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.

Genetic association of inflammatory marker GlycA with lung function and respiratory diseases.

Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory diseases (N = 497,000). GlycA showed significant genetic correlation with FEV1 (rg = -0.14), FVC (rg = -0.18), asthma (rg = 0.21) and COPD (rg = 0.31). We consistently identified ten shared loci (including chr3p21.31 and chr8p23.1) at both SNP and gene level revealing potential shared biological mechanisms involving ubiquitination, immune response, Wnt/ß-catenin signaling, cell growth and differentiation in tissues or cells including blood, epithelium, fibroblast, fetal thymus, and fetal intestine. Genetically elevated GlycA was significantly correlated with lung function and asthma susceptibility (354.13 ml decrement of FEV1, 442.28 ml decrement of FVC, and 144% increased risk of asthma per SD increment of GlycA) from MR analyses. Our findings provide insights into biological mechanisms of GlycA in relating to lung function, asthma, and COPD.

Long-term night shift work, genetic predisposition, and risk of incident asthma: a prospective cohort study.

BACKGROUND: Evidence about a potential link between current and lifetime night shift work and risk of incident asthma is insufficient. AIM: To investigate the association of current and lifetime night shift work with risk of incident asthma, and the modified effect of genetic susceptibility on this association. DESIGN AND METHODS: We included 253,773 individuals with complete night shift work information in the UK biobank. We calculated the standard polygenetic risk score (PRS) for asthma. The Cox proportional hazard models were conducted to estimate hazard ratios (HRs) and 95% CIs. RESULTS: After multivariable adjustments, we found that current night shift work was associated with an increased risk of incident asthma in a dose-response fashion (P for trend<0.001). Compared with day workers, those working usual/permanent night shifts had a 17% (95% CI: 1.04-1.33) higher risk of asthma incidence. In addition, we observed significant dose-dependent relationships of longer lifetime duration or frequency of night shift work with elevated risk of asthma incidence (all P for trend<0.05). Compared with never night shift workers, those with a duration (≥5 years) or frequency (≥8 nights/month) of night shift work exhibited a 20% (95% CI: 1.03-1.39) or 22% (95% CI: 1.03-1.44) higher risk of incident asthma, respectively. Moreover, the elevated risk of incident asthma related to current and lifetime night shift work exposure was strengthened by high PRS, although no significant shift work-PRS interactions were detected. CONCLUSION: Both current and lifetime night shift work may increase the risk of incident asthma, regardless of genetic predisposition to asthma.

Associations of coal mine dust exposure with arterial stiffness and atherosclerotic cardiovascular disease risk in chinese coal miners.

OBJECTIVE: Whether coal mine dust exposure increases cardiovascular diseases (CVDs) risk was rarely explored. Our objective was to examine the association between coal mine dust exposure and cardiovascular risk. METHODS: We estimated cumulative coal mine dust exposure (CDE) for 1327 coal miners by combining data on workplace dust concentrations and work history. We used brachial-ankle pulse wave velocity (baPWV, a representative indicator of arterial stiffness) and ten-year atherosclerotic cardiovascular disease (ASCVD) risk to assess potential CVD risk, exploring their associations with CDE. RESULTS: Positive dose-response relationships of CDE with baPWV and ten-year ASCVD risk were observed after adjusting for covariates. Specifically, each 1 standard deviation (SD) increase in CDE was related to a 0.27 m/s (95% CI: 0.21, 0.34) increase in baPWV and a 1.29 (95% CI: 1.14, 1.46) elevation in OR (odds ratio) of risk of abnormal baPWV. Moreover, each 1 SD increase in CDE was associated with a 0.74% (95% CI: 0.63%, 0.85%) increase in scores of ten-year ASCVD and a 1.91 (95% CI: 1.62, 2.26) increase in OR of risk of ten-year ASCVD. When compared with groups unexposed to coal mine dust, significant increase in the risk of arterial stiffness and ten-year ASCVD in the highest CDE groups were detected. CONCLUSION: The study suggested that cumulative exposure to coal mine dust was associated with elevated arterial stiffness and ten-year ASCVD risk in a dose-response manner. These findings contribute valuable insights for cardiovascular risk associated with coal mine dust.

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.

Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants.

BACKGROUND: Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. METHODS: A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. RESULTS: The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. CONCLUSIONS: Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.

Role and mechanism of WNT5A in benzo(a)pyrene-induced acute lung injury and lung function decline.

Benzo(a)pyrene was sparsely studied for its early respiratory impairment. The non-canonical ligand WNT5A play a role in pneumonopathy, while its function during benzo(a)pyrene-induced adverse effects were largely unexplored. Individual benzo(a)pyrene, plasma WNT5A, and spirometry 24-hour change for 87 residents from Wuhan-Zhuhai cohort were determined to analyze potential role of WNT5A in benzo(a)pyrene-induced lung function alternation. Normal bronchial epithelial cell lines were employed to verify the role of WNT5A after benzo(a)pyrene treatment. RNA sequencing was adopted to screen for benzo(a)pyrene-related circulating microRNAs and differentially expressed microRNAs between benzo(a)pyrene-induced cells and controls. The most potent microRNA was selected for functional experiments and target gene validation, and their mechanistic link with WNT5A-mediated non-canonical Wnt signaling was characterized through rescue assays. We found significant associations between increased benzo(a)pyrene and reduced 24-hour changes of FEF50% and FEF75%, as well as increased WNT5A. The benzo(a)pyrene-induced inflammation and epithelial-mesenchymal transition in BEAS-2B and 16HBE cells were attenuated by WNT5A silencing. hsa-miR-122-5p was significantly and positively associated with benzo(a)pyrene and elevated after benzo(a)pyrene induction, and exerted its effect by downregulating target gene TP53. Functionally, WNT5A participates in benzo(a)pyrene-induced lung epithelial injury via non-canonical Wnt signaling modulated by hsa-miR-122-5p/TP53 axis, showing great potential as a preventive and therapeutic target.

Early-life tobacco smoke exposure, genetic susceptibility and the risk of type 2 diabetes in adulthood: A large prospective cohort study.

OBJECTIVES: We aimed to assess the relationships between early-life tobacco smoke exposures and the incident risk of type 2 diabetes (T2D) in later life as well as the joint effects and interactions between genetic susceptibility and early-life tobacco exposures. METHODS: We used data on in utero tobacco exposure and the age of smoking initiation to estimate the status of early-life tobacco exposure in the UK Biobank. Cox proportion hazard models were applied to estimate the associations between early-life tobacco exposure and T2D risk and investigate joint effects and interactions of early-life tobacco smoke exposure with genetic susceptibility. RESULTS: Among 407,943 subjects from the UK Biobank, 17,115 incident cases were documented during a median follow-up of 12.80 years. Compared with subjects without prenatal tobacco exposure, those with in utero tobacco exposure had a higher risk of T2D with a hazard ratio (HR) (95 % confidence interval [CI]) of 1.11 (1.08, 1.15). Besides, the HRs (95 % CIs) of incident T2D for smoking initiation in adulthood, adolescence, and childhood (vs. never smokers) were 1.36 (1.31, 1.42), 1.44 (1.38, 1.50), and 1.78 (1.69, 1.88), respectively (P trend <0.001). No interaction between early-life tobacco exposure and genetic susceptibility was observed. In addition, participants with prenatal (HR 4.67 [95 % CI 4.31, 5.06]) or childhood (6.91 [6.18, 7.72]) tobacco exposure combined with high genetic risk showed the highest risk of T2D, compared to low genetic risk subjects without early-life smoke exposure. CONCLUSION: Early-life tobacco exposure was associated with an increased risk of T2D later in life regardless of genetic background. This highlights the significance of education campaigns aimed at reducing smoking among children, adolescents, and pregnant women as an effective measure to combat the T2D epidemic.

Effects of residential greenness and genetic predisposition on hemoglobin A1c and type 2 diabetes: Gene-environment interaction analysis from a nationwide study.

BACKGROUND: Current evidence on the relations of residential greenness with glucose homeostasis and type 2 diabetes (T2D) remained largely uncertain. Most importantly, no prior studies have investigated whether genetic predisposition modifies the above associations. METHODS: We leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010. Residential greenness was assessed by using the Normalized Difference Vegetation Index, and the weighting T2D-specific genetic risk score (GRS) was constructed based on previously published genome-wide association studies. Linear regression models and logistic regression models were used to investigate associations of residential greenness with glycated hemoglobin (HbA1c) and T2D prevalence, respectively. Interaction models explored whether genetic predisposition modifies greenness-HbA1c/T2D associations. RESULTS: Among 315,146 individuals (mean [SD] age, 56.59 [8.09] years), each one-unit increase in residential greenness was associated with reduction in HbA1c (ß: -0.87, 95% CI: -1.16 to -0.58) and a 12% decrease in odds of T2D (OR: 0.88, 95% CI: 0.79 to 0.98), respectively. Additionally, interaction analyses further demonstrated that residential greenness and genetic risk had cumulative effects on HbA1c and T2D. Compared with individuals who were exposed to low greenness and had high GRS, participants with low GRS and high greenness had a significant decline in HbA1c (ß: -2.96, 95% CI: -3.10 to -2.82, P for interaction = 0.04) and T2D (OR: 0.47, 95% CI: 0.45 to 0.50, P for interaction = 0.09). CONCLUSIONS: We add novel evidence that residential greenness has protective effects on glucose metabolism and T2D, and those beneficial effects can be amplified by low genetic risk. Our findings may facilitate the improvement of the living environment and the development of prevention strategies by considering genetic susceptibility to T2D.

Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures.

Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites (N-acetyl-S-(3-hydroxypropyl)-l-cysteine, N-acetyl-S-(2-carboxyethyl)-l-cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91-6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07-0.14 mmol/L, 4.02-4.57, 5.91-6.52, 19-20, 18-19, and 23-31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63-80, 87-99, and 120-154%, respectively (P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00-38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.

Polycyclic aromatic hydrocarbons exposure and plasma lncRNA signature: A profile and functional analysis.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants that pose detrimental effects on human health, and the exploration of the associations of PAHs exposure with long non-coding RNA (lncRNA) may provide novel clues to the underlying mechanisms. In the present study, we detected 10 urinary PAHs metabolites by GC-MS and plasma lncRNAs levels by Human LncRNA Array v4 among 230 participants from two panels (160 in the Shiyan panel and 70 in the Wuhan-Zhuhai panel). We applied linear regression models to assess the associations between PAHs metabolites and lncRNAs separately in each panel and combined the results using fixed-effect meta-analysis. To explore the potential origin of PAHs-related lncRNAs in plasma, we estimated their tissue-specificity and associations between lncRNAs levels in plasma and leukocytes. Leukocytes mRNA sequencing data and RNA binding proteins were utilized to explore implicated pathways of identified lncRNAs. We found that urinary 1-hydroxyphenanthrene (1-OH-Phe) was inversely associated with 8 lncRNAs and positively associated with 1 lncRNA, as well as 9-hydroxyphenanthrene (9-OH-Phe) was inversely associated with 11 lncRNAs (FDR < 0.1). Tissue specificity analysis using Genome Tissue Expression database suggested that several identified lncRNAs might specifically express in organs targeted by PAHs exposure (lung, liver, heart, kidney, and brain). Besides, plasma levels of 1-OH-Phe related ENSG00000260616 and 9-OH-Phe related STARD4-AS1 were inversely associated with their intra-leukocytes levels (P value < 0.05). Notably, STARD4-AS1 was positively associated with the expression levels of its neighboring protein-coding gene (CAMK4 and STARD4) in leukocytes and were involved in pathways related to cellular response to DNA damage, which we further confirmed using DNA damage biomarker, 8-hydroxydeoxyguanosine. Functional analysis also revealed vital pathways related to cytokine-mediated signaling and glucose homeostasis. Our findings provided novel insights into plausible biological mechanisms underlying the adverse effects of PAHs exposure.

The potential role of plasma miR-4301 in PM2.5 exposure-associated lung function reduction.

The effect of PM2.5 exposure on lung function reduction has been well-documented, but the underlying mechanism remains unclear. MiR-4301 may be involved in regulating pathways related to lung injury/repairment, and this study aimed to explore the potential role of miR-4301 in PM2.5 exposure-associated lung function reduction. A total of 167 Wuhan community nonsmokers were included in this study. Lung function was measured and personal PM2.5 exposure moving averages were evaluated for each participant. Plasma miRNA was determined by real-time polymerase chain reaction. A generalized linear model was conducted to assess the relationships among personal PM2.5 moving average concentrations, lung function, and plasma miRNA. The mediation effect of miRNA on the association of personal PM2.5 exposure with lung function reduction was estimated. Finally, we performed pathway enrichment analysis to predict the underlying pathways of miRNA in lung function reduction from PM2.5 exposure. We found that each 10 µg/m3 increase in the 7-day personal PM2.5 moving average concentration (Lag0-7) was related to a 46.71 mL, 1.15%, 157.06 mL/s, and 188.13 mL/s reductions in FEV1, FEV1/FVC, PEF, and MMF, respectively. PM2.5 exposure was negatively associated with plasma miR-4301 expression levels in a dose‒response manner. Additionally, each 1% increase in miR-4301 expression level was significantly associated with a 0.36 mL, 0.01%, 1.14 mL/s, and 1.28 mL/s increases in FEV1, FEV1/FVC, MMF, and PEF, respectively. Mediation analysis further revealed that decreased miR-4301 mediated 15.6% and 16.8% of PM2.5 exposure-associated reductions in FEV1/FVC and MMF, respectively. Pathway enrichment analyses suggested that the wingless related-integration site (Wnt) signaling pathway might be one of the pathways regulated by miR-4301 in the reduction of lung function from PM2.5 exposure. In brief, personal PM2.5 exposure was negatively associated with plasma miR-4301 or lung function in a dose‒response manner. Moreover, miR-4301 partially mediated the lung function reduction associated with PM2.5 exposure.

Plasma microRNA expression profiles associated with zinc exposure and type 2 diabetes mellitus: Exploring potential role of miR-144-3p in zinc-induced insulin resistance.

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

Associations of selenium exposure with blood lipids: Exploring mediating DNA methylation sites in general Chinese urban non-smokers.

Selenium (Se) is widely distributed in the total environment and people are commonly exposed to Se, while the potential effects and mechanisms of Se exposure on blood lipids have not been well established. This study aimed to assess the associations of urinary Se (SeU) with blood lipids and explore the potential mediating DNA methylation sites. We included 2844 non-smoke participants from the second follow-up (2017-2018) of the Wuhan-Zhuhai cohort (WHZH) in this study. SeU and blood lipids [i.e., total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL)] for all participants were determined. The associations of SeU with blood lipids were analyzed by generalized linear models. Then, we conducted the blood lipids related epigenome-wide association studies (EWAS) among 221 never smokers, and the mediation analysis was conducted to explore the potential mediating cytosine-phosphoguanine (CpG) sites in the above associations. In this study, the SeU concentration of the participants in this study was 1.40 (0.94, 2.08) µg/mmol Cr. The SeU was positively associated with TC and LDL, and not associated with TG and HDL. We found 131, 3, and 1 new CpG sites related to TC, HDL, and LDL, respectively. Mediation analyses found that the methylation of cg06964030 (within MIR1306) and cg15824094 (within PLCH2) significantly mediated the positive association between SeU and TC. In conclusion, high levels of Se exposure were associated with increased TC and LDL among non-smokers, and the methylation of MIR1306 and PLCH2 partly mediated Se-associated TC increase. These findings provide new insights into the effects and mechanisms of Se exposure on lipids metabolism and highlight the importance of controlling Se exposure and intake for preventing high blood lipids.

Neutralization of interleukin-11 attenuates silica particles-induced pulmonary inflammation and fibrosis in vivo.

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11 (IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines (i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins (i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α (IL-11Rα), Glycoprotein 130 (GP130), and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.

Short-term impacts of air pollution on the platelet-lymphocyte ratio and neutrophil-lymphocyte ratio among urban adults in China.

The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure. In this study, we included 3487 urban adults from the Wuhan-Zhuhai cohort. Individual inhalation exposure to air pollutants was estimated by combining participants' daily breath volume and ambient concentrations of six air pollutants (including fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3)). The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date. Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model. We found that PLR was negatively related to PM2.5 (lag02-lag06), PM10 (lag02-lag07), NO2 (lag02-lag07), and SO2 (lag03-lag05) and NLR was negatively related to PM10 (lag05 and lag07). In the BKMR model, a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed, whereas PM10 and NO2 appeared to be more important than the other pollutants in the mixture. The negative impact of air pollutants was stronger in males, participants with lower body mass index (< 24 kg/m2), those cooking meals at home, drinkers, and non-exercisers. In conclusion, short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood. PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.

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.

Exposures to volatile organic compounds, serum vitamin D, and kidney function: association and interaction assessment in the US adult population.

The relationships of exposures to volatile organic compounds (VOCs) with vitamin D and kidney function remain unclear. Our analyses included 6070 adults from 2003 to 2010 survey cycles of the National Health and Nutrition Examination Survey to explore associations of six VOCs with serum vitamin D, albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR). The results suggested that dibromochloromethane was positively associated with ACR, and chloroform was inversely associated with ACR. U-shaped associations of toluene, m-/p-xylene, bromodichloromethane, and 1,4-dichlorobenzene with ACR were observed. Toluene, m-/p-xylene, and 1,4-dichlorobenzene were associated with eGFR in U-shaped manners, while bromodichloromethane and chloroform were inversely associated with eGFR. Elevation in 1,4-dichlorobenzene was associated with decrease in vitamin D, while chloroform and m-/p-xylene were in U-shaped associations with vitamin D. VOCs mixture was U-shaped associated with ACR, inversely associated with eGFR, and inversely associated with vitamin D. Vitamin D was in a U-shaped association with ACR. Vitamin D significantly interacted with VOCs on the two kidney parameters. In the US adult population, exposures to VOCs were associated with kidney function and serum vitamin D level decline, and the serum vitamin D may have interaction effects with VOCs exposures on kidney function.

Characteristics of Diagnosed and Death Cases of Pneumoconiosis in Hubei Province, China, 1949-2019.

OBJECTIVE: This study aims to summarize the characteristics of diagnosed pneumoconiosis and pneumoconiosis death in the Hubei Province of China, between the years 1949 and 2019, and provide clues for the scientific prevention of pneumoconiosis. METHODS: We recruited 23,069 pneumoconiosis cases in Hubei Province, China, from 1949 to 2019. Basic information and occupational surveillance information were obtained from the Hubei Occupational Diseases and Health Risk Factors Information Surveillance System. RESULTS: The annually diagnosed pneumoconiosis cases showed an overall increasing trend from 1949 to 2019 in Hubei Province. The major types of pneumoconiosis were coal workers' pneumoconiosis (CWP, 49.91%) and silicosis (43.39%). Pneumoconiosis cases were mainly engaged in mining (75.32%) and manufacturing (12.72%), and were distributed in Huangshi (35.48%), Yichang (16.16%), and Jingzhou (7.97%). CWP (47.50%) and silicosis (44.65%) accounted for most of the deaths. CONCLUSIONS: The number of pneumoconiosis cases and deaths in Hubei increased in the period of 1949 to 2019. Silicosis and CWP contributed to the predominant types of pneumoconiosis. Prevention and control measures should continue to be taken to reduce the morbidity and mortality of pneumoconiosis.

The emerging role of epigenetic regulation in the progression of silicosis.

Silicosis is one of the most severe occupational diseases worldwide and is characterized by silicon nodules and diffuse pulmonary fibrosis. However, specific treatments for silicosis are still lacking at present. Therefore, elucidating the pathogenesis of silicosis plays a significant guiding role for its treatment and prevention. The occurrence and development of silicosis are accompanied by many regulatory mechanisms, including epigenetic regulation. The main epigenetic regulatory mechanisms of silicosis include DNA methylation, non-coding RNA (ncRNA), and histone modifications. In recent years, the expression and regulation of genes related to silicosis have been explored at epigenetic level to reveal its pathogenesis further, and the identification of aberrant epigenetic markers provides new biomarkers for prediction and diagnosis of silicosis. Here, we summarize the studies on the role of epigenetic changes in the pathogenesis of silicosis to give some clues for finding specific therapeutic targets for silicosis.