Associations of dinitroaniline herbicide exposure, genetic susceptibility, and lifestyle with glucose dysregulation: A gene-environment interaction study from the Wuhan-Zhuhai cohort.

OBJECTIVE: To assess the association of dinitroaniline herbicides as well as their interactions with genetic susceptibility and lifestyle with glucose dysregulation. METHODS: A total of 4310 Chinese urban adults from the baseline of the Wuhan-Zhuhai Cohort were included in the cross-sectional study. A follow-up panel from the cohort was included in the longitudinal study, including 158 participants with 432 observations. Glucose dysregulation, including fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), type 2 diabetes mellitus (T2DM), and impaired fasting glucose (IFG) were assessed. Serum dinitroaniline herbicides including benfluralin, trifluralin, and pendimethalin were measured. T2DM-related polygenic risk score (PRS) and healthy life scores were constructed. RESULTS: Cross-sectionally, each 2-fold increase in serum benfluralin was associated with a 1.12%, 2.03%, and 9% increase in FPG, HOMA-IR, and IFG risk, respectively. Each 2-fold increase in serum trifluralin was associated with a 0.70% increase in FPG. Each 2-fold increase in serum pendimethalin was associated with a 2.53% and 24% increase in FPG and IFG risk, respectively (all P < 0.05). Positive associations were found between the dinitroaniline herbicide mixture and glucose dysregulation. Longitudinally, serum benfluralin and pendimethalin were associated with the annual increases in FPG and HOMA-IR (P < 0.05). Joint and interaction effect analysis showed that compared with participants with high benfluralin/trifluralin/pendimethalin, high PRS, and unhealthy lifestyle, those with low benfluralin/trifluralin/pendimethalin, low PRS, and healthy lifestyle showed the greatest declines in FPG, i.e., -15.46%, -13.58%, and -10.51% changes, respectively; and the greatest reductions in IFG risks, i.e., 75%, 61%, and 73% reductions, respectively (all P < 0.05). CONCLUSIONS: This study highlighted the importance of controlling dinitroaniline herbicide exposure and following healthy lifestyles in glucose dysregulation prevention, especially among individuals with high genetic risk of T2DM.

Glycolytic reprogramming governs crystalline silica-induced pyroptosis and inflammation through promoting lactylation modification.

Prolonged inhalation of environmental crystalline silica (CS) can cause silicosis, characterized by persistent pulmonary inflammation and irreversible fibrosis, but the mechanism has not been elucidated. To uncover the role and underlying mechanism of glycolytic reprogramming in CS-induced pulmonary inflammation, the mouse silicosis models and glycolysis inhibition models were established in vivo. And the CS-induced macrophage activation models were utilized to further explore the underlying mechanism in vitro. The results showed that CS induced lung inflammation accompanied by glycolytic reprogramming and pyroptosis. The application of glycolysis inhibitor (2-DG) suppressed CS-induced pyroptosis and alleviated lung inflammation. In vitro, 2-DG effectively impeded CS-induced macrophage pyroptosis and inflammatory response. Mechanistically, 2-DG suppressed pyroptosis by inhibiting NLRP3 inflammasome activation both in vivo and in vitro. Furtherly, metabolite lactate facilitated NLRP3-dependent pyroptosis synergistically with CS particles, while blocking the source of lactate largely alleviated NLRP3 inflammasome activation and subsequent pyroptosis triggered by CS. More profoundly, the increment of lactate induced by CS might drive NLRP3-dependent pyroptosis by increasing histone lactylation levels. In conclusion, our findings demonstrated inhibiting glycolytic reprogramming could alleviate CS-induced inflammatory response through suppressing NLRP3 -dependent pyroptosis. Increased glycolytic metabolite lactate and protein lactylation modifications might represent significant mechanisms during CS-induced NLRP3 activation and macrophage pyroptosis.

Epidemiological Characteristics and Incubation Period of 7015 Confirmed Cases With Coronavirus Disease 2019 Outside Hubei Province in China.

BACKGROUND: Disease caused by SARS-CoV-2 broke out in Wuhan in December 2019. We utilized confirmed cases outside Hubei Province to analyze epidemiologic characteristics and evaluate the effect of traffic restrictions implemented in Hubei beginning on 23 January 2020. METHODS: Information on 7015 confirmed cases from 19 January to 8 February 2020 in all provinces outside Hubei was collected from the national and local health commissions in China. Incubation period and interval times were calculated using dates of the following events: contact with an infected person, onset, first visit, and diagnosis. We evaluated changes in incubation period and interval times. RESULTS: The average age of all cases was 44.24 years. The median incubation period was 5 days and extended from 2 days on 23 January to 15 days on 8 February. The proportion of imported cases decreased from 85.71% to 33.19% after 23 January. In addition, lengths of intervals between onset and diagnosis, onset and first visit, and first visit and diagnosis decreased over time. CONCLUSIONS: Rapidly transmitting COVID-19 has a short incubation period. The onset mainly occurred among young to middle-aged adults. Traffic restrictions played an important role in the decreased number of imported cases outside Hubei.

Heavy metals exposure, lipid peroxidation and heart rate variability alteration: Association and mediation analyses in urban adults.

Exposure to heavy metals was reported to be associated with heart rate variability (HRV) alteration. However, possible pathway of such association remains unclear. In this research, we investigated the possible role of lipid peroxidation in the associations between urinary heavy metals and HRV. We performed a cross-sectional study using baseline data of Wuhan-Zhuhai cohort. Urinary heavy metals (including lead, barium, antimony, cadmium, zinc, copper, iron and manganese), urinary 8-iso-prostaglandin-F2α levels (common biomarker for lipid peroxidation) and HRV indices (SDNN, r-MSSD, low frequency, high frequency and total power) were measured among 3022 participants. We conducted multivariable linear regression models to quantify associations between urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) and heavy metals or HRV indices. The potential role of 8-iso-PGF2α in the association of urinary heavy metals with HRV was evaluated through mediation analyses. After adjusting for potential confounders, urinary manganese, iron, copper, zinc, cadmium, antimony and barium were identified to be negatively associated with one or more HRV parameters. Each one-unit growth of log-transformed levels of urinary manganese, iron, copper, zinc, antimony and barium was associated with a 1.9%, 1.5%, 4.7%, 4.0%, 2.7% and 1.3% decrease in SDNN, respectively. We observed positive dose-response relationships between all eight urinary heavy metals and 8-iso-PGF2α, as well as negative association of urinary 8-iso-PGF2α with SDNN and total power (all P trend<0.05). The proportions mediated by 8-iso-PGF2α on SDNN were 4.6% for manganese, 9.3% for iron, 19.8% for antimony and 11.0% for barium. The proportions mediated by 8-iso-PGF2α on total power were 6.9% for manganese and 10.1% for cadmium (all P value < 0.05). This study suggested that urinary manganese, iron, copper, zinc, cadmium, antimony and barium were negatively associated with HRV indices. Lipid peroxidation may partly mediate the associations of urinary manganese, iron, cadmium, antimony and barium with specific HRV indices.

Association between Plasma HMGB-1 and Silicosis: A Case-Control Study.

High-mobility group box-1 (HMGB-1) has been associated with fibrotic diseases. However, the role of HMGB-1 in silicosis is still uncertain. In this study, we conducted a case-control study involving 74 patients with silicosis and 107 age/gender-matched healthy controls in China. An Enzyme-linked immunosorbent assay (ELISA) was used to examine the concentrations of plasma HMGB-1 among all subjects. A logistic regression model and receiver operating characteristic curve (ROC) analysis were performed to assess the relationships between HMGB-1 and silicosis. We observed that plasma HMGB-1 concentrations were significantly increased in silicosis patients when compared with healthy controls (p < 0.05). Each 1 ng/mL increase in plasma HMGB-1 was positively associated with increased odds of silicosis, and the odds ratio (OR) (95% confidence interval) was 1.86 (1.52, 2.27). Additionally, compared with subjects with lower HMGB-1 concentrations, increased odds of silicosis were observed in those with higher HMGB-1 concentrations, and the OR was 15.33 (6.70, 35.10). Nonlinear models including a natural cubic spline function of continuous HMGB-1 yielded similar results. In ROC analyses, we found that plasma HMGB-1 >7.419 ng/mL had 81.6% sensitivity and 80.4% specificity for silicosis, and the area under the curve (AUC) was 0.84. Our results demonstrated that elevated plasma HMGB-1 was positivity associated with increased OR of silicosis.

Associations of polychlorinated biphenyls exposure, lifestyle, and genetic susceptibility with dyslipidemias: Evidence from a general Chinese population.

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals that have been associated with various adverse health conditions. Herein we explored the associations of PCBs with dyslipidemia and further assessed the modification effect of genetic susceptibility and lifestyle factors. Six serum PCBs (PCB-28, 101, 118, 138, 153, 180) were determined in 3845 participants from the Wuhan-Zhuhai cohort. Dyslipidemia, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were determined, and lipid-specific polygenic risk scores (PRS) and healthy lifestyle score were constructed. We found that all six PCB congeners were positively associated with the prevalence of dyslipidemias, and ΣPCB level was associated with HyperTC, HyperTG, and HyperLDL-C in dose-response manners. Compared with the lowest tertiles of ΣPCB, the odds ratios (95% confidence intervals) in the highest tertiles were 1.490 (1.258, 1.765) for HyperTC, 1.957 (1.623, 2.365) for HyperTG, and 1.569 (1.316, 1.873) for HyperLDL-C, respectively. Compared with those with low ΣPCB, healthy lifestyle, and low genetic risk, participants with high ΣPCB, unfavorable lifestyle, and high genetic risk had the highest odds of HyperTC, HyperTG, and HyperLDL-C. Our study provided evidence that high PCB exposure exacerbated the association of genetic risk and unhealthy lifestyle with dyslipidemia.

Long-term effect of styrene and ethylbenzene exposure on fasting plasma glucose: A gene-environment interaction study.

Styrene and ethylbenzene (S/EB) are hazardous pollutants that have attracted worldwide concern. In this prospective cohort study, S/EB exposure biomarker (the sum of mandelic acid and phenylglyoxylic acid [MA+PGA]) and fasting plasma glucose (FPG) were repeatedly measured three times. The polygenic risk score (PRS) based on 137 single nucleotide polymorphisms for type 2 diabetes mellitus (T2DM) was calculated to evaluate cumulative genetic effect. In repeated-measures cross-sectional analyses, MA+PGA (ß [95% confidence interval]: 0.106 [0.022, 0.189]) and PRS (0.111 [0.047, 0.176]) were significantly related to FPG. For long-term effect assessment, participants with sustained high MA+PGA or with high PRS had 0.021 (95% CI: -0.398, 0.441) or 0.465 (0.064, 0.866) mmol/L increase in FPG, respectively, over 3 years follow-up, and had 0.256 (0.017, 0.494) or 0.265 (0.004, 0.527) mmol/L increase in FPG, respectively, over 6 years follow-up. We further detected a significant interaction effect between MA+PGA and PRS on FPG change, compared with participants with sustained low MA+PGA and low PRS, those with sustained high MA+PGA and high PRS had 0.778 (0.319, 1.258) mmol/L increase in FPG (P for interaction=0.028) over 6 years follow-up. Our study provides the first evidence that long-term exposure to S/EB potentially increases FPG, which might be aggravated by genetic susceptibility.

Cross-sectional and longitudinal associations of dichlorodiphenyltrichloroethane (DDT) metabolites exposure with lung function alternation in the Chinese general adults.

Exposure of dichlorodiphenyltrichloroethane (DDT) pesticide was suggested to be associated with adverse effects on the respiratory system. However, the effects of DDT exposure on lung function remain unclear. Our objectives were to investigate the potential associations of internal levels of DDT and its metabolites including dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) with lung function. Serum DDT, DDE, and DDD concentrations and lung function were measured among 3968 general adults from the Wuhan-Zhuhai cohort. The cross-sectional and longitudinal associations of serum DDT and its metabolites with lung function were assessed using linear mixed models. The results showed negative dose-response relationships of serum DDT, DDE, and DDD levels with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). In the cross-sectional analyses, each 1-unit increase in natural log-transformed values of p,p'-DDE, o,p'-DDT, o,p'-DDE, or p,p'-DDD was significantly associated with a 25.77-, 44.84-, 51.13-, or 43.44-mL decrease in FVC, respectively. Each 1-unit increase in natural log-transformed values of o,p'-DDT, o,p'-DDE, o,p'-DDD, or p,p'-DDD was significantly associated with a 35.72-, 31.87-, 29.54-, or 36.80-mL decrease in FEV1, respectively. In the three-year longitudinal analyses, each 1-unit increase in natural log-transformed serum p,p'-DDT and p,p'-DDE was significantly associated with a 35.10 mL and 36.38 mL decrease in FVC, and a 26.32 mL and 32.37 mL decrease in FEV1, respectively. In conclusion, DDT and its metabolites exposure were associated with lung function decline in the general Chinese adult population.

PM2.5-related DNA methylation and the association with lung function in non-smokers.

PM2.5 exposure leads to lung function alteration. The potential pathway underlying above association, especially the role of DNA methylation is unclear. The objectives of this study are to evaluate the associations of personal PM2.5 concentrations with DNA methylation at the epigenome-wide level, and investigate how PM2.5-related DNA methylation affects lung function. A total of 402 observations of non-smokers were selected from the Wuhan-Zhuhai cohort. PM2.5 exposure was estimated through a model established in the same population. Blood DNA methylation levels were determined through Illumina Infinium MethylationEPIC BeadChips. Lung function was tested through spirometry on the day of blood sampling. The associations of PM2.5 exposure with DNA methylation and DNA methylation with lung function were determined through linear mixed models. Ten PM2.5-related CpG sites (mapped to 7 different genes) were observed with false discovery rate <0.05. Methylation levels of cg24821877, cg24862131, cg23530876, cg11149743 and cg10781276 were positively associated with PM2.5 concentrations. While methylation levels of cg10314909, cg08968107, cg18362281, cg24663971 and cg17834632 were negatively associated with PM2.5 concentrations. The top CpG was cg24663971 (P = 1.51✕10-9). Among the above 10 sites, significantly positive associations of methylation levels of cg24663971 with FVC%pred and FEV1%pred, and cg10314909 with FVC, FVC%pred, and FEV1%pred were observed. Age had modification effect on the associations between cg24663971 methylation and FVC%pred, and the associations were more obvious among participants with age ≥58 years. In conclusion, PM2.5 exposure was associated with DNA methylation, and PM2.5-related DNA methylation was associated with lung function among Wuhan urban non-smokers.

Cross-sectional and longitudinal relationships between ozone exposure and glucose homeostasis: Exploring the role of systemic inflammation and oxidative stress in a general Chinese urban population.

The adverse health effects of ozone pollution have been a globally concerned public health issue. Herein we aim to investigate the association between ozone exposure and glucose homeostasis, and to explore the potential role of systemic inflammation and oxidative stress in this association. A total of 6578 observations from the Wuhan-Zhuhai cohort (baseline and two follow-ups) were included in this study. Fasting plasma glucose (FPG) and insulin (FPI), plasma C-reactive protein (CRP, biomarker for systemic inflammation), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG, biomarker for oxidative DNA damage), and urinary 8-isoprostane (biomarker for lipid peroxidation) were repeatedly measured. After adjusting for potential confounders, ozone exposure was positively associated with FPG, FPI, and homeostasis model assessment of insulin resistance (HOMA-IR), and negatively associated with HOMA of beta cell function (HOMA-ß) in cross-sectional analyses. Each 10 ppb increase in cumulative 7-days moving average ozone was associated with a 13.19%, 8.31%, and 12.77% increase in FPG, FPI, and HOMA-IR, respectively, whereas a 6.63% decrease in HOMA-ß (all P < 0.05). BMI modified the associations of 7-days ozone exposure with FPI and HOMA-IR, and the effects were stronger in subgroup whose BMI ≥24 kg/m2. Consistently high exposure to annual average ozone was associated with increased FPG and FPI in longitudinal analyses. Furthermore, ozone exposure was positively related to CRP, 8-OHdG, and 8-isoprostane in dose-response manner. Increased CRP, 8-OHdG, and 8-isoprostane could dose-dependently aggravate glucose homeostasis indices elevations related to ozone exposure. Increased CRP and 8-isoprostane mediated 2.11-14.96% of ozone-associated glucose homeostasis indices increment. Our findings suggested that ozone exposure could cause glucose homeostasis damage and obese people were more susceptible. Systemic inflammation and oxidative stress might be potential pathways in glucose homeostasis damage induced by ozone exposure.

Carbon disulfide exposure induced lung function reduction partly through oxidative protein damage: A cross-sectional and longitudinal analysis.

Carbon disulfide (CS2) exposure has been associated with lung function reduction in occupational population. However, evidence on the general population with relatively low CS2 exposure is lacking and the mechanism involved remains largely unknown. Urinary CS2 metabolite (2-mercaptothiazolidine-4-carboxylic acid, TTCA) and lung function were determined in the urban adults from the Wuhan-Zhuhai cohort at baseline in 2011-2012 and were repeated every 3 years. Cross-sectional and longitudinal associations between TTCA and lung function were estimated using linear mixed models. Inflammation and oxidative damage biomarkers in blood/urine were measured to evaluate their potential mediating roles involved. Cross-sectionally, participants in the highest quartile of TTCA level showed a 0.64% reduction in FEV1/FVC and a -308.22 mL/s reduction in PEF, compared to those in the lowest quartile. Longitudinally, participants with consistently high TTCA level had annually -90.27 mL/s decline in PEF, compared to those with consistently low TTCA level. Mediation analysis revealed that plasma protein carbonyl mediated 49.89% and 22.10% of TTCA-associated FEV1/FVC and PEF reductions, respectively. Conclusively, there was a cross-sectional and longitudinal association between CS2 exposure and lung function reduction in the general urban adults, and protein carbonylation (oxidative protein damage) partly mediated lung function reduction from CS2 exposure.

Associations of selenium exposure with blood lipids: Exploring mediating DNA methylation sites in general Chinese urban non-smokers.

Selenium (Se) is widely distributed in the total environment and people are commonly exposed to Se, while the potential effects and mechanisms of Se exposure on blood lipids have not been well established. This study aimed to assess the associations of urinary Se (SeU) with blood lipids and explore the potential mediating DNA methylation sites. We included 2844 non-smoke participants from the second follow-up (2017-2018) of the Wuhan-Zhuhai cohort (WHZH) in this study. SeU and blood lipids [i.e., total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL)] for all participants were determined. The associations of SeU with blood lipids were analyzed by generalized linear models. Then, we conducted the blood lipids related epigenome-wide association studies (EWAS) among 221 never smokers, and the mediation analysis was conducted to explore the potential mediating cytosine-phosphoguanine (CpG) sites in the above associations. In this study, the SeU concentration of the participants in this study was 1.40 (0.94, 2.08) µg/mmol Cr. The SeU was positively associated with TC and LDL, and not associated with TG and HDL. We found 131, 3, and 1 new CpG sites related to TC, HDL, and LDL, respectively. Mediation analyses found that the methylation of cg06964030 (within MIR1306) and cg15824094 (within PLCH2) significantly mediated the positive association between SeU and TC. In conclusion, high levels of Se exposure were associated with increased TC and LDL among non-smokers, and the methylation of MIR1306 and PLCH2 partly mediated Se-associated TC increase. These findings provide new insights into the effects and mechanisms of Se exposure on lipids metabolism and highlight the importance of controlling Se exposure and intake for preventing high blood lipids.

Cross-sectional and Longitudinal Associations Between Propylene Oxide Exposure and Lung Function Among Chinese Community Residents: Roles of Oxidative DNA Damage, Lipid Peroxidation, and Protein Carbonylation.

BACKGROUND: Toxicologic studies have reported propylene oxide (PO) exposure may harm the respiratory system, but the association between PO exposure and lung function and potential mechanism remains unclear. RESEARCH QUESTION: What is the association between PO exposure and lung function and potential mediating mechanism? STUDY DESIGN AND METHODS: Urinary PO metabolite [N-Acetyl-S-(2-hydroxypropyl)-L-cysteine (2HPMA)] as PO internal exposure biomarker and lung function were measured for 3,692 community residents at baseline and repeated at 3-year follow up. Cross-sectional and longitudinal associations between urinary 2HPMA and lung function were assessed by linear mixed model. Urinary 8-hydroxy-deoxyguanosine, urinary 8-iso-prostaglandin-F2α, and plasma protein carbonyls as biomarkers of oxidative DNA damage, lipid peroxidation, and protein carbonylation, respectively, were measured for all participants to explore their potential roles in 2HPMA-associated lung function decline by mediation analysis. RESULTS: After adjustment for potential covariates, each threefold increase in urinary 2HPMA was cross sectionally associated with a 26.18 mL (95% CI, -50.55 to -1.81) and a 21.83 mL (95% CI, -42.71 to -0.95) decrease in FVC and FEV1, respectively, at baseline (all P < .05). After 3 years of follow up, 2HPMA was observed to be longitudinally associated with FEV1/FVC decline. No significant interaction effect of smoking or passive smoking was observed (Pinteraction > .05), and the associations between 2HPMA and lung function indexes were persistent among participants who were not smoking and those who were not passive smoking in both baseline and follow-up evaluations. We observed urinary 8-hydroxy-deoxyguanosine partially mediated the associations of 2HPMA with FVC (mediation proportion, 5.48%) and FEV1 (mediation proportion, 6.81%), and plasma protein carbonyl partially mediated the association between 2HPMA and FEV1 (mediation proportion, 3.44%). INTERPRETATION: PO exposure was associated with lung function decline among community residents, and oxidative DNA damage and protein carbonylation partially mediated PO exposure-associated lung function decline. Further attention on respiratory damage caused by PO exposure is warranted.

Gene-environment interaction in long-term effects of polychlorinated biphenyls exposure on glucose homeostasis and type 2 diabetes: The modifying effects of genetic risk and lifestyle.

The longitudinal relationships of polychlorinated biphenyls (PCBs) exposure with glucose homeostasis and type 2 diabetes (T2D) risk among Chinese population have not been assessed, and interactions of PCB exposure with genetic susceptibility and lifestyle are unclear. In this prospective cohort study, fasting plasma glucose (FPG) and insulin (FPI) and seven serum indicator-PCBs were measured for each participant. We constructed polygenic risk score (PRS) of T2D and healthy lifestyle score. Each 1-unit increment of ln-transformed PCB-118 was related with a 0.141 mmol/L, 11.410 pmol/L, 0.661, and 74.5% increase in FPG, FPI, homeostasis model assessment of insulin resistance, and incident T2D risk over 6 years, respectively. Each 1-unit increment in T2D-PRS was related with a 0.169 mmol/L elevation of FPG and 65.5% elevation of incident T2D risk during 6 years. Compared with participants who had low T2D-PRS and low PCB-118, participants with high T2D-PRS and high PCB-118 showed a significant increase in FPG (0.162 mmol/L; P for interaction <0.001) and incident T2D risk [hazard ratio (HR)= 2.222]. Participants with low PCB-118, low PRS, and healthy lifestyle had the lowest incident T2D risk (HR=0.232). Our findings highlighted the significance of reducing PCB exposure and improvement in lifestyle for T2D prevention and management, especially for individuals with higher genetic risk of T2D.

Triazine herbicides exposure, natural immunoglobulin M antibodies, and fasting plasma glucose changes: Association and mediation analyses in general Chinese urban adults.

The effects of triazine herbicides on glucose metabolism remain unclear. In this study, we aimed to assess the associations between serum triazine herbicides and glycemia-related risk indicators in general adults, and to evaluate the mediating role of natural immunoglobulin M antibodies (IgM) in the above associations among uninfected participants. We measured the concentrations of atrazine, cyanazine, and IgM in serum, as well as fasting plasma glucose (FPG), and fasting plasma insulin in 4423 adult participants from the Wuhan-Zhuhai cohort baseline population, enrolled in 2011-2012. Generalized linear models were used to evaluate the associations of serum triazine herbicides with glycemia-related risk indicators, and mediation analyses were performed to evaluate the mediating role of serum IgM in the above associations. The median levels of serum atrazine and cyanazine were 0.0237 µg/L and 0.0786 µg/L, respectively. Our study found significant positive associations of serum atrazine, cyanazine, and Σtriazine with FPG levels, risk of impaired fasting glucose (IFG), abnormal glucose regulation (AGR), and type 2 diabetes (T2D). Additionally, serum cyanazine and Σtriazine were found to be significant positive associated with the homeostatic model assessment of insulin resistance (HOMA-IR) levels. Significant negative linear relationships were observed in associations of serum IgM with serum triazine herbicides, FPG, HOMA-IR levels, the prevalence of T2D, and AGR (P < 0.05). Furthermore, we observed a significant mediating role by IgM in the associations of serum triazine herbicides with FPG, HOMA-IR, and AGR, with the proportions ranging from 2.96% to 7.71%. To ensure the stability of our findings, we conducted sensitivity analyses in normoglycemic participants and found that the association of serum IgM with FPG and the mediating role by IgM remained stable. Our results suggest that triazine herbicides exposure is positively associated with abnormal glucose metabolism, and decreasing serum IgM may partly mediate these associations.

Associations of glucose metabolism and diabetes with heart rate variability: a population-based cohort study.

The present study aimed to investigate the potential causal pathways and temporal relationships of glucose metabolism and diabetes with heart rate variability (HRV). This cohort study was conducted among a sample of 3858 Chinese adults. At baseline and 6 years follow-up, participants underwent HRV measurement (low frequency [LF], high frequency [HF], total power [TP], standard deviation of all normal-to-normal intervals [SDNN], and square root of the mean squared difference between adjacent normal-to-normal intervals [r-MSSD]) and determination of glucose homeostasis (fasting plasma glucose [FPG] and insulin [FPI], homeostatic model assessment for insulin resistance [HOMA-IR]). The temporal relationships of glucose metabolism and diabetes with HRV were evaluated using cross-lagged panel analysis. FPG, FPI, HOMA-IR, and diabetes were cross-sectionally negatively associated with HRV indices at baseline and follow-up (P < 0.05). Cross-lagged panel analyses demonstrated significant unidirectional paths from baseline FPG to follow-up SDNN (ß = -0.06), and baseline diabetes to follow-up low TP group (ß = 0.08), low SDNN group (ß = 0.05), and low r-MSSD group (ß = 0.10) (P < 0.05). No significant path coefficients were observed from baseline HRV to follow-up impaired glucose homeostasis or diabetes. These significant findings persisted even after excluding participants who were taking antidiabetic medication. The results support that elevated FPG and the presence of diabetes may be the causes rather than the consequences of HRV reduction over time.

A review of practical statistical methods used in epidemiological studies to estimate the health effects of multi-pollutant mixture.

Environmental risk factors have been implicated in adverse health effects. Previous epidemiological studies on environmental risk factors mainly analyzed the impact of single pollutant exposure on health, while in fact, humans are constantly exposed to a complex mixture consisted of multiple pollutants/chemicals. In recent years, environmental epidemiologists have sought to assess adverse health effects of exposure to multi-pollutant mixtures based on the diversity of real-world environmental pollutants. However, the statistical challenges are considerable, for instance, multicollinearity and interaction among components of the mixture complicate the statistical analysis. There is currently no consensus on appropriate statistical methods. Here we summarized the practical statistical methods used in environmental epidemiology to estimate health effects of exposure to multi-pollutant mixture, such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regressions, shrinkage methods (least absolute shrinkage and selection operator, elastic network model, adaptive elastic-net model, and principal component analysis), environment-wide association study (EWAS), etc. We sought to review these statistical methods and determine the application conditions, strengths, weaknesses, and result interpretability of each method, providing crucial insight and assistance for addressing epidemiological statistical issues regarding health effects from multi-pollutant mixture.

Assessment for the associations of twenty-three metal(loid)s exposures with early cardiovascular damage among Chinese urban adults with five statistical methods: Insight into assessing health effect of multipollutant exposure.

The topic of cardiovascular hazards from multiple metal (loid)s exposures has attracted widespread attention. Here, we measured concentrations of twenty-three urinary metal (loid)s and mean platelet volume (MPV), an early cardiovascular damage biomarker, for 3396 Chinese adults. We aimed to comprehensively assess the associations of single metal (loid) and multiple metal (loid)s (as a mixture) with MPV by combined use of five statistical methods, including general linear models, Bayesian kernel machine regression (BKMR), weight quartile sum (WQS) regression, quantile g-computation (QGC), and adaptive elastic network regression (AENR). And based on that, we hope to provide insight into assessing the health effect of multipollutant exposure. After adjustment for potential covariates, at least three methods jointly suggested that of twenty-three metal (loid)s, iron, arsenic, and antimony were positively while aluminum, tungsten, and thallium were inversely associated with MPV. The environmental risk score of metal (loid)s construed by AENR was significantly positively associated with MPV, while the association between overall twenty-three metal (loid)s mixture and MPV was neutralized to be insignificant in QGC and BKMR. Conclusively, single metal (loid) may be inversely (iron, arsenic, and antimony) and positively (aluminum, tungsten, and thallium) associated with early cardiovascular damage, while the association of overall twenty-three metal (loid)s mixture with MPV was insignificant when concurrent exposures exist. It is crucial to select appropriate statistical methods based on study purpose and principles/characteristics of statistical methods, and combined employment of multimethod is insightfully suggested when assessing health effects of multipollutant exposure.

Longitudinal relationships between polycyclic aromatic hydrocarbons exposure and heart rate variability: Exploring the role of transforming growth factor-ß in a general Chinese population.

We aim to investigate the long-term adverse effects of polycyclic aromatic hydrocarbons (PAHs) exposure on heart rate variability (HRV) reduction, and to assess the potential role of transforming growth factor-ß1 (TGF-ß1) in such relationship. We enrolled 2985 adult residents with 4100 observations who participated at baseline and 6-years follow-up from Wuhan-Zhuhai cohort. Ten detectable urinary PAHs metabolites and two HRV indices were repeatedly measured at baseline and follow-up; and plasma TGF-ß1 levels were also determined for all subjects. We observed that both total urinary low molecular weight PAHs (ΣLWM OH-PAH) and total urinary high molecular weight PAHs (ΣHWM OH-PAH) were negatively associated with HRV reductions (P < 0.05). Subjects with persistent high levels of ΣHWM OH-PAH had a significant reduction in HRV over 6 years, and the incensement of TGF-ß1 could aggravate above adverse effects in a dose-response manner. All kinds of PAHs were positively associated with plasma TGF-ß1 elevation, which in turn, were negatively related to HRV indices. Increased TGF-ß1 significant mediated 1.34-3.62% of PAHs-associated HRV reduction. Our findings demonstrated that long-term high levels of PAHs exposure could cause HRV reductions, and TGF-ß1 may play an essential role in such association.