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Background: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City., Methods: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to identify norovirus types GI and GII in anal swab samples from all cases. Norovirus-positive samples were sequenced and analyzed for the open reading frame (ORF) 1/ORF2 hinge region., Results: 26 norovirus infectious outbreaks were reported among 39 acute diarrheal outbreaks, including 14 outbreaks in kindergartens, 8 in elementary schools, and 4 in universities. Based on clinical symptoms and epidemiological investigations, a total of 1295 individuals were identified as having been exposed to norovirus, yielding an attack rate of 35.75 %. A higher proportion of outbreaks was observed during the winter and spring seasons (38.46 %). Additionally, norovirus-positive samples were subjected to sequencing and analysis of the open reading frame (ORF) 1/ORF2 hinge region. Genotypic data for norovirus was successfully obtained from 18 (69.23 %) of the infectious outbreaks, revealing 10 distinct recombinant genotypes. GII.4 Sydney 2012 [P31] and GII.17[P17] were the predominant strains in 2021 and 2022, GII.3 [P12] emerged as the dominant strain in 2023., Conclusion: Norovirus outbreaks in Hongshan District predominantly occurred in crowded educational institutions, with peaks in the cold season and a high attack rate in universities. GII.3 [P12] has become the locally predominant strain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Environmental exposure to crystalline silica (CS) particles is common and occurs during natural, industrial, and agricultural activities. Prolonged inhalation of CS particles can cause silicosis, a serious and incurable pulmonary fibrosis disease. However, the underlying mechanisms remain veiled. Herein, we aim to elucidate the novel mechanisms of interleukin-11 (IL-11) driving fibroblast metabolic reprogramming during the development of silicosis. We observed that CS exposure induced lung fibrosis in mice and activated fibroblasts, accompanied by increased IL-11 expression and metabolic reprogramming switched from mitochondrial respiration to glycolysis. Besides, we innovatively uncovered that elevated IL-11 promoted the glycolysis process, thereby facilitating the fibroblast-myofibroblast transition (FMT). Mechanistically, CS-stimulated IL-11 activated the extracellular signal-regulated kinase (ERK) pathway and the latter increased the expression of hypoxia inducible factor-1α (HIF-1α) via promoting the translation and delaying the degradation of the protein. HIF-1α further facilitated glycolysis, driving the FMT process and ultimately the formation of silicosis. Moreover, either silence or neutralization of IL-11 inhibited glycolysis augmentation and attenuated CS-induced lung myofibroblast generation and fibrosis. Overall, our findings elucidate the role of IL-11 in promoting fibroblast metabolic reprogramming through the ERK-HIF-1α axis during CS-induced lung fibrosis, providing novel insights into the molecular mechanisms and potential therapeutic targets of silicosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: We aimed to evaluate the association of occupational noise with metabolic syndrome (MetS) and its components, and to assess the potential role of miRNAs in occupational noise-associated MetS., Methods: A total of 854 participants were enrolled in our study. Cumulative noise exposure (CNE) was estimated in conjunction with workplace noise test records and research participants' employment histories. Logistic regression models adjusted for potential confounders were used to assess the association of CNE and miRNAs with MetS and its components., Results: We observed linear positive dose-response associations between occupational noise exposure and the prevalence of MetS (OR: 1.031; 95 % CI: 1.008, 1.055). And linear and nonlinear relationship were also found for the association of occupational noise exposure with high blood pressure (OR: 1.024; 95 % CI: 1.007, 1.041) and reduced high-density lipoprotein (OR: 1.051; 95 % CI: 1.031, 1.072), respectively. MiR-200a-3p, miR-92a-3p and miR-21-5p were inversely associated with CNE, or the prevalence of MetS and its components (all P < 0.05). However, we did not find any statistically significant mediation effect of miRNAs in the associations of CNE with MetS. Furthermore, the prevalence of bilateral hearing loss in high-frequency increased (OR: 1.036; 95 % CI: 1.008, 1.067) with CNE level rising, and participants with bilateral hearing loss in high-frequency had a significantly higher risk of MetS (OR: 1.727; 95 % CI: 1.048, 2.819)., Conclusion: Our study suggests that occupational noise exposure is associated with MetS and its components, and the role of miRNAs in noise-induced increasing MetS risk needs to be confirmed in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Kidney damage is common in patients with Fabry disease (FD), but more accurate information about the risk of progression to kidney failure is needed for clinical decision-making. In particular, FD patients with mild renal involvement often lack timely intervention and treatment. We aimed to utilize a model to predict the risk of renal progression in FD patients., Methods: Between November 2011 and November 2019, ERT-naive patients with FD were recruited from three medical centers in China. To assess the risk of a 50% decline in the estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD), Cox proportional hazards models were utilized. The performance of these models was assessed using discrimination, calibration, and reclassification., Results: A total of 117 individuals were enrolled. The mean follow-up time was 4.8 years, during which 35 patients (29.9 %) progressed to the composite renal outcomes. Male sex, baseline proteinuria, eGFR and globotriaosylsphingosine (Lyso-Gb3) were found to be independent risk factors for kidney progression by the Cox model, based on which a combined model containing those clinical variables and Lyso-Gb3 and clinical models including only clinical indicators were constructed. The two prediction models had relatively good performance, with similar model fit measured by R 2 (59.8 % vs. 61.1 %) and AIC (51.54 vs. 50.08) and a slight increase in the C statistic (0.949 vs. 0.951). Calibration curves indicated closer alignment between predicted and actual renal outcomes in the combined model. Furthermore, subgroup analysis revealed that Lyso-Gb3 significantly improved the predictive performance of the combined model for kidney prognosis in low-risk patients with a baseline eGFR over 60 ml/min/1.73 m 2 or proteinuria levels less than 1 g/d when compared to the clinical model., Conclusions: Lyso-Gb3 improves the prediction of kidney outcomes in FD patients with a low risk of progression, suggesting that these patients may benefit from early intervention to assist in clinical management. These findings need to be externally validated., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Silica particles are commonly encountered in natural and industrial activities. Long-term environmental exposure to silica can result in silicosis, which is characterized by chronic inflammation and abnormal tissue repair in lung. To uncover the role of m 6 A modification in silica-induced pulmonary inflammation, we conducted this study using established mouse and macrophage models. In this study, the aerodynamic diameter of silica particles was approximately 1-2 µm. We demonstrated that silica exposure in mice caused pulmonary inflammation and increased global m 6 A modification levels, the downregulation of alkB homolog 5 (ALKBH5) might contribute to this alteration. Besides, we found that F4/80, a macrophage-specific biomarker, was co-expressed with ALKBH5 through dual immunofluorescent staining. In vitro studies using MeRIP assays suggested that Slamf7 was a target gene regulated by m 6 A modification, and specific inhibition of ALKBH5 increased Slamf7 expression. Mechanistically, ALKBH5 promoted m 6 A modification of Slamf7, which decreased Slamf7 mRNA stability in an m 6 A-dependent manner, ultimately regulating Slamf7 expression. In addition, silica exposure activated PI3K/AKT and induced macrophage autophagy. Inhibition of Slamf7 promoted autophagy, reduced the secretion of pro-inflammatory cytokines, and improved silica-induced pulmonary inflammation. In summary, ALKBH5 can regulate silica-induced pulmonary inflammation by modulating Slamf7 m 6 A modification and affecting the function of macrophage autophagy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Evidence on the association between occupational noise exposure and blood pressure is inconsistent, and the underlying mechanism remains unknown. This study aimed to evaluate the association between occupational noise exposure and blood pressure, and explore the potential role of miRNAs in the association. A total of 894 subjects from two companies in Wuhan, China were included. Occupational noise exposure was assessed using cumulative noise exposure (CNE), and six candidate plasma miRNAs (miR-92a-3p, miR-21-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-1-3p) which were not only associated with blood pressure/hypertension but also related to oxidative stress were selected according to previous studies and tested. A linear dose-response relationship was found between occupational noise exposure and blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP). Each 1-unit increase in CNE levels was significantly associated with a 0.130 (95 % confidence interval [CI] = 0.026, 0.234) unit increase in SBP and a 0.141 (95 % CI = 0.063, 0.219) unit increase in DBP. However, the association between occupational noise and hypertension is not statistically significant (P > 0.05). In the meanwhile, occupational noise exposure was negatively associated with miRNA-92a-3p (β = -0.019, 95 % CI = -0.032, -0.006) and miRNA-21-5p (β = -0.031, 95 % CI = -0.052, -0.010), and miRNA-92a-3p mediated 24.66 % of the association between occupational noise exposure and DBP. In addition, bilateral high-frequency hearing loss was not only positively associated with occupational noise exposure (OR = 1.974, 95 % CI = 1.084, 3.702) but also DBP (β = 2.546, 95 % CI = 0.160, 4.932). Our study suggests that occupational noise exposure is positively associated with SBP and DBP, and miRNA-92a-3p partially mediate the association between occupational noise exposure and DBP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 (FEV 1 ). 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 FEV 1 , 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 FEV 1 , respectively. In conclusion, DDT and its metabolites exposure were associated with lung function decline in the general Chinese adult population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that pose detrimental effects on human health, and the exploration of the associations of PAHs exposure with long non-coding RNA (lncRNA) may provide novel clues to the underlying mechanisms. In the present study, we detected 10 urinary PAHs metabolites by GC-MS and plasma lncRNAs levels by Human LncRNA Array v4 among 230 participants from two panels (160 in the Shiyan panel and 70 in the Wuhan-Zhuhai panel). We applied linear regression models to assess the associations between PAHs metabolites and lncRNAs separately in each panel and combined the results using fixed-effect meta-analysis. To explore the potential origin of PAHs-related lncRNAs in plasma, we estimated their tissue-specificity and associations between lncRNAs levels in plasma and leukocytes. Leukocytes mRNA sequencing data and RNA binding proteins were utilized to explore implicated pathways of identified lncRNAs. We found that urinary 1-hydroxyphenanthrene (1-OH-Phe) was inversely associated with 8 lncRNAs and positively associated with 1 lncRNA, as well as 9-hydroxyphenanthrene (9-OH-Phe) was inversely associated with 11 lncRNAs (FDR < 0.1). Tissue specificity analysis using Genome Tissue Expression database suggested that several identified lncRNAs might specifically express in organs targeted by PAHs exposure (lung, liver, heart, kidney, and brain). Besides, plasma levels of 1-OH-Phe related ENSG00000260616 and 9-OH-Phe related STARD4-AS1 were inversely associated with their intra-leukocytes levels (P value < 0.05). Notably, STARD4-AS1 was positively associated with the expression levels of its neighboring protein-coding gene (CAMK4 and STARD4) in leukocytes and were involved in pathways related to cellular response to DNA damage, which we further confirmed using DNA damage biomarker, 8-hydroxydeoxyguanosine. Functional analysis also revealed vital pathways related to cytokine-mediated signaling and glucose homeostasis. Our findings provided novel insights into plausible biological mechanisms underlying the adverse effects of PAHs exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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 (β [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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 FEV 1 , respectively, at baseline (all P < .05). After 3 years of follow up, 2HPMA was observed to be longitudinally associated with FEV 1 /FVC decline. No significant interaction effect of smoking or passive smoking was observed (P interaction > .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 FEV 1 (mediation proportion, 6.81%), and plasma protein carbonyl partially mediated the association between 2HPMA and FEV 1 (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., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The chemical - 1,3-butadiene (BD) is a volatile organic compound ubiquitous in the environment. However, the relationships and underlying mechanisms between BD exposure and glucose dyshomeostasis and diabetes in the general population remain unclear. We sought to explore the associations of BD exposure with glucose homeostasis, prediabetes, and diabetes, as well as the role of serum alkaline phosphatase (ALP) in these associations. This study included 5092 US general residents from the National Health and Nutrition Examination Survey with measurements of urinary BD metabolite (N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, DHBMA) and serum ALP. Glucose homeostasis was evaluated by fasting plasma glucose (FPG), fasting serum insulin (FINS), glycohemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). HOMA-IR>2.6 was considered as insulin resistance (IR). Prediabetes and diabetes were determined according to the recommendations of the American Diabetes Association. The associations of DHBMA with glucose homeostasis, prediabetes, and diabetes were assessed by linear regression models and logistic regression models. The mediating role of ALP was evaluated by mediation analysis. We observed positive dose-response relationships of DHBMA level with glucose homeostasis indices and ALP levels, as well as with the risks of prediabetes and diabetes (all P < 0.05 and/or P for trend <0.05). Each 2-fold increase in DHBMA was associated with a 1.32%, 9.20%, 0.72%, and 10.64% increase in FPG, FINS, HbA1c, and HOMA-IR, respectively (all P < 0.05). And the corresponding odds ratios (ORs) and 95% confidence intervals (CIs) for IR, prediabetes, and diabetes were 1.36 (1.14, 1.61), 1.51 (1.26, 1.83), and 1.20 (0.90, 1.61), respectively. Furthermore, increased ALP significantly mediated 15.29%-41.12% of the associations of DHBMA with glucose dyshomeostasis and increased risks of prediabetes and diabetes. Our findings indicated that BD exposure was associated with glucose dyshomeostasis and increased risks of prediabetes and diabetes. The upregulation of ALP might play a significant role in these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Silicosis is one of the most severe interstitial lung fibrosis diseases worldwide, caused by crystalline silica exposure. While the mechanisms and pathogenesis underlying silicosis remained unknown. N 6 -methyladenosine (m 6 A) methylation has received significant attention in a variety of human diseases. However, whether m 6 A methylation is involved in silicosis has not been clarified. In this study, we conducted methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and transcriptome sequencing (RNA-Seq) to profile the m 6 A modification in normal and silicosis mouse models (n = 3 pairs). The global levels of m 6 A methylation were further assessed by m 6 A RNA methylation quantification kits, and the major regulators of m 6 A RNA methylation were verified by qRT-PCR. Our results showed that long-term exposure to crystalline silica led to silicosis, accompanied by increasing levels of m 6 A methylation. Upregulation of METTL3 and downregulation of ALKBH5, FTO, YTHDF1, and YTHDF3 might contribute to aberrant m 6 A modification. Compared with controls, 359 genes showed differential m 6 A methylation peaks in silicosis (P < 0.05 and FC ≥ 2). Among them, 307 genes were hypermethylated, and 52 genes were hypomethylated. RNA-Seq analysis revealed 1091 differentially expressed genes between the two groups, 789 genes were upregulated and 302 genes were downregulated in the lungs of silicosis mice (P < 0.05 and FC ≥ 2). In the conjoint analysis of MeRIP-Seq and RNA-Seq, we identified that 18 genes showed significant changes in both m 6 A modification and mRNA expression. The functional analysis further noted that these 18 m 6 A-mediated mRNAs regulated pathways that were closely related to "phagosome", "antigen processing and presentation", and "apoptosis". All findings suggested that m 6 A methylation played an essential role in the formation of silicosis. Our discovery with multi-omics approaches not only gives clues for the epigenetic mechanisms underlying the pathogenesis of silicosis but also provides novel and viable strategies for the prevention and treatment of silicosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The effect of long-term PM 2.5 exposure on lung function has not been well established., Objectives: To investigate the effects of long-term personal PM 2.5 exposure on lung function decline, obstructive, and restrictive ventilatory disorders., Method: Personal PM 2.5 concentrations were evaluated using an estimation model. Lung function parameters including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ) and peak expiratory flow (PEF) were measured in 3053 Wuhan participants from the Wuhan-Zhuhai cohort and were repeated every 3 years. Participants were classified into persistently high exposure group, persistently low exposure group and inconsistent exposure group according to the median of PM 2.5 concentration of each visit. Mixed linear models with subject-specific random intercept were used to assess the association of 3-year change of lung function with personal PM 2.5 exposure, and generalized linear models were used to assess the association of 6-year change of lung function with personal PM 2.5 exposure. Cox regression models were applied to assess the associations of PM 2.5 with obstructive and restrictive ventilatory disorders., Results: The medians of personal PM 2.5 concentrations at baseline and two follow-ups were 153.18, 209.57 and 83.78 μg/m 3 , respectively. Compared with participants in the persistently low exposure group, participants in the persistently high exposure group showed a 2.99 % (95 % CI: 0.91, 5.08), a 380.15 mL/s (95 % CI: 32.82, 727.48) and a 5.98 % (95 % CI: 0.84, 11.11) additional decline in FEV 1 /FVC, PEF and PEFpred after 6 years, respectively. Stratified analyses showed that age, gender, body mass index, smoking status and drinking status had no significant modification effect on the associations. The associations of PM 2.5 exposure with obstructive and restrictive ventilatory disorders were not significant, except for a positive association between persistently high PM 2.5 exposure and restrictive ventilatory disorder among ever drinkers., Conclusion: Long-term high PM 2.5 exposure was associated with FEV 1 /FVC, PEF and PEFpred declines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Styrene and ethylbenzene (S/EB) are the monomers of polystyrene (PS) and polyethylene (PE), respectively, and have been identified as significant hazardous air pollutants by the U.S. Environmental Protection Agency. However, the adverse effects of S/EB on human health, especially cardiovascular health, have not been well established. Urinary biomarker of S/EB exposure and heart rate variability (HRV) were measured in urban adults from the Wuhan-Zhuhai cohort and were repeated after 3-year and 6-year follow-ups. Linear mixed models were used to estimate associations of S/EB exposure biomarker with HRV and longitudinal additional annual change of HRV. The mediating role of transforming growth factor (TGF)-β1 was tested by using mediation analysis. A total of 2842 general adults were included at baseline analysis, and 4748 observations were included in the repeated measurement study. In the cross-sectional analysis, each 1% increment in urinary S/EB exposure biomarker was significantly associated with a 0.106 % (95 % CI: -0.160, -0.052), 0.109 % (-0.169, -0.049), 0.099 % (-0.145, -0.053), 0.040 % (-0.060, -0.020), and 0.031 % (-0.054, -0.007) decrement in 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 interval, respectively. Smoking status modified the relationships of urinary S/EB exposure biomarker with TP and SDNN. TGF-β1 mediated 3.09-5.16 % of the association between urinary S/EB biomarker and lower HRV. The follow-up analyses detected a negative association between urinary S/EB exposure biomarker and the additional annual change of LF (β: -0.016; 95 % CI: -0.028, -0.004), HF (-0.014; -0.026, -0.001), and TP (-0.011; -0.021, -0.001). Our findings demonstrated that S/EB exposure was associated with HRV reduction among the general urban adults and the TGF-β pathway may play a part of the mediating role in this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To investigate the associations of arsenic exposure with lung function and ventilatory impairment. The repeated-measures study was developed with 8479 observations from three study periods of the Wuhan-Zhuhai cohort. Urinary arsenic and lung function were measured during each period. Linear mixed models were used to estimate the cross-sectional and longitudinal relationships between urinary arsenic and lung function. Logistic regression models and COX regression models were used to evaluate the cross-sectional and longitudinal associations between urinary arsenic and ventilatory impairment, respectively. In the cross-sectional analysis, each 1-unit increase in log-transformed urinary arsenic was associated with a -22.499 mL (95 % confidence interval (CI): -35.832 to -9.165), -15.081 mL (-25.205 to -4.957), and -0.274 % (-0.541 to -0.007) change in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC, respectively. In the longitudinal analysis, each 1-unit increase in log-transformed urinary arsenic was associated with an annual change rate of -6.240 mL/year (95 % CI: -12.429 to -0.051), -5.855 mL/year (-10.632 to -1.079), and -0.143 %/year (-0.234 to -0.051) in FVC, FEV1, and FEV1/FVC, respectively. Stratified analyses suggested a modification role of gender on the cross-sectional and longitudinal associations between urinary arsenic and FEV1, with the stronger associations were found among males (P for modification 0.0384 and 0.0168). Furtherly, each 1-unit increase in log-transformed urinary arsenic was associated with a 14.8 % (odds ratio 1.148, 95 % CI: 1.043 to 1.263) and 11.7 % (hazard ratio 1.117, 95 % CI: 1.023 to 1.218) increase in the prevalent and incident risk of restrictive ventilatory impairment, respectively. Source analyses suggested that fish intake and fine particulate matter inhalation positively associated with the total arsenic levels. In conclusion, arsenic exposure was associated with lung function decline and the risk of restrictive ventilatory impairment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Wnt5a is a key mediator of non-canonical Wnt signaling, and an early indicator of epithelial injury and lung dysfunction. Polycyclic aromatic hydrocarbons (PAHs) could induce acute pulmonary pathogenesis, of which the underlying mechanism remains unclear. To elucidate the potential role of Wnt5a-mediated non-canonical Wnt-YAP/TAZ signaling in the lung injury induced by short-term exposure of benzo(a)pyrene (BaP, a representative PAHs), intratracheally instilled mouse model was used and further interfered with its Wnt5a level by small molecule antagonists and agonists. Our data revealed that BaP exposure induced the lung inflammatory response and reduced the expression of Clara cell secretory protein (CC16) in a dose-dependent manner. More importantly, the activation of Wnt5a and downstream YAP/TAZ were accompanied with the enhanced release of epithelial-derived thymic stromal lymphopoietin and interleukin-33, which acted as pro-inflammatory cytokines. Functionally, inhibition of Wnt5a attenuated the BaP-induced inflammation and recuperated CC16 expression, as well as suppressed the epithelial cytokines release. Whereas promoting Wnt5a expression affected the toxic effects of BaP oppositely. Our findings together suggest that Wnt5a is a potential endogenous regulator in lung inflammation and airway epithelial injury, and Wnt5a-YAP/TAZ signaling contributes to lung dysfunction in acute exposure to BaP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Environmental exposure to silica or particles is very common in natural, agricultural and industrial activities. Chronic silica exposure can lead to silicosis, which remains one of the most serious interstitial lung diseases all through the world, while viable therapeutic choices are restricted. Triiodothyronine (T3) has been shown to exert a defensive role in many pulmonary diseases, however, rare data are available regarding the role of T3 on silica-induced injury. We constructed an experimental silicosis mouse model and T3 was intraperitoneally administrated after instillation of silica to observe the effect of T3 on silica-induced lung inflammation and fibrosis. Our results showed that the silicosis mouse model was accompanied by changes in thyroid morphology and function, and T3 supplement reduced silica-induced lung damage, inflammation and collagen deposition. The protective properties of T3 on silica-induced lung injury could be partially mediated through thyroid hormone receptors. And the mechanism by which T3 treatment ameliorated silica-induced fibrosis appeared to be via the reduction of glycolysis. Also, T3 could sufficiently postpone the progression of pulmonary fibrosis in established silicosis. Our findings reveal that administration of T3 could down-regulate the inflammatory response, pulmonary fibrosis and other lung damage caused by silica. The reduction of glycolysis may be one of the mechanisms., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Heavy metal exposures have been reported to be associated with increased risk for liver injury. However, the potential mechanisms of the association remain unclear. A repeated-measure study of 9367 observations was conducted to quantify the associations of urinary heavy metals with serum alanine aminotransferase (ALT), a biomarker for liver injury, and assess the mediating role of systemic inflammation in such associations among general Chinese adults. In single-metal models, positive dose-response relationships between urinary vanadium (V), chromium (Cr), copper (Cu), arsenic (As), cadmium (Cd), tungsten (W), and lead (Pb) and serum ALT were observed. In the multiple-metal model containing the seven metals mentioned above, V and Cu remained positively associated with ALT. In longitudinal analyses of 3-6 years, each 1-unit increase in log-transformed levels of V and Cu was associated with an additional rate of annual ALT increase (95% CI) for 1.3% (0.7-1.8%) and 1.3% (0.7-2.0%), respectively. Plasma CRP concentrations were not only positively associated with urinary Cu and Cd, but also positively related with ALT. Furthermore, mediation analyses showed that CRP mediated 4.70% and 7.03% of urinary Cu- and Cd-associated ALT elevations. Our study provides clues for the prevention of heavy metal-induced liver injury., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acrylamide exposure along with resultant potential adverse health effects have attracted global concern, and the World Health Organization calls for more and urgent studies on the health risks from acrylamide. However, the association and mechanism between acrylamide exposure and pulmonary dysfunction remain unclear. Our goals were to investigate the relationship of internal acrylamide exposure with lung function reduction, and the potential mediating role of systematic inflammation in that relationship. Our study was conducted within the Wuhan-Zhuhai cohort. Urinary biomarkers of acrylamide exposure (N-acetyl-S-(2-carbamoylethyl)-l-cysteine, AAMA; N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine, GAMA) and lung function were determined among 3271 general adults, of whom 2595 had test results of systemic inflammatory marker plasma C-reactive protein (CRP). We employed linear mixed models to assess the relations among urinary acrylamide metabolites, pulmonary function and plasma CRP, and PRODCLIN program to evaluate the mediating role of CRP. We observed that urinary acrylamide metabolites were inversely and dose-dependently related to lung function (P trend<0.05). Each 1-unit increment in log-transformed level of AAMA, GAMA, or AAMA+GAMA (ΣUAAM) was significantly (P < 0.05) related to a 59.9-, 64.2-, or 64.3-mL reduction in FVC, and a 53.9-, 59.7-, or 58.5-mL reduction in FEV 1 , respectively. Such relationships were independent of smoking, and were significant in physically inactive rather than physically active participants. AAMA (β = 0.10), GAMA (β = 0.16) and ΣUAAM (β = 0.12) were significantly (P < 0.05) related to increased CRP, which was significantly (P < 0.05) related to reduced FVC (β = -55.3) and FEV 1 (β = -40.6). We further found that increased CRP significantly (P < 0.05) mediated 6.34-11.1% of the urinary acrylamide metabolites-associated lung function reductions. For the first time, our findings suggested that exposure to acrylamide in daily life was related to reduced lung function and increased systemic inflammation in general population, and systemic inflammation further mediated acrylamide-associated lung function reduction, indicating a potential mechanistic role of systemic inflammation underlying pulmonary dysfunction from acrylamide exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Short-term effects of fine particulate matter (PM 2.5 ) exposure on lung function have been reported. However, few studies have assessed PM 2.5 exposure on the personal level, and the mechanism underlying the effects of PM 2.5 exposure on lung function remains less clear., Objectives: To evaluate the association between personal PM 2.5 exposure and lung function alteration in general population and to explore the roles of systematic inflammation and oxidative damage in this association., Methods: A total of 7685 lung function tests were completed among 4697 urban adults in Wuhan, China. Plasma C-reactive protein (CRP), urinary 8-iso-prostaglandin-F 2α (8-iso-PGF 2α ) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured. Personal PM 2.5 exposure levels were estimated using an estimation model from the actual measurements of individual PM 2.5 levels in 191 participants. Mixed linear models were used to evaluate the association between personal PM 2.5 exposure and lung function. Mediation analyses were conducted to investigate the roles of CRP, 8-iso-PGF 2α and 8-OHdG in above associations., Results: After adjusting for confounders, each 10 μg/m 3 increase in the previous-day personal PM 2.5 exposure was associated with 2.94 mL, 2.02 mL and 16.14 mL/s decreases in forced vital capacity (FVC), forced expiration volume in 1 s (FEV 1 ) and peak expiratory flow, respectively. The associations were more obvious among never smokers compared with current smokers. Cumulative 7-day exposure to PM 2.5 led to the strongest adverse effects on lung function. Among never smokers with high PM 2.5 exposure levels, a positive relationship was observed between personal PM 2.5 level and urinary 8-iso-PGF 2α , and 8-iso-PGF 2α meditated 4.69% and 12.30% of the association between the 7-day moving PM 2.5 concentration and FVC and FEV 1 , respectively. We did not observe a significant positive association between PM 2.5 exposure and plasma CRP or urinary 8-OHdG., Conclusion: Short-term personal exposure to PM 2.5 is associated with reduced pulmonary ventilation function. Urinary 8-iso-PGF 2α partly mediates these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published evidences have shown that autophagy plays an important role in silica-induced lung inflammation and collagen deposition. Our previous study found that the level of growth arrest-specific protein 6 (Gas6) in bronchoalveolar lavage fluid was increased after silica exposure. However, it is unclear whether Gas6 is involved in the regulation of silica-induced autophagy dysfunction. In this study, we observed an autophagosomes accumulation in wild-type C57BL/6 (WT) mice lung after silica intratracheal instillation and then investigated whether genetic loss of Gas6 (Gas6 -/- ) could ameliorate it. Our data showed that Gas6 -/- mice exhibited a limited autophagosomes accumulation from days 7-84 after silica exposure, revealed by reduced induction and increased degradation of autophagosomes in mice lung tissue. Interestingly, silica particles could elevate the expression of Mer receptor, which was significantly decreased in Gas6 -/- mice (P < 0.05). Furthermore, we found that Mer deficiency (Mer -/- ) could also reduce the formation of autophagosomes and restore the function of impaired lysosomes in silica-treated mice. Taken together, our results indicate that genetic loss of Gas6 attenuates silica-induced autophagosomes accumulation partly through down-regulating the expression of Mer receptor. Targeting Gas6/Mer-mediated autophagy pathway may provide a novel insight into the prevention and therapy of silica-induced pulmonary fibrosis., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previous studies found that exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with type 2 diabetes (T2D) prevalence. However, the potential mechanism is still unclear. In this study, we investigated 3031 Chinese urban adults to discover the relationship between PAH exposure and plasma Interleukin-22 (IL-22) and potential role of IL-22 in the association between PAH and fasting plasma glucose (FPG) or risk of T2D. After adjustment for potential confounders, significant dose-response relationships were observed between several urinary PAH metabolites with FPG and the prevalence of T2D. Each 1-U increase in ln-transformed value of 2-hydroxynaphthalene (2-OHNa), 2-hydroxyphenanthrene (2-OHPh), 3-hydroxyphenanthrene (3-OHPh), 4-hydroxyphenanthrene (4-OHPh), 9-hydroxyphenanthrene (9-OHPh), 1-hydroxypyrene (1-OHP) or total PAH metabolites was significantly associated with a 0.053, 0.026, 0.037, 0.045, 0.051, 0.041 or 0.047 unit decrease in IL-22 level, respectively. In addition, plasma IL-22 level was negatively associated with FPG and prevalence of T2D in a dose-dependent manner. Mediation analysis showed that IL-22 mediated 8.48 %, 3.87 %, 6.64 %, 6.47 %, and 8.67 % of the associations between urinary 2-OHNa, 1-OHPh, 3-OHPh, 4-OHPh, and 9-OHPh with the prevalence of T2D, respectively. These results indicated that urinary PAHs metabolites were inversely associated with plasma levels of IL-22, but positively related to FPG and the T2D prevalence. Downregulation of IL-22 might play a significant role in mediating PAHs exposure-associated risk increasement of T2D., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Limited information is available about the bio-methylation of inorganic mercury (iHg) under aerobic conditions. In this study, two γ-proteobacteria strains (P. fluorescens TGR-B2 and P. putida TGR-B4) were obtained from the soil of The Three Gorges Reservoir (TGR), demonstrating effective aerobic transformation capacities of iHg into methylmercury (MeHg). Based on periodical changes in soil oxygen content of the TGR, a culture system was established, in which 300 ng Hg (II) L -1 and O 2 were set at 7%, 14%, and 21%, respectively. Results indicated that the two strains differed significantly in bacterial growth rate and MeHg production. The kinetic model of MeHg showed typical characteristics of a "two-staged" process: The first stage was dominated by bio-methylation, which was shown by increasing of net MeHg content. Moreover, the second stage was dominated by bio-demethylation, which decreased net MeHg content. Thus, we hypothesized that the mechanism of aerobic bacterial iHg bio-methylation: (1) should inefficiency compared to anaerobic bacteria i.e.SRB, which were regulated by hgcA/B gene clusters, (2) might be regarded as a passive stress response and depended on the bacterial iHg intoxication threshold and MeHg tolerance threshold., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: 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., Objective: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Little is known about the different risk of silicosis in metal mines and pottery factories. We aimed to compare the silicosis risks among silica-exposed workers in different industrial circumstances., Research Question: Are the silicosis risks among silica-exposed workers in industrial circumstances different?, Study Design and Methods: We studied 39,808 workers followed up from January 1, 1960 to December 31, 2003 in China. Cumulative respirable silica dust exposure (CDE) was estimated by linking a job-exposure matrix to personal work history. Silicosis of stage I or higher was diagnosed by Chinese pneumoconiosis Roentgen diagnostic criteria., Results: A total of 9,377 silicosis patients were diagnosed during 1,153,580.9 person-years' follow-up in the cohort. Hazard ratios of silicosis for each 1 mg/m 3 -year increase in CDE were 1.08 (1.07-1.08) for tungsten mines, 1.41 (1.33-1.48) for iron and copper mines, 1.14 (1.11-1.17) for tin mines, and 1.03 (1.02-1.04) for pottery factories, respectively. When exposed to 0.05 mg/m 3 of respirable silica dust for 45 years, the cumulative risks in metal mines (2.3%, 9.9%, 1.5% for tungsten mines, iron and copper mines, and tin mines, respectively) were still higher than those in pottery factories (0.6%). The joint effect of silica and smoking on silicosis was more than multiplicative., Interpretation: The risk of silicosis in metal miners is higher than that in pottery workers when exposed to the same level of silica dust. The silica dust exposed years should be under 10 years for metal miners and 40 years for pottery workers at 0.05 mg/m 3 to keep lifetime risk within 0.1%. Current exposure limits should take into account differences in various industrial circumstances. Smoking cessation could help reduce silicosis risk for silica-exposed workers., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest All authors declare they have no actual or potential competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Dimethylformamide (DMF) is a volatile organic compound listed as one of the four toxicants with the highest priority for human field study. However, the effect of DMF exposure on lung function and the underlying mechanisms remain unknown. We aimed to investigate the exposure-response relationship and possible mechanism between internal DMF exposure and lung function alteration. We studied 3701 Chinese adults from the Wuhan-Zhuhai cohort with a 3-year follow-up. The cross-sectional relationship between urinary biomarker of DMF exposure (N-Acetyl-S-(N-methylcarbamoyl)-L-cysteine, AMCC) and lung function, and the mediating role of plasma C-reactive protein (CRP) were assessed. We also convened a sub-cohort (N = 138) to assess the stability of AMCC in repeated urine samples collected for continuous 3 days and intervals of 1, 2 and 3 years. The longitudinal association between AMCC and lung function change in 3 years was further assessed. We found a dose-response relationship between AMCC and lung function reduction. Each 2-fold increase in AMCC was cross-sectionally associated with a 23.12-mL (95% CI: -36.68, -9.55) decrease in FVC and a 19.01-mL (95% CI: -31.08, -6.93) decrease in FEV 1 . Increased CRP significantly mediated 5.39% and 5.87% of the AMCC-associated FVC and FEV 1 reductions, respectively. With 3-year follow-up, AMCC showed a fair to excellent stability (intra-class correlation coefficients were 0.88, 0.55, 0.60 and 0.50 for continuous 3 days, intervals of 1, 2 and 3 years, respectively) and was dose-dependently associated with longitudinal lung function decline. Compared with those with persistent low AMCC levels, participants with persistent high AMCC levels had a 101.09-mL/year (95% CI: -167.40, -34.77) decline in FVC and a 66.27-mL/year (95% CI: -114.14, -18.41) decline in FEV 1 in the sub-cohort. Similar results were found in the full-cohort. Our findings suggest that exposure of general population to environmental DMF may impair lung function, and systematic inflammation may be an underlying mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Exposure to fine particulate matter (PM 2.5 ) have been associated with adverse respiratory outcomes, but long-term effect of personal exposure on lung function remains largely unknown. We conducted a panel study of 158 adult residents with 394 measurements of personal PM 2.5 concentration and lung function within six years to investigate the long-term association. Linear mixed models were used to identify the associations between lung function changes in relation to different levels of persistent personal PM 2.5 exposure in three or six years. We further attempted to validate resident areas (city) and smoking status as potential predictors of the long-term PM 2.5 exposure levels (persistently high/ persistently low) by generating ROC curves. Compared with subjects who had persistently low exposure level, those with persistently high levels of personal PM 2.5 exposure had an additional 3.63 % decline in FEV 1 /FVC in three years (-3.63 [-7.25, -0.02]), while 7.15 % decline in six years (-7.15 [-14.27, -0.03]). BMI can modify the association. The AUCs were 0.68 (95 %CI: 0.54, 0.82), 0.75 (0.64, 0.86), and 0.82 (0.71, 0.93) for models including smoking status, resident areas, and smoking status combining resident areas respectively. These findings provide new evidence for the long-term effect of personal PM 2.5 exposure on lung function decline., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Silicosis is an inflammatory and fibrotic lung disease caused by prolonged inhalation of silica. The potential role of high-mobility group box-1 (HMGB-1) and its underlying mechanisms in silicosis remain unclear. In this study, intratracheal instillation of a silica suspension was used to establish silicosis in male C57BL/6 mice. To elucidate the effects of HMGB-1 on the pathogenesis of silicosis, we used HMGB-1 neutralizing antibody (anti-HMGB-1) and recombinant HMGB-1 (rmHMGB-1) to abrogate or increase the HMGB-1 levels, respectively. At days 7, 28, and 84, the accumulation of macrophages and neutrophils decreased by anti-HMGB-1 treatment. The expression levels of interleukin-6 and tumor necrosis factor-α in lung increased in response to silica exposure across three time points; anti-HMGB-1 could alleviate those expressions at day 28 and 84. In contrast, rmHMGB-1 aggravated this process. At days 28 and 84, the protein expression of fibronectin and col1a1 decreased in the silica + anti-HMGB-1 groups but increased in silica + rmHMGB-1 groups compared to mice with silica alone. Further study suggested that HMGB-1-mediated epithelial-mesenchymal transition participated in the development of silicosis. In conclusion, the findings demonstrate that HMGB-1 participates in the pathogenesis of silicosis and may represent a potential therapeutic target for the treatment of silicosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Long-term inhalation of crystalline silica particles leads to silicosis characterized by pulmonary inflammation and interstitial fibrosis. The growth arrest-specific protein 6 (Gas6) and its tyrosine receptor Mer have been implicated to involve in the regulation of inflammation, innate immunity and tissue repair. However, the role of Gas6 or Mer in silica-induced lung inflammation and fibrosis has not been investigated previously. In this study, we observed a remarkable increase of Gas6 in bronchoalveolar lavage fluid (BALF) from wild-type C57BL/6 mice after silica intratracheal administration. Then, we investigated whether genetic loss of Gas6 or Mer could attenuate silica-induced lung inflammation and fibrosis. Our results showed that Gas6 -/- and Mer -/- mice exhibited reduced lung inflammation response from days 7 to 84 after silica exposure. We also uncovered an overexpression of the suppressor of cytokine signaling protein 1 in silica-treated deficient mice. Moreover, Gas6 or Mer deficiency attenuated silica-induced collagen deposition by inhibiting the expression of transforming growth factor-β. We conclude that gene absence of Gas6 or Mer is protective against silica-induced lung inflammation and fibrosis in mice. Targeting Gas6/Mer pathway may be a potential therapeutic approach to treat pulmonary fibrosis in patients with silicosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fine particulate matter (PM 2.5 ) exposure has been associated with lung function decline, but impact of PM 2.5 constituents especially for polycyclic aromatic hydrocarbons (PAHs) on lung function is unclear among community population. We enrolled 224 Chinese participants who participated in two study periods (2014-2015 and 2017-2018) of the Wuhan-Zhuhai cohort as a panel, and quantified the associations of personal PM 2.5 and sixteen PM 2.5 -bound PAHs with lung function levels as well as lung function change in three years by linear mixed models. Diagnostic ratios were calculated to identify potential sources of PM 2.5 -bound PAHs in Wuhan and Zhuhai separately. In single-constituent models, we found that each one interquartile-range increase of naphthalene, acenaphthene, fluoranthene and pyrene were associated with 26.82, 60.99, 45.25 and 23.37 mL decline in FVC respectively; while fluoranthene and pyrene were associated with 27.43 and 15.49 mL decline in FEV 1 respectively. Similar results were observed in consitituent-PM 2.5 joint models and single-constituent residual models. Persistently long-term high levels of three HMW-PAHs (benzo[a]anthracene, dibenzo[a,h]anthracene, and benzo[ghi]perylene) were associated with 214.65, 226.13, and 265.00 mL decline in FVC decline in three years, compared with persistently low exposure level groups. The associations were different between Wuhan and Zhuhai. The results of diagnostic ratios suggested the differences in PAH emissions between two cities. Our findings provide evidence that both short- and long-term PM 2.5 -bound PAH exposures might affect lung function., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pulmonary fibrosis induced by prolonged exposure to silica particles is a chronic and irreversible lung disease without effective treatment till now. Our previous study has shown that early intervention with MARCO antagonist PolyG could alleviate pulmonary fibrosis in silica-exposed rats. However, the therapeutic effects of PolyG on silica-induced pulmonary fibrosis have rarely been reported. In this study, we explored the effects of administration (on the 28th day after silica exposure) of PolyG (MARCO inhibitor) on an established rat silicosis model. The lungs were analyzed histopathologically in rats using HE and Masson staining. The silica-induced ERS-related apoptosis, EMT and fibrosis were evaluated using western blotting, qRT-PCR and immunohistochemical analyses. The results suggested that silica exposure could increase the MARCO activity, and induce ERS and EMT in lung tissues. Pharmacological targeting of MARCO with PolyG attenuated the development of pulmonary fibrosis in silica-exposed rats. Further study indicated that PolyG could inhibit silica-induced ERS-related apoptosis and EMT process. Together, our findings reveal an essential function of ERS-related apoptosis and EMT in the processes of pulmonary fibrosis caused by silica, and identify MARCO as a potential therapeutic pharmacological target for silicosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Central obesity and polycyclic aromatic hydrocarbons (PAHs) exposure were reported as independent risk factors for lung function decline. However, the interaction between central obesity and PAHs exposure on lung function is still unclear., Objectives: To evaluate the impact of central obesity, urinary polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and their combined effects on lung function in general population., Methods: Lung function and urinary OH-PAHs were measured for 3,749 participants from the Wuhan-Zhuhai cohort. Central obesity was evaluated by waist-to-hip ratio. Generalized linear regression was used to estimate combined effect of central obesity and OH-PAHs on lung function., Results: Compared with participants without central obesity and with low urinary total OH-PAHs (∑OH-PAHs) level, those with central obesity and high urinary ∑OH-PAHs level had 59.4 mL and 61.0 mL reductions for forced vital capacity (FVC) and forced expiratory volume in 1s (FEV 1 ), respectively (P < 0.05). The reductions were more evident in smokers and males. Additive interactions between central obesity and urinary ∑OH-PAHs on lung function were observed, especially on FEV 1 (P < 0.05). Each 1-unit increase in log-transformed value of ∑OH-PAHs was associated with -34.4 ml (95% confidence interval [CI]: -66.9, -1.8) and -34.8 mL (-61.1, -8.5) changes in FVC and FEV 1 among those without central obesity, while -21.4 ml (-49.9, 7.1) and -19.7 ml (-43.4, 4.0) changes among those with central obesity., Conclusion: Polycyclic aromatic hydrocarbons exposure has combined effect with central obesity on lung function parameters., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with increased risk of diabetes, whereas socioeconomic status (SES) may contribute to the development of diabetes. However, the mechanisms underlying the relationships between them are unclear. We used structural equation modeling (SEM) to identify mediating factors in the associations of PAHs exposure, low SES with diabetes risk. Data were collected from 2751 Wuhan participants at baseline from the Wuhan-Zhuhai Cohort Study (n = 3053). They answered the questionnaires regarding socio-demographic, participated physical examinations and provided urine samples for measurements of urinary monohydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) levels. SEM was used to identify the mediating factors (such as hypertension, body mass index (BMI), triglycerides (TG) and total cholesterol (TCHO)) in the associations of low SES or PAHs exposure with diabetes risk. We observed that partial effect of PAHs exposure (β = 0.281, p = 0.034), BMI (β = 0.182, p = 0.000), TG (β = 0.358, p = 0.000), TCHO (β = 0.203, p = 0.009) or hypertension (β = 0.385, p = 0.000) on diabetes was directive. Moreover, low SES also exhibited a directive effect on PAHs exposure (β = -0.084, p = 0.000), BMI (β = 0.301, p = 0.000), hypertension (β = 0.134, p = 0.003) and TG (β = 0.087, p = 0.001). PAHs exposure directly affected TCHO levels (β = 0.080, p = 0.002) and TG (β = 0.076, p = 0.017). The proportion of the effect of PAHs exposure on diabetes mediated by TG and TCHO was 15.6%. The proportion of the effect of low SES on diabetes mediated by BMI, hypertension and TG was 89.1%. The results suggested that low SES increased diabetes risk, which may be partially explained by BMI, hypertension and triglycerides, and exposure to high levels of PAHs may have indirect contribution to increased risk for diabetes with dyslipidemia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The relation between nonalcoholic fatty liver disease (NAFLD) and hypertension is not fully understood. To examine the effect of the change in NAFLD status on the risk of incident hypertension, and vice versa, 6704 eligible hypertension-free subjects and 9328 NAFLD-free subjects from the Dongfeng-Tongji cohort study at baseline were enrolled in the study. Among the hypertension-free subjects, development and persistence of NAFLD were associated with an increased odds ratio (OR) for incident hypertension (OR: 1.49, 95% confidence interval [CI]: 1.26-1.76, P < .0001; OR: 1.50, 95% CI: 1.27-1.78, P < .0001). However, the resolution of NAFLD was not a risk factor for incident hypertension. Among the NAFLD-free subjects, the risk of new-emerging NAFLD was robust for hypertension status both in no-yes (OR: 1.45, CI: 1.23-1.71) and yes-yes (OR: 1.61, CI: 1.35-1.92). Moreover, stratified analysis by diabetes and overweight/obese for the risk of incident NAFLD showed that incident hypertension (no-yes) and persistent hypertension (yes-yes) were associated with risk of incident NAFLD in subjects without diabetes or overweight/obesity. In the overweight/obese participants, persistent hypertension (yes-yes) was a risk factor for incident NAFLD (OR: 1.29, 95% CI: 1.01-1.64, P = .0387). Conclusively, incidence and persistence of NAFLD are associated with increased risk of hypertension, and vice versa., (Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.)

Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose ≥7.0mmol/L. Concentrations of urinary metals and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17-3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value<0.05). Our findings suggested that urinary arsenic and antimony concentrations were associated with an increased prevalence of T2DM by a mechanism partly involving oxidative DNA damage., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: The association between hearing loss and coronary heart disease (CHD) is inconsistent. We aimed to investigate the association of hearing loss with prevalent CHD and CHD-related biomarkers among a middle aged and elderly Chinese population., Methods: We included 14,755 Chinese aged 64.6 years from the Dongfeng-Tongji Cohort in 2013. Hearing loss was classified into normal, mild, moderate or greater levels by the pure tone average (PTA) at low frequency and high frequency, respectively. Logistic regression models were used to estimate the odds ratios (ORs) of CHD risk in relation to hearing loss. Linear regression models were used to evaluate the effect of hearing loss on CHD-related biomarkers., Results: The adjusted ORs for prevalent CHD increased gradually with the increasing hearing loss levels. Compared with normal hearing, individuals having mild- and moderate or greater-hearing loss had a higher CHD risk of 19% and 20% at low frequency, and 33% and 41% at high frequency, respectively (all p for trend < 0.05). The associations were more evident among subjects who were females, overweight, exposed to occupational noise and with hyperglycemia, hypertension or dyslipidemia at low frequency, and those with hyperglycemia at high frequency. Meanwhile, moderate or greater hearing loss combined with overweight, hyperglycemia, hypertension or dyslipidemia had joint effects on CHD. In addition, the majority of CHD-related biomarkers worsened with increasing hearing loss levels., Conclusions: There may be a dose-response relationship between hearing loss and CHD prevalence, and the association could partially be explained by intermediate CHD-related biomarkers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Exposure to Polycyclic aromatic hydrocarbons (PAHs) has been associated with inflammatory responses. Fractional exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) are both important inflammatory mediators especially in airways. However, few studies have investigated associations of PAH exposures with FeNO or eCO. Therefore, we aimed to quantify the associations of urinary PAH metabolites with FeNO and eCO levels, and investigate their potential effect modifiers by linear mixed models among 4133 participants from the Wuhan-Zhuhai cohort in China. We further performed stratified analyses to estimate effect modification. We found significant associations of increased urinary PAH metabolites with elevated eCO and FeNO. Among all participants, each 1% increase of 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 3-hydroxyphenanthrene, and total PAH metabolites was significantly associated with a 12.6% (95% confidence interval: 9.3%, 15.9%), 9.7% (6.5%, 12.9%), 7.5% (4.1%, 10.9%), 3.2% (0.2%, 6.2%), 2.7% (0.1%, 5.3%), and 6.5% (2.7%, 10.4%) increased eCO level, respectively; while each 1% increase of urinary 1-hydroxynaphthalene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 2-hydroxyphenanthrene was associated with a -3.0% (-5.8%, -0.2%), 2.9% (0.3%, 5.6%), 3.2% (1.0%, 5.4%), and 4.5% (2.2%, 6.9%) change of FeNO level, respectively. Positive associations between certain urinary PAH metabolites and eCO were observed among both ever-smokers and non-smokers, and the associations were stronger among ever-smokers than that among non-smokers. Increased urinary PAH metabolites were associated with decreased FeNO among ever-smokers and elevated FeNO levels among non-smokers. Our findings suggest that PAH exposures may impair airway through inducing inflammatory response, especially among ever-smokers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The association between occupational noise exposure and hypertension is unclear. We aimed to explore the association in a Chinese population and to summarize our findings with previous published articles. The cross-sectional study included 22,450 participants from Dongfeng-Tongji Cohort Study. In a subsample of 10,636 subjects, we assessed the association between hearing loss and hypertension. For the meta-analysis, we searched PubMed and EMBASE until April 2017, and the pooled odds ratio (OR) was combined using a random effect model. Compared with participants without occupational noise exposure, the risk of hypertension was significantly higher for noise exposure duration ≥20 (OR = 1.09, 95% confidence interval [CI] = 1.00-1.18). In the sex-specific analysis, the association was only significantly pronounced in males (OR = 1.16, 95% CI = 1.03-1.31), but not in females (OR = 1.01, 95% CI = 0.88-1.14). In the subsample analyses, hearing loss, which was an indicator for exposure to loud noise, was associated with a higher risk of hypertension, especially for participants who were bilateral hearing loss (OR = 1.39, 95% CI = 1.24-1.54). In the meta-analysis, the pooled OR for the association between occupational noise exposure and hypertension was 1.25 (95% CI = 1.10-1.42). On the basis of an indicator for exposure to occupational noise, the cross-sectional study and meta-analysis identified occupational noise exposure as a potential risk factor for increased hypertension risk., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)