Role of autophagy-related genes in liver cancer prognosis.

Autophagy, a highly conserved process of protein and organelle degradation, has emerged as a critical regulator in various diseases, including cancer progression. In the context of liver cancer, the predictive value of autophagy-related genes remains ambiguous. Leveraging chip datasets from the TCGA and GTEx databases, we identified 23 differentially expressed autophagy-related genes in liver cancer. Notably, five key autophagy genes, PRKAA2, BIRC5, MAPT, IGF1, and SPNS1, were highlighted as potential prognostic markers, with MAPT showing significant overexpression in clinical samples. In vitro cellular assays further demonstrated that MAPT promotes liver cancer cell proliferation, migration, and invasion by inhibiting autophagy and suppressing apoptosis. Subsequent in vivo studies further corroborated the pro-tumorigenic role of MAPT by suppressing autophagy. Collectively, our model based on the five key genes provides a promising tool for predicting liver cancer prognosis, with MAPT emerging as a pivotal factor in tumor progression through autophagy modulation.

Personal exposure to airborne organic pollutants and lung function changes among healthy older adults.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

Association of PM2.5 Components with Acceleration of Aging: Moderating Role of Sex Hormones.

Fine particulate matter (PM2.5) has been linked to aging risk, and a lack of knowledge about the relationships between PM2.5 components and aging risk impeded the development of healthy aging. Participants were recruited through a multicenter cross-sectional study in the Beijing-Tianjin-Hebei region in China. Middle-age and older males and menopausal women completed the collection of basic information, blood samples, and clinical examinations. The biological age was estimated by Klemera-Doubal method (KDM) algorithms based on clinical biomarkers. Multiple linear regression models were applied to quantify the associations and interactions while controlling for confounders, and a restricted cubic spline function estimated the corresponding dose-response curves of the relationships. Overall, KDM-biological age acceleration was associated with PM2.5 component exposure over the preceding year in both males and females, with calcium [females: 0.795 (95% CI: 0.451, 1.138); males: 0.712 (95% CI: 0.389, 1.034)], arsenic [females: 0.770 (95% CI: 0.641, 0.899); males: 0.661 (95% CI: 0.532, 0.791)], and copper [females: 0.401 (95% CI: 0.158, 0.644); males: 0.379 (95% CI: 0.122, 0.636)] having greater estimates of the effect than total PM2.5 mass. Additionally, we observed that the associations of specific PM2.5 components with aging were lower in the higher sex hormone scenario. Maintaining high levels of sex hormones may be a crucial barrier against PM2.5 component-related aging in the middle and older age groups.

Personal PM2.5 Elemental Components, Decline of Lung Function, and the Role of DNA Methylation on Inflammation-Related Genes in Older Adults: Results and Implications of the BAPE Study.

Epidemiological evidence of the effects of PM2.5 elements on lung function and DNA methylation is limited. We conducted a longitudinal panel study of 76 healthy older adults aged 60-69 years in Jinan, China, from September 2018 to January 2019. We periodically measured individual 72 h PM2.5 and element concentrations, lung function, and DNA methylation levels of eight inflammation-related genes. We used linear mixed-effect models to investigate the effects of exposure to personal PM2.5 elements on the lung function and DNA methylation. Mediation analysis was used to investigate the underlying effect mechanism. Negative changes in the ratio of forced expiratory volume in 1 s to forced vital capacity, ranging from -1.23% [95% confidence interval (CI): -2.11%, -0.35%] to -0.77% (95% CI: -1.49%, -0.04%), were significantly associated with interquartile range (IQR) increases in personal PM2.5 at different lag periods (7-12, 13-24, 25-48, 0-24, 0-48, and 0-72 h). Arsenic (As), nickel, rubidium (Rb), selenium, and vanadium were significantly associated with at least three lung function parameters, and IQR increases in these elements led to 0.12-5.66% reductions in these parameters. PM2.5 elements were significantly associated with DNA methylation levels. DNA methylation mediated 7.28-13.02% of the As- and Rb-related reduced lung function. The findings indicate that exposure to elements in personal PM2.5 contributes to reduced lung function through DNA methylation.

Associations of Carbonaceous Compounds and Water-Soluble Inorganic Ions in Ambient PM2.5 with Renal Function in Older Individuals: The China BAPE Study.

Exposure to fine particulate matter (PM2.5) is proven to be associated with a decline in renal function. However, few studies have explored the acute renal damage from carbonaceous compounds and water-soluble inorganic ions (WSIIs), which constitute the bulk of total PM2.5 mass. We examined the acute effect of these constituents of ambient PM2.5 on renal function in older Chinese individuals. Seventy-one healthy people aged 60-69 years from Jinan, China, were enrolled and visited monthly and asked to complete survey questionnaires, undergo physical exams, and provide blood samples. The hourly concentrations of organic carbon, elemental carbon (EC), and WSIIs in ambient PM2.5 were collected from a fixed-site monitoring station. The association between PM2.5 constituents and estimated glomerular filtration rate (eGFR) was evaluated using linear mixed-effects models after controlling for a series of covariates. We observed that ambient carbonaceous compounds and WSIIs were associated with a significant decline in renal function. The interquartile range increased in the 24 h moving average of carbonaceous compounds, and WSIIs in ambient PM2.5 were associated with -13.11% [95% confidence interval (95% CI): -19.49, -6.21%] to -0.81% (95% CI: -4.17, 2.67%) changes in eGFR. We found significant associations between EC, chlorine (Cl-), sodium (Na+), and magnesium (Mg2+) and eGFR in single-pollutant, constituent-PM2.5, and residual-constituent models with a lag period of 0-24 h. This study demonstrated that carbonaceous compounds and WSIIs in PM2.5 were inversely associated with renal function.

Associations between Individual Exposure to Fine Particulate Matter Elemental Constituent Mixtures and Blood Lipid Profiles: A Panel Study in Chinese People Aged 60-69 Years.

Dyslipidemia may be a potential mechanism linking fine particulate matter (PM2.5) to adverse cardiovascular outcomes. However, inconsistent associations between PM2.5 and blood lipids have resulted from the existing research, and the joint effect of PM2.5 elemental constituents on blood lipid profiles remains unclear. We aimed to explore the overall associations between PM2.5 elemental constituents and blood lipid profiles and to identify the significant PM2.5 elemental constituents in this association. Sixty-nine elderly people were recruited between September 2018 and January 2019. Each participant completed a survey questionnaire, 3 days of individual exposure monitoring, health examination, and biological sample collection at each follow-up visit. Bayesian kernel machine regression (BKMR) models were used to identify the joint effects of the 17 elemental constituents on blood lipid profiles. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly increased in older adults when exposed to the mixture of PM2.5 elemental constituents. Copper and titanium had higher posterior inclusion probabilities than other constituents, ranging from 0.76 to 0.90 (Cu) and 0.74 to 0.94 (Ti). Copper and titanium in the PM2.5 elemental constituent mixture played an essential role in changes to blood lipid levels. This study highlights the importance of identifying critical hazardous PM2.5 constituents that may cause adverse cardiovascular outcomes in the future.

Associations of Fine Particulate Matter Constituents with Metabolic Syndrome and the Mediating Role of Apolipoprotein B: A Multicenter Study in Middle-Aged and Elderly Chinese Adults.

Fine particulate matter (PM2.5) was reported to be associated with metabolic syndrome (MetS), but how PM2.5 constituents affect MetS and the underlying mediators remains unclear. We aimed to investigate the associations of long-term exposure to 24 kinds of PM2.5 constituents with MetS (defined by five indicators) in middle-aged and elderly adults and to further explore the potential mediating role of apolipoprotein B (ApoB). A multicenter study was conducted by recruiting subjects (n = 2045) in the Beijing-Tianjin-Hebei region from the cohort of Sub-Clinical Outcomes of Polluted Air in China (SCOPA-China Cohort). Relationships among PM2.5 constituents, serum ApoB levels, and MetS were estimated by multiple logistic/linear regression models. Mediation analysis quantified the role of ApoB in "PM2.5 constituents-MetS" associations. Results indicated PM2.5 was significantly related to elevated MetS prevalence. The MetS odds increased after exposure to sulfate (SO42-), calcium ion (Ca2+), magnesium ion (Mg2+), Si, Zn, Ca, Mn, Ba, Cu, As, Cr, Ni, or Se (odds ratios ranged from 1.103 to 3.025 per interquartile range increase in each constituent). PM2.5 and some constituents (SO42-, Ca2+, Mg2+, Ca, and As) were positively related to serum ApoB levels. ApoB mediated 22.10% of the association between PM2.5 and MetS. Besides, ApoB mediated 24.59%, 50.17%, 12.70%, and 9.63% of the associations of SO42-, Ca2+, Ca, and As with MetS, respectively. Our findings suggest that ApoB partially mediates relationships between PM2.5 constituents and MetS risk in China.

Emerging and Legacy Per- and Polyfluoroalkyl Substances in an Elderly Population in Jinan, China: The Exposure Level, Short-Term Variation, and Intake Assessment.

Human exposure to per- and polyfluoroalkyl substances (PFASs) has gained worldwide attention due to their widespread presence in the environment and adverse health effects, but the exposure assessment in the elderly is still lacking. This study aimed to assess exposures to 3 emerging PFASs (chlorinated polyfluoroalkyl ether sulfonic acids, Cl-PFESAs) and 15 legacy PFASs. The temporal variability of internal exposures and intake amounts of these PFASs were evaluated among a population of 76 healthy elderly adults (age: 60-69) in Jinan, China over 5 consecutive months. Fifteen PFASs were detected in whole blood with the mean total concentration (ΣPFAS) at 20.1 ng/mL (range: 5.0-135.9 ng/mL) dominated by perfluorooctanoic acid (PFOA) (9.0 ng/mL), perfluorooctanesulfonic acid (PFOS) (5.3 ng/mL), and 6:2 Cl-PFESA (1.6 ng/mL). Across the 5 month assessment period, significant variation was only observed for short-chain (C4-C7) perfluoroalkyl carboxylic acids, and their variations ranged from 53 to 334%. The median intake of PFOA and PFOS was estimated to be 1.46 and 0.92 ng/kg bw/day, respectively. Regression analysis showed that dietary ingestion, especially fish, was likely an important exposure pathway for PFASs among the elderly adults. Various pathways (e.g., dietary, water, air, and dust) should thus be considered to fully understand human exposure to PFASs.

Linking the Fasting Blood Glucose Level to Short-Term-Exposed Particulate Constituents and Pollution Sources: Results from a Multicenter Cross-Sectional Study in China.

Ambient PM2.5 (fine particulate matter with aerodynamic diameters ≤ 2.5 µm) is thought to be associated with the development of diabetes, but few studies traced the effects of PM2.5 components and pollution sources on the change in the fasting blood glucose (FBG). In the present study, we assessed the associations of PM2.5 constituents and their sources with the FBG in a general Chinese population aged over 40 years. Exposure to PM2.5 was positively associated with the FBG level, and each interquartile range (IQR) increase in a lag period of 30 days (18.4 µg/m3) showed the strongest association with an elevated FBG of 0.16 mmol/L (95% confidence interval: 0.04, 0.28). Among various constituents, increases in exposed elemental carbon, organic matter, arsenic, and heavy metals such as silver, cadmium, lead, and zinc were associated with higher FBG, whereas barium and chromium were associated with lower FBG levels. The elevated FBG level was closely associated with the PM2.5 from coal combustion, industrial sources, and vehicle emissions, while the association with secondary sources was statistically insignificant. Improving air quality by tracing back to the pollution sources would help to develop well-directed policies to protect human health.

Using an Exposome-Wide Approach to Explore the Impact of Urban Environments on Blood Pressure among Adults in Beijing-Tianjin-Hebei and Surrounding Areas of China.

Existing studies mostly explored the association between urban environmental exposures and blood pressure (BP) in isolation, ignoring correlations across exposures. This study aimed to systematically evaluate the impact of a wide range of urban exposures on BP using an exposome-wide approach. A multicenter cross-sectional study was conducted in ten cities of China. For each enrolled participant, we estimated their urban exposures, including air pollution, built environment, surrounding natural space, and road traffic indicator. On the whole, this study comprised three statistical analysis steps, that is, single exposure analysis, multiple exposure analysis and a cluster analysis. We also used deletion-substitution-addition algorithm to conduct variable selection. After considering multiple exposures, for hypertension risk, most significant associations in single exposure model disappeared, with only neighborhood walkability remaining negatively statistically significant. Besides, it was observed that SBP (systolic BP) raised gradually with the increase in PM2.5, but such rising pattern slowed down when PM2.5 concentration reached a relatively high level. For surrounding natural spaces, significant protective associations between green and blue spaces with BP were found. This study also found that high population density and public transport accessibility have beneficially significant association with BP. Additionally, with the increase in the distance to the nearest major road, DBP (diastolic BP) decreased rapidly. When the distance was beyond around 200 m, however, there was no obvious change to DBP anymore. By cluster analysis, six clusters of urban exposures were identified. These findings reinforce the importance of improving urban design, which help promote healthy urban environments to optimize human BP health.

Epigenetic age stratifies the risk of blood pressure elevation related to short-term PM2.5 exposure in older adults.

BACKGROUND: Exposure to fine particulate matter (PM2.5) is a prominent risk factor for cardiovascular aging in older adults and causes mild syndromes or other comorbidities in otherwise healthy older adults. Accordingly, a precise tool for PM2.5 exposure risk stratification is urgently needed. We aimed to address this need by comparing the performances of seven types of epigenetic age and chronological age to classify the effects of short-term PM2.5 exposure on blood pressure (BP), a typical clinical surrogate marker of cardiovascular aging. METHODS: We conducted a panel study of the Chinese healthy adults aged 60-69 years through five monthly visits. Personal PM2.5 exposures were measured using wearable monitoring devices for three consecutive days, and DNA methylation was determined by the Illumina MethylationEPIC BeadChip using blood samples collected at each visit. Systolic BP, diastolic BP, mean arterial pressure and pulse pressure were measured by the electronic BP monitor. Linear mixed models with interaction terms between PM2.5 and different ages were used to assess their potential usefulness for stratification. RESULTS: DNAmPhenoAge, Skin & blood clock, DNAmGrimAge acceleration, and DunedinPoAm had significant modifying effects on the relationship between PM2.5 and BP. For instance, a 10-µg/m3 increase in the 72-h moving mean PM2.5 was significantly associated with 0.30% (95% CI: 0.10%, 0.51%) and -0.07% (95% CI: -0.32%, 0.18%) increases in systolic BP at higher and lower DNAmPhenoAge acceleration, respectively. Joint models further revealed that using a combination of epigenetic ages could more precisely stratify the effect of PM2.5 on BP. CONCLUSIONS: Our research indicates that epigenetic age may be a useful tool for evaluating the effect of short-term PM2.5 exposure on cardiovascular aging status.

Depression and Anxiety Associated with Exposure to Fine Particulate Matter Constituents: A Cross-Sectional Study in North China.

The association between fine particulate matter (PM2.5) exposure and mental disorders is attracting increasing attention, but the roles of specific PM2.5 chemical constituents have yet to be explored. We conducted a multicenter cross-sectional study in nine cities located in the Beijing-Tianjin-Hebei region in China to assess the effects of PM2.5 and chemical constituents on depression and anxiety. The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale were used to quantify the depression and anxiety status, atmospheric monitoring data from fixed stations was used to calculate exposure concentrations. We performed multiple logistic regression models to assess the associations of PM2.5 chemical constituents exposure over the preceding 2 weeks with depression and anxiety. Overall, anxiety and depression were significantly associated with organic carbon (OC), elemental carbon (EC), copper (Cu), cadmium (Cd), nickel (Ni), and zinc (Zn). Subgroup analysis showed a stronger effect of PM2.5 constituents on depression during the heating period. This study provide evidence for the possible link between PM2.5 constituents and mental disorders among middle-aged and elderly Chinese adults, which requires further validation of the causal correlation. Our findings support the need for a stricter regulation on emissions of certain specific constituents, in addition to targeting control of total PM2.5 emission concentration.

Associations between Personal PM2.5 Elemental Constituents and Decline of Kidney Function in Older Individuals: the China BAPE Study.

Long-term exposure to fine particulate matter (PM2.5) is associated with kidney dysfunction. However, few studies have investigated acute effects of PM2.5 elemental constituents on renal function. We evaluated associations between personal PM2.5 and its elemental constituents and kidney function, assessed by an estimated glomerular filtration rate (eGFR) in Biomarkers of Air Pollutants Exposure in the Chinese aged 60-69 study. Seventy one older individuals were visited monthly between September 2018 and January 2019. Each participant wore a PM2.5 monitor for 72 h, responded to a questionnaire, and underwent a physical examination with blood sampling. Linear mixed-effect models were used to estimate associations between personal PM2.5 elemental constituents and eGFR. We found that significant changes in eGFR from -1.69% [95% confidence interval (CI): -3.34%, -0.01%] to -3.27% (95% CI: -5.04%, -1.47%) were associated with interquartile range (IQR) increases in individual PM2.5 exposures at various lag periods (7-12, 13-24, 0-24, 25-48, and 49-72 h). An IQR increase in 72 h moving averages of copper, manganese, and titanium in personal PM2.5 corresponded to -2.34% (95% CI: -3.67%, -0.99%) to -4.56% (95% CI: -7.04%, -2.00%) changes in eGFR. Personal PM2.5 and some of its elemental constituents are inversely associated with eGFR in older individuals.

Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity.

Evidence on the effects of internal chemical mixture exposures on biological age is limited. It also remains unclear whether hormone homeostasis and lifestyle factors can modify such a relationship. Based on the Biomarkers for Air Pollutants Exposure (BAPE) study, which involved healthy older adults aged 60-69 years in China, we found that chemical mixture exposures, including metals, polycyclic aromatic hydrocarbons (PAHs), per- and polyfluoroalkyl substances (PFASs), phthalates (PAEs), and organophosphate esters (OPEs), were significantly associated with shortened DNAmTL and accelerated SkinBloodClock, in which PFASs and OPEs in blood were the primary contributors to DNAmTL, while metals and PAEs had relatively higher contributions in urine. Furthermore, lower levels of thyroxin appeared to exacerbate the adverse effects of environmental chemicals on epigenetic ageing but relatively higher levels of physical activity had the beneficial impact. These findings may have important implications for the development of healthy ageing strategy and aged care policy, particularly in light of the global acceleration of population ageing.

Acute Effects of Exposure to Fine Particulate Matter and Its Constituents on Sex Hormone Among Postmenopausal Women - Beijing, Tianjin, and Hebei PLADs, China, 2018-2019.

What is already known on this topic?: Exposure to fine particulate matter (PM2.5) was linked to endocrine hormone disruption in the reproductive system. Nonetheless, it was unclear which specific components of PM2.5 were primarily responsible for these associations. What is added by this report?: The study presented the initial epidemiological evidence that brief exposure to PM2.5 can elevate estradiol levels in postmenopausal women. Various particle components had unique effects, with water-soluble ions and specific inorganic elements like Ag, As, Cd, Hg, Ni, Sb, Se, Sn, and Tl potentially playing significant roles in increasing estradiol levels. What are the implications for public health practice?: The study established that the prevalence of air pollution, along with its specific components, has been recognized as a novel risk factor affecting the balance of sex hormones.

Association between Personal Abiotic Airborne Exposures and Body Composition Changes among Healthy Adults (60-69 Years Old): A Combined Exposome-Wide and Lipidome Mediation Approach from the China BAPE Study.

BACKGROUND: Evidence suggested that abiotic airborne exposures may be associated with changes in body composition. However, more evidence is needed to identify key pollutants linked to adverse health effects and their underlying biomolecular mechanisms, particularly in sensitive older adults. OBJECTIVES: Our research aimed to systematically assess the relationship between abiotic airborne exposures and changes in body composition among healthy older adults, as well as the potential mediating mechanisms through the serum lipidome. METHODS: From September 2018 to January 2019, we conducted a monthly survey among 76 healthy adults (60-69 years old) in the China Biomarkers of Air Pollutant Exposure (BAPE) study, measuring their personal exposures to 632 abiotic airborne pollutions using MicroPEM and the Fresh Air wristband, 18 body composition indicators from the InBody 770 device, and lipidomics from venous blood samples. We used an exposome-wide association study (ExWAS) and deletion/substitution/addition (DSA) model to unravel complex associations between exposure to contaminant mixtures and body composition, a Bayesian kernel machine regression (BKMR) model to assess the overall effect of key exposures on body composition, and mediation analysis to identify lipid intermediators. RESULTS: The ExWAS and DSA model identified that 2,4,5-T methyl ester (2,4,5-TME), 9,10-Anthracenedione (ATQ), 4b,8-dimethyl-2-isopropylphenanthrene, and 4b,5,6,7,8,8a,9,10-octahydro-(DMIP) were associated with increased body fat mass (BFM), fat mass indicators (FMI), percent body fat (PBF), and visceral fat area (VFA) in healthy older adults [Bonferroni-Hochberg false discovery rate (FDRBH)<0.05]. The BKMR model demonstrated a positive correlation between contaminants (anthracene, ATQ, copaene, di-epi-α-cedrene, and DMIP) with VFA. Mediation analysis revealed that phosphatidylcholine [PC, PC(16:1e/18:1), PC(16:2e/18:0)] and sphingolipid [SM, SM(d18:2/24:1)] mediated a significant portion, ranging from 12.27% to 26.03% (p-value <0.05), of the observed increase in VFA. DISCUSSION: Based on the evidence from multiple model results, ATQ and DMIP were statistically significantly associated with the increased VFA levels of healthy older adults, potentially regulated through lipid intermediators. These findings may have important implications for identifying potentially harmful environmental chemicals and developing targeted strategies for the control and prevention of chronic diseases in the future, particularly as the global population is rapidly aging. https://doi.org/10.1289/EHP13865.

Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study.

BACKGROUND: Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain. OBJECTIVES: We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics. METHODS: A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency >50% and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways. RESULTS: Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis. DISCUSSION: It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864.

Plastic additive components of PM2.5 increase corrected QT interval: Screening for exposure markers based on airborne exposome.

The impact of industrial chemical components of ambient fine particles (e.g. PM2.5) on cardiovascular health has been poorly explored. Our study reports for the first time the associations between human exposure to complex plastic additive (PA) components of PM2.5 and prolongation of heart rate-corrected QT (QTC) interval by employing a screening-to-validation strategy based on a cohort of 373 participants (136 in the screening set and 237 in the validation set) recruited from 7 communities across China. The high-throughput airborne exposome framework revealed ubiquitous occurrences of 95 of 224 target PAs in PM2.5, totaling from 66.3 to 555 ng m-3 across the study locations. Joint effects were identified for 9 of the 13 groups of PAs with positive associations with QTC interval. Independent effect analysis also identified and validated tris(2-chloroisopropyl) phosphate, di-n-butyl/diisobutyl adipate, and 3,5-di-tert-butyl-4-hydroxybenzaldehyde as the key exposure markers for QTC interval prolongation and changes of selected cardiovascular biomarkers. Our findings highlight the important contributions of airborne industrial chemicals to the risks of cardiovascular diseases and underline the critical need for further research on the underlying mechanisms, toxic modes of action, and human exposure risks.

Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study.

BACKGROUND: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. OBJECTIVES: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60-69 years of age to elucidate the underlying mechanisms using a multi-omics approach. METHODS: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. RESULTS: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso-butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis further indicated the adverse effect of OPE mixtures. Multi-omics analyses revealed that the endogenous changes in the transcriptional and metabolic levels were associated with OPE exposure. The putative AOPs model suggested that triggers of molecular initiation events (e.g., insulin receptor and glucose transporter type 4) with subsequent key events, including disruptions in signal transduction pathways (e.g., phosphatidylinositol 3-kinase/protein kinase B and insulin secretion signaling) and biological functions (glucose uptake and insulin secretion), may constitute the diabetogenic effects of OPEs. DISCUSSION: OPEs are associated with the elevated risk of T2D among older Chinese adults 60-69 years of age. Implementing OPE exposure reduction strategies may help reduce the T2D burden among these individuals, if the relationship is causal. https://doi.org/10.1289/EHP11896.

Horizontal Integration and Financing Reform of Rural Primary Care in China: A Model for Low-Resource and Remote Settings.

Primary health care (PHC) systems are compromised by under-resourcing and inadequate governance, and fail to provide high-quality health care services in most low- and middle-income countries (LMICs). As a response to solve the problems of underfunding and understaffing, Pengshui County, an impoverished area in rural Chongqing, China, implemented a profound reform of its PHC delivery system in 2009, focusing on horizontal integration and financing mechanisms. This paper aims to present new evidence from the Pengshui model, and to assess the relevant changes over the past 10 years (2009-2018). An inductive approach was adopted, based on analysis of national and local policy documents and administrative data. From 2009 to 2018, the proportion of outpatients who sought first-contact care in rural community or township health centers increased from 29% (522,700 of 1,817,600) in 2009, to 40% (849,900 of 2,147,800) in 2018 (the national average in 2018 was 23%). Our findings suggest that many positive results have been achieved through the reform, and that innovations in financial governance and incentive mechanisms are the main driving forces behind the improvement. Pengshui County's experience has proven to be a successful experiment, particularly in rural and low-income areas.