As the primary receptor of oxidized low-density lipoprotein (ox-LDL), LOX-1 is a putative therapeutic target for atherosclerotic disorders including ischemic stroke (IS), whereas the regulatory mechanism of LOX-1 remains largely unknown in IS. We employed computational algorithms to screen candidate miRNAs, followed by integrative analysis of differentially expressed miRNA profiles derived from blood cells of 25 acute IS cases and 25 controls matched with age and gender. MiR-187-3p-mediated regulation of LOX-1 was confirmed by a dual-luciferase reporter assay and Western Blot in THP-1 derived macrophages. Elevated blood levels of miR-187-3p were observed both in IS patients and the atherosclerotic mice. In a case-control study enrolling 279 IS cases and 279 controls, we found that miR-187-3p level was significantly associated with the occurrence of IS (adjusted OR = 1.204; 95% CI: 1.086-1.335; p < 0.001). Similar results were replicated in another coronary heart disease case-control population. In vivo, systemic delivery of agomiR-187-3p significantly reduced atherosclerotic plaque burden alongside decreased plasma lipids and suppressed inflammation. In vitro, miR-187-3p over-expression attenuated foam cell formation induced by ox-LDL and down-regulated pro-inflammatory mediators in macrophages. Conversely, miR-187-3p inhibition exacerbated these effects, which were partially rescued by LOX-1 inhibitor BI-0115. This study establishes miR-187-3p as a novel epigenetic regulator of LOX-1 and provides critical evidence supporting its therapeutic potential for modulating IS progression.

BackgroundNumerous studies have delved into the relationship between magnesium (Mg) and metabolic diseases, however, the impact of Mg on novel glycolipid metabolic indicators remains largely unexplored. This study aims to conduct a comprehensive evaluation of the relationship between plasma Mg levels and glycolipid metabolism among a general population in Shenzhen, China.MethodsA cross-sectional study was performed in 1,429 adults who underwent medical check-ups at a hospital in Shenzhen, China. Plasma Mg levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). To investigate the association between plasma Mg levels and glycolipid metabolism indicators, the multivariate linear and logistic regression models, along with the restricted cubic spline (RCS) model were employed.ResultsRegarding to the glucose indicators, plasma Mg showed a negative linear association with the triglyceride-glucose index adjusted for Body Mass Index (TyG-BMI) and a positive linear association with the single point insulin sensitivity estimator (SPISE), while demonstrating a negative non-linear association with fasting blood glucose (FBG) and the metabolic score for insulin resistance (METS-IR). For lipid indicators, Mg exhibited a negative linear association with the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol ratio (HDL-c), while the LDL-c/HDL-c ratio showed a V-shaped non-linear relationship with Mg. Furthermore, the level of Mg exhibited a negative linear association with diabetes and a V-shaped non-linear association with hyperlipidemia.ConclusionsMg plays a critical role in the glucose and lipid metabolism, particularly highlighting its association with the novel indicators for glycolipid metabolism. The results of our study need to be confirmed in large-scale prospective research in the future.

Background: Hospital wastewater (HWW) is a critical reservoir for carbapenem-resistant Gram-negative bacteria. Methods: Between November 2024 and August 2025, sixty 24 h composite wastewater samples were collected from five tertiary hospitals. Of the 244 carbapenem-resistant isolates recovered, 34 blaNDM-1-positive Acinetobacter isolates were subjected to phenotypic, genotypic, and plasmid analyses. Results: Eleven species were identified among the 34 carbapenem-resistant Acinetobacter isolates, predominantly non-baumannii Acinetobacter (NBA). All isolates were carbapenem-resistant (34/34, 100%) with high-level MICs (meropenem MIC50/90, 32/64 mg/L; imipenem MIC50/90, >128/>128 mg/L); 21% (7/34) of isolates were resistant to colistin, and resistance to ceftazidime, cefepime, and trimethoprim-sulfamethoxazole was 100%, 94%, and 76%, respectively. Core-genome SNP analysis revealed highly similar isolates across hospitals within the same season (1-2 SNPs) or within the same hospital across seasons (19 SNPs). Genomic analysis showed that blaNDM-1 was present in all isolates (34/34, 100%), with plasmid carriage in 85.3% (29/34); blaOXA-58 co-occurred in 62.1% (18/29), mainly on Rep_3 plasmids (19/29), especially R3-T28 (15/29) that frequently carried blaOXA-58 (10/15). Two unclassified plasmids co-harboring blaNDM-1 and blaOXA-23 were detected in Acinetobacter tandoii isolates. The blaNDM-1 gene was embedded in a conserved Tn125-like structures with variable flanks. Conclusions: Overall, carbapenem-resistant Acinetobacter from hospital wastewater frequently carried Rep_3 plasmid-borne blaNDM-1, especially R3-T28 and often co-occurring with blaOXA-58, within a conserved Tn125-like core structures. These findings highlight HWW as a potential hotspot for dissemination of carbapenem resistance and support routine genomic surveillance under a One Health framework.

Macrophages are pivotal in the progression of metabolic dysfunction-associated steatohepatitis (MASH), yet their specific markers remain elusive. Herein, we employed an integrated bioinformatics strategy, combining single-cell and bulk transcriptomic data from human MASH livers, to identify macrophage-related differentially expressed genes (Mϕ-DEGs). We pinpointed five core Mϕ-DEGs— FRMD4B, PTK2B, CPM, SPTLC2, and EPB41L2—that were predominantly expressed in macrophages and enriched within profibrotic M2 subsets. A diagnostic model constructed from these genes demonstrated high accuracy (area under the curve = 0.9865) and was robustly validated in an independent cohort. In human and murine MASH samples, FRMD4B and PTK2B were consistently downregulated, whereas CPM, SPTLC2, and EPB41L2 were upregulated. Protein-level validation by immunohistochemistry and immunofluorescence confirmed these expression patterns in human and mouse livers and in polarized THP-1-derived macrophages. Mendelian randomization analysis identified CPM as a significant causal protective factor, suggesting that its upregulation may represent a compensatory response. These genes correlated with altered immune cell infiltration (e.g., T follicular helper and regulatory cells) and were enriched in key MASH pathways, including fatty acid metabolism, sphingolipid signaling, and transforming growth factor beta/PI3K-Akt. Our findings were further corroborated through a multilevel validation framework encompassing clinical samples, a murine MASH model, and in vitro macrophage cultures. This study characterized a robust macrophage-specific gene signature for MASH diagnosis and offered genetic evidence regarding the causal protective role of CPM. The pronounced enrichment of these genes in M2 macrophages underscores their critical contribution to immunometabolic dysregulation, offering novel insights into MASH pathogenesis and potential diagnostic and therapeutic targets.

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is a persistent food-chain pollutant targeting the liver, whose genotoxic potential remains poorly understood. Here we investigated BDE-47-triggered DNA damage using HepG2 cells and C3H/He mice. BDE-47 exposure markedly elevated DNA damage-related γ-H2AX foci in mouse liver. Cellular tests further validated BDE-47-induced DNA damage, manifested as elevated γ-H2AX foci, a higher comet tail DNA percentage, and a longer tail length. Mechanistically, BDE-47 activated the aryl hydrocarbon receptor (AHR) and raised hepatic reactive oxygen species (ROS) and malondialdehyde levels. In cellular assays, antioxidants alleviated DNA damage, whereas AHR inhibitors suppressed ROS overproduction. BDE-47 also upregulated hepatic CYP1A1/2, whose expression positively correlated with the severity of hepatic DNA injury in mice. In conclusion, BDE-47 exposure induces hepatocellular DNA damage, and its mechanism of action is closely associated with AHR-mediated oxidative stress and CYP1A1/2 upregulation, which offers new experimental evidence to clarify the hepatotoxic and genotoxic mechanisms of BDE-47.

Fipronil (FPN), a widely used insecticide, poses health risks through environmental contamination. Although its toxicity is increasingly recognized, the impact of fipronil on glucose metabolism remains poorly understood. In this study, mice on a normal diet (ND) or high-fat diet (HFD) received a daily oral administration of fipronil (0, 0.25, 1, or 4 mg/kg) for 35 days. Blood glucose and insulin were measured, and glucose/insulin/pyruvate tolerance tests were performed. We found that fipronil compromised glucose tolerance in mice fed an ND. Gut microbiota composition was assessed by 16S rRNA sequencing and the expression of inflammatory factors was detected in the tissues. Serum fibroblast growth factor 15 (FGF15) and bile acid were determined. In HFD-fed mice, fipronil exacerbated glucose metabolic disorders and enhanced insulin resistance. These metabolic disturbances were associated with gut microbiota dysbiosis, particularly a marked reduction in Akkermansia muciniphila (A. muciniphila) abundance, and increased systemic inflammation. Fipronil exposure also decreased serum FGF15 and elevated serum bile acids. Our results suggest that fipronil disrupts glucose metabolism in association with gut microbiota alterations, impairment of the FGF15-bile acid axis, and induction of inflammation, highlighting its potential relevance to diabetes risk. Further studies are warranted to validate our findings.

Heatwaves frequently coincided with ozone to form one of the most imminent health threats under global climate change. Identifying hotspots of compound heatwave and ozone pollution events (CHOEs) has crucial significance in developing targeted mitigation strategies, which is largely unknown. We therefore performed the comprehensive global and regional analyses on the spatiotemporal variation and death burden of CHOEs during 2000-2021. In addition to CHOE exposure, we estimated its population exposure through multiplying the exposure by total population. We observed that the frequency, duration, and intensity of CHOEs and their population exposures significantly increased in most midlatitudes, particularly in the Middle East and North Africa and South Asia. The population exposures increased at an accelerating pace and were mainly driven by the CHOE itself. We estimated that the death burden of CHOEs increased over time especially in the Middle East and North Africa, with a population attributable fraction of 0.99% in 2000 to 2.01% in 2021. Our findings add novel evidence that CHOEs markedly increased and posed substantial death burdens both regionally and globally in the past two decades. This evidence highlights urgent needs to develop regional targeted mitigation and adaptation actions to reduce health risks due to CHOEs, particularly in hotspots.

Compound heatwave and ozone pollution events threaten public health as warming and photochemistry intensify. Yet the internal architecture of these events—how heatwaves and ozone separately influence frequency versus intensity—remains poorly resolved at national scale. Here we show, using 1 km resolution grids across China from 2000 to 2023, that heatwaves dominate the frequency of compound extremes while ozone dominates their intensity, and that this asymmetry strengthened after 2016. Population exposure rose primarily because the events themselves intensified, rather than from population growth. City-level influencing factors proved highly heterogeneous, reflecting local combinations of meteorology, pollution and socioeconomic conditions. These findings uncover an asymmetric architecture of compound risk and identify distinct levers—heat versus ozone—for targeted mitigation under continued warming.

The IL-33/ST2 pathway plays a crucial role in the development of essential hypertension (EH). This study aimed to investigate the relationship between EH and genetic variations in this pathway in the Chinese Han population. A total of 1,151 EH patients and 1,135 healthy controls were included in the study. Sixteen single nucleotide polymorphisms (SNPs) in the interleukin-33 (IL-33) and interleukin-1receptor associated protein (IL-1RAcP) genes were genotyped using the Sequenom MassArray and TaqMan assays. Genotype and allele frequencies were compared between the EH patients and controls using logistic regression analysis. The rs16865597 SNP in the IL-1RAcP gene was found to be associated with the risk of EH. Specifically, the presence of the C allele of rs16865597 was negatively correlated with EH susceptibility in both the additive model (P = 0.014, OR = 0.75, 95

Lead is an important heavy metal material and also an omnipresent environmental pollutant, which poses extensive hazards to human health, including its nephrotoxicity. However, there are still many unknowns regarding its toxic mechanism and intervention strategy. Here, we revealed that lead exposure promoted the activation of PERK in HK - 2 cells (p - PERK and the ratio of p - PERK / PERK increased), enhanced the expression of its molecular chaperone binding immunoglobulin protein (BIP) and its downstream signaling molecule CCAAT / enhancer - binding protein homologous protein (CHOP). This indicated that lead exposure resulted in the occurrence of the unfolded protein response (UPR) in HK - 2 cells. Further, lead induced significant DNA damage, oxidative stress and apoptosis in HK-2 cells. Especially, when human umbilical cord mesenchymal stem cell - derived exosomes (hucMSC - exos) were ingested by HK-2 cells, all the levels of p - PERK, p - PERK / PERK ratio, BIP and CHOP were significantly down - regulated, which suggested that the UPR was significantly alleviated. Simultaneously, the above-mentioned toxic effects of lead were significantly reduced. Moreover, when GSK2606414 was employed to block the phosphorylation of PERK, the toxic effects of lead were also significantly alleviated. Hence, we conclude that hucMSC - exos can alleviate the toxicity of lead to HK-2 cells via interfering with the UPR, in which PERK plays a crucial role, and it may be a promising target for intervening in the toxicity of lead.

Cadmium (Cd) exposure is an emerging environmental risk factor for atherosclerotic cardiovascular diseases (ASCVDs), particularly ischemic stroke (IS). MicroRNAs are potential mediators linking environmental exposure to health hazards. However, the role of miRNAs in the development of IS triggered by Cd exposure remains largely unknown. In this study, we first demonstrate that Cd exposure, even at a relatively low dosage (4 mg/L), significantly facilitates the progression of atherosclerosis in apolipoprotein E-deficient mice fed a high-fat diet. This pro-atherogenic effect was accompanied by comprehensive disturbances in systemic and vascular cholesterol homeostasis, evidenced by altered plasma lipid profiles, hepatic lipid accumulation, and dysregulated expression of key genes governing cholesterol uptake (CD36), efflux (ABCA1), and hydrolysis (NCEH1) within the aortic wall. Integrated transcriptomic and metabolomic analyses further corroborated the profound disruption of the lipid metabolism pathways. Through miRNA microarray, bioinformatics analysis, and qRT-PCR validation, we identified miR-30d-5p and miR-504-3p as novel epigenetic regulators mediating Cd-induced foam cell formation. Specifically, Cd treatment upregulated miR-30d-5p and downregulated miR-504-3p, which directly targeted NCEH1 and CD36, respectively, thereby promoting intracellular lipid accumulation. In a case-control population (494 IS patients and 494 controls), plasma miR-30d-5p levels were positively associated with Cd exposure and partially mediated the Cd-stroke association, accounting for 16.4% of the total effect. Moreover, miR-30d-5p significantly improved the discrimination and reclassification of IS patients beyond the traditional risk factors. In summary, our findings reveal that Cd induces atherosclerosis by disrupting cholesterol homeostasis and modulating miRNA-regulated pathways with plasma miR-30d-5p serving as a potential biomarker and mediator for Cd-related ischemic stroke. Further perspective investigations are warranted to validate our findings.

BackgroundAir pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. ObjectiveTo quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. MethodsBased on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. ResultsThis study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m−3, 42.85 (28.42) μg·m−3, 8.53 (3.39) μg·m−3, 29.47 (13.56) μg·m−3, 0.77 (0.27) mg·m−3, and 86.53 (51.39) μg·m−3, respectively. The moving average concentrations of PM2.5 and PM10 over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO2 demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM2.5, PM10, and SO2 with myocardial infarction mortality were approximately linear, whereas NO2 exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO2 exposure was observed when the NO2 concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM2.5 and NO2 exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O3 and restricting the study period to 2013—2019, the effect estimates for PM2.5, PM10, NO2, and SO2 on myocardial infarction mortality slightly increased. ConclusionShort-term exposure to air pollutants, including PM2.5, PM10, NO2, and SO2, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

Background:Bisphenol AF (BPAF), an alternative to Bisphenol A (BPA), is increasingly utilized in various industrial applications, yet its toxicological profile remains incompletely understood. This study aims to investigate the impact of BPAF exposure on obesity and lipid metabolism in male mice subjected to either a normal chow diet (ND) or a high-fat diet (HFD). Methods:Mice were exposed to BPAF at a concentration of 100 μg/kg every other day for five months under different dietary conditions, and body weight, rectal temperature, and food intake were monitored regularly. After the mice were sacrificed, the hepatic lipid metabolism was analyzed by measuring serum, hepatic lipids and performing hepatic metabolomics; energy metabolism was elucidated by assessing thermogenic pathways in brown adipose tissue (BAT) and factors affecting ingestion in the hypothalamus; the development and pathways of obesity were indicated by exploring lipogenesis and lipolysis pathways and fat accumulation in white adipose tissue (WAT). Results:Histomorphometric analyses indicated that BPAF exposure induced drived fat deposition in white adipose tissue through adipocyte hypertrophy-mediated pathways in eWAT of ND and HFD mice, accompanied by weight gain in HFD mice. Energy metabolism analysis showed that BPAF exposure decreased resting body temperature and reduced thermogenic factor expression in BAT of ND and HFD mice, which may affect energy expenditure. Hepatic metabolomics analysis suggested that BPAF exposure interfered with hepatic lipid metabolism in ND and HFD mice, with elevated levels of hepatic triglycerides, total cholesterol, and free fatty acids in HFD mice. Transcript analysis revealed altered expression levels of genes regulating lipid metabolism in white adipose tissue of ND and HFD mice, with a down-regulation observed in p-HSL protein expression, indicative of a potential inhibition effects of BPAF on lipolysis signaling pathway. Conclusion:Chronic BPAF exposure differentially exacerbates fat deposition in mice fed normal or high-fat diets via affecting lipid metabolism. Given the widespread prevalence of obesity and the pervasive environmental presence of BPAF, our findings provide valuable insights into the metabolic toxicity of BPAF, thereby raise further concern on the safe utilization and precision prevention of this unique chemical.

Exposure to extreme temperature events (ETEs) and ambient fine particulate matter (PM2.5) has been linked to an increased risk of pneumonia mortality, but their interactive effects remain largely unknown. We investigated 50,196 pneumonia deaths from 2015 to 2022 in Jiangsu province, China, with a time-stratified case-crossover design. An individual-level exposure to heat wave, cold spell, and PM2.5 was assessed at each subject’s residential address using validated grid datasets. Conditional logistic regression models integrated with a distributed lag nonlinear model were used to quantitatively estimate both independent and interactive effects. With different ETE definitions, the cumulative odds ratio (OR) of pneumonia mortality associated with heat wave and cold spell ranged from 1.22 (95% confidence interval [CI]: 1.14, 1.31) to 1.60 (1.40, 1.81), and from 1.08 (1.002, 1.17) to 1.18 (1.01, 1.38), respectively, while the OR for PM2.5 ranged from 1.013 (1.006, 1.021) to 1.016 (1.009, 1.024). We observed a synergistic effect (relative excess risk due to interaction [RERI] ranging from 0.40 [0.06, 0.76] to 1.16 [0.41, 2.09]) of co-exposure to heat wave and PM2.5, as well as an antagonistic effect (RERI ranging from −0.20 [−0.40, −0.03] to −1.02 [−1.78, −0.38]) of co-exposure to cold spell and PM2.5 on pneumonia mortality. It was estimated that up to 6.49% of pneumonia deaths were attributable to heat wave and PM2.5 exposures. We found that heat wave and cold spell interacted oppositely with PM2.5 to increase the odds of pneumonia mortality, highlighting the needs to reduce co-exposures to heat wave and PM2.5.

Emerging evidence suggests that heat waves and ozone (O3) contribute to increased mortality risks. Since widowhood is a common event that can increase individuals' susceptibility to the environment, it is of great importance and interest to elucidate the widowhood disparity in mortality attributable to heat waves and O3. We therefore conducted a case-crossover study of 1,214,763 nonaccidental deaths in Jiangsu Province, China, during 2015-2021 to investigate the independent and interactive associations of exposure to heat waves and O3 with mortality by widowhood status. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential heat waves and O3 exposures were assessed using validated grid datasets. Conditional logistic regression models were applied for exposure-response analyses and evaluations of additive interactions. Exposure to heat waves and O3 was significantly associated with increased odds of mortality in both widowed (odds ratio for heat waves, 1.25; O3, 1.06 per interquartile range increase) and married subjects (1.08; 1.03), and these associations were higher in widowed subjects. A significant synergistic interaction was observed between heat waves and O3, which was stronger in widowed subjects (relative excess odds due to interaction, 0.14 vs. 0.03). Up to 6.43% and 3.56% of deaths were attributable to heat waves, O3 pollution, and their compound events in widowed and married subjects, respectively. Our findings suggest that widowed individuals are more susceptible to heat waves and O3 and highlight the need to consider differences associated with widowhood disparities in preventing premature deaths due to heat waves and O3 exposures.

Abstract Background The relationships between air pollutants and mental and behavioral disorders (MBDs) remain unclear. We aimed to identify the primary pollutants affecting mental health and evaluate the short-term effects on emergency ambulance dispatches (EADs) due to MBDs. Methods Time-stratified case-crossover study and conditional logistic regression model were adopted to explore the impact of air pollutants on EADs due to MBDs from 2013 to 2020 in Shenzhen, China. In order to clarify the influence of gender and age on association, subgroup analysis was carried out. We also applied binary response surface model and distributed lag interaction model to examine the interaction effects between pollutants and meteorological factors on EADs due to MBDs. Results Nitrogen dioxide (NO2) was the primary pollutant in Shenzhen that affects the EADs due to mental and behavioral disorders, exhibiting significant immediate exposure effects and cumulative lag effects. As NO2 concentration increased, the risk of EADs due to mental and behavioral disorders showed a linear upward trend without a threshold. For each interquartile range (IQR) increase of NO2, the odds ratio (OR) associated with MBDs was highest at lag 2 in the single-day lag pattern (OR = 1.035, 95% CI: 1.012–1.060) and the effect of NO2 reached its maximum at lag 0–6 with OR of 1.078 (95% CI: 1.037–1.122). We did not observe significant associations between PM2.5, PM10, SO2, O3 and CO exposures and EADs due to MBDs. In addition, there was an interaction effect between NO2 and Humidity index (Humidex). Both high and low Humidex would aggravate the influence of pollutants on mental health. Conclusions Short exposure to NO2 was positively associated with acute onset of MBDs in Shenzhen, China. Health departments should take effective measures to raise public awareness of NO2 and Humidex, as well as their interaction effects.

Previous studies have evaluated the obesogenic effects of phthalates or metal(loid)s individually, but the association between their co-exposure and abdominal obesity (AOB) indices, remains largely unknown. We thus aimed to investigate the individual and combined effects of metal(loid)s and phthalates exposure on AOB among adults in Shenzhen, China. The urinary levels of 21 metal(loid)s and 11 phthalates were detected in 652 adults in this study. Significant positive associations were found between urinary phthalates, metal(loid)s levels as single contaminants and all five AOB indices, including waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), conicity-index (C-index) and lipid accumulation product (LAP). Bayesian Kernel Machine Regression (BKMR) models indicated that the pollutant mixture was positively associated with WHR, WtHR, C-index and LAP but not WC, and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Vanadium (V), Chromium (Cr) and Zinc (Zn) were the key contributors. Furthermore, the relationships between Cr, MEHHP and the indices C-index, WHR or LAP might be partially mediated by high sensitivity C-reactive protein (hs-CRP) or homeostasis model assessment of insulin resistance (HOMA-IR). TP53 was identified as the core target in Cr-induced AOB by network toxicology analysis. Further studies with larger samples are needed to confirm these findings.

Few studies have examined the effects of co-exposure to metals and phenols on heart rate variability (HRV), and the underlying mechanisms are unknown. We aim to investigate individual and joint associations of metals and phenols with HRV and the mediating role of oxidative stress among 118 adults in Wuhan with 3 repeated visits. Urine samples of 23 metals, 6 phenols and 3 oxidative stress biomarkers were measured. The associations were estimated using linear mixed-effect models (LMEs), weighted quantile sum (WQS) regression, adaptive Least Absolute Shrinkage and Selection Operator (LASSO) and mediation analyses. WQS regression revealed that the mixture of metals and phenols had an overall inverse association with standard deviation of normal-to-normal intervals (SDNN) and a positive relationship with low-frequency/high-frequency ratio (LF/HF). For SDNN, urinary thallium (Tl) and propyl paraben (PrP) were selected by adaptive LASSO, and urinary Tl was selected for LF/HF. After multivariate adjustments, we found that per doubling of urinary Tl and PrP was associated with a 3.54 % (95 % CI: -6.01 %, -1.01 %) and 1.20 % (95 % CI: -2.05 %, -0.33 %) decrease in SDNN, respectively. Additionally, the inverse relationships of urinary Tl and PrP with SDNN were mediated by urinary 8-iso-prostaglandin-F2α (8-isoPGF2ɑ) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), with the mediated proportions of 15.83 % and 8.36 %, respectively. Our findings suggest that environmental exposure to Tl and PrP was associated with decreased HRV, and the association was partly mediated by oxidative stress.

Metals disequilibrium is crucial in the progress of metabolic syndrome (MetS), whereas the underlying mechanism remains largely unclear. Aging is closely related with the major diseases, and recent studies show environmental exposure also accelerate aging. Therefore, we aimed at investigating the mediation impact of biological age (BA) on relationships of metals exposure with MetS risk. A cross-sectional study with 1,504 participants was conducted. BA predictors were established by Klemera and Doubal method (KDM) and Mahalanobis distance, based on clinical measures. KDM-accel [the residual difference of regressing KDM-BA to chronological age] and physiological dysregulation (PD) were further calculated and recorded as biological aging indexes (BAIs). Seven plasma metals (calcium, cobalt, copper, magnesium, molybdenum, selenium, and zinc), reported to be linked with MetS in our preceding study, were involved. Multivariate linear and logistic regression models were performed to evaluate the relationships of BAIs with metals exposure or MetS risk, respectively. The mediation effect of BA linking metals to MetS was also explored. Quantiles of magnesium, molybdenum, and cobalt showed significant negative relationships with MetS risk and two BAIs (all p-trend<0.05). Significant positive associations were observed for two BAIs and MetS risk (P<.001). Mediation analysis showed that BAIs mediated 19.15% and 13.23% of the negative associations between plasma molybdenum, magnesium and MetS risk, respectively. Our findings suggested that essential metals might reduce MetS risk via decelerating biological aging, emphasizing the significance of essential metals in prevention of aging and MetS.