Global patterns of asthma burden related to environmental risk factors during 1990-2019: an age-period-cohort analysis for global burden of disease study 2019.

BACKGROUND: Change in asthma burden attributed to specific environmental risk factor has not been evaluated. OBJECTIVE: We aimed to explore the age, period, and cohort effects on asthma burden attributable to smoking and occupational asthmagens in different socio-demographic index (SDI) regions and the region and sex disparities. METHODS: Risk factor-specific asthma deaths and disability-adjusted life years (DALYs) rates were extracted from Global Burden of Disease study 2019, estimated by standard Combined Cause of Death Model and DisMod-MR 2.1 modeling tool. Age-period-cohort analysis was conducted to decompose age, period, and cohort effects on asthma burden. RESULTS: Smoking- and occupational asthmagens-related asthma deaths and DALYs rates dropped by > 45% during 1990-2019. In 2019, Africa, South and Southeast Asia had higher asthma burden than other regions. Male had higher asthma burden than female. Among nearly all age groups, low-middle SDI region had the highest smoking-related asthma burden, and low SDI region had the highest occupational asthmagens-related asthma burden. Inverse "V" shaped trend was observed in the above regions with increasing age. For smoking-related asthma deaths and DALYs rates, the most significant improvement of period rate ratio (RR) occurred in high SDI region, decreased from 1.67 (1.61, 1.74) to 0.34 (0.33, 0.36) and 1.61 (1.57, 1.66) to 0.59 (0.57, 0.61), respectively, as well as the cohort effect on smoking-related asthma burden. For occupational asthmagens-related asthma deaths and DALYs rates, the most sharply decrease of period and cohort RR appeared in the high and high-middle SDI regions. Low SDI region showed least progress in period and cohort RR of smoking- and occupational asthmagens-linked asthma burden. CONCLUSION: Smoking- and occupational asthmagens-related asthma burden sharply decreases, but region and sex disparities exist. Policy makers from low SDI region should reinforce tobacco control and prioritize workplace protection.

Trend and heterogeneity in forced vital capacity among Chinese students during 1985-2019: results from Chinese National Survey on Students' Constitution and Health.

BACKGROUND: Forced vital capacity (FVC) reflects respiratory health, but the long-term trend and heterogeneity in FVC of Chinese students were understudied. METHODS: Data were from Chinese National Survey on Students' Constitution and Health 1985-2019. Super Imposition by Translation and Rotation model was used to draw FVC growth curves. Sex-, region-, and nationality-heterogeneity in FVC was evaluated. Spearman correlation and generalized additive model was used to reveal influencing factors for FVC. RESULTS: Compared to 1985, age at peak FVC velocity was 1.09, 3.17, 0.74, and 1.87 years earlier for urban male, urban female, rural male, and rural female in 2019, respectively. Peak FVC velocity first decreased and then increased during 1985-2019, only male rebounded to larger than 1985 level. FVC declined from 1985 to 2005 and then raised. Males consistently had higher FVC than females, with disparities increasing in the 13-15 age group. Urban students also had higher FVC than rural students. In 2019, FVC difference between 30 Chinese provinces and the national average showed four scenarios: consistently above national average; less than national average until age 18, then above; greater than national average until age 18, then this advantage reversed; less than national average in almost all the age. Most Chinese ethnic minority students had lower FVC levels compared to Han students. Spearman correlation and generalized additive model showed that age, sex, and height were the leading influencing factors of FVC, followed by socioeconomic and environmental factors. CONCLUSIONS: Chinese students experienced advanced FVC spurt, and there was sex-, region- and nationality-heterogeneity in FVC. Routine measurement of FVC is necessary in less developed areas of China.

Boosting Thermal and Mechanical Properties: Achieving High-Safety Separator Chemically Bonded with Nano TiN Particles for High Performance Lithium-Ion Batteries.

Currently, the commercial separator (Celgard2500) of lithium-ion batteries (LIBs) suffers from poor electrolyte affinity, mechanical property and thermal stability, which seriously affect the electrochemical performances and safety of LIBs. Here, the composite separators named PVDF-HFP/TiN for high-safety LIBs are synthesized. The integration of PVDF-HFP and TiN forms porous structure with a uniform and rich organic framework. TiN significantly improves the adsorption between PVDF-HFP and electrolyte, causing a higher electrolyte absorption rate (192%). Meanwhile, XPS results further demonstrate the tight link between PVDF-HFP and TiN due to the existence of TiF bond in PVDF-HFP/TiN, resulting in a strong impediment for the puncture of lithium dendrites as a result of the improved mechanical strengths. And PVDF-HFP/TiN can effectively suppress the growth of lithium dendrites by means of uniform lithium flux. In addition, the excellent heat resistance of TiN improves the thermal stability of PVDF-HFP/TiN. As a result, the LiFePO4 ||Li cells assembled PVDF-HFP/TiN-12 exhibit excellent specific capacity, rate performance, and capacity retention rate. Even the high specific capacity of 153 mAh g-1 can be obtained at the high temperature of 80 °C. Meaningfully, a reliable modification strategy for the preparation of separators with high safety and electrochemical performance in LIBs is provided.

Associations of mitochondrial DNA copy number with incident risks of gastrointestinal cancers: A prospective case-cohort study.

Epidemiological investigations implied that mitochondrial DNA copy number (mtDNAcn) variations could trigger predisposition to multiple cancers, but evidence regarding gastrointestinal cancers (GICs) was still uncertain. We conducted a case-cohort study within the prospective Dongfeng-Tongji cohort, including incident cases of colorectal cancer (CRC, n = 278), gastric cancer (GC, n = 138), and esophageal cancer (EC, n = 72) as well as a random subcohort (n = 1173), who were followed up from baseline to the end of 2018. We determined baseline blood mtDNAcn and associations of mtDNAcn with the GICs risks were estimated by using weighted Cox proportional hazards models. Significant U-shaped associations were observed between mtDNAcn and GICs risks. Compared to subjects within the second quartile (Q2) mtDNAcn subgroup, those within the 1st (Q1), 3rd (Q3), and 4th (Q4) quartile subgroups showed increased risks of CRC (hazard ratio [HR] [95% confidence interval, CI] = 2.27 [1.47-3.52], 1.65 [1.04-2.62], and 2.81 [1.85-4.28], respectively) and total GICs (HR [95%CI] = 1.84 [1.30-2.60], 1.47 [1.03-2.10], and 2.51 [1.82-3.47], respectively], and those within Q4 subgroup presented elevated GC and EC risks (HR [95% CI] = 2.16 [1.31-3.54] and 2.38 [1.13-5.02], respectively). Similar associations of mtDNAcn with CRC and total GICs risks remained in stratified analyzes by age, gender, smoking, and drinking status. This prospective case-cohort study showed U-shaped associations between mtDNAcn and GICs risks, but further research works are needed to uncover underlying biological mechanisms.

Prenatal single and combined exposure to phthalates associated with girls' BMI trajectory in the first six years.

Evidence of the influence of prenatal phthalate exposure on childhood longitudinal obesity markers is limited. Nested on the Ma'anshan birth cohort study, 990 mother-daughter pairs were included. Seven phthalate metabolites were determined in urine collected in each trimester. Each child underwent a physical examination from birth to 6 years of age twelve times. Latent class growth models were used to identify three trajectories of girls' body mass index (BMI). Logistic regression, quantile g-computation and Bayesian kernel machine regression models analyzed the relationships of prenatal exposure to individual and mixed phthalates with girls' body mass index (BMI) trajectory. Compared to the "lowest trajectory" class, prenatal average concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, ORcrude = 2.095, 95 % CI = 1.014-4.328) and di(2-ethylhexyl) phthalate (DEHP, ORcrude = 2.336, 95 % CI = 1.022-5.338) during pregnancy were associated with an increased probability of being in the "highest trajectory" class. The average concentration of DEHP (ORcrude = 1.879, 95 % CI = 1.002-3.522) was associated with an increased probability of being in the "moderate trajectory" class. Stratified analyses by trimester of pregnancy mainly showed that third-trimester exposure to monoethyl phthalate (MEP, ORadjusted = 1.584, 95 % CI = 1.094-2.292), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP, ORadjusted = 2.885, 95 % CI = 1.367-6.088), MEHHP (ORadjusted = 2.425, 95 % CI = 1.335-4.407), DEHP (ORadjusted = 2.632, 95 % CI = 1.334-5.193) and high molecular weight phthalate (ORadjusted = 2.437, 95 % CI = 1.239-4.792) was associated with an increased probability of being in the "highest trajectory" class. However, the mixture of phthalates was not significantly related to the girl's BMI trajectory. In conclusion, in utero exposure to phthalates, including MEP and DEHP metabolites (MEHHP and MEOHP), was significantly associated with early childhood high BMI trajectories in girls. The third trimester of pregnancy seemed to be the window of vulnerability to phthalate exposure for girls' high BMI trajectory at periods of prenatal development. No evidence supported a significant relationship between combined exposure to phthalate metabolites and girls' high BMI trajectory.

Sex Discrepancy Observed for Gestational Metabolic Syndrome Parameters and Polygenic Risk Associated With Preschoolers' BMI Growth Trajectory: The Ma'anshan Birth Cohort Study.

Background: Few studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children's genetic susceptibility. Objective: To investigate the effects of gestational metabolic syndrome (GMS) risks and children's polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age. Methods: A total of 2,603 mother-child pairs were recruited from the Ma'anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children's PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory. Results: Maternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child's PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys' and girls' BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group. Conclusions: Maternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child's BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children's BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

Relationship of individual and mixed prenatal phthalate exposure with placental structure and efficiency in the prospective Ma'anshan Birth Cohort Study.

BACKGROUND: Few studies have investigated the associations between prenatal phthalate exposure and placental structure and function with inconsistent conclusions. METHODS: Nested on the Ma'anshan Birth Cohort study, 2723 women provided spot urine samples during the first, second and third trimesters of pregnancy to analyze six phthalate metabolites. The outcomes of interest were placental weight, efficiency (birth weight/placental weight), chorionic disc area and disc eccentricity. The relationships of prenatal exposure to a single phthalate with placental measures were analyzed. The associations between prenatal phthalate mixture exposure and placental measures were also evaluated. RESULTS: Most phthalate metabolites were significantly associated with placental weight, efficiency and chorionic disc area during the whole gestation and in each trimester of pregnancy, with different directions of relationships. Sensitivity analyses revealed similar findings, indicating the robustness of the statistical results. Furthermore, inverted U-shaped nonlinear relationships of prenatal exposure to some phthalate metabolites with placental weight, efficiency and chorionic plate area were observed. However, quantile g-computation mixture models did not reveal any association between maternal combined exposure to the total phthalate metabolites and placental measures. CONCLUSIONS: Maternal exposure to most phthalates and their metabolites was associated with placental weight, efficiency and chorionic plate area in both a linear manner and an inverted U-shaped nonlinear manner. However, the mixture of multiple phthalate metabolites was not observed to be associated with any placental measure.

A machine learning-based biological aging prediction and its associations with healthy lifestyles: the Dongfeng-Tongji cohort.

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng-Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV1 ), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all-cause (HR (95% CI) = 1.12 (1.10-1.14) and 1.08 (1.07-1.10), respectively) and cause-specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1-point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7-9 h/night) was associated with a 0.21-year decrease in the AgingAccel (95% CI: -0.27 to -0.15) and a 0.4% decrease in the aging rate (95% CI: -0.5% to -0.3%). This study developed a machine learning-based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions.

Trends in the asthma burden among children and adolescents in China from 1990-2019 / 中国学校卫生

Objective@#To explore trends in the asthma burden among Chinese children and adolescents 1-19 years old during 1990-2019.@*Methods@#Based on data from the 2019 Global Burden of Disease Study, joinpoint regression was used to analyze the dynamic changes in the gender and age specific asthma burden, and the asthma burden in China was compared with countries that have different socio demographic indices(SDI). In addition, trends in asthma burden attributed to different risk factors were also investigated.@*Results@#The asthma burden decreased slightly from 1990 to 1996 [annual percent change (APC)=-1.7%], then rapidly decreased from 1996 to 2005 (APC=-5.7%). The age standardized disability adjusted life years (DALYs) rate decreased from 158.55/100 000 to 88.59/100 000 in patients 1-19 years of age. From 2005 to 2017, the DALYs rate for asthma increased slowly, then rapidly. In 2017, the DALYs rate peaked at 176.18/100 000, then decreased to 126.79/100 000 in 2019. The burden of asthma in boys was higher than girls, and the DALYs rate for asthma in the group 5-9 years of age was higher than the remaining age groups. Furthermore, the age standardized DALYs rate for asthma among Chinese children and adolescents was relatively low among countries with a different SDI. In addition, the DALYs rate attributed to high body mass index increased in all age groups in China. Specifically, the average APC (AAPC) was 2.9% in group 1-4 years of age and the AAPC was 4.2% in the remaining age groups. The DALYs rate attributed to occupational asthmagens in the group 15-19 years of age decreased from 1990 to 2019 and the AAPC was -2.5%.@*Conclusion@#The asthma burden was relatively low among Chinese children and adolescents, and there were gender and age differences. The gender and age specific DALYs rate for asthma had a tendency to decrease, increase, then decrease. More attention should be paid to boys and the group 5-9 years of age, and strengthen the intervention of obesity and occupational asthmagens.

Circulating white blood cells and lung function impairment: the observational studies and Mendelian randomization analysis.

BACKGROUND: Circulating white blood cell (WBC) counts have been related to lung function impairment, but causal relationship was not established. We aimed to evaluate independent effects and causal relationships of WBC subtypes with lung function. METHODS: The 19,159 participants from NHANES 2011-2012 (n = 3570), coke-oven workers (COW, n = 1762) and Dongfeng-Tongji (DFTJ, n = 13,827) cohorts were included in the observational studies. The associations between circulating counts of WBC subtypes and prebronchodilator lung function were evaluated by linear regression models and LASSO regression was used to select effective WBC subtypes. Summary statistics for WBC-associated SNPs were extracted from literature, and Mendelian randomization (MR) analysis with inverse-variance weighted (IVW) method was applied to estimate the causal effects of total WBC and subtypes on lung function among 4012 subjects from COW (n = 1126) and DFTJ cohorts (n = 2886). RESULTS: Total WBC counts were negatively associated with lung function among three populations and their pooled analysis indicated that per 1 × 109 cells/L increase in total WBC was associated with 36.13 (95% CI: 30.35, 41.91) mL and 25.23 (95% CI: 19.97, 30.50) mL decrease in FVC and FEV1, respectively. Independent associations with lung function were found for neutrophils, monocytes, eosinophils and basophils (all p < .05), except lymphocytes. Besides, IVW MR analysis showed that genetically predicted total WBC and neutrophil counts were associated with reduced FVC (p = .017 and .021, respectively) and FEV1 (p = .048 and .043, respectively). CONCLUSIONS: WBC subtypes were independently associated with lower lung function except lymphocytes. Our findings suggest that circulating neutrophils may be causal factors in lung function impairment.KEY MESSAGESWhite blood cell (WBC) subtypes were negatively associated with lung function level except lymphocytes in the observational studies.Associations of WBC subtypes with lung function may be modified by sex and smoking.Mendelian randomization analysis shows that neutrophils may be causal factors in lung function impairment.

Physical activity attenuates the associations of systemic immune-inflammation index with total and cause-specific mortality among middle-aged and older populations.

Systemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999-2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality [hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03-1.22) and 1.26 (1.16-1.36), respectively) and CVD mortality [HR (95%CI) = 1.36 (1.19-1.55) and 1.50 (1.32-1.71), respectively]; those within the high SII subgroup had a higher risk of other causes mortality [HR (95%CI) = 1.28 (1.09-1.49)]. In the NHANES 1999-2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality [HR (95%CI) = 1.38 (1.27-1.49), 1.33 (1.11-1.59), 1.22 (1.04-1.45) and 1.47 (1.32-1.63), respectively]. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999-2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations.

Epigenome-wide DNA methylation signature of benzo[a]pyrene exposure and their mediation roles in benzo[a]pyrene-associated lung cancer development.

Benzo[a]pyrene (B[a]P) is a typical carcinogen associated with increased lung cancer risk, but the underlying mechanisms remain unclear. This study aimed to investigate epigenome-wide DNA methylation associated with B[a]P exposure and their mediation effects on B[a]P-lung cancer association in two lung cancer case-control studies of 462 subjects. Their plasma levels of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and genome-wide DNA methylations were separately detected in peripheral blood by using enzyme-linked immunosorbent assay (ELISA) and genome-wide methylation arrays. The epigenome-wide meta-analysis was performed to analyze the associations between BPDE-Alb adducts and DNA methylations. Mediation analysis was applied to assess effect of DNA methylation on the B[a]P-lung cancer association. We identified 15 CpGs associated with BPDE-Alb adducts (P-meta < 1.0 × 10-5), among which the methylation levels at five loci (cg06245338, cg24256211, cg15107887, cg02211741, and cg04354393 annotated to UBE2O, SAMD4A, ACBD6, DGKZ, and SLFN13, respectively) mediated a separate 38.5%, 29.2%, 41.5%, 47.7%, 56.5%, and a joint 58.2% of the association between BPDE-Alb adducts and lung cancer risk. Compared to the traditional factors [area under the curve (AUC) = 0.788], addition of these CpGs exerted improved discriminations for lung cancer, with AUC ranging 0.828-0.861. Our results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure.

Arsenic exposure and its joint effects with cigarette smoking and physical exercise on lung function impairment: Evidence from an occupational cohort study.

BACKGROUND: Arsenic (As) is an established toxic metal, but its effect on longitudinal lung function change among occupational workers is less conclusive. METHODS: 1243 participants were recruited in a coke-oven plant and followed up from 2010 to 2014. Each individual provided 20 mL morning urine sample at baseline, which was then used for urinary levels of As (U-As) and polycyclic aromatic hydrocarbon (PAH) metabolites detecting. Lung function levels at both baseline and the end of follow-up were determined. Multiple linear regression models were used to analyze the associations between U-As with annual lung function changes, and to evaluate the joint effects of U-As with cigarette smoking and regular physical exercise. RESULTS: Among all participants, each 2-fold increase in U-As was associated with -12.09 (95%CI: -19.37, -4.81) mL, -0.32% (95%CI: -0.54%, -0.10%), -15.04 (95%CI: -24.62, -5.46) mL, and -0.36% (95%CI: -0.64%, -0.08%) annual changes in reduced forced expiratory volume in 1 second (FEV1), percent predicted FEV1 (ppFEV1), forced vital capacity (FVC), and percent predicted FVC (ppFVC), respectively. These effects were more pronounced among coke-oven workers with smoking (especially heavy smoking with pack-years≥15) and without regular physical exercise. Compared to low-As-exposed (≤4.70 µg/mmol creatinine) non-smokers with regular physical exercise, the high-As-exposed (>4.70 µg/mmol creatinine) smokers without regular physical exercise had the worst annual declines in FEV1 [ß (95%CI) = -69.01 (-106.67, -31.34) mL], ppFEV1 [ß (95%CI) = -1.94% (-3.02%, -0.87%)], FVC [ß (95%CI) = -78.66 (95%CI: -129.46, -27.86) mL], and ppFVC [ß (95%CI) = -1.80% (-3.23%, -0.37%)]. CONCLUSIONS: The findings in our prospective cohort study suggested the positively linear dose-response relationship of U-As with annual lung function decline. The adverse effects of As could be enhanced by cigarette smoking and attenuated by regular physical exercise. Specific emphasizes on tobacco control and physical exercise were suggested to prevent As exposure induced pulmonary impairment.

Mediation of the association between polycyclic aromatic hydrocarbons exposure and telomere attrition by oxidative stress: A prospective cohort study.

Previous studies have reported associations between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere attrition, but the underlying mechanisms remain to be elucidated. This study aimed to explore the mediation role of oxidative stress on the effects of PAHs exposure on telomere attrition in a cohort study of 1180 coke-oven workers. We determined baseline urinary concentrations of ten urinary PAH metabolites, two oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-isoPGF2α)] and peripheral leukocytes telomere length (TL) in both baseline and follow-up visits. Mediation analysis was applied to assess effects of oxidative stress biomarkers on the PAHs-TL attrition associations. The baseline 8-OHdG had a significant dose-response relationship with TL decline [ß(95 %CI) = 0.07(0.03-0.12), P = 0.001] and TL ratio [ß(95 %CI)]=0.07 (0.02-0.12), P = 0.003]. Mediation analyses indicated that 8-OHdG mediated a separate 39.1 %, 47.0 %, 43.3 %, and 58.0 % of the associations between 1-hydroxynaphthalene (1-OHNa), 2-OHNa, ΣOHNa, 1-hydroxypyrene (1-OHP) and TL decline (P = 0.016, 0.008, 0.012, and 0.014, respectively). Additionally, 8-OHdG mediated a separate 44.8 %, 49.4 %, 49.2 %, and 35.5 % of the associations between 1-OHNa, 2-OHNa, ΣOHNa, 1-OHP and TL ratio (P = 0.012, 0.008, 0.012, and 0.046, respectively). Our study proposed the positive association of 8-OHdG with TL attrition and revealed the mediation roles of 8-OHdG in PAHs-TL attrition associations.

Lead exposure and its interactions with oxidative stress polymorphisms on lung function impairment: Results from a longitudinal population-based study.

Exposure to lead (Pb) and cadmium (Cd) were related to lung function impairment, and this association may be modified by genetic variants in oxidative stress response. Here we enrolled 1243 coke-oven workers in a prospective cohort who were followed up from 2010 to 2014, assessed the associations of Pb and Cd exposure with 4-year lung function impairment, and further explored the interaction effects of Pb with 2664 single nucleotide polymorphisms (SNPs) in 345 oxidative stress related genes. Urinary levels of Pb, Cd, and two oxidative stress biomarkers [8-iso-prostaglandin F2α (8-iso-PGF2α) for lipid peroxidation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative DNA damage] were measured at baseline only and their lung function levels were measured both at baseline and at the end of follow-up. Each 10-fold increase in urinary Pb was associated with -159 (95%CI: -254, -64.2) mL and -3.63% (95%CI: -6.48%, -0.78%) changes in FEV1 and percent predicted FEV1 (ppFEV1), respectively. But none significant associations were observed for Cd. NQO1 rs2917670 showed significant interaction with Pb on elevated FEV1 decline after multiple comparison (Pint=1.54 × 10-5). In addition, urinary Pb increased with 8-iso-PGF2α and the rs2917670-C could significantly decrease NQO1 expression in normal lung tissues. These findings suggested the gene-environmental interaction of NQO1 rs2917670 and Pb exposure on the reduction of FEV1. The effect of Pb exposure on elevated oxidative stress and the decreased expression of antioxidant enzyme NQO1 caused by rs2917670-C allele may partly explain the underlying biological mechanism.

Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length.

OBJECTIVE: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere length (LTL). METHODS: This study included 842 workers from a coke-oven plant, of whom plasma concentrations of 23 metals and LTL were determined. Genetic variations in TERT-CLPTM1L were genotyped by using the Global Screening Array. Multipollutant-based statistical methods, including the Bonferroni-correction, backward elimination procedure, and LASSO penalized regression analysis, were used to select the LTL-associated metals. Generalized linear regression models were used to evaluate the joint effects of TERT-CLPTM1L variants with positive metal on LTL. RESULTS: Each 1% increase in plasma concentration of manganese (Mn) was significantly associated with a 0.153% increase in LTL [ß(95%CI) = 0.153(0.075, 0.230), P < 0.001] in single-metal models after Bonferroni-correction. The multiple-metal models and the LASSO penalized regression analysis both indicated Mn as the sole significant predictor for LTL. Furthermore, 5 tagSNPs (rs33954691, rs6554759, rs465498, rs2455393, and rs31489) in TERT-CLPTM1L with high plasma Mn (>4.21 µg/L) showed joint effects on increasing LTL. CONCLUSIONS: Our study revealed the independent and positive association between plasma Mn and LTL when accounting for co-exposure to other metals. This effect can be further enhanced by TERT-CLPTM1L variants. These results may advance our understanding of the complex interplay between genetic and environmental factors on telomere length. Further experimental studies are warranted to elucidate the underlying mechanisms.

Polycyclic aromatic hydrocarbons exposure and their joint effects with age, smoking, and TCL1A variants on mosaic loss of chromosome Y among coke-oven workers.

Mosaic loss of chromosome Y (mLOY) is the most common structure somatic event that related to increased risks of various diseases and mortality. Environmental pollution and genetic susceptibility were important contributors to mLOY. We aimed to explore the associations of polycyclic aromatic hydrocarbons (PAHs) exposure, as well as their joint effects with age, smoking, and genetic variants on peripheral blood mLOY. A total of 1005 male coke-oven workers were included in this study and their internal PAHs exposure levels of 10 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts were measured. mLOY was defined by the median log R ratio(mLRR) of 1480 probes in male-specific region of chromosome-Y from genotyping array. We found that the PAHs exposure levels were linearly associated with mLOY. A 10-fold increase in urinary 1-hydroxynaphthalene (1-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, 1-hydroxypyrene (1-OHP), ΣOH-PAHs, and plasma BPDE-Alb adducts could generate 0.0111, 0.0085, 0.0069, 0.0103, 0.0134, and 0.0152 decrease in mLRR-Y, respectively. Additionally, mLOY accelerated with age, smoking pack-years, and TCL1A rs1122138-C allele, and we observed the most severe mLOY among subjects carrying more than 3 of the above risk factors. Our results revealed the linear dose-effect associations between PAHs exposure and mLOY. Elder male smokers carrying rs1122138CC genotype were the most susceptible subpopulations to mLOY, who should be given protections for PAHs exposure induced chromosome-Y aberration.

Daily cooking duration and its joint effects with genetic polymorphisms on lung cancer incidence: Results from a Chinese prospective cohort study.

OBJECTIVES: In this study, we conducted a prospective cohort study to investigate the joint effects of daily cooking duration with single nucleotide polymorphisms (SNPs) on lung cancer incidence. MATERIALS AND METHODS: A total of 33,868 individuals recruited in 2013 from Dongfeng-Tongji cohort study were included in our research, in which 5178 participants were genotyped. Daily cooking duration was accessed by questionnaire, and the incident lung cancer cases were confirmed. Fifteen lung cancer related SNPs were selected according to the previous reports. We used the multiple Cox regression models to evaluate the separate and joint effects of daily cooking duration and SNPs on lung cancer incidence. RESULTS: Each 1-h increase in daily cooking duration was associated with a 17% elevated risk of lung cancer incidence [hazard ratio (HR) (95%CI) = 1.17(1.03, 1.33)]. Specifically, subjects with daily cooking duration >2 h/day had a 2.05-fold increased incident risk of lung cancer than those without cooking [HR(95%CI) = 2.05(1.20, 3.53)] (Ptrend = 0.011). The rs2395185 and rs3817963, both located at 6p21.32, were significantly associated with lung cancer incidence. Compared with no cooking subjects with rs2395185GG or rs3817963TT genotype, subjects with daily cooking >2 h/day and carrying rs2395185GT + TT genotypes had a 2.48-fold increased risk of lung cancer [HR(95%CI) = 2.48(1.03, 5.97)], and there were significant joint effects of rs3817963TC + CC with daily cooking 1-2 and >2 h/day [HR(95%CI) = 2.23(1.07, 4.64) and 2.22(1.05, 4.68), respectively]. CONCLUSIONS: Longer daily cooking duration, especially daily cooking >2 h/day, was associated with increased risk of lung cancer. There were significant joint effects of rs2395185 and rs3817963 with daily cooking duration on lung cancer incidence. This study offered a new indicator of cooking related pollution exposure and added new evidence for the joint effects of environment and genetic factors on lung cancer incidence.