Single-Cell Insights into Mouse Testicular Toxicity under Peripubertal Exposure to Di(2-ethylhexyl) phthalate.

Male fertility depends on normal pubertal development. Di(2-ethylhexyl) phthalate (DEHP) is a potent antiandrogen chemical, and exposure to DEHP during peripuberty can damage the developing male reproductive system, especially the testis. However, the specific cellular targets and differentiation processes affected by DEHP, which lead to testicular toxicity, remain poorly defined. Herein, we presented the first single-cell transcriptomic profile of the pubertal mouse testis following DEHP exposure. To carry out the experiment, two groups (n = 8 each) of three-week old male mice were orally administered 0.5% carboxymethylcellulose sodium salt or 100 mg/kg body weight DEHP daily from postnatal day 21 to 48, respectively. Using single-cell RNA sequencing, a total of 31 distinct cell populations were identified, notably, Sertoli and Leydig cells emerged as important targets of DEHP. DEHP exposure significantly decreased the proportions of Sertoli cell clusters expressing mature Sertoli markers (Sox9 and Ar), and selectively reduced the expression of testosterone synthesis genes in fetal Leydig cells. Through cell-cell interaction analyses, we observed changed numbers of interactions in Sertoli cells 1 (SCs1), Leydig cells 1 (LCs1) and interstitial macrophages (ITMs), and we also identified cell-specific ligand gene expressions in these clusters, such as Inha, Fyn, Vcam1, and Apoe. Complementary in vitro assays confirmed that DEHP directly reduced the expression of genes related to Sertoli cell adhesion and intercellular communication. In conclusion, peripubertal DEHP exposure reduced the number of mature Sertoli cells and may disrupt testicular steroidogenesis by affecting the testosterone synthesis genes in fetal Leydig cells rather than adult Leydig cells.

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.

[Silver nanoparticles-resistance of HeLa cell associated with its unusually high concentration of α-ketoglutarate and glutathione].

Silver nanoparticles (AgNPs) is known as one of the most valuable metal nanoparticles in antibacterial and anticancer application. AgNPs-resistant bacteria has been documented, but it is unclear whether cancer cells can also escape the anti-cancer effect of AgNPs. In this study, we aimed to investigate this phenomenon and its underlying mechanism. The antibacterial activity and cytotoxicity of AgNPs were measured in the presence of HeLa cell metabolites. The status of AgNPs in the system associated with metabolites were characterized by UV-Vis, Zetasizer Nano ZS, and transmission electron microscopy. Non-targeted metabolomics was used to reveal the metabolites components that bind with AgNPs. HeLa cells were injected intraperitoneally to establish the tumor-bearing mice model, and the stability of AgNPs in mice serum was analyzed. The results manifested that HeLa cell metabolites inhibited the anticancer and antibacterial effects of AgNPs in a dose-dependent manner by causing AgNPs aggregation. Effective metabolites that inhibited the biological activity of AgNPs were stable in 100 ℃, insoluble in chloroform, containing sulfur elements, and had a molecular weight less than 1 kDa in molecular weight. There were 115 compounds bound with AgNPs. In vitro experiments showed that AgNPs aggregation occurred only when the concentration of α-ketoglutarate (AKG) and glutathione (GSH) together reached a certain threshold. Interestingly, the concentration of AKG and GSH in HeLa cellular metabolites was 10 and 6 times higher than that in normal cervical epithelial cells, respectively, which explained why the threshold was reached. Furthermore, the stability of AgNPs in the serum of tumor-bearing mice decreased by 20% (P < 0.05) compared with the healthy mice. In conclusion, our study demonstrates that HeLa cells escaped the anti-cancer effect of AgNPs through the synergistic effect of AKG and GSH, suggesting the need to develop strategies to overcome this limitation.

Multi-omics reveals 2-bromo-4,6-dinitroaniline (BDNA)-induced hepatotoxicity and the role of the gut-liver axis in rats.

2-Bromo-4, 6-dinitroaniline (BDNA) is a widespread azo-dye-related hazardous pollutant. However, its reported adverse effects are limited to mutagenicity, genotoxicity, endocrine disruption, and reproductive toxicity. We systematically assessed the hepatotoxicity of BDNA exposure via pathological and biochemical examinations and explored the underlying mechanisms via integrative multi-omics analyses of the transcriptome, metabolome, and microbiome in rats. After 28 days of oral administration, compared with the control group, 100 mg/kg BDNA significantly triggered hepatotoxicity, upregulated toxicity indicators (e.g., HSI, ALT, and ARG1), and induced systemic inflammation (e.g., G-CSF, MIP-2, RANTES, and VEGF), dyslipidemia (e.g., TC and TG), and bile acid (BA) synthesis (e.g., CA, GCA, and GDCA). Transcriptomic and metabolomic analyses revealed broad perturbations in gene transcripts and metabolites involved in the representative pathways of liver inflammation (e.g., Hmox1, Spi1, L-methionine, valproic acid, and choline), steatosis (e.g., Nr0b2, Cyp1a1, Cyp1a2, Dusp1, Plin3, arachidonic acid, linoleic acid, and palmitic acid), and cholestasis (e.g., FXR/Nr1h4, Cdkn1a, Cyp7a1, and bilirubin). Microbiome analysis revealed reduced relative abundances of beneficial gut microbial taxa (e.g., Ruminococcaceae and Akkermansia muciniphila), which further contributed to the inflammatory response, lipid accumulation, and BA synthesis in the enterohepatic circulation. The observed effect concentrations here were comparable to the highly contaminated wastewaters, showcasing BDNA's hepatotoxic effects at environmentally relevant concentrations. These results shed light on the biomolecular mechanism and important role of the gut-liver axis underpinning BDNA-induced cholestatic liver disorders in vivo.

Serum protein coating enhances the antisepsis efficacy of silver nanoparticles against multidrug-resistant Escherichia coli infections in mice.

Antimicrobial resistance poses a significant threat to public health and social development worldwide. This study aimed to investigate the effectiveness of silver nanoparticles (AgNPs) in treating multidrug-resistant bacterial infections. Eco-friendly spherical AgNPs were synthesized using rutin at room temperature. The biocompatibility of both polyvinyl pyrrolidone (PVP) and mouse serum (MS)-stabilized AgNPs was evaluated at 20 µg/mL and showed a similar distribution in mice. However, only MS-AgNPs significantly protected mice from sepsis caused by the multidrug-resistant Escherichia coli (E. coli) CQ10 strain (p = 0.039). The data revealed that MS-AgNPs facilitated the elimination of Escherichia coli (E. coli) in the blood and the spleen, and the mice experienced only a mild inflammatory response, as interleukin-6, tumor necrosis factor-α, chemokine KC, and C-reactive protein levels were significantly lower than those in the control group. The results suggest that the plasma protein corona strengthens the antibacterial effect of AgNPs in vivo and may be a potential strategy for combating antimicrobial resistance.

PPARγ As a Potential Target for Adipogenesis Induced by Fine Particulate Matter in 3T3-L1 Preadipocytes.

Mounting evidence has shown that ambient PM2.5 exposure is closely associated with the development of obesity, and adipose tissue represents an important endocrine target for PM2.5. In this study, the 3T3-L1 preadipocyte differentiation model was employed to comprehensively explore the adipogenic potential of PM2.5. After 8 days of PM2.5 exposure, adipocyte fatty acid uptake and lipid accumulation were significantly increased, and adipogenic differentiation of 3T3-L1 cells was promoted in a concentration-dependent manner. Transcriptome and lipidome analyses revealed the systematic disruption of transcriptional and lipid profiling at 10 µg/mL PM2.5. Functional enrichment and visualized network analyses showed that the peroxisome proliferator-activated receptor (PPAR) pathway and the metabolism of glycerophospholipids, glycerolipids, and sphingolipids were most significantly affected during adipocyte differentiation. Reporter gene assays indicated that PPARγ was activated by PM2.5, demonstrating that PM2.5 promoted adipogenesis by activating PPARγ. The increased transcriptional and protein expressions of PPARγ and downstream adipogenesis-associated markers (e.g., Fabp4 and CD36) were further cross-validated using qRT-PCR and western blot. PM2.5-induced adipogenesis, PPARγ pathway activation, and lipid remodeling were significantly attenuated by the supplementation of a PPARγ antagonist (T0070907). Overall, this study yielded mechanistic insights into PM2.5-induced adipogenesis in vitro by identifying the potential biomolecular targets for the prevention of PM2.5-induced obesity and related metabolic diseases.

Dietary supplementation with jasmine flower residue improves meat quality and flavor of goat.

Jasmine flower residue (JFR) is a by-product retained in the production process of jasmine tea and can be used as an unconventional feed due to its rich nutrient value. This study aimed to evaluate the effects of the addition of JFR to the diet of goats on their meat quality and flavor. Twenty-four castrated Nubian male goats were randomly divided into two groups and fed a mixed diet containing 10% JFR (JFR, n = 12) or a conventional diet (CON, n = 12) for 45 days. Meat quality and flavor were measured at the end of the treatment. The addition of JFR to the diet could reduce the shear force of the longissimus dorsi muscle, as well as, the cross-sectional area and diameter of muscle fibers, indicating that the addition of JFR improved meat quality. JFR also increased the content of glutamic acid and ω-3 polyunsaturated fatty acid (C18:3n3 and C20:5N3) and reduced the content of C24:1 and saturated fatty acid (C20:0 and C22:0). In addition, the use of JFR increased the content of acetaldehyde and hexanal in the meat. Furthermore, JFR introduced new volatile components in the meat. The umami, saltiness, and richness of the meat also improved. In conclusion, the addition of jasmine flower residue to the diet can improve the meat quality and flavor of goat.

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.

Short-term exposure to antimony induces hepatotoxicity and metabolic remodeling in rats.

Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved in apical hepatotoxicity. Our study demonstrated that short-term exposure to Sb induces hepatotoxicity, possibly through a glycolipid metabolism disorder, providing an important reference for the health risks of Sb pollution.

Neglected Aspects of SARS-CoV-2 Aerosol Transmission in Bathrooms of Multistory and High-Rise Buildings - Beijing Municipality, China, October 2022.

What is already known about this topic?: There is a toilet flush-soil stack-floor drain pathway of aerosol transmission in multistory and high-rise buildings, but the influencing factors are not completely clear. What is added by this report?: The poor airtightness of the connecting parts of the floor drain, as well as pressure fluctuations in the sewage pipe during toilet flushing caused by blockage of the soil stack vent, may lead to the cross-floor transmission of viral aerosols through the soil stack and floor drains. What are the implications for public health practice?: In multistory and high-rise buildings, the bathroom floor drains should be kept sealed, and floor drain connecting parts should be airtight. Furthermore, the soil stack vent should not be blocked. In this way, the cross-floor transmission of viral aerosols can be effectively reduced.

Personal airborne chemical exposure and epigenetic ageing biomarkers in healthy Chinese elderly individuals: Evidence from mixture approaches.

BACKGROUND: Air pollution is associated with accelerated biological ages determined by DNA methylation (DNAm) patterns, imposing further risks of age-related adverse effects. However, little is known about the independent and joint effects of exposure to gaseous organic chemicals that may share a common source. METHODS: We conducted a panel study with the 3-day exposure assessment monthly among 73 Chinese healthy elderly people aged 60 to 69 years in Jinan, Shandong province during September 2018 to January 2019.Exposure to 26 ambient organic chemical contaminants were measured by wearable passive samplers, including volatile organic compounds, polycyclic aromatic hydrocarbons (PAHs), phthalates (PAEs), nitroaromatics (NIs), polybrominated diphenyl ethers, chlorinated hydrocarbons, and organophosphate esters. The Illumina MethylationEPIC BeadChip was used to measure DNA methylation levels in blood samples, and based on which, epigenetic ageing biomarkers, including Hannum clock, Horvath clock, DNAm PhenoAge, DNAm GrimAge, and DNAm estimator of telomere length (DNAmTL) were calculated. Linear mixed effect models were used to estimate the linear associations between 3-day personal chemical exposure and the epigenetic biomarkers, Weighted quantile sum (WQS) regression and the Bayesian kernel machine regression (BKMR) model were further used to evaluate the effect of chemical mixtures. RESULTS: Multiple linear mixed effects regression models showed that DNAmPhenoAge acceleration was significantly and positively associated with exposure to PAEs, NIs, and PAHs in healthy elderly individuals. Both WQS regression and BKMR models showed a significant positive association with DNAmPhenoAge acceleration with chemical exposures, in which the effect of di-n-butyl phthalate exposure showed the greatest importance. CONCLUSION: These findings suggest that exposure to a mixture of airborne chemicals significantly increase the acceleration of the epigenetic biomarker of phenotypic age. These findings serve to identify toxic chemicals in the air and facilitate the evaluation of their potentially severe health effects.

Independent and Interactive Effects of Environmental Conditions on Aerosolized Surrogate SARS-CoV-2 - Beijing, China, June to September 2020.

What is already known about this topic?: Environmental factors such as temperature and humidity play important roles in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via droplets/aerosols. What is added by this report?: Higher relative humidity (61%-80%), longer spreading time (120 min), and greater dispersal distance (1 m) significantly reduced SARS-CoV-2 pseudovirus loads. There was an interaction effect between relative humidity and spreading time. What are the implications for public health practice?: The findings contribute to our understanding of the impact of environmental factors on the transmission of SARS-CoV-2 via airborne droplets/aerosols.

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.

Sleep disturbance exacerbates the cardiac conduction abnormalities induced by persistent heavy ambient fine particulate matter pollution: A multi-center cross-sectional study.

Fine particulate matter (PM2.5) exposure and sleep disturbance have been significantly associated with adverse cardiovascular outcomes, however, the combined effects of these two factors are still unclear. We conducted a multi-center cross-sectional study from November 2018 to May 2019 in the Beijing-Tianjin-Hebei region in China to investigate the potential modifying effects of sleep disturbance on associations between cardiac conduction abnormalities and PM2.5 exposure, as well as the combined effects of sleep disturbance and heavy pollution episodes, which were defined based on the PM2.5 mass concentration (≥75 µg/m3, falling in the 75th/90th percentile) and duration (1 day and ≥2 days). The sleep quality and sleep duration of all participants were evaluated using the Pittsburgh Sleep Quality Index. Standard 12-lead electrocardiogram (ECG) test was performed to measure the heart rate (HR), QRS duration (time taken for ventricular depolarization), HR corrected QT interval (time for ventricular depolarization and repolarization) and PR interval (time for atrioventricular conduction). Multivariable linear regression models were performed to evaluate the associations of PM2.5 and heavy pollution events on ECG parameters and the joint effects with sleep disturbance. We found PM2.5 exposure was independently associated with prolonged QRS and QTc intervals. Association between PM2.5 and the QTc interval was significantly stronger in participants with poor sleep quality. For each 10-µg/m3 increase in PM2.5 concentration, the QTc interval in the participants with poor sleep quality increased by 0.41 % (95 % confidence interval: 0.19, 0.64). In addition, heavy PM2.5 pollution episodes, especially extremely heavy pollution of long duration, were found to have synergistic effects with sleep disturbance on ECG parameters. Our findings provide evidence that PM2.5 exposure, especially heavy pollution episodes, may increase abnormal cardiac conduction and have a synergistic effect with sleep disturbance. Improving sleep hygiene is crucial to protect the heart health of the general population.

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.

PM2.5 exposure associated with microbiota gut-brain axis: Multi-omics mechanistic implications from the BAPE study.

Recent studies have shown that PM2.5 may activate the hypothalamus-pituitary-adrenal (HPA) axis by inducing hormonal changes, potentially explaining the increase in neurological and cardiovascular risks. In addition, an association between PM2.5 and gut microbiota and metabolites was established. The above evidence represents crucial parts of the gut-brain axis (GBA). In view of this evidence, we proposed a hypothesis that PM2.5 exposure may affect the HPA axis through the gastrointestinal tract microbiota pathway (GBA mechanism), leading to an increased risk of neurological and cardiovascular diseases. We conducted a real-world prospective repeated panel study in Jinan, China. At each visit, we measured real-time personal PM2.5 and collected fecal and blood samples. A linear mixed-effects model was used to analyze the association between PM2.5 and serum biomarkers, gut microbiota, and metabolites. We found that PM2.5 was associated with increased serum levels of hormones, especially the adrenocorticotropic hormone (ACTH) and cortisol, which are reliable hormones of the HPA axis. Gut microbiota and tryptophan metabolites and inflammation, which are important components of the GBA, were significantly associated with PM2.5. We also found links between PM2.5 and changes in the nervous and cardiovascular outcomes, e.g., increases of 19.77% (95% CI: -36.44, 125.69) in anxiety, 1.19% (95% CI: 0.65, 1.74) in fasting blood glucose (FBG), 2.09% (95% CI: 1.48, 2.70) in total cholesterol (TCHOL), and 0.93% (95% CI: 0.14, 1.72) in triglycerides (TG), were associated with 10 µg/m3 increase in PM2.5 at the lag 0-72 h, which represent the main effects of GBA. This study indicated the link between PM2.5 and the microbiota GBA for the first time, providing evidence of the potential mechanism for PM2.5 with neurological and cardiovascular system dysfunction.

PM2.5 and Serum Metabolome and Insulin Resistance, Potential Mediation by the Gut Microbiome: A Population-Based Panel Study of Older Adults in China.

BACKGROUND: Insulin resistance (IR) affects the development of type 2 diabetes mellitus (T2DM), which is also influenced by accumulated fine particle air pollution [particulate matter (PM) with aerodynamic diameter of <2.5µm (PM2.5)] exposure. Previous experimental and epidemiological studies have proposed several potential mechanisms by which PM2.5 contributes to IR/T2DM, including inflammation imbalance, oxidative stress, and endothelial dysfunction. Recent evidence suggests that the imbalance of the gut microbiota affects the metabolic process and may precede IR. However, the underlying mechanisms of PM2.5, gut microbiota, and metabolic diseases are unclear. OBJECTIVES: We investigated the associations between personal exposure to PM2.5 and fasting blood glucose and insulin levels, the IR index, and other related biomarkers. We also explored the potential underlying mechanisms (systemic inflammation and sphingolipid metabolism) between PM2.5 and insulin resistance and the mediating effects between PM2.5 and sphingolipid metabolism. METHODS: We recruited 76 healthy seniors to participate in a repeated-measures panel study and conducted clinical examinations every month from September 2018 to January 2019. Linear mixed-effects (LME) models were used to analyze the associations between PM2.5 and health data (e.g., functional factors, the IR index, inflammation and other IR-related biomarkers, metabolites, and gut microbiota). We also performed mediation analyses to evaluate the effects of mediators (gut microbiota) on the associations between exposures (PM2.5) and featured metabolism outcomes. RESULTS: Our prospective panel study illustrated that exposure to PM2.5 was associated with an increased risk of higher IR index and functional biomarkers, and our study provided mechanistic evidence suggesting that PM2.5 exposure may contribute to systemic inflammation and altered sphingolipid metabolism. DISCUSSION: Our findings demonstrated that PM2.5 was associated with the genera of the gut microbiota, which partially mediated the association between PM2.5 and sphingolipid metabolism. These findings may extend our current understanding of the pathways of PM2.5 and IR. https://doi.org/10.1289/EHP9688.

Detection of the SARS-CoV-2 Delta Variant in the Transboundary Rivers of Yunnan, China.

Ruili and Longchuan, two border counties in southwestern China, are facing epidemic control challenges due to the high rate of COVID-19 infections originating from neighboring Myanmar. Here, we aimed to establish the applicability of wastewater and environmental water surveillance of SARS-CoV-2 and conduct whole-genome sequencing (WGS) to trace the possible infection origin. In August 2021, total 72 wastewater and river water samples were collected from 32 sampling sites. SARS-CoV-2 ORF1ab and N genes were measured by RT-qPCR. We found that 19 samples (26.39%) were positive, and the viral loads of ORF1ab and N genes were 6.62 × 102-2.55×105 and 1.86 × 103-2.32 × 105 copies/L, respectively. WGS further indicated the sequences in two transboundary river samples, and one hospital wastewater sample belonged to the delta variant, suggesting that the infection source might be areas with high COVID-19 delta variant incidence in Southeast Asia (e.g., Myanmar). We reported for the first time the detection and quantification of SARS-CoV-2 RNA in the transboundary rivers of Myanmar-China. Our findings demonstrate that wastewater and environmental water may provide independent and nonintrusive surveillance points to monitor the global spread of emerging COVID-19 variants of concern, particularly in high-risk regions or border areas with considerable epidemic challenges and poor wastewater treatment facilities.

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.