Incidence, mortality, and disability-adjusted life years due to silicosis worldwide, 1990-2019: evidence from the global burden of disease study 2019.

Silicosis is an occupational lung disease because of exposure to silica dust in the workplace. Evidence on the spatiotemporal change of silicosis burden worldwide remains limited. This study utilized data extracted from the Global Burden of Disease Study 2019 to examine the numbers and age-standardized rates of incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) caused by silicosis between 1990 and 2019. Average annual percentage changes (AAPCs) were calculated to evaluate the temporal trends of age-standardized indicators by sex, region, and socio-demographic index (SDI) since 1990. Results indicated an increase in new silicosis cases globally, rising by 64.61% from 84,426 in 1990 to 138,971 in 2019, with a sustained high number of DALYs attributed to this disease. Although the global age-standardized rates of incidence, mortality, and DALYs of silicosis have decreased since 1990, the number of new cases has increased in 168 countries and territories, and the ASIR of silicosis has also risen in 118 countries and territories, primarily in developing countries. Since 1990, the burden of silicosis among the elderly has significantly increased. Countries with higher SDI experienced a more rapid decline in the silicosis burden. Silicosis remains a public health problem that requires significant attention. Programs for prevention and elimination of this public health issue need to be established in more countries and territories. Protecting young workers from silica dust exposure is crucial to prevent the onset of silicosis in their later years and to reduce the disease burden among older workers.

Air pollution exposure, accelerated biological aging, and increased thyroid dysfunction risk: Evidence from a nationwide prospective study.

BACKGROUND: Long-term air pollution exposure is a major health concern, yet its associations with thyroid dysfunction (hyperthyroidism and hypothyroidism) and biological aging remain unclear. We aimed to determine the association of long-term air pollution exposure with thyroid dysfunction and to investigate the potential roles of biological aging. METHODS: A prospective cohort study was conducted on 432,340 participants with available data on air pollutants including particulate matter (PM2.5, PM10, and PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) from the UK Biobank. An air pollution score was calculated using principal component analysis to reflect joint exposure to these pollutants. Biological aging was assessed using the Klemera-Doubal method biological age and the phenotypic age algorithms. The associations of individual and joint air pollutants with thyroid dysfunction were estimated using the Cox proportional hazards regression model. The roles of biological aging were explored using interaction and mediation analyses. RESULTS: During a median follow-up of 12.41 years, 1,721 (0.40 %) and 9,296 (2.15 %) participants developed hyperthyroidism and hypothyroidism, respectively. All air pollutants were observed to be significantly associated with an increased risk of incident hypothyroidism, while PM2.5, PM10, and NO2 were observed to be significantly associated with an increased risk of incident hyperthyroidism. The hazard ratios (HRs) for hyperthyroidism and hypothyroidism were 1.15 (95 % confidence interval: 1.00-1.32) and 1.15 (1.08-1.22) for individuals in the highest quartile compared with those in the lowest quartile of air pollution score, respectively. Additionally, we noticed that individuals with higher pollutant levels and biologically older generally had a higher risk of incident thyroid dysfunction. Moreover, accelerated biological aging partially mediated 1.9 %-9.4 % of air pollution-associated thyroid dysfunction. CONCLUSIONS: Despite the possible underestimation of incident thyroid dysfunction, long-term air pollution exposure may increase the risk of incident thyroid dysfunction, particularly in biologically older participants, with biological aging potentially involved in the mechanisms.

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.

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

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

Association between dietary vitamin intake and mortality in US adults with diabetes: A prospective cohort study.

AIMS: To explore the association of dietary vitamin intake from food and/or supplement with mortality in US adults with diabetes. MATERIALS AND METHODS: This prospective cohort study was conducted on 5418 US adults with diabetes from the National Health and Nutrition Examination Survey 1999-2018. Vitamin intake from food and supplements was estimated via dietary recall. Sufficient intake from food or food + supplement was defined as ≥ estimated average requirement (EAR) and ≤ tolerable upper intake level (UL), insufficient intake, < EAR; and excess intake, > UL. Medium supplementary intake was classified as > median level and ≤75th percentile; low intake, ≤ median level; and high intake, >75th percentile, as reported by supplement users. RESULTS: A total of 1601 deaths occurred among the participants over a median follow-up of 11.0 years. Cox regression analysis of the single-vitamin model demonstrated that sufficient vitamin A and folate intake from food and food + supplement and medium vitamin A and folate intake from supplement; sufficient riboflavin, niacin, and vitamin B6 intake from food and food + supplement; and sufficient thiamin and vitamin E intake from food + supplement were significantly associated with reduced all-cause mortality (all p < 0.05). In the multivitamin model, sufficient vitamin A and folate intake from food and food + supplement, medium vitamin A and folate intake from the supplement, and sufficient niacin intake from food and food + supplement were inversely associated with mortality (all p < 0.05). CONCLUSIONS: Vitamin A and folate intake from food or supplement and niacin intake from food were significantly associated with reduced mortality in US adults with diabetes.

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.

Ambient temperature exposure causes lung function impairment: The evidence from Controlled Temperature Study in Healthy Subjects (CTSHS).

BACKGROUND: The effect of non-optimal ambient temperatures (low and high temperatures) on lung function and the underlying mechanisms remains unclear. METHODS: Forty-three (20 males, 23 females) healthy non-obese volunteers with an average of 23.9 years participated in the controlled temperature study. All volunteers underwent three temperature exposures in a sequence (moderate [18 °C], low [6 °C], and high [30 °C] temperatures) lasting 12 h with air pollutants controlled. lung function parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) were determined in each exposure. Blood and urine samples were collected after each exposure and assayed for inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)] and oxidative damage markers [protein carbonylation (PCO), 4-hydroxy-2-nominal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F2α (8-isoPGF2α), and 8-hydroxy-2-deoxyguanosine (8-OHdG)]. Mixed-effects models were constructed to assess the changes of the above indexes under low or high temperatures relative to moderate temperature, and then the repeated measures correlation analyses were performed. RESULTS: Compared with moderate temperature, a 2.20% and 2.59% net decrease in FVC, FEV1, and a 5.68% net increase for PEF were observed under low-temperature exposure, while a 1.59% net decrease in FVC and a 7.29% net increase in PEF under high-temperature exposure were found (all P < 0.05). In addition, low temperature elevated inflammatory markers (PCT, PLR, and NLR) and oxidative damage markers (8-isoPGF2α, 8-OHdG), and high temperature elevated HNE-MA. Repeated measures correlation analyses revealed that PCT (r = -0.33) and NLR (r = -0.31) were negatively correlated with FVC and HNE-MA (r = -0.35) and 8-OHdG (r = -0.31) were negatively correlated with the FEV1 under low-temperature exposure (all P < 0.05). CONCLUSION: Non-optimal ambient temperatures exposure alters lung function, inflammation, and oxidative damage. Inflammation and oxidative damage might be involved in low temperature-related lung function reduction.

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

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

Temporal trend and global burden of type 2 diabetes attributable to non-optimal temperature, 1990-2019: an analysis for the Global Burden of Disease Study 2019.

Exposure to hot or cold temperatures was reported to be associated with increased mortality and morbidity of type 2 diabetes, but few studies have estimated the temporal trend and global burden of type 2 diabetes attributable to non-optimal temperature. Based on the Global Burden of Disease Study 2019, we collected data on the numbers and rates of deaths and disability-adjusted life years (DALYs) of type 2 diabetes attributed to non-optimal temperature. The joinpoint regression analysis was used to estimate the temporal trends of the age-standardized rate of mortality and DALYs from 1990 to 2019 by average annual percentage change (AAPC). From 1990 to 2019, globally, the numbers of deaths and DALYs of type 2 diabetes attributable to non-optimal temperature increased by 136.13% (95% (uncertainty interval) UI: 87.04% to 277.76%) and 122.26% (95% UI: 68.77% to 275.59%), with the number from 0.05 (95% UI: 0.02 to 0.07) million and 0.96 (95% UI: 0.37 to 1.51) million in 1990 to 0. 11 (95% UI: 0.07 to 0.15) million and 2.14 (95% UI: 1.35 to 3.13) million in 2019. The age-standardized mortality rate (ASMR) and DALYs rate (ASDR) of type 2 diabetes attributable to non-optimal temperature showed an increasing trend in the high temperature effect and lower (low, low-middle and middle) socio-demographic index (SDI) region, with AAPCs of 3.17%, 1.24%, 1.61%, and 0.79% (all P < 0.05), respectively. The greatest increased ASMR and ASDR were observed in Central Asia, followed by Western Sub-Saharan Africa and South Asia. Meanwhile, the contribution of type 2 diabetes burden attributable to high temperature gradually increased globally and in five SDI regions. In addition, the global age-specific rate of mortality and DALYs of type 2 diabetes attributable to non-optimal temperature for both men and women almost increased with age in 2019. The global burden of type 2 diabetes attributable to non-optimal temperature increased from 1990 to 2019, particularly in high temperature, regions with lower SDI, and the older population. Appropriate temperature interventions are necessary to curb climate change and increasing diabetes.

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

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

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

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

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.

Obesity modifies the association of environmental pyrethroid exposure with glucose homeostasis in the US general adults.

Environmental pyrethroids are concerning due to their widespread residues and potential implications on human health. We aimed to assess the association of pyrethroid exposure with glucose homeostasis and examine the interaction between obesity and pyrethroid exposure. A total of 4233 US general adults from the National Health and Nutrition Examination Survey with measured urinary pyrethroid metabolites, fasting plasma glucose (FPG), fasting insulin (FINS), and glycated hemoglobin A1c (HbA1c) were included in the study. The homeostasis model assessment (HOMA2) calculator was utilized to assess insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-IS), and beta-cell function (HOMA2-ß). We estimated the associations of pyrethroid metabolites with glucose homeostasis parameters (FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-ß) using multivariate linear regression models and restricted cubic spline models and further assessed the interaction between obesity and pyrethroid metabolites on glucose dyshomeostasis. Urinary 3-phenoxybenzoic acid (3-PBA) was the most detected pyrethroid metabolite (81%) with a median concentration of 0.43 (interquartile range 0.20-1.01) µg/g urinary creatinine. Compared with the participants in the lowest quartile, those in the highest quartile of 3-PBA had a 1.93% (95% confidence interval: 0.46%, 3.42%), 6.69% (1.96%, 11.64%), 1.60% (0.64%, 2.57%), 7.06% (2.33%, 12.01%), -6.59% (-10.72%, -2.28%), and 1.10% (-2.69%, 5.04%) alteration in FPG, FINS, HbA1c, HOMA2-IR, HOMA2-IS, and HOMA2-ß, respectively. The restricted cubic spline model displayed a linear positive association between 3-PBA and FPG, FINS, HbA1c, and HOMA2-IR, and a negative association with HOMA2-IS (all P for overall <0.05 and P for non-linear >0.05). Additionally, the association between urinary 3-PBA and FPG was modified by general obesity (P for interaction <0.05), with a more pronounced association observed in obese participants than in non-obese participants. Our findings suggested that pyrethroid exposure was associated with glucose dyshomeostasis. General obesity significantly heightened the association between pyrethroid exposure and increased FPG level.

Circ_0000029 Interacts with the miR-576-5p/KCNA1 Axis to Hamper the Development of Pediatric Asthma in an Asthma-Like in vitro Assessment.

OBJECTIVE: Numerous circular RNAs (circRNAs) have been verified to execute crucial roles in "asthma-like" progression of the airway smooth muscle cells (ASMCs). The present study aimed to scrutinize the function and mechanism of circ_0000029 in pediatric asthma etiology in vitro. METHODS: A cell model of asthma was developed using ASMCs induced by platelet-derived growth factor BB (PDGF-BB). Western blotting and qRT-PCR were performed to determine the expression levels of circ_0000029, miR-576-5p, and KCNA1 in PDGF-BB-treated ASMCs. Dual-luciferase reporter, RNA-binding protein immunoprecipitation, and RNA pull-down experiments were conducted to validate targeting relationships. CCK-8 and Transwell assays were performed to evaluate the proliferative and migratory potential of ASMCs. The rate of apoptosis was analyzed using flow cytometry. RESULTS: Pronounced circ_0000029 and KCNA1 downregulation and high levels of miR-576-5p were observed in PDGF-BB-treated ASMCs. Circ_0000029 targets miR-576-5p to regulate KCNA1 expression. The loss of KCNA1 and upregulation of miR-576-5p dramatically impeded apoptosis but promoted ASMC migration and proliferation. Ectopic expression of circ_0000029 manifested the opposite outcome among ASMCs. Furthermore, KCNA1 deficiency and miR-576-5p upregulation counteracted the effects of circ_0000029 overexpression on ASMCs. CONCLUSIONS: Circ_0000029 represses the abnormal migration and growth of ASMCs by mediating miR-576-5p and KCNA1 expression levels. This suggests that the regulatory axis circ_0000029/miR-576-5p/KCNA1 is a potential target for pediatric asthma treatment.

Arsenic exposure incurs hyperglycemia mediated by oxidative damage in urban adult population: A prospective cohort study with three repeated measures.

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 ß (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.

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.

Cross-sectional and longitudinal associations of urinary zinc with glucose-insulin homeostasis traits and type 2 diabetes: Exploring the potential roles of systemic inflammation and oxidative damage in Chinese urban adults.

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

Associations of bifenthrin exposure with glucose homeostasis and type 2 diabetes mellitus in a general Chinese population: Roles of protein carbonylation.

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

The global burden of disease attributable to high fasting plasma glucose in 204 countries and territories, 1990-2019: An updated analysis for the Global Burden of Disease Study 2019.

AIMS: High fasting plasma glucose (HFPG) is an independent risk factor for several adverse health outcomes and has become a serious public health problem. We aimed to evaluate the spatial pattern and temporal trend of disease burden attributed to HFPG from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. MATERIALS AND METHODS: Using data from GBD 2019, we estimated the numbers and age-standardized rates of deaths and disability-adjusted life years (DALYs) attributed to HFPG by calendar year, age, gender, country, region, Socio-demographic Index (SDI), and specific causes. The joinpoint regression analysis was used to assess the temporal trends of deaths and DALYs from 1990 to 2019. RESULTS: In 2019, globally, the numbers of deaths and DALYs attributable to HFPG were approximately 6.50 million and 172.07 million, respectively, with age-standardized rates of 83.00 per 100,000 people and 2104.26 per 100,000 people, respectively. From 1990 to 2019, the global numbers of deaths and DALYs attributed to HFPG have over doubled. The age-standardized rate of DALYs showed an increasing trend, particularly in males and in regions with middle SDI or below. The leading causes of the global disease burden attributable to HFPG in 2019 were diabetes mellitus, ischaemic heart disease, stroke, and chronic kidney disease. CONCLUSIONS: HFPG is an important contributor to increasing the global and regional disease burden. Necessary measures should be taken to curb the growing burden attributed to HFPG, particularly in males and in regions with middle SDI or below.