The environmental factors underlying idiopathic membranous nephropathy (IMN) remain inadequately comprehended. Our purpose is to investigate the environmental factors that contribute to the IMN. Polycyclic aromatic hydrocarbons (PAHs) as a major harmful component of airborne particulate matter, are suspected to be associated with IMN. We employed a 1:1 pair-matched case-control, network toxicology and molecular docking to validate the role of urinary PAHs metabolites in IMN pathogenesis. Urine samples from 146 IMN patients and 146 controls were analyzed for six monohydroxylated PAHs using UPLC-MS/MS. The creatinine-adjusted 1-hydroxynaphthalene (1-OHNAP), 2-hydroxynaphthalene (2-OHNAP), total hydroxynaphthalene (∑OHNAP), and total OHPAHs (∑OHPAHs) were significantly higher in IMN patients (P < 0.05) with odds ratios of 1.42, 1.66, 1.29, and 1.19 respectively, indicating a significantly increased risk of IMN. 8-OHdG were higher in the IMN group. Subgroup analyses indicated stronger associations among males and drinkers. The RCS curve shows that PAHs concentration increases, the risk of IMN generally rises. (P < 0.05). Integrated network toxicology and molecular docking identified TGFβ1 as a key potential target. Molecular dynamics simulations confirmed a stable binding interaction between 2-OHNAP and TGFβ1. This finding was further supported by external RNA-seq data showing elevated TGFβ1 expression in the glomeruli of IMN patients. We report novel evidence suggesting that exposure to PAHs may contribute to the risk of IMN by disrupting immune system, highlighting the environmental factors driving IMN and offering potential therapeutic targets for this increasingly prevalent glomerular disease.

KEY POINTS:Higher planetary health diet score was related to improved kidney function, reduced prevalence and incidence of CKD, and lower all-cause mortality. Higher planetary health diet score was correlated with lower greenhouse gas emission and land use, but with higher water use. Socioeconomic deprivation linked to lower planetary health diet adherence and weakened planetary health diet benefits on cystatin C and all-cause mortality. BACKGROUND:While planetary health diet (PHD) benefits human and environmental health, its effect on CKD under socioeconomic deprivation remains unclear. We investigated the associations between PHD and kidney function, CKD, mortality, and environmental effects, while evaluating the moderating role of socioeconomic deprivation. METHODS:We included 125,581 UK Biobank and 35,021 National Health and Nutrition Examination Surveys (NHANES) participants. The associations between PHD score, kidney function, CKD, mortality, and environmental impacts were assessed using Cox proportional-hazards model, logistic regression, or multiple linear regression models. Multiplicative interactions between PHD scores and index of multiple deprivation and its domains on these associations were evaluated. RESULTS:In the UK Biobank and NHANES, median PHD score was 62.34 (53.74-70.97) and 40.45 (31.38-50.21), respectively. In UK biobank, each one-point higher PHD score was associated with greater eGFR ( β [95% confidence interval], 0.05 [0.04 to 0.05]). Compared with the lowest quartile (Q1) of PHD score, the highest quartile (Q4) was associated with lower CKD (hazard ratio [95% confidence interval], 0.75 [0.69 to 0.81]) and all-cause mortality (0.83 [0.78-0.89]). Similarly, in NHANES participants each one-point higher PHD adherence was associated with greater eGFR (0.06 [0.05-0.08]), lower CKD prevalence (OR Q4 versus Q1 : 0.80 [0.73-0.88]), and lower risk of all-cause mortality (hazard ratio Q4 versus Q1 : 0.85 [0.77-0.93]). Higher PHD score was correlated with lower greenhouse gas emission and land use, but with higher water use. Stronger inverse associations of PHD with cystatin C were observed among individuals with higher health deprivation ( P < 0.01), while stronger inverse associations with all-cause mortality were observed among those with higher employment and living environment deprivation ( P = 0.01). CONCLUSIONS:PHD was associated with improved kidney health, lower all-cause mortality, greenhouse gas emission, and land use, with strongest health benefits in socioeconomically deprived populations. Our study supports PHD as a strategy for concurrent human and planetary health, highlighting its potential to address health inequities.

Disentangling the nonlinear and interactive effects of chemical mixtures remains a central challenge in environmental health, hindering etiologic understanding of immune-mediated diseases such as primary membranous nephropathy (PMN). We developed a multi-stage pipeline integrating exposure clustering, penalized feature selection, interpretable machine learning, and model-based causal inference framework to dissect metal impacts on immune-renal dysfunction. Among 795 adults in Guangxi, China, we quantified 21 plasma metals and three endpoints: PMN diagnosis, estimated glomerular filtration rate (eGFR), and uric acid. Clustering revealed Zn-dominant profiles enriched in PMN patients versus Fe-centered patterns in controls. Tree-based models with SHAP interpretation identified Ba and Tl as being positively associated with PMN, while Co and Ni showed inverse associations. Mo was further linked to elevated uric acid and reduced eGFR, indicating coordinated relationships across metabolic and renal biomarkers rather than definitive evidence of toxicity. Interaction analyses revealed complex, nonlinear relationships, including NiCu antagonism and CoNi dose-modulated associations, highlighting the collective dynamics of metal mixtures in influencing PMN risk. As the first study to couple plasma metal exposomics with interpretable and causal-inspired machine learning in PMN, this work identifies novel exposure patterns and generates etiologic hypotheses, offering a transferable analytic framework for environmental health research.

AbstractBackground: Primary membranous nephropathy (PMN) is hypothesized to result from interactions between genetic susceptibility, particularly polymorphisms in the phospholipase A2 receptor 1 (PLA2R1) gene, and environmental factors. However, the joint effects of metal exposure and PLA2R1 variants on PMN risk remain largely unknown.Methods: This hospital-based case-control study enrolled 125 PMN patients and 375 healthy controls. Plasma levels of 16 metals were measured via inductively coupled plasma mass spectrometry (ICP-MS). Eight functional single nucleotide polymorphisms (SNPs) in the PLA2R1 gene (rs16844715, rs2715918, rs1511223, rs3749117, rs3749119, rs3828323, rs4664308, and rs4665143) were genotyped by Sanger sequencing. Associations and interactions were analyzed using logistic regression, weighted quantile sum (WQS) regression, extreme gradient boosting (XGBoost), the least absolute shrinkage and selection operator (LASSO), and multiplicative and additive interaction models.Results: After adjusting for confounders, higher plasma levels of vanadium (V), manganese (Mn), zinc (Zn), arsenic (As), strontium (Sr), molybdenum (Mo), cadmium (Cd), tungsten (W), thallium (Tl), and lead (Pb) were associated with increased risk of PMN, whereas cobalt (Co), nickel (Ni), selenium (Se), and rubidium (Rb) were associated with decreased PMN risk (all P < 0.05). Multi-method screening identified Zn, Mo, Tl, and Ni as key metals associated with PMN. The PLA2R1 SNPs rs3749117 and rs3749119 were significantly associated with susceptibility to PMN (P < 0.05). And the rs3749117 polymorphism exhibited negative additive interactions with plasma Zn (relative excess risk due to interaction (RERI) = −12.59; 95% confidence interval (CI): −65.86 to −1.56) and Mo (RERI = −6.25; 95% CI: −33.60 to −0.44), as well as a negative multiplicative interaction with Ni (odds ratio (OR) = 0.10; 95% CI: 0.01–0.99) on PMN risk. The rs3749119 polymorphism also demonstrated a negative additive interaction with Mo (RERI = −18.46; 95% CI: −116.62 to −2.49) in modulating susceptibility to PMN.Conclusions: The development of PMN appears to result from the combined effects of environmental metal exposure and genetic susceptibility. PLA2R1 polymorphisms interact with Zn, Mo, and Ni exposure, collectively contributing to PMN pathogenesis.

Phthalates (PAEs), widely used in plastics and consumer products, have raised growing concern due to the potential adverse health effects of their metabolites. While several epidemiological studies have linked PAE metabolites to nephrotoxicity, most have focused on exposure-response associations, leaving their molecular targets and mechanisms insufficiently defined. Here, we observed that mono-2-ethylhexyl phthalate (MEHP) was associated with reduced estimated glomerular filtration rate (eGFR) (WQS weight = 0.31) and increased albuminuria (WQS weight = 0.15) in patients with chronic kidney disease (CKD). In vivo, MEHP exposure preferentially induced glomerular injury, characterized by foot process effacement, while renal tubules remained unaffected. A genome-wide CRISPR-Cas9 screen highlighted toll-like receptor 4 (TLR4) as a potential mediator of MEHP-induced podocyte damage via MyD88-JNK pathway activation. In vitro experiments demonstrated that TLR4 activation by MEHP triggered downstream MyD88 recruitment and JNK phosphorylation, leading to podocyte injury. Notably, MEHP did not change TLR4 expression levels but directly interacted with TLR4 at Glu439 and MD2 at Arg90, promoting dimerization of the TLR4-MD2 complex and subsequent JNK activation. Furthermore, inhibition or genetic deletion of TLR4 mitigated MEHP-related nephrotoxic responses in acute kidney injury and CKD models. These findings suggest a TLR4-dependent mechanism that may contribute to MEHP-associated kidney effects, supporting the importance of continued efforts to reduce PAE exposure.

Although excessive manganese (Mn) exposure is known to cause neuromotor function in cases of poisoning, its effect on grip strength (a neuromotor marker) in older adults at environmental levels remains unclear. To investigate this issue, we conducted an integrated investigation combining epidemiology and animal experimentation to examine the association between urinary manganese and grip strength. A cross-sectional study of 375 elderly men (60–74 years) was conducted in Guangxi, China, from 2016 to 2017. Urinary Mn concentrations were determined by ICP-MS, and their associations with grip strength were evaluated using generalized linear models and restricted cubic splines. In parallel, 32 six-week-old male C57BL/6J mice were exposed to 0, 5, 10, or 15 mg/kg MnCl2·4H2O via intraperitoneal injection for 6 weeks. Forelimb grip strength of the mice was measured after the final exposure, and mRNA expression of inflammatory markers and cytokines (C reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in triceps) in triceps tissue was quantified. The median urinary Mn concentration in the study population was 0.22 μg/g creatinine. After adjusting for confounders, urinary Mn was inversely associated with hand grip strength (highest vs. lowest tertile: β = −3.57 kg; 95% CI: −5.68 to −1.47; p-trend = 0.007). Similarly, in male C57BL/6J mice, grip strengths declined significantly with increasing Mn exposure (p-trend < 0.0001), accompanied by upregulation of the mRNA levels of CRP, IL-6 and TNF-α in muscle tissue. Together, our findings suggest that environmental manganese exposure is inversely associated with grip strength in elderly men. While the manganese doses used in the animal study exceeded typical human environmental exposure, the experimental results further indicate that such grip strength reduction may be linked to muscle inflammation.

Manganese (Mn) is an essential micronutrient required for various biological processes but excess exposure to Mn can cause neurotoxicity. However, there are few reports regarding the toxicity effect of Mn on the kidney as well as the underlying molecule mechanism. Herein, in vivo experiments were adopted to assess the toxicity effects associated with Mn, and found that chronic Mn treatment induced the injury of glomerular podocytes but not renal tubule in rats. Genome-wide CRISPR/Cas9 knockout screen was then employed to explore the biotargets of the toxic effect of Mn on podocytes. Through functional analyses of the enriched candidate genes, NLRP10 was found to be significantly up-regulated and mediated Mn-induced podocyte apoptosis. Further mechanism investigation revealed that NLRP10 expression was regulated by demethylase AlkB homolog 5 (ALKBH5) in an m6A-dependent fashion upon Mn treatment. Moreover, Mn could directly bind to Metadherin (MTDH) and promoted its combination with ALKBH5 to promote NLRP10 expression and cell apoptosis. Finally, logistic regressions, restricted cubic spline regressions and uniform cubic B-spline were used to investigate the association between Mn exposure and the risk of chronic kidney disease (CKD). A U-shaped nonlinear relationship between CKD risk and plasma Mn level, and a positive linear relationship between CKD risk and urinary Mn levels was found in our case-control study. To sum up, our findings illustrated that m6A-dependent NLRP10 regulation is indispensable for podocyte apoptosis and nephrotoxicity induced by Mn, providing fresh insight into understanding the health risk of Mn and a novel target for preventing renal injury in Mn-intoxicated patients.

Immunoglobulin A nephropathy (IgAN) is the most common type of glomerulonephritis in adults worldwide. Environmental metal exposure has been reported to be involved in the pathogenic mechanisms of kidney diseases, yet no further epidemiological study has been conducted to assess the effects of metal mixture exposure on IgAN risk. In this study, we conducted a matched case‒control design with three controls for each patient to investigate the association between metal mixture exposure and IgAN risk. A total of 160 IgAN patients and 480 healthy controls were matched for age and sex. Plasma levels of arsenic, lead, chromium, manganese, cobalt, copper, zinc, and vanadium were measured using inductively coupled plasma mass spectrometry. We used a conditional logistic regression model to assess the association between individual metals and IgAN risk, and a weighted quantile sum (WQS) regression model to analyze the effects of metal mixtures on IgAN risk. Restricted cubic splines were used to evaluate overall associations between plasma metal concentrations and estimated glomerular filtration rate (eGFR) levels. We observed that except for Cu, all the metals analyzed were nonlinearly associated with decreased eGFR, and higher concentrations of arsenic and lead were associated with elevated IgAN risk in both single-metal [3.29 (1.94, 5.57), 6.10 (3.39, 11.0), respectively] and multiple-metal [3.04 (1.66, 5.57), 4.70 (2.47, 8.97), respectively] models. Elevated manganese [1.76 (1.09, 2.83)] levels were associated with increased IgAN risk in the single-metal model. Copper was inversely related to IgAN risk in both single-metal [0.392 (0.238, 0.645)] and multiple-metal [0.357 (0.200, 0.638)] models. The WQS indices in both positive [2.04 (1.68, 2.47)] and negative [0.717 (0.603, 0.852)] directions were associated with IgAN risk. Lead, arsenic, and vanadium contributed significant weights (0.594, 0.195, and 0.191, respectively) in the positive direction; copper, cobalt, and chromium carried significant weights (0.538, 0.253, and 0.209, respectively). In conclusion, metal exposure was related to IgAN risk. Lead, arsenic, and copper were all significantly weighted factors of IgAN development, which may require further investigation.

It has been recognized for some time that a number of different neuropeptides exert powerful effects on food intake. During the last few years, the neurocircuitry within which these peptides operate has also begun to be elucidated. Peptidergic feeding-regulatory neurones are found both in the hypothalamus and the brainstem, where they act as input stations for hormonal and gastrointestinal information, respectively. These cell populations both project to several other brain regions and interconnect extensively. The present review summarizes the neuroanatomy and connectivity of some prominent peptides involved in food intake control, including neuropeptide Y, melanocortin peptides, agouti gene-related protein, cocaine- and amphetamine-regulated transcript, orexin/hypocretin, melanin-concentrating hormone and cholecystokinin. Disturbances in the hypothalamic neuropeptide systems have been implicated in the phenotype of a genetic model of fatal hypophagia, the mouse anorexia (anx) mutation, which is also discussed.

Household animal fat has been linked to increased incidence of cancers compared with vegetable fat. However, few epidemiological studies have associated these two cooking oil types with precancerous genotoxic effects, such as occurrence of micronuclei (MN). This study aimed to explore the association between oral MN frequency and household cooking oil type and whether the association can be attributed to polycyclic aromatic hydrocarbons (PAHs). We collected information about individual cooking oil use, measured genotoxic effects by MN tests and urinary PAHs metabolites (OHPAHs) in 245 nonsmokers. The associations between household cooking oil type and MN frequency and OHPAHs were analyzed using generalized linear models (GLMs) and logistic regression models, evaluating odds ratios and coefficient (95% confidence intervals) (ORs, 95% Cls; β, 95% Cls). The odds of animal fat consumers, rather than vegetable fat consumers, was positively associated with higher MN frequency (OR = 1.94, P < 0.05). The associations were discovered in participants only using kitchen ventilation (OR = 2.04, P < 0.05). Animal fat consumers had higher total OHPAHs than vegetable fat consumers (1.58 ± 0.22 mg/mol, Cr vs 1.20 ± 0.12 mg/mol, Cr; P = 0.028). Significant correlations were observed between total OHPAHs quartiles and increased MN frequency (β = 0.38, P-trend = 0.026). After stratifying by household cooking oil type, sensitivity analyses showed that the positive association between total OHPAHs quartiles and increased MN frequency was only observed in animal fat consumers (β = 0.61, P-trend = 0.030). In conclusion, usage of household animal fat was associated with an increased odds of oral MN frequency in Chinese nonsmokers and the odds correlated with increased PAHs exposure. This finding supplemented evidence associating cooking oil type with genotoxic effects and explained its association with PAHs exposure.

Background: Elevated manganese (Mn) exposure impairs cognition in adults and children, but the association between Mn and cognitive function in elderly people is unclear. Previous studies have linked Mn neurotoxicity in AD to A beta-dependent mechanisms. However, the association between Mn and plasma APP and A beta in the general elderly population remains unknown. This study aimed to investigate the association between Mn exposure and cognitive function, plasma APP and plasma A in older adults. Methods: Cognitive abilities in 375 men aged 60 and older in Guangxi, China were assessed using the Mini-Mental State Examination (MMSE) and cognitive impairment were identified using education-stratified cut-off points of MMSE scores. Urinary Mn levels and plasma APP, and A beta levels were measured using ICP-MS and ELISA, respectively. Results: A total of 109 (29.07 %) older men were identified as having cognitive impairment. The median urinary Mn level was 0.22 mu g/g creatinine. Urinary Mn levels were negatively correlated with MMSE scores (beta = -1.35, 95 % CI: -2.65 to -0.06; p = 0.041). In addition, higher concentrations of urinary manganese were associated with a greater risk of cognitive impairment (OR - 2.03, 95 % CI: 1.14-3.59; comparing the highest and lowest manganese; p = 0.025). Moreover, plasma APP levels were inversely associated with urinary Mn levels (r = -0.123, p = 0.020), and positively associated with MMSE scores (r = 0.158, p = 0.002). Surprisingly, no correlations were observed between plasma A beta 42, A beta 40, A beta 40/A beta 42, or A beta 42/A beta 40 and urinary Mn levels and MMSE scores. Conclusion: These results suggested that Mn exposure is negatively associated with older men's cognition and plasma APP levels, but not plasma A beta levels.

Kitchen emissions are mixed indoor air pollutants with adverse health effects, but the large-scale assessment is limited by costly equipment and survey methods. This study aimed to discuss the application of backpropagation (BP) neural network models in the assessment of kitchen emissions based on the exposure marker. A total of 3686 participants were recruited for the kitchen survey, and their sleep quality was measured by the Pittsburgh sleep quality index (PSQI). After excluding the confounders, 365 participants were selected to assess their urinary hydroxy polycyclic aromatic hydrocarbons (OH-PAHs) concentrations by ultra-high-performance liquid chromatography/tandem mass spectrometry. Two BP neural network models were then set up using the survey and detection data from the 365 participants and used to predict the total urinary OH-PAHs concentrations of all participants. The total urinary OH-PAHs and 1-hydroxy-naphthalene (1-OHNap) concentrations were significantly higher among the 365 participants with poor sleep quality (global PSQI score > 5; P < 0.05). Results from internal and external validation showed that our model has high credibility (model 2). Further, the participants with higher predicted total urinary OH-PAHs concentrations were associated with the global PSQI score of >5 (odds ratio (OR) = 1.284, 95% confidence interval (CI) = 1.082–1.525 for participants with predicted total urinary OH-PAHs concentrations of over 1.897 μg/mmol creatinine in model 1, and OR = 1.467, 95% CI = 1.240–1.735 for participants with predicted total urinary OH-PAHs concentrations of over 2.253 μg/mmol creatinine in model 2) after adjusting for the confounders. Findings suggest that the BP neural network model is suitable for assessing kitchen emissions, and the urinary OH-PAHs concentrations can be taken as the model outlay.

Cadmium (Cd) is a known neurotoxicant and its relation with cognition has been well studied in children. However, evidence linking Cd and cognitive function among older individuals is limited. To evaluate the association between Cd exposure and cognitive function in older age, we conducted a cross-sectional study involving 375 older men aged 60-74 years (mean age: 66.0 years) in Guangxi, China. Urinary Cd concentrations were measured. Cognitive function was assessed by the Chinese version of Mini-Mental State Examination (MMSE) and cognitive impairment was identified using education-specific cutoff points of MMSE scores. General linear regression and logistic regression models were applied to evaluate the associations of urinary Cd concentrations with MMSE scores and the risk of cognitive impairment, respectively. The median urinary Cd concentration of all participants was 1.58 mu g/g creatinine. Urinary Cd levels were inversely associated with MMSE scores [beta = -0.76; 95% confidence interval (CI): -1.28 to -0.23 for a 2-fold increase in urinary Cd]. A 2-fold increase in urinary Cd was associated with increased risk of cognitive impairment [adjusted odds ratio (OR) = 1.46; 95% CI: 1.14 to 1.86]. When urinary Cd levels were analyzed as quartiles, higher urinary Cd levels were also significantly associated with increased risk of cognitive impairment in a dose-response manner (adjusted OR = 2.68; 95% CI: 1.33 to 5.38 for the highest vs. lowest quartile; p for trend = 0.002). Our findings suggest that long-term exposure to Cd may have adverse consequences for older men's cognitive function, but these results need further confirmation. (C) 2020 Published by Elsevier Ltd.

Few studies have explored the associations of ischemic heart disease (IHD) hospitalizations with fine (diameter <= 2.5 mu m, PM2.5) and coarse particulate matter (diameter between 2.5 and 10 mu m, PMC) simultaneously; and studies to distinguish the susceptible populations by sex, age, and comorbidity status are sparse and inconsistent. This study aimed to assess the differential effects of PM2.5 and PMC on IHD hospitalizations and to investigate modifiers of demographic characters, causes of hospitalizations, and comorbidity status on these differential effects. A time-series analysis using an over-dispersed generalized additive model on 33017 IHD hospitalizations was conducted in urban areas of Chengdu, Southwestern China, from 1 January 2015 to 31 December 2016. Z-test was used to test whether PMC- or PM2.5-related effects were differential within each modifier. Furthermore, to evaluate the robustness of the key findings for gaseous pollutants exposure adjustment, co-pollutant models were constructed. We identified differential effects of PM2.5 and PMC on IHD hospitalizations in terms of the effect magnitude, effect stability, and susceptible populations. A 10 mu g/m(3) increment of PM2.5 and PMC at lag06 was associated with a 1.2% (95% confidence interval (CI): 0.3%, 2.2%) and 2.5% (95%CI: 1.1%, 3.8%) increase in IHD hospitalizations, respectively. After adjustment for gaseous pollutants, PMC effect was independent, particularly among males, angina, chronic IHD, and patients with comorbidity of chronic heart failure, hypertension, or chronic obstructive pulmonary disease (COPD); whereas, PM2.5 effect remained significant among patients with comorbidity of hypertension. Males, comorbidity of hypertension or COPD substantially increased the PMC-related risk for IHD hospitalizations; whereas, only comorbidity of hypertension increased the PM2.5-related risk for IHD hospitalizations. Interestingly, the PMC effect was comparable between the middle-aged and the elderly. Our study found differential effects of PM2.5 and PMC on IHD hospitalizations and identified susceptible populations, which are important to establish guidelines or recommendations for high-risk individuals.

Some literature has documented ambient fine particulate matter (PM2.5) pollution and corresponding health burden in China, however, the knowledge of spatial disequilibrium of PM2.5 and PM2.5-induced disease burden is scarce. With the help of gravity center model, spatial autocorrelation analysis as well as the region-specific exposure-response coefficient and ground-based PM2.5 daily concentrations over 336 cities in China from January 2016 to December 2017, this paper provides a completive assessment for spatial disequilibrium of PM2.5-induced health burden. Improving PM2.5 concentrations and declining PM2.5-induced health burden were found in China. The 2-year city-average concentration of the 336 cities was 45 +/- 17 mu g/m(3) with a range from 11 mu g/m(3) to 128 mu g/m(3). PM2.5-related deaths from stroke, ischemic heart disease, chronic obstructive pulmonary disease, hypertensive heart disease and lower respiratory infection amounted to 0.766 million in 2016 and 0.720 million in 2017. Much higher but decreasing PM2.5-induced mortality happened in the west, while higher and increasing PM2.5-induced deaths existed in the south. Strong spatial autocorrelation of PM2.5 and PM2.5-induced disease burden existed among cities, illustrated by high-high (HH) clusters with significant spatial homogeneity and spatial spillover effect. The cities included in PM(2.5 )concentration HH cluster had average PM2.5 concentration 68.5 mu g/m(3), about 1.5 times higher than the national average; the cities involved in combined mortality HH cluster had mortality 90.5/10(5), 1.8 times as much as the national city-average level; about 46.4% of PM2.5-induced combined deaths happened in HH cluster cities. The cities embraced in the HH clusters of PM2.5 concentration, population, deaths and mortality simultaneously, mostly located in Hebei, Shandong and Henan provinces, should be the top priorities for joint air pollution control. This paper provides important implications for policymakers regarding priority areas of joint air pollution control in China. (C) 2019 Elsevier Ltd. All rights reserved.

Massive monitoring data requires effective statistical analysis methods. This paper aims to visualize the spatiotemporal characteristics and spillover effect of air pollutants. Ground-based PM2.5 data in 336 cities across China revealed a tough but improving situation. The PM2.5 average annual concentrations in 2016 and 2017 were 47 ± 18 µg/m3 and 44 ± 16 µg/m3 respectively, but a worse, or at least a not-improving PM2.5 situation happened in winter. A slight declining north-south disequilibrium and a growing east-west disequilibrium exhibited in 2017, along with an increasing weight of eastern and southern pollution in the proportion of the overall pollution level. North-south disequilibrium existed stably throughout the year but east-west disequilibrium was erratic. Nearly half of the cities exhibited significant spillover effects, presenting 2 clusters with spillover by high concentrations and 3 clusters with spillover by low concentrations. Most cities in Hebei, Shandong and Henan provinces showed a high but decreasing spillover effect, but increasing trend happened in the cities in Anhui and Shanxi provinces. A significant correlation appeared between the city population and PM2.5 concentration. Population density explained about 25% of the PM2.5 concentration change, and the explanation ability increased in 2017. A higher influence of population on PM2.5 concentration happened in the early stage of city development, and the influence exhibited spatial differences. The city population and PM2.5 spillover effect existed an overall positive correlation, but the population only addressed about 10% of the spillover effect change. Our findings provide important information for the joint prevention and control of air pollution in China, and the approach proposed in this paper is applicable to other fields.

Exposure to the heavy metal cadmium has adverse effects on human health, including DNA methylation. This study aimed to investigate the effects of cadmium on liver and kidney functions and Klotho gene methylation and to explore the relationship of methylation level with indicators of liver and kidney functions. Graphite furnace atomic absorption spectrometry was conducted to determine urinary cadmium, and an automatic biochemical analyzer was used to detect indices of liver and kidney functions. PCR pyrosequencing was performed to detect the methylation rate of Klotho. One-way ANOVA was adopted to compare the differences between groups, and the linear correlation to variables was analyzed. Cadmium exposure was negatively correlated with albumin level (r=-0.143, p=0.021) and positively correlated with urinary β2-microglobulin level (r=0.229, p<0.001). However, the methylation levels of Klotho gene was decreased and increased by low and high doses of cadmium exposure, respectively. And Klothomethylation levels were negatively correlated with albumin levels and positively correlated with β2-microglobulin levels.In this study, cadmium exposure affects liver and kidney functions as well as Klotho methylation levels, but the effect on Klotho methylation levels is not linear. Klotho methylation levels also influence liver and kidney functions.

Few studies have reported on the effects of fixed and rotating shift systems on the prevalence of sleep disturbance. Thus, in this study, the relationships between different work schedules and sleep disturbance in Chinese workers were investigated. A total of 2180 workers aged 19-65years responded to the self-report questionnaire on shift work schedule (fixed day-shift, fixed night-shift, two-shift or three-shift system), working hours a day, and working days a week, physical effort, subjective sleep quality and subjective mental state. It was found that the rotating shift workers, namely, two- and three-shift workers, exhibited higher risks of sleep disturbance than with the fixed day-shift workers did (OR 1.37; 95% CI 1.07 to 1.74; and OR 2.19; 95% CI 1.52 to 3.15, respectively). The risk was particularly high among two- or three-shift workers who worked more than 8 hours a day or more than 5 days a week and among three-shift workers who reported both light and heavy physical effort at work. Moreover, the two- and three-shift workers (rotating shift workers) suffered from poorer sleep quality than the fixed night shift workers did (OR 1.84; 95% CI 1.01 to 3.32; and OR 2.94; 95% CI 1.53 to 5.64, respectively). Consequently, rotating shift work (two- and three-shift work) is a risk factor for sleep disturbance, and the fixed work rhythm may contribute to the quality of sleep.

INTRODUCTION Tobacco use has been implicated as an important factor for poor sleep quality. However, in most studies, the sleep quality of smokers was only assessed though a self-reported questionnaire, without measuring any internal biomarkers that reflect the levels of tobacco exposure. We examined the association of active and passive smoking with sleep quality, assessed smoking exposure using urinary 1-hydroxypyrene (1-HOP) as an internal biomarker, and further explored the relationship between 1-HOP and sleep quality. METHODS A cross-sectional survey was conducted in Liuzhou city, Guangxi, China. A total of 1787 male enterprise workers were enrolled. The smoking attribute data were collected by self-reported questionnaire, and individual sleep quality was evaluated through the Pittsburgh Sleep Quality Index (PSQI). The concentration of urinary 1-HOP was measured by high-performance liquid chromatography. RESULTS Compared with non-smoking, active smoking and passive smoking were significantly associated with long sleep latency (odds ratio, OR=1.84, 95% confidence interval, CI=1.28-2.64; 1.45, 1.00-2.11, respectively), short sleep duration (OR=2.72, 95% CI=1.45-5.09; 1.94, 1.01-3.71, respectively), daytime dysfunction (OR=1.54, 95% CI=1.10-2.17; 1.44, 1.02-2.03, respectively), and overall poor sleep quality with PSQI total score > 5 (OR=1.41, 95% CI=1.05-1.88; 1.34, 1.00-1.79, respectively). Compared with non-smokers, active smokers had higher urinary 1-OHP concentrations that were significant (p=0.004), while passive smokers had no significant difference in urinary 1-OHP concentration (p=0.344). The high concentration group was significantly associated with daytime dysfunction and overall poor sleep quality with PSQI total score > 5 (OR=1.73, 95% CI=1.06-2.81; 1.76, 1.18-2.63, respectively). CONCLUSIONS Both active smoking and passive smoking are risk factors for poor sleep quality among Chinese male enterprise workers. Active smokers had significantly higher levels of urinary 1-OHP than non-smokers, and high concentration of 1-OHP was associated with daytime dysfunction and overall poor sleep quality.

Poor sleep quality is an important symptom of many medical or psychiatric disorders. However, the impact of cooking oil fumes (COFs) on sleep quality has not been studied. This population-based cross-sectional study was conducted to examine the association between COFs of Chinese household cooking and sleep quality. Individual sleep quality assessment was completed in 2197 participants with an average age of 37.52 years, through Pittsburgh Sleep Quality Index (PSQI). Information about their cooking practice were also collected by self-reported questionnaire. As an internal biomarker of COFs, urinary 1-hydroxypyrene (1-HOP) (n = 562) was further measured using high-performance liquid chromatography. Binary logistic regression models were performed to evaluate the association between exposure to COFs and individual sleep quality. We found that, subjective poor kitchen ventilation, preheating oil to smoking, and cooking for over 30 minutes were positively associated with overall poor sleep quality (global PSQI score > 5) [odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.43-2.16; 1.25, (1.03-1.52); 1.42, (1.15-1.76), respectively]. After adjusting for potential confounders, subjective poor kitchen ventilation still tend to increase the risk of long sleep latency, sleep disturbances, and daytime dysfunction [OR = 1.37, 95% CI = 1.09-1.73; 1.91, (1.39-2.61); 1.54, (1.23-1.93), respectively]. Similar results were observed in participants who preheated oil to smoking [OR = 1.36, 95% CI = 1.08 -1.72; 1.55, (1.14-2.14); 1.25, (1.02-1.55), respectively] and cooked for over 30 minutes [OR = 1.34, 95% CI = 1.05-1.72; 1.46, (1.03-2.06); 1.36, (1.08-1.72), respectively]. Furthermore, high urinary 1-HOP level was also positively associated with overall poor sleep quality (OR = 2.30, 95% CI = 1.31-4.05). The results indicated that exposure to COFs from Chinese household cooking may be a risk factor for poor sleep quality among middle-aged Chinese population. (C) 2017 Elsevier Ltd. All rights reserved.