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Iron overload has been associated with acute/chronic organ failure, but whether iron overload induces liver injury remains unclear. The objectives of this study were to assess the relationship between urinary iron and serum alanine aminotransferase (ALT, a biomarker for liver injury), and investigate the potential mediating roles of lipid peroxidation and oxidative DNA damage in such association. Levels of urinary iron, serum ALT, and urinary biomarkers of lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]) and oxidative DNA damage (8-hydroxy-deoxyguano-sine [8-OHdG]) were measured among 5386 observations of 4220 participants from the Wuhan-Zhuhai cohort. The relationships of urinary iron with serum ALT and risk of hyperALT were evaluated by linear mixed model and logistic regression model, respectively. The mediating roles of 8-iso-PGF2α and 8-OHdG were assessed by mediation analyses. This cross-sectional analysis found that urinary iron was positively associated with ALT (β = 0.032; 95% CI: 0.020, 0.044) and hyperALT prevalence (OR = 1.127; 95% CI: 1.065, 1.192). After 3 years of follow-up, participants with persistent high iron levels had increased risk of developing hyperALT (RR = 3.800; 95% CI: 1.464, 9.972) when compared with those with persistent low iron levels. In addition, each 1% increase in urinary iron was associated with a 0.146% (95% CI: 0.128%, 0.164%) increase and a 0.192% (95% CI: 0.154%, 0.229%) increase in 8-iso-PGF2α and 8-OHdG, respectively. Urinary 8-iso-PGF2α (β = 0.056; 95% CI: 0.039, 0.074) was positively associated with ALT, while the association between 8-OHdG and ALT was insignificant. Furthermore, increased 8-iso-PGF2α significantly mediated 22.48% of the urinary iron-associated ALT increment. Our study demonstrated that iron overload was significantly associated with liver injury, which was partly mediated by lipid peroxidation. Controlling iron intake and regulating lipid peroxidation may help in preventing liver injury. [ABSTRACT FROM AUTHOR]

To quantify the association of polycyclic aromatic hydrocarbons (PAHs) and the polygenic risk score (PRS) with lung function decline, we developed a repeated-measures study with 4681 observations from baseline and 6-year follow-up of the Wuhan–Zhuhai cohort. Lung function and urinary monohydroxylated PAH metabolites (OH-PAHs) were measured for each observation. The PRS was derived from 246 lung function-associated genetic variants weighted by the effect size of the decreasing ratio of forced expiratory volume in 1 s by forced vital capacity (FEV1/FVC). Linear mixed models were used to estimate the longitudinal exposure–response relationships between OH-PAHs and lung function, and to evaluate the interactions between OH-PAHs and PRS on the longitudinal change of lung function. We found that each 1-unit increase in log-transformed values of 9-hydroxyfluorene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 2-hydroxyphenanthrene, 1-hydroxyphenanthrene, 1-hydroxypyrene, low molecular weight OH-PAHs (ΣLMW–OH–PAHs), and total OH-PAHs (ΣOH-PAHs) was associated with an annual change in FEV1/FVC of −0.140, −0.112, −0.260, −0.300, −0.159, −0.220, −0.145, −0.156, and −0.177 %/year, respectively. Interactions on the annual decline of FEV1/FVC were detected between ΣLMW–OH–PAHs and PRS (−0.010 %/year, 95% confidence interval −0.018 to −0.001, P int = 0.0228), and between ΣOH-PAHs and PRS (−0.010 %/year, −0.018 to −0.001, P int = 0.0203). These results indicated that specific and total urinary OH-PAHs were associated with the longitudinal FEV1/FVC decline, and ΣLMW–OH–PAHs as well as ΣOH-PAHs interacted with PRS on the annual decline of FEV1/FVC. [Display omitted] • Positive longitudinal association between PAHs and lung function among general population. • The longitudinal lung function decline associated with PAHs enhanced across increased PRS. • Repeated-measures study was conducted to assess individual PAH exposure from varied sources over a long period. [ABSTRACT FROM AUTHOR]

Background: Obesity is reported to be associated with oxidative stress which can cause lipid peroxidation. However, the effects of gain in various weight-related anthropometric indices on lipid peroxidation remain unclear. We aimed to examine the cross-sectional and longitudinal associations between altered weight-related anthropometric indices and a marker of lipid peroxidation among urban adults in China. Methods: A total of 3762 participants from the Wuhan-Zhuhai cohort were included in the present study, with a follow-up of 3 years. Six weight-related anthropometric indicators were measured and calculated, including waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body adiposity index (BAI). Individual urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) was determined via enzyme-linked immunosorbent assay to evaluate lipid peroxidation. We used generalized linear models to analyze the cross-sectional and longitudinal associations of weight-related anthropometric indices with a marker of lipid peroxidation and stratified analyses to estimate effect modification. Results: We found significant relationships between WHR, WHtR, ABSI, and urinary 8-iso-PGF2α at baseline. Each 1% increase in WHR, WHtR, and ABSI was significantly associated with a 0.007, 0.004, and 0.104 increase in log-transformed 8-iso-PGF2α concentration, respectively (P< 0.05). In longitudinal analysis, positive dose–response relationships were observed between gains in BMI, BAI, and increased 8-iso-PGF2α after adjusting for potential confounders (Ptrend< 0.05). We also found that gender and smoking status modified the association of BMI gain and 8-iso-PGF2α increment, and such an association was more obvious in female and non-smokers. Conclusion: Our research implied that gain in anthropometric indices may result in a higher level of lipid peroxidation. [ABSTRACT FROM AUTHOR]

Objective: Acrylamide exposure from daily-consumed food has raised global concern. We aimed to assess the exposure-response relationships of internal acrylamide exposure with oxidative DNA damage, lipid peroxidation, and fasting plasma glucose (FPG) alteration and investigate the mediating role of oxidative DNA damage and lipid peroxidation in the association of internal acrylamide exposure with FPG.Research Design and Methods: FPG and urinary biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine [8-OHdG]), lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]), and acrylamide exposure (N-acetyl-S-[2-carbamoylethyl]-l-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-l-cysteine [GAMA]) were measured for 3,270 general adults from the Wuhan-Zhuhai cohort. The associations of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG were assessed by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis.Results: We found significant linear positive dose-response relationships of urinary acrylamide metabolites with 8-OHdG, 8-iso-PGF2α, and FPG (except GAMA with FPG) and 8-iso-PGF2α with FPG. Each 1-unit increase in log-transformed level of AAMA, AAMA + GAMA (ΣUAAM), or 8-iso-PGF2α was associated with a 0.17, 0.15, or 0.23 mmol/L increase in FPG, respectively (P and/or P trend < 0.05). Each 1% increase in AAMA, GAMA, or ΣUAAM was associated with a 0.19%, 0.27%, or 0.22% increase in 8-OHdG, respectively, and a 0.40%, 0.48%, or 0.44% increase in 8-iso-PGF2α, respectively (P and P trend < 0.05). Increased 8-iso-PGF2α rather than 8-OHdG significantly mediated 64.29% and 76.92% of the AAMA- and ΣUAAM-associated FPG increases, respectively.Conclusions: Exposure of the general adult population to acrylamide was associated with FPG elevation, oxidative DNA damage, and lipid peroxidation, which in turn partly mediated acrylamide-associated FPG elevation. [ABSTRACT FROM AUTHOR]

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is related to decreased lung function. However, whether oxidative damage is involved in this relationship remains unclear. This study was aimed to explore the potential mediating role of oxidative DNA or lipid damage in the association between PAH exposure and lung function.Methods: The urinary levels of monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and lung function parameters were measured among 3367 participants from the baseline of the Wuhan-Zhuhai cohort. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-iso-PGF2α) were determined to evaluate the individuals' oxidative DNA and lipid damage degrees, respectively. Linear mixed models were used to investigate the associations of urinary OH-PAHs, 8-OHdG and 8-iso-PGF2α with lung function parameters. Mediation analysis was further conducted to assess the potential role of oxidative damage in the association between urinary OH-PAHs and lung function.Results: Each one-percentage increase in the sum of urinary OH-PAHs, high-molecular-weight or low-molecular-weight OH-PAHs (ƩOH-PAHs, ƩHMW OH-PAH or ƩLMW OH-PAHs, respectively) was associated with a 0.2152-, 0.2076- or 0.1985- ml decrease in FEV1, and a 0.1891-, 0.2195- or 0.1634- ml decrease in FVC, respectively. Additionally, significantly positive dose-response relationships of ƩOH-PAHs, ƩHMW OH-PAH and ƩLMW OH-PAHs with urinary 8-OHdG or 8-iso-PGF2α, as well as an inverse dose-response relationship between urinary 8-OHdG and FVC, were observed (all P for trend < 0.05). Mediation analysis indicated that urinary 8-OHdG mediated 14.22% of the association between ƩHMW OH-PAH and FVC.Conclusion: Higher levels of oxidative DNA damage might be involved in the decreased levels of FVC caused by high-molecular-weight PAH exposure. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported that obesity indices were inversely associated with lung function. However, the underlying mechanisms remain unclear. We aimed to assess the potential mediating effect of systemic inflammation in the associations between obesity indices and lung function decline among a general population. Methods: We conducted a cross-sectional study among 3442 participants from the Wuhan-Zhuhai cohort. Plasma C-reactive protein (CRP) was assayed as a marker of systemic inflammation. The relationships among several obesity indices (body mass index, BMI; waist circumference, WC; waist-to-hip ratio, WHR; waist-to-height ratio, WHtR), plasma CRP and lung function were assessed by generalized linear models. The role of CRP in the associations between obesity indices and lung function was analyzed using mediation analysis. Results: We observed inverse associations between abdominal obesity indices (WC, WHR and WHtR) and lung function parameters, including forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) (all P< 0.05). Each 1-unit increase in WC was associated with a 3.39 mL decrease in FEV 1 and a 3.96 mL decrease in FVC (all P< 0.05). Each 1% increase in WHR and WHtR was associated with a 5.42 mL and a 14.23 mL decrease in FEV 1, and a 5.70 mL and a 16.92 mL decrease in FVC (all P< 0.05). Mediation analysis indicated that plasma CRP partly mediated the associations between abdominal obesity and lung function. The mediated proportions of CRP in associations of WC, WHR and WHtR with FEV 1 were 7.96%, 9.59% and 5.76%, respectively. The mediated proportions of CRP in associations of WC and WHR with FVC were 8.33% and 11.40%, respectively. Conclusion: Abdominal obesity indices were negatively associated with lung function, and the associations may be partly mediated by systemic inflammation. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Serum samples were measured for atrazine and cyanazine among general urban adults. • Triazine herbicide exposure was associated with abnormal glucose metabolism. • Triazine herbicide exposure was negatively associated with serum IgM level. • Down-regulated serum IgM level was associated with abnormal glucose metabolism. • IgM mediated triazine herbicide exposure-associated abnormal glucose metabolism. [ABSTRACT FROM AUTHOR]

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-β) 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-β (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. [Display omitted] • Ozone exposure could cause glucose homeostasis disorder. • Effects of ozone exposure on FPI and HOMA-IR were more susceptible in obese people. • Ozone exposure was positively associated with CRP, 8-OHdG, and 8-isoprostane. • CRP, 8-OHdG, and 8-isoprostane aggravated glucose homeostasis harm caused by ozone. • CRP and 8-isoprostane partly mediated ozone-associated glucose homeostasis disorder. [ABSTRACT FROM AUTHOR]

PM 2.5 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 PM 2.5 concentrations with DNA methylation at the epigenome-wide level, and investigate how PM 2.5 -related DNA methylation affects lung function. A total of 402 observations of non-smokers were selected from the Wuhan-Zhuhai cohort. PM 2.5 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 PM 2.5 exposure with DNA methylation and DNA methylation with lung function were determined through linear mixed models. Ten PM 2.5 -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 PM 2.5 concentrations. While methylation levels of cg10314909, cg08968107, cg18362281, cg24663971 and cg17834632 were negatively associated with PM 2.5 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 FEV 1 %pred, and cg10314909 with FVC, FVC%pred, and FEV 1 %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, PM 2.5 exposure was associated with DNA methylation, and PM 2.5 -related DNA methylation was associated with lung function among Wuhan urban non-smokers. [Display omitted] • Ten CpGs were linked to PM 2.5 exposure with false discovery rate <0.05. • Cg24663971 and cg10314909 methylation was positively associated with lung function. • PM 2.5 exposure concentrations at the individual level were estimated. • Blood DNA methylation at the epigenome level were determined. [ABSTRACT FROM AUTHOR]

The adverse health effects of pyrethroids exposure have attracted wide concern. We aimed to assess the associations of bifenthrin, a widely used pyrethroid, with glucose homeostasis and risk of type 2 diabetes mellitus (T2DM) and to explore the underlying mechanism. Serum bifenthrin, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and plasma protein carbonyl (PCO) were determined among 3822 participants from the Wuhan-Zhuhai cohort. Glucose homeostasis was evaluated by FPG, FPI, homeostasis model assessment of insulin resistance (HOMA-IR), impaired fasting glucose (IFG), and abnormal glucose regulation (AGR). The associations of serum bifenthrin with glucose homeostasis and risk of T2DM were assessed by generalized linear models and logistic regression models. The role of PCO in the above associations was evaluated by mediation analyses. After adjusting for covariates, each 2-fold increase in serum bifenthrin was associated with a 0.21 mmol/L increase in FPG and a 5.19%, 10.49%, and 12.18% increase in FPI, HOMA-IR, and PCO levels, respectively. Monotonically elevated ORs of IFG and AGR (all P and P for trend <0.05), but not T2DM (P > 0.05) were detected to be associated with increased bifenthrin. Compared with the participants with low bifenthrin and low PCO, participants with high bifenthrin exposure and high PCO showed a 0.40 mmol/L, 11.07%, and 22.50% increase in FPG, FPI, and HOMA-IR, as well as a 119.97% and 48.88% increase in risks of IFG and AGR, respectively (P for trend <0.05). Moreover, PCO mediated 13.61%–24.98% of the serum bifenthrin-associated glucose dyshomeostasis. The study suggested that bifenthrin exposure was dose-dependently associated with glucose dyshomeostasis in the general Chinese urban adults, and these associations were exacerbated and partly mediated by PCO. Given that other pollutants were not included in this study, the effect of co-exposure of pyrethroids with multiple pollutants is necessary to be considered in future studies. [Display omitted] • Serum bifenthrin was dose-dependently associated with glucose dyshomeostasis. • Protein carbonylation exacerbated bifenthrin-associated glucose dyshomeostasis. • Protein carbonylation partly mediated bifenthrin-associated glucose dyshomeostasis. [ABSTRACT FROM AUTHOR]

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2′-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2′-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder. [Display omitted] • Zinc exposure was associated with glycometabolic disorder. • Zinc exposure was associated with T2D cross-sectionally and longitudinally. • Inflammation and oxidative stress reinforced zinc-related glycometabolic disorder. • Inflammation and oxidative stress reinforced zinc-related elevated T2D risk. • C-reactive protein mediated zinc-related glycometabolic disorder. [ABSTRACT FROM AUTHOR]

1-bromopropane is a US Environmental Protection Agency-identified significant hazardous air pollutant with concerned adverse respiratory effect. We aimed to investigate the relationship between 1-bromopropane exposure and pulmonary function and the underlying role of oxidative damage, which all remain unknown. Pulmonary function and urinary biomarkers of 1-bromopropane exposure (N-Acetyl-S-(n-propyl)-L-cysteine, BPMA) and oxidative damage to DNA (8-hydroxy-deoxyguanosine, 8-OHdG) and lipid (8-iso-prostaglandin-F2α, 8-iso-PGF2α) were measured for 3259 Chinese urban adults from the Wuhan-Zhuhai cohort. The cross-sectional relationship of BPMA with pulmonary function and the joint relationship of BPMA and 8-OHdG or 8-iso-PGF2α with pulmonary function were investigated by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. Additionally, a panel of 138 subjects was randomly convened from the same cohort to evaluate the stability of BPMA repeatedly measured in urine samples collected over consecutive three days and intervals of one, two, and three years, and to estimate the longitudinal relationship of BPMA with pulmonary function change in three years. We found each 3-fold increase in BPMA was cross-sectionally related to FVC and FEV 1 reductions by 29.88-mL and 25.67-mL, respectively (all P < 0.05). Joint relationship of BPMA and 8-OHdG rather than 8-iso-PGF2α with reduced pulmonary function was observed. Moreover, 8-OHdG significantly mediated 9.44% of the BPMA-related FVC reduction. Findings from the panel revealed a fair to excellent stability (intraclass correlation coefficient: 0.43–0.79) of BPMA in repeated urines collected over a period of three years. Besides, BPMA was longitudinally related to pulmonary function reduction in three years: compared with subjects with persistently low BPMA level, those with persistently high BPMA level had 79.08-mL/year and 49.80-mL/year declines in FVC and FEV 1 , respectively (all P < 0.05). Conclusively, 1-bromopropane exposure might impair pulmonary function of urban adult population, and oxidative DNA damage might be a potential mechanism underlying 1-bromopropane impairing pulmonary function especially FVC. [Display omitted] • BPMA was cross-sectionally associated with decreased pulmonary function. • BPMA was longitudinally associated with pulmonary function decline in 3 years. • 8-OHdG partly mediated BPMA-associated pulmonary function reduction. [ABSTRACT FROM AUTHOR]

As a polycyclic aromatic hydrocarbon, environmental exposure to phenanthrene is widespread worldwide. The potential effects and mechanism of phenanthrene exposure on fasting plasma glucose (FPG) have not been well determined. In this study, we aim to explore the effects of phenanthrene exposure and AMER3 variants on fasting plasma glucose (FPG) through a longitudinal epidemiological study. Repeated measurements of five urinary hydroxyphenanthrene (OHPh) for 5739 participants with 7083 observations from the Wuhan-Zhuhai cohort were performed to analyze the relationships between total OHPh (ΣOHPh) and FPG using linear mixed models and restricted cubic spline functions. Then, we genotyped 2777 participants (4104 observations) using the Infinium OmniZhongHua-8 BeadChip and included all 14 single nucleotide polymorphisms (SNPs) within the AMER3 gene to analyze the interaction of the AMER3 on the relationship between ΣOHPh and FPG. We observed a U-shaped relationship between ΣOHPh and FPG, and the turning point of ΣOHPh was 2.512 μg/mmol Cr. When lower than the turning point, ΣOHPh was negatively associated with FPG, while higher than the turning point, ΣOHPh was positively associated with FPG. Furthermore, we observed interactions (P int <0.05) between two common variants (rs72854995 and rs72854999) of the AMER3 and ΣOHPh on FPG change: the U-shaped relationship was still observed in the GG genotype groups but not in the allele A carriers. Our results suggested that the AMER3 gene can modify the U-shaped relationship between phenanthrenes exposure and FPG, which showed a new gene-environment interaction and will provide a new perspective on the relationship between phenanthrene exposure and FPG. [Display omitted] • A U-shaped relationship was observed between ΣOHPh and FPG. • AMER3 variants modify the U-shaped relationship between ΣOHPh and FPG. • The role of AMER3 in glucose metabolism warrants further investigation. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) exposure has been related to the abnormal glucose metabolism and the risk of diabetes. However, the joint effects of various PCBs are uncertain and the potential mechanisms remain unclear. Our objectives were to evaluate the associations of serum PCBs with fasting plasma glucose (FPG) and the risk of diabetes among a general Chinese population, and to estimate the mediating effects of oxidative stress in the above associations. Serum levels of seven indicator-PCBs (PCB-28, 52, 101, 118, 138, 153, and 180) and FPG values were determined among 4498 subjects from the Wuhan-Zhuhai cohort. Oxidative DNA damage biomarker (urinary 8-hydroxy-2′-deoxyguanosine, 8-OHdG) and lipid peroxidation biomarker (urinary 8-isoprostane, 8-iso-PGF 2α) were also measured. Positive relationships of serum PCBs with FPG values as well as the risk of diabetes were observed. With each 1% increment in the natural log-transformed values of wet weight serum PCBs, FPG levels increased a 0.125% for PCB-52, 0.168% for PCB-118, 0.221% for PCB-138, 0.273% for PCB-153, and 0.379% for ΣPCB (the sum of seven PCBs). The adjusted odds ratios of diabetes associated with wet weight PCBs were 1.186 for PCB-52, 1.373 for PCB-118, 1.635 for PCB-153, and 1.456 for ΣPCB. The seven serum PCBs showed positive overall effect on the risk of diabetes. Elevated PCB-28, PCB-52, PCB-118, PCB-138, PCB-153, and ΣPCB were associated with the increased urinary 8-iso-PGF 2α , which was positively related with FPG values. Furthermore, urinary 8-iso-PGF 2α partially mediated the positive associations between PCBs and FPG values, with the mediated proportions ranged from 3.20 to 12.93%. In conclusion, our results suggested that serum PCBs were positively related with increased oxidative stress, FPG values, and the risk of diabetes among a general Chinese population. Serum PCBs mixture had positive overall effect on the risk of diabetes. Lipid peroxidation partly mediated the FPG elevation induced by PCB exposure. [Display omitted] • Serum PCB-52, 118, 138, and 153 and ∑PCB were positively associated with FPG levels. • Serum PCB-52, 118, and 153 and ∑PCB were positively associated with risk of diabetes. • PCBs mixture showed positive overall effect on the risk of diabetes. • Increased serum PCBs were associated with elevated urinary 8-iso-PGF 2α. • Urinary 8-iso-PGF 2α mediated the associations between serum PCBs and increased FPG. [ABSTRACT FROM AUTHOR]

Carbon disulfide (CS 2) has been reported to induce disorder of glucose metabolism. However, the associations of CS 2 exposure with plasma glucose levels and risk of diabetes have not been explored in general population, and the underlying mechanisms remain unclear. We aim to examine the relationships between CS 2 exposure and fasting plasma glucose (FPG) levels, as well as diabetes, and assess the potential role of oxidative stress among the abovementioned relationships in Chinese general adults. The concentrations of urinary biomarkers of CS 2 exposure (2-thiothiazolidin-4-carboxylic acid, TTCA), and biomarkers for lipid peroxidation (8-isoprostane, 8-iso-PGF 2α) and DNA oxidative damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) were measured among 3338 urban adults from the Wuhan-Zhuhai cohort. Additionally, FPG levels were tested promptly. Generalized linear models and logistic regression models were used to quantify the associations among urinary TTCA, oxidative damage markers, FPG levels and diabetes risk. Mediation analysis was employed to estimate the role of oxidative damage markers in the association between urinary TTCA and FPG levels. We discovered a significant relationship between urinary TTCA and FPG levels with regression coefficient of 0.080 (95% CI: 0.002,0.157). Besides, the risk of diabetes was positively related to urinary TTCA (OR:1.282, 95% CI: 1.055,1.558), particularly among those who did not exercise regularly. Each 1% increase of urinary TTCA concentration was associated with a 0.096% and 0.037% increase in urinary 8-iso-PGF 2α and 8-OHdG, respectively. Moreover, we found an upward trend of FPG level as urinary 8-iso-PGF 2α gradually increased (P trend <0.05), and urinary 8-iso-PGF 2α mediated 21.12% of the urinary TTCA-associated FPG increment. Our findings indicated that urinary CS 2 metabolite was associated with increased FPG levels and diabetes risk in general population. Lipid peroxidation partly mediated the association of urinary CS 2 metabolite with FPG levels. Image 1 • Urinary CS 2 metabolite was associated with elevated 8-iso-PGF 2α, 8-OHdG, FPG levels and diabetes in general population. • We found linear dose-response relationships of urinary CS 2 metabolite with 8-iso-PGF 2α , and urinary 8-iso-PGF 2α with FPG. • Urinary 8-iso-PGF 2α mediated 21.12% of the urinary TTCA-associated FPG increment. Urinary CS 2 metabolite was associated with increased FPG levels and diabetes risk, and lipid peroxidation partly mediated the relationship between urinary CS 2 metabolite and FPG levels. [ABSTRACT FROM AUTHOR]

Copper have been reported to be associated with metabolic diseases. However, results on copper exposure with blood lipid profiles are inconsistent, and the underlying mechanisms of this association remain unclear. This study focused on investigating associations between urinary copper and blood lipid profiles; and exploring the potential role of systemic inflammation in such relationships. Concentrations of urinary copper, plasma C-reactive protein (CRP), and four blood lipid parameters (e.g., Total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured in the adult participants from Wuhan-Zhuhai cohort. The associations between copper, CRP, and four blood lipids were assessed by the multivariable linear regression models, and the 3D mesh graphs was used to examine the joint effects of copper exposure and CRP on four blood lipid parameters. In addition, we used mediation analysis to investigate the mediated effects of CRP in the relationships between copper exposure and blood lipid profiles. Each 1% increase in urinary copper was statistically significantly associated with a 5.32% (95% CI: 2.48%, 8.24%) increase in TG after adjusting for the confounders (P < 0.05). No significant associations were observed between urinary copper and the other three blood lipid parameters (all P > 0.05). In addition, urinary copper increased monotonically with plasma CRP elevation, which in turn, was positively associated with TC, TG, and LDL-C and negatively related to HDL-C (all P < 0.05). Results from 3D mesh graphs demonstrated that increased levels of plasma CRP with higher urinary copper corresponded to higher TC, TG, LDL-C, and lower HDL-C concentrations. Mediation analysis observed that CRP mediated 6.27% in the relationships of urinary copper and TG. These findings suggest that systemic inflammation partly mediated the association between copper exposure and abnormal blood lipid, and may contribute to the development of dyslipidemias. Image 1 • Urinary copper was positively associated with TG. • Urinary copper was positively associated with plasma CRP. • CRP were positively associated with TC, TG, LDL-C, and negatively related to HDL-C. • Increased CRP levels with higher urinary copper corresponded to poor blood lipid. • Systemic inflammation mediated the associations of copper and TG. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbon (PAH) exposure has been considered a risk factor for cardiovascular diseases (CVD), whereas possible mechanisms for this association have not been fully understood. This study focused on exploring the potential effect of oxidatively damaged DNA on the relationships between PAH exposure and the 10-year atherosclerotic CVD (ASCVD) risk. Urinary levels of monohydroxy PAH metabolites (OH-PAHs) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG, the typical biomarker for oxidatively damaged DNA) were measured among 3052 subjects in the baseline of the Wuhan-Zhuhai cohort. The relationships between urinary OH-PAHs, 8-oxodG and 10-year risk of ASCVD were analyzed by linear mixed models and logistic regression models, respectively. The mediation analysis was further applied to explore the role of 8-oxodG in the relationship between urinary OH-PAHs and 10-year ASCVD risk. After controlling for potential confounders, the log-transformed level of total urinary low molecular weight OH-PAHs (∑LMW OH-PAHs) was significantly associated with an elevated risk of 10-year ASCVD [odds ratio (OR) = 1.222, 95% confidence interval (CI): 1.065–1.402]. More specifically, significantly positive dose-response relationships between total urinary hydroxynaphthalene (∑OHNa), hydroxyfluorene (∑OHFlu), hydroxyphenanthrene (∑OHPh) and 10-year ASCVD risk were observed (all P for trend <0.05). We also found positive relationships between urinary OH-PAH levels and 8-oxodG, as well as between urinary 8-oxodG levels and 10-year risk of ASCVD. Moreover, mediation analyses indicated that urinary 8-oxodG mediated 14.49%, 12.62% and 10.55% of the associations between urinary ∑LMW OH-PAHs, ∑OHNa, ∑OHFlu and 10-year ASCVD risk, respectively. These findings suggest that the oxidatively damaged DNA pathway may be a possible mechanism underlying PAH-associated ASCVD risk elevation. Image 1 • Urinary levels of low molecular weight OH-PAHs were positively associated with the 10-year ASCVD risk. • Urinary 8-oxodG levels were both positively associated with urinary OH-PAHs and 10-year ASCVD risk. • Urinary 8-oxodG partially mediated the associations between urinary low molecular weight OH-PAHs and 10-year ASCVD risk. Urinary 8-oxodG may partially mediate the association between low molecular weight PAH exposure and elevated risk of 10-year ASCVD in a Chinese population. [ABSTRACT FROM AUTHOR]

Exposure to environmental metals has been reported to be associated with airway inflammation. Fractional exhaled nitric oxide (FeNO) is an important inflammatory biomarker of the airway. However, the associations between metal exposures and FeNO change and the underlying mechanisms remain unclear. To investigate the associations between urinary metals and FeNO, and the potential role of Club cell secretory protein (CC16), a lung epithelial biomarker, in these associations. We conducted a cross-sectional study from the Wuhan-Zhuhai cohort and measured eight urinary metals, plasma CC16 and FeNO among 3067 subjects by using inductively coupled plasma-mass spectrometry, enzyme-linked immunosorbent assay kit and Nano Coulomb Nitric Oxide Analyzer, respectively. Mixed linear models were used to quantify dose-relationships between urinary metals and FeNO, as well as urinary metals and plasma CC16. The potential role of plasma CC16 in the associations between urinary metals and FeNO was estimated using mediationanalyses. After adjusting for covariates, one percent increase in urinary vanadium, nickel or antimony was associated with a respective 6.60% (95% CI: 3.52%, 9.68%), 2.18% (0.45%, 3.91%), 4.87% (1.47%, 8.27%) increase in FeNO level. The adverse associations were much stronger among participants with low concentration of plasma CC16 than those with high CC16 level. Moreover, plasma CC16 decreased monotonically with increasing quartiles of urinary vanadium, nickel or antimony. Mediation analyses found that CC16 mediated the associations between urinary metals and FeNO by 5.64%, 39.06% and 25.18% for vanadium, nickel and antimony respectively. CC16 plays an important role in airway inflammation. General population with lower plasma CC16 concentration is more likely to suffer from airway inflammation when exposed to high levels of vanadium, nickel or antimony. Image 1 • Estimating associations of urinary metals, CC16 and FeNO. • Vanadium, nickel and antimony were significantly associated with increased FeNO level. • CC16 may mediate associations of vanadium, nickel and antimony with FeNO. Capsule: We found positive associations between urinary metals and FeNO, which were stronger among participants with low plasma CC16 concentration. The associations were mediated by plasma CC16. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic heavy metal that is widely distributed in the environment. However, the mechanisms linking Cd exposure and type 2 diabetes risks are not completely elucidated. In this study, we aim to investigate the roles of C-reactive protein (CRP) on the association between urinary Cd and type 2 diabetes risk. We determined urinary Cd and plasma CRP concentrations among 3,140 adults from Wuhan-Zhuhai cohort. Dose-response relationships between urinary Cd, plasma CRP, and type 2 diabetes were explored using multivariate logistic regression and linear mixed regression models. Mediation analysis was performed to investigate the role of plasma CRP in the associations between urinary Cd and type 2 diabetes risk. With adjustment for potential confounders, the odds ratios (ORs) of type 2 diabetes showed an upward trend when urinary Cd concentration gradually increased (P trend <0.01). Significantly positive dose-response relationships were observed between urinary Cd and plasma CRP, as well as between plasma CRP and type 2 diabetes risk. Compared to those when both Cd and CRP levels were low, the adjusted ORs (95%CI) of type 2 diabetes was the highest [2.053(1.395–3.020)] in individuals with high levels of urinary Cd and plasma CRP. Mediation analysis estimated that plasma CRP mediated 4.01% of the association between urinary Cd and type 2 diabetes risk [mediating effect: OR (95%CI) = 1.019(1.002–1.057)]. Individuals with high levels of urinary Cd and plasma CRP had a much higher risk of type 2 diabetes. Plasma CRP may serve as a mediator in the association between urinary Cd and type 2 diabetes risk, providing clues for further study on the biological pathway for type 2 diabetes related to Cd exposure. Image 1 • Data on the biomarkers of urinary Cd was enriched in Chinese urban adults. • Urinary Cd was significantly associated with increased risk of type 2 diabetes. • Individuals with high levels of Cd and CRP had a much higher type 2 diabetes risk. • No significant interactions of Cd and CRP on type 2 diabetes risk were observed. • Associations between Cd and type 2 diabetes were partially mediated by CRP. [ABSTRACT FROM AUTHOR]

• Repeated measures were performed in chinese adults with low-moderate arsenic levels. • Arsenic was associated with increased levels of 8-isoPGF2α, 8-OHdG, and PCO. • Arsenic was linked to annual increased rates of 8-isoPGF2α, 8-OHdG, and PCO. • Results remain stable in different models, stratification and sensitivity analyses. Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2′-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (β: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners. [Display omitted] [ABSTRACT FROM AUTHOR]

The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure. In this study, we included 3487 urban adults from the Wuhan-Zhuhai cohort. Individual inhalation exposure to air pollutants was estimated by combining participants' daily breath volume and ambient concentrations of six air pollutants (including fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), sulfur dioxide (SO 2), carbon monoxide (CO) and ozone (O 3)). The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date. Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model. We found that PLR was negatively related to PM 2.5 (lag02-lag06), PM 10 (lag02-lag07), NO 2 (lag02-lag07), and SO 2 (lag03-lag05) and NLR was negatively related to PM 10 (lag05 and lag07). In the BKMR model, a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed, whereas PM 10 and NO 2 appeared to be more important than the other pollutants in the mixture. The negative impact of air pollutants was stronger in males, participants with lower body mass index (< 24 kg/m2), those cooking meals at home, drinkers, and non-exercisers. In conclusion, short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood. PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants. [Display omitted] [ABSTRACT FROM AUTHOR]

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. [Display omitted] ● Total and specific PCBs exposure were associated with increased prevalence of dyslipidemias. ● Individuals with higher genetic risk, higher PCB exposure, and unhealthier lifestyle have higher risk of dyslipidemia. ● High PCB exposure exacerbated the association of genetic risk and unhealthy lifestyle with dyslipidemia. [ABSTRACT FROM AUTHOR]

Benzo(a)pyrene was sparsely studied for its early respiratory impairment. The non-canonical ligand WNT5A play a role in pneumonopathy, while its function during benzo(a)pyrene-induced adverse effects were largely unexplored. Individual benzo(a)pyrene, plasma WNT5A, and spirometry 24-hour change for 87 residents from Wuhan-Zhuhai cohort were determined to analyze potential role of WNT5A in benzo(a)pyrene-induced lung function alternation. Normal bronchial epithelial cell lines were employed to verify the role of WNT5A after benzo(a)pyrene treatment. RNA sequencing was adopted to screen for benzo(a)pyrene-related circulating microRNAs and differentially expressed microRNAs between benzo(a)pyrene-induced cells and controls. The most potent microRNA was selected for functional experiments and target gene validation, and their mechanistic link with WNT5A-mediated non-canonical Wnt signaling was characterized through rescue assays. We found significant associations between increased benzo(a)pyrene and reduced 24-hour changes of FEF 50% and FEF 75% , as well as increased WNT5A. The benzo(a)pyrene-induced inflammation and epithelial-mesenchymal transition in BEAS-2B and 16HBE cells were attenuated by WNT5A silencing. hsa-miR-122–5p was significantly and positively associated with benzo(a)pyrene and elevated after benzo(a)pyrene induction, and exerted its effect by downregulating target gene TP53. Functionally, WNT5A participates in benzo(a)pyrene-induced lung epithelial injury via non-canonical Wnt signaling modulated by hsa-miR-122–5p/TP53 axis, showing great potential as a preventive and therapeutic target. [Display omitted] • Individual BaP was related to increased circulating WNT5A among community residents. • BaP induced inflammation and EMT in two epithelial cells dose- and time-dependently. • 3 WNT5A regulated BaP-induced inflammation and EMT via non-canonical Wnt signaling. • hsa-miR-122–5p was related to BaP and acted on BaP-induced inflammation and EMT. • WNT5A-mediated non-canonical Wnt signaling was modulated by hsa-miR-122–5p/TP53 axis. [ABSTRACT FROM AUTHOR]

The associations and potential mechanisms of low to moderate arsenic exposure with fasting plasma glucose (FPG) and type 2 diabetes mellitus (T2DM) are still unclear. To assess the effects of short-term and long-term arsenic exposure on hyperglycemia and the mediating effect of oxidative damage on such association, three repeated-measures studies with 9938 observations were conducted in the Wuhan-Zhuhai cohort. The levels of urinary total arsenic, FPG, urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2α), urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), and plasma protein carbonyls (PCO) were measured. Generalized linear mixed models were used to evaluate the exposure-response relationships of urinary total arsenic with FPG and the prevalent risks of impaired fasting glucose (IFG), T2DM, and abnormal glucose regulation (AGR). Cox regression models were applied to assess the associations of arsenic exposure with incident risks of IFG, T2DM, and AGR. Mediation analyses were performed to assess the mediating effects of 8-iso-PGF2α, 8-OHdG, and PCO. In cross-sectional analyses, each one-unit increase in natural log-transformed urinary total arsenic was associated with a 0.082 (95% CI: 0.047 to 0.118) mmol/L increase in FPG, as well as a 10.3% (95% CI: 1.4%–20.0%), 4.4% (95% CI: 5.3%–15.2%), and 8.7% (95% CI: 1.2%–16.6%) increase in prevalent risks of IFG, T2DM, and AGR, respectively. In longitudinal analyses, arsenic exposure was further associated with the annual increased rate of FPG with a β (95% CI) of 0.021 (95% CI: 0.010 to 0.033). The incident risks of IFG, T2DM, and AGR were increased without statistical significance when arsenic levels increased. Mediation analyses showed that 8-iso-PGF2α and PCO mediated 30.04% and 10.02% of the urinary total arsenic-associated FPG elevation, respectively. Our study indicated that arsenic exposure was associated with elevated level and progression rate of FPG among general Chinese adults, where lipid peroxidation and oxidative protein damage might be the potential mechanisms. [Display omitted] • Three repeated-measures surveys were conducted among the general Chinese adults. • Arsenic exposure was cross-sectionally and longitudinally associated with FPG. • Arsenic exposure was positively associated with 8-iso-PGF2α, 8-OHdG, and PCO. • The 8-iso-PGF2α and PCO partially mediated arsenic-associated FPG elevation. [ABSTRACT FROM AUTHOR]

Carbon disulfide (CS 2) exposure has been associated with lung function reduction in occupational population. However, evidence on the general population with relatively low CS 2 exposure is lacking and the mechanism involved remains largely unknown. Urinary CS 2 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 FEV 1 /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 FEV 1 /FVC and PEF reductions, respectively. Conclusively, there was a cross-sectional and longitudinal association between CS 2 exposure and lung function reduction in the general urban adults, and protein carbonylation (oxidative protein damage) partly mediated lung function reduction from CS 2 exposure. [Display omitted] • Exposure to CS 2 was cross-sectionally associated with lung function reduction. • Exposure to CS 2 was longitudinally associated with lung function reduction. • Protein carbonylation partly mediated TTCA-associated lung function reduction. • A novel report on the respiratory impacts of low exposure to carbon disulfide. [ABSTRACT FROM AUTHOR]

[Display omitted] • Plasma miRNAs expression profiles for zinc exposure and T2DM were identified. • MiR-144-3p were positively associated with zinc exposure and T2DM risk. • MiR-144-3p partially mediated zinc exposure-related hyperglycemia and T2DM. • MiR-144-3p interacted with Nrf2 to regulate zinc-induced insulin resistance. Zinc exposure has been linked with disordered glucose metabolism and type 2 diabetes mellitus (T2DM) development. However, the underlying mechanism remains unclear. We conducted population-based studies and in vitro experiments to explore potential role of microRNAs (miRNAs) in zinc-related hyperglycemia and T2DM. In the discovery stage, we identified plasma miRNAs expression profile for zinc exposure based on 87 community residents from the Wuhan-Zhuhai cohort through next-generation sequencing. MiRNAs profiling for T2DM was also performed among 9 pairs newly diagnosed T2DM-healthy controls. In the validating stage, plasma miRNA related to both of zinc exposure and T2DM among the discovery population was measured by qRT-PCR in 161 general individuals derived from the same cohort. Furthermore, zinc treated HepG2 cells with mimic or inhibitor were used to verify the regulating role of miR-144-3p. Based on the discovery and validating populations, we observed that miR-144-3p was positively associated with urinary zinc, hyperglycemia, and risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance. Our findings provided a novel clue for mechanism underlying zinc-induced glucose dysmetabolism and T2DM development, emphasizing the important role of miR-144-3p dysregulation. [ABSTRACT FROM AUTHOR]

Adverse effects of fine particulate matter (particulate matter ≤2.5 μm aerodynamic diameter, PM 2.5) and PM 2.5 -bound polycyclic aromatic hydrocarbons (PAHs) on blood lipid profiles remain uncertain. We designed a panel study with repeated measures. In this panel study, we enrolled 215 adult residents who participated in two study periods from the Wuhan-Zhuhai cohort. Personal 24-h PM 2.5 , sixteen kinds of 24-h PM 2.5 -bound PAHs, and blood lipid profiles were repeatedly measured across two study periods. We observed that an interquartile-range increase in four-ring or five-ring PAHs was linked with a 0.112 and 0.108 mmol/l increase in triglyceride, respectively in single-constituent models. These associations remained robust in both constituent-PM 2.5 joint models and single-constituent residual models. Additionally, we observed that the significant relationships of four/five-ring PAHs with triglycerides were stronger among females, non-smokers, and participants without hypertension and diabetes. Bayesian kernel machine regression models further revealed that combining sixteen kinds of PM 2.5 -bound PAHs as a mixture of pollutants could result in a cumulative toxic effect on total cholesterol and triglycerides. No significant relationships were observed between personal PM 2.5 exposure and blood lipid changes. Our findings suggest that exposure to PM 2.5 -bound PAHs may adversely affect lipid metabolism, which provides new evidence for formulating pollution abatement strategies for cardiovascular health. [Display omitted] • 4-/5-ring atmospheric PAHs exposure is positively associated with TG. • Combining 16 kinds of PAHs results in a cumulative toxic effect on TC and TG. • Females or non-smokers were more susceptible to atmospheric PAHs exposure. [ABSTRACT FROM AUTHOR]

[Display omitted] • Urinary acrolein metabolites (UAMs) were repeatedly measured over a period of 3 years. • UAMs were cross-sectionally associated with pulmonary function (PF) reduction. • UAMs were longitudinally associated with PF decline in 3 years. • 8-OHdG, CRP, and CC16 aggravated and/or mediated acrolein-associated PF reduction. • This is the first study to report the associations of UAMs with PF. Acrolein is a significant high priority hazardous air pollutant with pulmonary toxicity and the leading cause of most noncancer adverse respiratory effects among air toxics that draws great attention. Whether and how acrolein exposure impacts pulmonary function remain inconclusive. To assess the association of acrolein exposure with pulmonary function and the underlying roles of oxidative DNA damage, inflammation, and pulmonary epithelium integrity. Among 3,279 Chinese adults from the Wuhan-Zhuhai cohort, associations of urinary acrolein metabolites (N-Acetyl-S-(2-carboxyethyl)-L-cysteine, CEMA; N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, 3HPMA) as credible biomarkers of acrolein exposure with pulmonary function were analyzed by linear mixed models. Joint effects of biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine), inflammation (C-reactive protein, CRP), and pulmonary epithelium integrity (Club cell secretory protein, CC16) with acrolein metabolites on pulmonary function and the mediating roles of these biomarkers were assessed. Besides, a subgroup (N = 138) was randomly recruited from the cohort to assess the stabilities of acrolein metabolites and their longitudinal associations with pulmonary function change in three years. Significant inverse dose–response relationships between acrolein metabolites and pulmonary function were found. Each 10-fold increment in CEMA, 3HPMA, or ΣUACLM (CEMA + 3HPMA) was cross-sectionally related to a 68.56-, 40.98-, or 46.02-ml reduction in FVC and a 61.54-, 43.10-, or 50.14-ml reduction in FEV 1 , respectively (P < 0.05). Furthermore, acrolein metabolites with fair to excellent stabilities were found to be longitudinally associated with pulmonary function decline in three years. Joint effects of acrolein metabolites with 8-hydroxy-deoxyguanosine, CRP, and CC16 on pulmonary function were identified. CRP significantly mediated 5.97% and 5.51% of CEMA-associated FVC and FEV 1 reductions, respectively. 8-hydroxy-deoxyguanosine significantly mediated 6.78%, 6.88%, and 7.61% of CEMA-, 3HPMA-, and ΣUACLM-associated FVC reductions, respectively. Acrolein exposure of general adults was cross-sectionally and longitudinally related to pulmonary function decline, which was aggravated and/or partly mediated by oxidative DNA damage, inflammation, and pulmonary epithelium injury. [ABSTRACT FROM AUTHOR]

[Display omitted] • Exposure to PAHs is associated with increased blood lipid profiles over 6 years. • Individual with higher lipid-PRS could be more susceptible to hyperlipidemias. • Higher lipid-PRS aggravate and modify blood lipid when exposure to PAHs. We aim to analyze the effects of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic predisposition on blood lipid through a longitudinal epidemiological study. We enrolled 4,356 observations who participated at baseline (n = 2,435) and 6-year follow-up (n = 1,921) from Wuhan-Zhuhai cohort. Ten urinary PAHs metabolites and blood lipid (i.e. , total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured at both baseline and follow-up. The polygenic risk scores (PRS) of blood lipid were constructed by the corresponding genome-wide association studies. Linear mixed models were fit to identify associations between urinary PAHs metabolites, blood lipid, and lipid-PRSs in the repeated-measure analysis. Besides, longitudinal relationships of blood lipid with urinary PAHs metabolites and respective lipid-PRSs were examined by using linear regression models. Compared with subjects who had persistently low urinary total hydroxyphenanthrene (ΣOHPh), those with persistently high levels had an average increase of 0.137 mmol/l for TC and 0.129 mmol/l for LDL-C over 6 years. Each 1-unit increase of TC-, TG-, LDL-C-, and HDL-C-specific PRS were associated with an average increase of 0.438 mmol/l for TC, 0.264 mmol/l for TG, 0.198 mmol/l for LDL-C, and 0.043 mmol/l for HDL-C over 6 years, respectively. Compared with subjects who had low genetic risk and persistently low ΣOHPh, subjects with high LDL-specific PRS and persistently high ΣOHPh had an average increase of 0.652 mmol/l for LDL-C. Our results suggest that high-level ΣOHPh exposure is associated with an average increase of LDL-C over 6 years, and those relationships can be aggravated by a higher LDL-C-genetic risk. No significant relationships were observed between other PAHs metabolites (including hydroxynaphthalene, hydroxyfluorene, and hydroxypyrene) and blood lipid changes over 6 years. Our findings emphasize the importance of preventing PAHs exposure, particularly among those with a higher genetic predisposition of hyperlipidemia. [ABSTRACT FROM AUTHOR]

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-β1 (TGF-β1) 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-β1 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-β1 could aggravate above adverse effects in a dose-response manner. All kinds of PAHs were positively associated with plasma TGF-β1 elevation, which in turn, were negatively related to HRV indices. Increased TGF-β1 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-β1 may play an essential role in such association. [Display omitted] • Long-term exposure of PAHs may cause HRV reductions over 6 years. • TGF-β1 aggravate HRV reductions caused by PAHs exposure over 6 years. • TGF-β1 may be a possible mechanism underlying the reduction of HRV caused by PAHs. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause various health damages. However, some PAH derivatives are still used as agents, and some of them have hypoglycemic effects. Till now, few studies explored the relationship between urinary PAH metabolites and fasting plasma glucose (FPG). In this study, A total of 2682 non-smokers in the second follow-up of the Wuhan-Zhuhai cohort were included to explore the relationship between urinary PAH metabolites and FPG. FPG related epigenome-wide association study (EWAS) was conducted among 212 never smokers, and the mediation analysis was performed to find potential mediator cytosine-phosphoguanine (CpG) sites in the above relationship. The concentration of total urinary PAH metabolites was 3.60 (2.37, 5.85) μg/mmol Cr. The urinary PAH metabolites were negatively associated with FPG. Each 1-U increase in ln-transformed levels of 1-hydroxynaphthalene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, or 2- hydroxyphenanthrene was associated with 0.008-, 0.007-, 0.010-, or 0.010- unit decreased in ln-transformed levels of FPG, respectively (all p < 0.05). We found 28 new CpG sites related to FPG (FDR <0.05) through EWAS. Mediation analysis found that cg11350141 on AMER3 mediated 41.91% of the negative association of total urinary PAH metabolites with FPG. These results provide a new clue for the development of hypoglycemic agents. [Display omitted] • This is the first study that found low doses of urinary PAH metabolites were negatively associated with FPG. • The cg11350141 in the AMER3 gene mediated the PAH-associated FPG reduction. • We have newly discovered 28 CpG sites related to FPG. [ABSTRACT FROM AUTHOR]

To investigate the cross-sectional and longitudinal associations between aluminum exposure and lung function and the risk of chronic obstructive pulmonary disease (COPD). The repeated-measure study was developed with 3917 adults from the Wuhan-Zhuhai cohort and they were followed-up after 3 years and 6 years. Urinary aluminum and lung function were measured at each period. Linear mixed models were used to estimate the exposure–response relationship between urinary aluminum and lung function. COX regression models were used to evaluate the association of urinary aluminum with the risk of COPD. A total of 6996 observations including 2251 (32.2%) males with a mean age of 54.8 years were included. In the cross-sectional analyses, each 1-unit increase in log-transformed urinary aluminum was associated with a −33.34 mL (95% confidence interval (CI) −45.71 to −20.96) change in forced vital capacity (FVC) and a −17.89 mL (−27.80 to −7.97) change in forced expiratory volume in 1 s (FEV1). The follow-up analyses detected a negative association between urinary aluminum and the annual change of FVC (−6.73 mL/year, 95% CI –10.92 to −2.54), while the association of annual decline of FEV1 with urinary aluminum was statistically insignificant (−2.26 mL/year, −5.76 to 1.23). In the adjusted COX regression model, each 1-unit increase in log-transformed urinary aluminum was associated with a 29% increase in the incident risk of COPD (hazard ratio 1.29, 95% CI 1.04–1.62). Increased urinary aluminum was associated with lung function reduction and the increased risk of COPD in a general urban population. • Aluminum exposure was associated with the progression of decline in FVC and FEV1. • Elevated urinary aluminum was associated with the increased incident risk of COPD. • Traffic pollution was a source of aluminum exposure among general adults. [ABSTRACT FROM AUTHOR]

Urban environmental air pollution has become a serious public issue in China. However, the potential adverse effects of different air pollutants on liver function are still unclear. We aimed to explore the associations of air pollutants exposure with liver function, and analyzed short-term impact in two cities with different levels of air pollution. We included 3892 residents from the Wuhan (high-pollution area)-Zhuhai (low-pollution area) cohort. Liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in fasting peripheral blood were determined by a fully automatic biochemical analyzer. Individual air pollutants inhalation exposure was estimated by combining his/her daily breathing volume and the concentrations of six air pollutants, including particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), sulfur dioxide (SO 2), carbon monoxide (CO) and ozone (O 3), from local ambient air monitoring stations. The associations of air pollutants with ALT and AST were evaluated using linear mixed models. We found positive associations of PM 2.5 (lag01-lag07), PM 10 (lag01-lag07), NO 2 (lag01-lag07), SO 2 (lag01-lag07), CO (lag01-lag06) and O 3 (lag01-lag02) with ALT and PM 10 (lag04-lag07) with AST. In Wuhan, exposure to PM 2.5 (lag01-lag07), PM 10 (lag01-lag07), NO 2 (lag01-lag07) and SO 2 (lag01-lag07) was associated with increased ALT, and PM 10 (lag04-lag07) and NO 2 (lag01-lag03) exposure was significantly associated with increased AST. While in Zhuhai, although all six air pollutants (PM 2.5 [lag01-lag07], PM 10 [lag01-lag02], NO 2 [lag01-lag04], SO 2 [lag01-lag03], CO [lag01-lag07] and O 3 [lag01-lag03]) were significantly associated with increased ALT, no pollutant was significantly associated with increased AST. Our results suggest that short-term exposure to air pollutants has adverse effects on liver function among urban adults. Such adverse effects last longer in high-pollution area than that in low-pollution area. Image 1 • We explored adverse effect of air pollutants with higher levels on liver function. • The short-term impact in different air pollution area was analyzed in this study. • A method was adopted to assess personal air pollutants inhalation exposure. • Short-term exposure to air pollutants can affect serum ALT and AST levels. [ABSTRACT FROM AUTHOR]

Cadmium is a recognized human carcinogen, raising global concern for its ubiquitously environmental exposure on public health. Diabetogenic effects of cadmium have been suggested in previous studies, but the longitudinal associations of chronic cadmium exposure with fasting blood glucose changes and type 2 diabetes mellitus have not been fully elucidated. To investigate the effects of long-term cadmium exposure on the fasting blood glucose changes and type 2 diabetes mellitus risk in a longitudinal prospective study of China. A total of 3521 urban adults were included as baseline study population from the Wuhan-Zhuhai cohort, and followed up three years later. Urinary cadmium concentrations were determined repeatedly during the follow-up of a three-year period. The within-person and between-person variability of urinary cadmium concentrations over three years was estimated using multilevel random-effects mixed models. Multivariate regression models were performed to evaluate the associations of cadmium exposure with fasting blood glucose changes and type 2 diabetes mellitus risk. The geometric means of creatinine-corrected urinary cadmium concentration at baseline were 1.13 μg/g creatinine, which were close to the levels of follow-up (1.14 μg/g creatinine). The intra-class correlation coefficient of creatinine-corrected urinary cadmium concentrations was 0.71, achieving good reproducibility of cadmium over three years. With adjustment for potential confounders, each one-unit increase in log10-transformed cadmium was associated with a 0.11 (95%CI: 0.03 to 0.19) elevation in fasting blood glucose concentration, and was associated with a 42% (95%CI: 1.16 to 1.73) increase in risk of prevalent type 2 diabetes mellitus. Upward trends of fasting blood glucose changes and type 2 diabetes mellitus incidence were observed with increasing cadmium exposure. Individuals with the highest urinary cadmium exposure had a significant increase in fasting blood glucose change at follow-up [β (95% CI): 0.49 (0.31–0.67)]. Risk of incident type 2 diabetes mellitus were gradually elevated across increasing quartiles of cadmium exposure, though associations did not reach statistical significance (P = 0.15). Our findings suggested that relatively high chronic cadmium exposure for general population adults might contribute to elevated changes of fasting blood glucose resulting in the development of type 2 diabetes mellitus. • Excellent reproducibility was achieved for urinary Cd levels over three years. • Significant associations observed for urinary Cd with FBG and prevalent T2DM risk. • Individuals with high Cd exposure had a significant increase in FBG at follow-up. • Risk of incident T2DM were gradually elevated across increasing urinary Cd. • Associations were further confirmed in penalized regression splines models. [ABSTRACT FROM AUTHOR]

• This is the first study to assess the association between acrylamide exposure and HRV alteration. • Urinary acrylamide metabolites were significantly associated with HRV reduction. • Urinary GAMA was significantly associated with plasma TGF-β1 elevation. • Plasma TGF-β1 was significantly associated with HRV reduction. • Plasma TGF-β1 mediated 5.71–7.41 % of the GAMA-associated HRV reduction. The potential adverse health effects of acrylamide have drawn worldwide attention and the World Health Organization has urged further urgent studies on its health threat. Herein we explored the exposure-response relationship and underlying mechanism between internal acrylamide exposure and heart rate variability (HRV) alteration, a marker of cardiac autonomic dysfunction. We measured six HRV indices and two urinary acrylamide metabolites (N-Acetyl-S-(2-carbamoylethyl)- l -cysteine, AAMA; N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)- l -cysteine, GAMA) for 2997 general Chinese adults from the Wuhan-Zhuhai cohort, of whom 2414 had data on plasma transforming growth factor-β1 (TGF-β1). The associations among urinary acrylamide metabolites, HRV and TGF-β1 were evaluated by linear mixed models and restricted cubic spline models. The mediating role of TGF-β1 was investigated by conducting mediation analysis. We found significantly negative dose-response relationships of all urinary acrylamide metabolites and TGF-β1 with all six HRV indices after adjusting for potential confounders (all P < 0.05). Urinary GAMA (β=0.074, P < 0.05) rather than AAMA (β=0.024, P > 0.05) was positively and dose-dependently associated with TGF-β1, which in turn significantly mediated 5.71–7.41 % of the GAMA-associated HRV reduction. Our findings suggest for the first time that daily exposure of general population to acrylamide is associated with cardiac autonomic dysfunction, where a mechanism involving TGF-β pathway may be involved. [ABSTRACT FROM AUTHOR]

• Urinary copper and zinc were positively associated with MetS prevalence. • Urinary copper and zinc were positively associated with plasma CRP. • Higher concentration of plasma CRP was positively related to MetS prevalence. • Associations of copper and zinc with MetS was partly mediated through CRP. Essential metals have been reported to be associated with metabolic diseases. However, the relationships between essential metals exposure and Metabolic Syndrome (MetS) is still uncertain, and the underlying mechanisms of the association remain unclear. To investigate the associations of urinary essential metals with MetS prevalence; and further to explore potential role of systemic inflammation biomarker, C-reactive protein (CRP), in relationships between essential metals exposure and MetS prevalence in a cross-sectional study. Concentrations of 8 urinary essential metals and plasma C-reactive protein (CRP) were quantified in 3272 adults from Wuhan-Zhuhai cohort. Urinary essential metals were adjusted by the corresponding urinary creatinine concentrations and reported as μg/mmol creatinine. Multivariable logistic regression and linear regression models were used to evaluate dose–response relationships between essential metals, plasma CRP, and MetS prevalence. Mediation analysis was performed to investigate the role of plasma CRP in the associations between urinary essential metals and MetS prevalence. In the single-metal models, we observed positive dose-dependent relationships of urinary copper and zinc with MetS prevalence. Compared with the lowest quartiles of urinary metals, the ORs (95% CI) of MetS in the highest quartiles were 1.40 (1.03, 1.91) for urinary copper and 2.07 (1.51, 2.84) for zinc, respectively. The dose-dependent relationships of zinc and copper with MetS remained significant in the multiple-metal models and Bayesian kernel machine regression (BKMR) models. No significant associations were observed between others essential metals (e.g. manganese, iron, cobalt, selenium, chromium, molybdenum) and MetS in this general population (all P value > 0.05). In addition, urinary copper and zinc increased monotonically with plasma CRP elevation, and plasma CRP was positively associated with the MetS prevalence. Mediation analysis indicated that plasma CRP mediated 5.2% and 3.2% in the associations of urinary copper and zinc with MetS prevalence, respectively. Elevated concentrations of urinary copper and zinc were associated with increased prevalence of MetS. Systemic inflammation may play an important role in the associations of copper and zinc exposure with MetS. [ABSTRACT FROM AUTHOR]

• Urinary 1-BP metabolites positively associated with FPG levels. • Exposure to 1-BP increased the risk of diabetes in Chinese urban adults. • Lipid peroxidation mediated the association between 1-BP and FPG. Exposure to 1-bromopropane (1-BP) has been reported to cause glutathione depletion and increase the level of oxidative damage, which play critical roles in diabetes. However, the possible associations or mechanisms of the exposure of 1-BP with the plasma glucose level and the risk of diabetes are unclear. In this study, we explored the relationships of the urinary 1-BP metabolite N-Acetyl-S-(n-propyl)- l -cysteine (BPMA) with fasting plasma glucose (FPG) levels and the risk of diabetes, and the mediating role of oxidative damage in the above relationships in 3678 urban adults from the Wuhan-Zhuhai cohort in China. We found a significant dose–response relationship between BPMA and FPG levels with a β of 0.09 (95 % CI: 0.04, 0.14). In addition, mediating effect of urinary BPMA on FPG levels was observed depending on elevated 8-isoprostane level, with a median proportion of 32.06 %. Furthermore, we observed a significant association between urinary BPMA and the risk of diabetes, with an adjusted odds ratio of 1.34 (1.18, 1.52) for all participants. These results indicated that urinary 1-BP metabolites were positively associated with FPG levels and the risk of diabetes among urban adults in this cross-sectional study. Lipid peroxidation partially mediated the association between urinary 1-BP metabolites and FPG levels. [ABSTRACT FROM AUTHOR]

Urinary polycyclic aromatic hydrocarbon (PAH) metabolites, biomarkers of internal PAH exposure, are commonly used to explore the effects of PAH on human health. However, the correlation between environmental PAH exposure and the species or levels of urinary PAH metabolites remains unclear. We collected detailed information on PAH exposure sources, including cigarette smoking, cooking, traffic and diet habits via structured questionnaires, and determined 12 urinary monohydroxylated PAH metabolites (OH-PAHs) among 4092 participants from the Wuhan-Zhuhai cohort. Linear mixed models and generalized linear models were conducted to explore the associations of urinary metabolite levels with single or multiple PAH exposure sources. We also calculated the standardized regression coefficients to further compare the contributions of different sources to urinary OH-PAH levels. Our results showed that increasing levels of urinary 1-, 2-hydroxynaphthalene (1-, 2- OHNa) and 2-hydroxyfluorene (2-OHFlu) were significantly correlated with tobacco smoking (all P < 0.01). The concentrations of 1-, 2- OHNa and 9-hydroxyfluorene (9-OHFlu) were positively correlated with dietary intake (all P < 0.05). Individuals who spent a long time in traffic showed elevated levels of 9-OHFlu and 1-hydroxyphenanthrene (1-OHPh) compared with individuals who spent a short time in traffic (all P < 0.05). Self-cooking was associated only with elevated 1-hydroxypyrene (1-OHP) levels. Moreover, good kitchen ventilation resulted in significantly decreased urinary low-molecular-weight OH-PAH levels. These findings suggested that cigarette smoking, self-cooking, high dietary PAH intake and a long time spent in traffic were associated with increased levels of specific urinary PAH metabolites, and good kitchen ventilation effectively reduced the exposure to low-molecular-weight PAHs in self-cooking participants. Image 1 • Cigarette smoking had the greatest contribution to urinary levels of naphthalene metabolites. • Self-cooking was closely related to exposure to higher-molecular-weight PAHs. • Good kitchen ventilation effectively reduced the exposure of self-cooking participants to low-molecular-weight PAHs. [ABSTRACT FROM AUTHOR]