Exposure to volatile organic compounds and mortality in US adults: A population-based prospective cohort study.

Volatile organic compounds (VOCs) are ubiquitous in both indoor and outdoor environments. Evidence on the associations of individual and joint VOC exposure with all-cause and cause-specific mortality is limited. Measurements of 15 urinary VOC metabolites were available to estimate exposure to 12 VOCs in the National Health and Nutritional Examination Survey (NHANES) 2005-2006 and 2011-2018. The environment risk score (ERS) was calculated using LASSO regression to reflect joint exposure to VOCs. Follow-up data on death were obtained from the NHANES Public-Use Linked Mortality File through December 31, 2019. Cox proportional hazard models and restricted cubic spline models were applied to evaluate the associations of individual and joint VOC exposures with all-cause and cause-specific mortality. Population attributable fractions were calculated to assess the death burden attributable to VOC exposure. During a median follow-up of 6.17 years, 734 (8.34 %) deaths occurred among 8799 adults. Urinary metabolites of acrolein, acrylonitrile, 1,3-butadiene, and ethylbenzene/styrene were significantly associated with all-cause, cardiovascular disease (CVD), respiratory disease (RD), and cancer mortality in a linear dose-response manner. Linear and robust dose-response relationships were also observed between ERS and all-cause and cause-specific mortality. Each 1-unit increase in ERS was associated with a 33.6 %, 39.1 %, 109.8 %, and 67.8 % increase for all-cause, CVD, RD, and cancer mortality risk, respectively. Moreover, joint exposure to VOCs contributed to 17.95 % of all-cause deaths, 13.49 % of CVD deaths, 35.65 % of RD deaths, and 33.85 % of cancer deaths. Individual and joint exposure to VOCs may enhance the risk of all-cause and cause-specific mortality. Reducing exposure to VOCs may alleviate the all-cause and cause-specific death burden.

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

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

Daily folate consumption is associated with reduced all-cause and cardiovascular disease mortality among US adults with diabetes, prediabetes, or insulin resistance.

We hypothesized that daily folate consumption may have a beneficial effect on mortality among adults with dysglycemia. This prospective cohort study was conducted on 9266, 12,601, and 16,025 US adults with diabetes, prediabetes, and insulin resistance (IR; homeostasis model assessment of IR >2.6), respectively, from the National Health and Nutrition Examination Survey Ⅲ and 1999-2018. Daily folate consumption was obtained from dietary recall. All-cause, cardiovascular disease (CVD), and cancer mortality were obtained by linking to the National Death Index Mortality Data. During 117,746.00, 158,129.30, and 210,896.80 person-years of follow-up, 3356 (1053 CVD and 672 cancer), 3796 (1117 CVD and 854 cancer), and 4340 (1286 CVD and 928 cancer) deaths occurred among participants with diabetes, prediabetes, and IR, respectively. After multivariate adjustment, each 1-unit increase in ln-transformed daily folate consumption was linearly associated with 7.1% (hazard ratio [HR], 0.929; 95% confidence interval [CI], 0.914-0.945), 12.4% (HR, 0.886; 95% CI, 0.860-0.912), and 6.4% (HR, 0.936; 95% CI, 0.903-0.972) decreases in risk of all-cause, CVD, and cancer mortality, respectively, among participants with diabetes. Among participants with prediabetes, each 1-unit increase in ln-transformed daily folate consumption was linearly associated with 3.6% (HR, 0.964; 95% CI, 0.949-0.980), 7.8% (HR, 0.922; 95% CI, 0.895-0.949), and 3.6% (HR, 0.964; 95% CI, 0.932-0.997) decreases in risk of all-cause, CVD, and cancer mortality, respectively. Among participants with IR, each 1-unit increase in ln-transformed daily folate consumption was linearly associated with 5.7% (HR, 0.943; 95% CI, 0.929-0.956) and 9.0% (HR, 0.910; 95% CI, 0.885-0.933) decreases in risk of all-cause and CVD mortality, respectively. Increased daily folate consumption may be beneficial in reducing all-cause and CVD mortality of adults with dysglycemia. More research is needed to explore the underlying mechanisms.

Associations of urinary 1,3-butadiene metabolite with glucose homeostasis, prediabetes, and diabetes in the US general population: Role of alkaline phosphatase.

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.

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

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

Acrylamide exposure increases cardiovascular risk of general adult population probably by inducing oxidative stress, inflammation, and TGF-ß1: A prospective cohort study.

Acrylamide (ACR) exposure and consequent health hazards are alarming public health issues that attract worldwide concern. The World Health Organization urges more researches into health hazards from ACR exposure. However, whether and how ACR exposure increases cardiovascular risk remain unclear, and we sought to address these issues in this prospective cohort study conducted on 3024 general adults with 3-year follow-up (N = 871 at follow-up). Individual urinary ACR metabolites (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) as credible biomarkers of ACR exposure were detected to assess their cross-sectional and longitudinal relationships with 10-year cardiovascular disease (CVD) risk, a well measure of overall cardiovascular risk. Besides, biomarkers of oxidative stress (urinary 8-hydroxy-deoxyguanosine [8-OHdG] and 8-iso-prostaglandin-F2α [8-iso-PGF2α]) and inflammation (circulating mean platelet volume [MPV] and plasma C-reactive protein [CRP]) as well as plasma transforming growth factor-ß1 (TGF-ß1) were measured to assess their mediating/mechanistic roles in the relationships of ACR metabolites with 10-year CVD risk. We found AAMA, GAMA, and ΣUAAM (AAMA + GAMA) were cross-sectionally and longitudinally related to increased 10-year CVD risk with odds ratios (95% confidence intervals [CIs]) of 1.32 (1.04, 1.70), 1.81 (1.36, 2.40), and 1.40 (1.07, 1.82), respectively, and risk ratios (95% CIs) of 1.99 (1.10, 3.60), 2.48 (1.27, 4.86), and 2.13 (1.15, 3.94), respectively. Furthermore, 8-OHdG, 8-iso-PGF2α, MPV, CRP, and TGF-ß1 were found to significantly mediate 8.06-48.92% of the ACR metabolites-associated 10-year CVD risk increment. In summary, daily ACR exposure of general adults was cross-sectionally and longitudinally associated with increased cardiovascular risk, which was partly mediated by oxidative stress, inflammation, and TGF-ß1, suggesting for the first time that ACR exposure may well increase cardiovascular risk of general adult population partly by mechanisms of inducing oxidative stress, inflammation, and TGF-ß1. Our findings have important public health implications that provide potent epidemiological evidence and vital mechanistic insight into cardiovascular risk increment from ACR exposure.

Urinary acrolein metabolites, systemic inflammation, and blood lipids: Results from the National Health and Nutrition Examination Survey.

Exposure to acrolein was reported to be related with adverse health effects. However, the associations between acrolein exposure and blood lipids remain largely unknown. We assessed the associations of urinary acrolein metabolites with blood lipids using data from the National Health and Nutrition Examination Survey (NHANES) and further investigated the existence of mediation by systemic inflammation in the associations. Urinary acrolein metabolites, N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) and N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA), blood lipids, and serum high sensitivity C-reactive protein (hs-CRP) were measured in the NHANES. The associations of urinary acrolein metabolites with blood lipids and dyslipidemia and hs-CRP were estimated by multiple linear and logistic regression models. Mediation analysis was conducted to evaluate the mediating effects of hs-CRP on the associations between urinary acrolein metabolites and blood lipids. We found urinary CEMA+3-HPMA (∑acrolein) was significantly associated with higher levels of serum triglycerides (TG), hs-CRP, and lower levels of high-density lipoprotein cholesterol (HDL-C). Each 1-unit increment in ln-transformed level of ∑acrolein was associated with a 0.06 mmol/L increment in TG and 0.02 mmol/L decrement in HDL-C (all P <0.05). A positive dose-response relationship was observed between urinary ∑acrolein and dyslipidemia risk. In addition, hs-CRP significantly mediated the associations of urinary ∑acrolein with serum TG and HDL-C, with mediated proportions of 22.12% and 41.41%, respectively. In conclusion, acrolein exposure is associated with the levels of serum TG, HDL-C, and hs-CRP. Hs-CRP may mediate acrolein-associated alterations of blood lipids. Our results indicated that decreased exposure to acrolein may reduce systemic inflammation and dyslipidemia risk.

MicroRNA-21 Regulates PI3K/Akt/mTOR Signaling by Targeting TGFßI during Skeletal Muscle Development in Pigs.

MicroRNAs (miRNAs), which are short (22-24 base pairs), non-coding RNAs, play critical roles in myogenesis. Using Solexa deep sequencing, we detected the expression levels of 229 and 209 miRNAs in swine skeletal muscle at 90 days post-coitus (E90) and 100 days postnatal (D100), respectively. A total of 138 miRNAs were up-regulated on E90, and 31 were up-regulated on D100. Of these, 9 miRNAs were selected for the validation of the small RNA libraries by quantitative RT-PCR (RT-qPCR). We found that miRNA-21 was down-regulated by 17-fold on D100 (P<0.001). Bioinformatics analysis suggested that the transforming growth factor beta-induced (TGFßI) gene was a potential target of miRNA-21. Both dual luciferase reporter assays and western blotting demonstrated that the TGFßI gene was regulated by miRNA-21. Co-expression analysis revealed that the mRNA expression levels of miRNA-21 and TGFßI were negatively correlated (r = -0.421, P = 0.026) in skeletal muscle during the 28 developmental stages. Our results revealed that more miRNAs are expressed in prenatal than in postnatal skeletal muscle. The miRNA-21 is a novel myogenic miRNA that is involved in skeletal muscle development and regulates PI3K/Akt/mTOR signaling by targeting the TGFßI gene.