated with central obesity (WHR and waist-to-height ratio (WHtR)). Mediation analyses suggested that testosterone partially mediated the association of childhood famine exposure with central obesity (WC), BMI, WC, and WHtR in males, with mediation effect proportions ranging from 3.27% to 11.85%. In females, testosterone mediates the role of childhood famine in increasing the risk of central obesity (WHR), WHR, and WHtR, with mediating effect proportions of 5.50%, 3.60%, and 7.17%, respectively. Fetal famine exposure increases the risk of central obesity. Childhood famine exposure showed sex-specific effects on central obesity, with a negative association in males and a positive association in females. Additionally, testosterone has been found for the first time to partially mediate the positive association of childhood famine on obesity.

Aging and polycyclic aromatic hydrocarbon (PAH) exposure are linked to chronic liver disease. However, the potential mechanisms and roles of aging in the effect of PAHs on liver fibrosis are unclear. A subpopulation ( n = 2537) was derived from the Henan Rural Cohort study. Plasma PAHs and telomere length (TL) were measured by the GC‐MS and RT‐PCR methods. The impacts of TL and PAH exposure on liver fibrosis were assessed. Furthermore, the potential mechanisms of PAH exposure–induced aging were explored in vitro. Several PAHs and 10‐PAH mixture were positively related to liver fibrosis, particularly in smoking and cooking participants. Joint effects of shortened TL and high PAH exposure on increased liver fibrosis risk were observed. Compared to the solvent control group, increased ROS generation of intracellular and mitochondria, upregulation of expression of inflammation‐related genes ( cGAS and STING ), senescence‐related modulation genes of p53 , p21 , p16 , and SASPs ( IL-6 and IL-8 ) at RNA levels and AST/ALT ratio, and downregulation of albumin were found in cells treated with 300.00 μ M Phe plus 0.30 μ M BaP groups. The findings indicated that aging may aggravate PAH exposure–related liver fibrosis via inducing inflammation‐ and senescence‐related pathways, suggesting that delaying the aging process may be an effective measure to reduce the negative effect of PAH exposure. Trial Registration: ClinicalTrials.gov identifier: ChiCTR‐OOC‐15006699

This study aimed to evaluate the association of TCs (triclosan (TCS) and triclocarban) exposure with T2DM and glucose metabolism-related indicators and the mediating effect of SOCS3 methylation on their associations. A total of 956 participants (330 T2DM and 626 controls) were included in this case-control study. Logistic regression and generalized linear models were used to assess the effect of TCs on T2DM and glucose metabolism-related indicators. The dose–response relationship between TCs and T2DM was analyzed by restricted cubic spline. Finally, after evaluating the association between TCs and SOCS3 methylation levels, the mediating effect of SOCS3 methylation on the TC−associated T2DM was estimated. Each 1-unit increase in TCS levels was associated with a 13.2% increase in the risk of T2DM (OR = 1.132, 95% CI: 1.062, 1.207). A linear dose–response relationship was found between TCS and T2DM. TCS was negatively associated with Chr17:76356190 methylation. Moreover, mediation analysis revealed that Chr17:76356190 methylation mediated 14.54% of the relationship between TCS exposure and T2DM. Exposure to TCS was associated with a higher prevalence of T2DM. SOCS3 methylation partially mediated the association of TCS with T2DM. Our findings may provide new insights into the treatment of T2DM, and the study of the biological mechanisms of T2DM.

Evidence for the relationship between individual and combined volatile organic compounds (VOCs) and cardiovascular disease (CVD) is limited. Besides, the mediating role of biological aging (BA) has not been studied. Therefore, this study aimed to examine the association between VOCs and CVD risk and to explore the mediating effects of BA. Logistic regression models were used to investigate the relationships of metabolites of volatile organic compounds (mVOCs) and BA with CVD. In addition, weighted quantile sum (WQS) regression, adaptive elastic networks, and Environmental Risk Score (AENET-ERS) were utilized to assess overall associations of mixed VOCs co-exposure with CVD. Mediation analyses were used to identify potential mediating effects of BA. In the single-pollutant model, CYMA was shown to be associated with an increased risk of CVD. Additionally, we identified significantly positive associations between the WQS index and CVD (odds ratio (OR) = 1.292, 95% confidence interval (CI): 1.006, 1.660), and DHBMA had the greatest contribution for CVD (0.246). Furthermore, the AENET-ERS results showed that 8 mVOCs were significantly associated with CVD, and ERS was related to an elevated risk of CVD (OR = 1.538, 95%CI: 1.255, 1.884). Three BA indicators mediated the association of the mVOCs mixture with CVD, with mediating effect proportions of 11.32%, 34.34%, and 7.92%, respectively. The risk of CVD was found to increase with both individual and combined exposure to VOCs. BA mediates the positive effects of VOCs on CVD, suggesting that this pathway may be one of the mechanisms of CVD. Individual and mixed exposure to VOCs were associated with elevated CVD risk. DHBMA dominates mixtures of mVOCs for increased CVD risk. BA mediates the effect of VOCs mixture exposure on CVD.