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Bile acids (BAs) play a crucial role in lipid metabolism of children. However, the association between per- and polyfluoroalkyl substance (PFAS) exposure and BAs in children is scarce. To address this need, we selected 252 children from the Maoming Birth Cohort and measured 32 PFAS, encompassing short- and long-chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) in the cord blood. Additionally, we analyzed nine primary and eight secondary BAs in the serum of three-year-old children. Generalized linear models with FDR-adjusted and Bayesian kernel machine regression (BKMR) were used to explore the associations of individual and mixture effects of PFAS and BAs. We found negative associations between cord blood long-chain PFCAs exposure and serum primary BAs in three-year-old children. For example, one ln-unit (ng/mL) increase of perfluoro-n-tridecanoic acid (PFTrDA), perfluoro-n-undecanoic acid (PFUnDA) and perfluoro-n-decanoic acid (PFDA) were associated with decreased taurochenodeoxycholic acid, with estimated percentage change of -24.28% [95% confidence interval (CI): -36.75%, -9.35%], -25.84% (95% CI: -39.67%, -8.83%), and -22.97% (95% CI: -34.45%, -9.47%) respectively. Notably, the observed associations were more pronounced in children with lower vegetable intake. Additionally, the BKMR model also demonstrated a monotonical decline in primary BAs as the PFAS mixture increased. We provided the first evidence of the association between intrauterine exposure to PFAS and its mixture with BAs in children. Further large-sample-size studies are needed to verify this finding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fine particulate matter (PM 2.5 ) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM 2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM 2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM 2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM 2.5 . Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM 2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM 2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Evidence on the early life risk factors of adult CRS, and the history of asthma and allergies across the life course, is limited., Aim: To investigate relationships between respiratory infective/allergic conditions in childhood, and asthma and allergies across the life course and CRS in middle age., Methods: Data were from the population-based Tasmanian Longitudinal Health Study (TAHS) cohort, first studied in 1968 when aged 6-7 years (n = 8583) and serially followed into middle age (n = 3609). Using a well-accepted epidemiological definition, participants were assigned a CRS-severity subtype at age 53: no sinusitis/CRS (reference); past doctor diagnosis only; current symptoms without doctor diagnosis; and doctor-diagnosed CRS with current symptoms. Relationships with infective/allergic respiratory illnesses at age 7, and previously published asthma-allergy trajectories from 7 to 53 years, were examined using multinominal regression., Results: In middle age, 5.8% reported current CRS symptoms with 2.5% doctor-diagnosed. Childhood conditions associated with symptomatic doctor-diagnosed CRS included frequent head colds (multinomial odds ratio [mOR] = 2.04 (95% confidence interval [95% CI]: 1.24, 3.37)), frequent tonsillitis (mOR = 1.61 [95% CI: 1.00, 2.59]) and current childhood asthma (mOR = 2.23 [95% CI: 1.25, 3.98]). Life course trajectories that featured late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age; early-onset persistent asthma and allergies (mOR = 6.74, 95% CI: 2.76, 16.4); late-onset asthma allergies (mOR = 15.9, 95% CI: 8.06, 31.4), and late-onset hayfever (mOR = 3.02, 95% CI: 1.51, 6.06) were associated with symptomatic doctor-diagnosed CRS., Conclusion: Current asthma, frequent head colds and tonsillitis at age 7 could signal a susceptible child who is at higher risk for CRS in mid-adult life and who might benefit from closer monitoring and/or proactive management. Concurrent asthma and allergies were strongly associated and are potential treatable traits of adult CRS., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Recent evidences highlight the potential impact of outdoor Light at Night (LAN) on executive function. However, few studies have investigated the association between outdoor LAN exposure and executive function., Methods: We employed data from 48,502 Chinese children aged 5-12 years in a cross-sectional study conducted in Guangdong province during 2020-2021, to examine the association between outdoor LAN and executive function assessed using the validated parent-completed Behavior Rating Inventory of Executive Function. We assessed children's outdoor LAN exposure using the night-time satellite images based on the residential addresses. We used generalized linear mixed models to estimate the association between outdoor LAN exposure and executive function scores and executive dysfunction., Results: After adjusting for potential covariates, higher quintiles of outdoor LAN exposure were associated with poorer executive function. Compared to the lowest quintile (Q1), all higher quintiles of exposure showed a significant increased global executive composite (GEC) score with β (95% confidence intervals, CI) of 0.58 (0.28, 0.88) in Q2, 0.59 (0.28, 0.9) in Q3, 0.85 (0.54, 1.16) in Q4, and 0.76 (0.43, 1.09) in Q5. Higher quintiles of exposure were also associated with higher risks for GEC dysfunction with odd ratios (ORs) (95% CI) of 1.34 (1.18, 1.52) in Q2, 1.40 (1.24, 1.59) in Q3, 1.40 (1.23, 1.59) in Q4, and 1.39 (1.22, 1.58) in Q5. And stronger associations were observed in children aged 10-12 years., Conclusions: Our study suggested that high outdoor LAN exposure was associated with poor executive function in children. These findings suggested that future studies should determine whether interventions to reduce outdoor LAN exposure can have a positive effect on executive function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Metabolic syndrome (MetS) is a significant public health problem and presents an escalating clinical challenge globally. To combat this problem effectively, urgent measures including identify some modifiable environmental factors are necessary. Outdoor artificial light at night (LAN) exposure garnered much attention due to its impact on circadian rhythms and metabolic process. However, epidemiological evidence on the association between outdoor LAN exposure and MetS remains limited. To determine the relationship between outdoor LAN exposure and MetS, 15,477 adults participated the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. Annual levels of outdoor LAN exposure at participants' residential addresses were assessed using satellite data from the Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS). Generalized linear mixed effect models were utilized to assess the association of LAN exposure with MetS and its components, including elevated waist circumference (WC), triglycerides (TG), blood pressure (BP), fasting blood glucose (FBG), and reduced high-density lipoprotein cholesterol (HDL-C). Effect modification by various social demographic and behavior factors was also examined. Overall, 4701 (30.37 %) participants were defined as MetS. The LAN exposure ranged from 6.03 to 175.00 nW/cm 2 /sr. The adjusted odds ratio (OR) of MetS each quartile increment of LAN exposure were 1.43 (95 % CI: 1.21-1.69), 1.44 (95 % CI: 1.19-1.74) and 1.52 (95 % CI: 1.11-2.08), respectively from Q2-Q4. Similar adverse associations were also found for the components of MetS, especially for elevated BP, TG and FBG. Interaction analyses indicated that the above associations were stronger in participants without habitual exercise compared with those with habitual exercise (e.g. OR were 1.52 [95 % CI: 1.28-1.82] vs. 1.27 [95 % CI, 1.04-1.55], P -interaction  = 0.042 for MetS). These findings suggest that long-term exposure to LAN can have a significant deleterious effect on MetS, potentially making LAN an important modifiable environmental factor to target in future preventive strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Air pollution is a significant contributor to morbidity and mortality globally and has been linked to an increased risk of dementia. Previous studies within the Betula cohort in Northern Sweden have demonstrated associations between air pollution and dementia, as well as distinctive metabolomic profiles in dementia patients compared to controls. This study aimed to investigate whether air pollution is associated with quantitative changes in metabolite levels within this cohort, and whether future dementia status would modify this association., Methods: Both short-term and long-term exposure to air pollution were evaluated using high spatial resolution models and measured data. Air pollution from vehicle exhaust and woodsmoke were analyzed separately. Metabolomic profiling was conducted on 321 participants, including 58 serum samples from dementia patients and a control group matched for age, sex, and education level, using nuclear magnetic resonance spectroscopy., Results: No statistically significant associations were found between any metabolites and any measures of short-term or long-term exposure to air pollution. However, there were trends potentially suggesting associations between both long-term and short-term exposure to air pollution with lactate and glucose metabolites. Notably, these associations were observed despite the lack of correlation between long-term and short-term air pollution exposure in this cohort. There were also tendencies for associations between air pollution from woodsmoke to be more pronounced in participants that would later develop dementia, suggesting a potential effect depending on urban/rural factors., Discussion: While no significant associations were found, the trends observed in the data suggest potential links between air pollution exposure and changes in lactate and glucose metabolites. These findings provide some new insights into the link between air pollution and metabolic markers in a low-exposure setting. However, addressing existing limitations is crucial to improve the robustness and applicability of future research in this area. The pronounced associations in participants who later developed dementia may indicate an influence of urban/rural factors, warranting further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Raza, Öhman, Kanninen, Jalava, Zeng, de Crom, Ikram and Oudin.)

Objectives: Evidence on the link between long-term ambient particulate matter (PM) exposures and childhood sleep disorders were scarce. We examined the associations between long-term exposures to PM 2.5 and PM 1 (PM with an aerodynamic equivalent diameter <2.5 μm and <1 μm, respectively) with sleep disorders in children., Methods: We performed a population-based cross-sectional survey in 177,263 children aged 6 to 18 years in 14 Chinese cities during 2012-2018. A satellite-based spatiotemporal model was employed to estimate four-year annual average PM 2.5 and PM 1 exposures at residential and school addresses. Parents or guardians completed a checklist using the Sleep Disturbance Scale for Children. We estimated the associations using generalized linear mixed models with adjustment for characteristics of children, parents, and indoor environments., Results: Long-term PM 2.5 and PM 1 exposures were positively associated with odds of sleep disorders for almost all domains. For example, increments in PM 2.5 and PM 1 per 10 μg/m 3 were associated with odds ratios of global sleep disorder of 1.24 (95 % confidence interval [CI]: 1.14, 1.35) and 1.31 (95 %CI: 1.18, 1.46), respectively. Similar results were observed for subtypes of sleep disorder. These associations were heterogeneous regionally, with stronger associations among children residing in southeast region than in northeast and northwest regions. Moreover, larger estimates of PM 1 were found than that of PM 2.5 in southeast region., Conclusion: Long-term PM 2.5 and PM 1 exposures are independently associated with higher risks of childhood sleep disorders, and these associations vary by geographical region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 μg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 μg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to PM 2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions., Objectives: To explore the associations between long-term exposure to PM 2.5 constituents and neurodegenerative diseases., Methods: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM 2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH 4 + ), nitrate (NO 3 - ) and sulfate (SO 4 2- )) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence., Results: PM 2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45-2.27; 1.78; 95% CI, 1.37-2.32; and 1.99; 95% CI, 1.54-2.57 for the second, third, and fourth quartiles, respectively)., Conclusions: Long-term exposure to PM 2.5 and its constituents, particularly combustion-related BC, OM, and SO 4 2- , was significantly associated with higher prevalence of AD and PD in Chinese individuals., Environmental Implication: PM 2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM 2.5 constituents to health effects is scarce. This study firstly investigated the association between PM 2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM 2.5 that have significant impacts. This study provides important implications for the development of targeted PM 2.5 prevention and control policies to reduce specific hazardous PM 2.5 constituents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chlorinated polyfluorinated ether sulfonate (F-53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F-53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F-53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F-53B (0, 4, 40, and 400 μg/L) for 28 days. Our findings revealed a significant accumulation of F-53B in the liver, followed by small intestines, and feces. In addition, F-53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid β-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1β, and Mcp1) in the liver. Meanwhile, F-53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F-53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae&#95;NK3B31&#95;group in the feces. F-53B-altered microbiota compositions were significantly associated with genes related to fatty acid β-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F-53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F-53B-induced enterohepatic toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although the indoor environment has been proposed to be associated with childhood sleep health, to our knowledge no study has investigated the association between home renovation and childhood sleep problems., Methods: The study included 186,470 children aged 6-18 years from the National Chinese Children Health Study (2012-2018). We measured childhood sleeping problems via the Chinese version of the Sleep Disturbance Scale for Children (C-SDSC). Information on home renovation exposure within the recent 2 years was collected via parent report. We estimated associations between home renovation and various sleeping problems, defined using both continuous and categorized (binary) C-SDSC t-scores, using generalized mixed models. We fitted models with city as a random effect variable, and other covariates as fixed effects., Results: Out of the overall participants, 89,732 (48%) were exposed to recent home renovations. Compared to the unexposed group, children exposed to home renovations had higher odds of total sleep disorder (odd ratios [OR] = 1.3; 95% confidence interval [CI] = 1.2, 1.4). Associations varied when we considered different types of home renovation materials. Children exposed to multiple types of home renovation had higher odds of sleeping problems. We observed similar findings when considering continuous C-SDSC t-scores. Additionally, sex and age of children modified the associations of home renovation exposure with some of the sleeping problem subtypes., Conclusions: We found that home renovation was associated with higher odds of having sleeping problems and that they varied when considering the type of renovation, cumulative exposure, sex, and age differences., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The emissions and exposure limits for airborne PM 0.1 are lacking, with limited scientific data for toxicity. Therefore, we continuously monitored and calculated the number and mass concentrations of airborne PM 0.1 in December 2017, January 2018 and March 2018 during the high pollution period in Guangzhou. We collected PM 0.1 from the same period and analyzed their chemical components. A549, THP-1 and A549/THP-1 co-cultured cells were selected for exposure to PM 0.1 , and evaluated for toxicological responses. Our aims are to 1) measure and analyze the number and mass concentrations, and chemical components of PM 0.1 ; 2) evaluate and compare PM 0.1 toxicity to different airway cells models at different time points. Guangzhou had the highest mass concentration of PM 0.1 in December 2017, while the number concentration was the lowest. Chemical components in PM 0.1 vary significantly at different time periods, and the correlation between the chemical composition or source of PM 0.1 and the mass and number concentration of PM 0.1 was dissimilar. Exposure to PM 0.1 disrupted cell membranes, impaired mitochondrial function, promoted the expression of inflammatory mediators, and interfered with DNA replication in the cell cycle. The damage caused by exposure to PM 0.1 at different times exhibited variations across different types of cells. PM 0.1 in March 2018 stimulated co-cultured cells to secrete more inflammatory mediators, and CMA was significantly related to the expression of them. Our study indicates that it is essential to monitor both the mass and number concentrations of PM 0.1 throughout all seasons annually, as conventional toxicological experiments and the internal components of PM 0.1 may not effectively reveal the health damages caused by elevated number levels of PM 0.1 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Previous studies have linked exposure to light at night (LAN) with various health outcomes, but evidence is limited for the LAN-obesity association. Thestudy analysed data from 24,845 participants of the 33 Communities Chinese Health Study and obesity (BMI ≥28 kg/m 2 ) was defined according to the Working Group on Obesity in China. The Global Radiance Calibrated Nighttime Lights data were used to estimate participants' LAN exposure. The mixed-effect regression models examined the LAN-BMI and LAN-obesity association. We found that higher LAN exposure was significantly associated with greater BMI and higher risk of obesity. Changes of BMI and the odds ratios (ORs) of obesity and 95% confidence intervals (CIs) for 2 nd , 3 rd , and 4 th against the 1 st quartile of LAN exposure were 0.363 (0.208, 0.519), 0.364 (0.211, 0.516) and 0.217 (0.051, 0.383); 1.228 (1.099, 1.371), 1.356 (1.196, 1.538) and 1.269 (1.124, 1.433), respectively. Age and regular exercise showed significant modification effects on the LAN-obesity association.

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) ( P inter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Background: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation., Methods: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 μg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice., Results: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein expression of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) levels were decreased, as compared to control (0.367-fold, P < 0.001; 0.366-fold, P < 0.001; respectively). We also observed the upregulation of dopamine transporter (DAT) (2.940-fold, P < 0.001) consistent with the trend of dopamine content (1.313-fold, P < 0.001) in the hippocampus., Conclusion: Early life exposure to F-53B is associated with adverse neurobehavioral changes in developing children and weaning mice which may be modulated by dopamine-dependent synaptic plasticity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Estrogens play a critical role in parturition, and poly- and perfluoroalkyl substances (PFAS), which have estrogenic effects, have been associated with preterm birth. However, the impact of estrogens on the association between PFAS and preterm birth is unknown., Objective: The objective of this study is to investigate if estrogens modified the association between PFAS and preterm birth, using a nested case-control study design., Methods: A total of 371 preterm births and 508 controls were selected from a birth cohort study in China between 2016 and 2018. Perfluorobutanoic acid (PFBA), perfluorohexanesulfonic acid (PFHxS) and its branched isomer, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and its branched isomer, and perfluorononanoic acid (PFNA) were quantified in maternal serum (mean gestational age of 32 wk). Estradiol and estriol were quantified in cord serum. Preterm birth was defined as live delivery at < 37 gestational weeks. Causal mediation analysis was used to estimate the mediation and interaction effects of estrogen on the association between PFAS and preterm birth. Latent profile analysis was used to identify important estrogen profiles. Multiple linear regression was used to estimate associations between PFAS and preterm birth and interactions between PFAS and estrogens on preterm birth., Results: Overall, higher odds ratios (ORs) of preterm birth were associated with each 1 ln-unit PFAS increase: PFBA [1.20, 95% confidence interval (CI): 1.14, 1.26], PFNA (1.30, 95% CI: 1.21, 1.39), PFOA (1.98, 95% CI: 1.54, 2.55), and PFOS (1.91, 95% CI: 1.76, 2.07) and its branched isomer (1.91, 95% CI: 1.90, 1.92). We detected statistically significant interactions between cord estradiol and PFAS on preterm birth, while no mediation effects of cord estrogen were observed. The ORs of PFOS (4.29, 95% CI: 1.31, 8.25), its branched isomer (6.71, 95% CI: 1.06, 11.91), and preterm birth were greater for participants with high cord estrogen levels than for participants with low cord estrogen levels., Discussion: Our findings suggest that estrogen modified the association between maternal PFAS exposure and preterm birth. Further studies on maternal PFAS exposure and preterm birth, taking interaction effects of cord estrogens into account, are warranted. https://doi.org/10.1289/EHP11377.

Exposure to Fine particulate matter (PM 2.5) has been associated with various neurological disorders. However, the underlying mechanisms of PM 2.5 -induced adverse effects on the brain are still not fully defined. Multi-omics analyses could offer novel insights into the mechanisms of PM 2.5 -induced brain dysfunction. In this study, a real-ambient PM 2.5 exposure system was applied to male C57BL/6 mice for 16 weeks, and lipidomics and transcriptomics analysis were performed in four brain regions. The findings revealed that PM 2.5 exposure led to 548, 283, 304, and 174 differentially expressed genes (DEGs), as well as 184, 89, 228, and 49 distinctive lipids in the hippocampus, striatum, cerebellum, and olfactory bulb, respectively. Additionally, in most brain regions, PM 2.5 -induced DEGs were mainly involved in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, and calcium signaling pathway, while PM 2.5 -altered lipidomic profile were primarily enriched in retrograde endocannabinoid signaling and biosynthesis of unsaturated fatty acids. Importantly, mRNA-lipid correlation networks revealed that PM 2.5 -altered lipids and DEGs were obviously enriched in pathways involving in bile acid biosynthesis, De novo fatty acid biosynthesis, and saturated fatty acids beta-oxidation in brain regions. Furthermore, multi-omics analyses revealed that the hippocampus was the most sensitive part to PM 2.5 exposure. Specifically, dysregulation of Pla2g1b, Pla2g, Alox12, Alox15, and Gpx4 induced by PM 2.5 were closely correlated to the disruption of alpha-linolenic acid, arachidonic acid and linoleic acid metabolism in the hippocampus. In summary, our findings highlight differential lipidomic and transcriptional signatures of various brain regions by real-ambient PM 2.5 exposure, which will advance our understanding of potential mechanisms of PM 2.5 -induecd neurotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) have attracted worldwide attention as one of persistent organic pollutants; however, there is limited knowledge about the exposure concentrations of PFAS-contained ambient particulate matter and the related health risks. This study investigated the abundance and distribution of 32 PFAS in fine particulate matter (PM 2.5 ) collected from 93 primary or secondary schools across the Pearl River Delta region (PRD), China. These chemicals comprise four PFAS categories which includes perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkyl sulfonic acids (PFSAs), perfluoroalkyl acid (PFAA) precursors and PFAS alternatives. In general, concentrations of target PFAS ranged from 11.52 to 419.72 pg/m 3 (median: 57.29 pg/m 3 ) across sites. By categories, concentrations of PFSAs (median: 26.05 pg/m 3 ) were the dominant PFAS categories, followed by PFCAs (14.25 pg/m 3 ), PFAS alternatives (2.75 pg/m 3 ) and PFAA precursors (1.10 pg/m 3 ). By individual PFAS, PFOS and PFOA were the dominant PFAS, which average concentration were 24.18 pg/m 3 and 6.05 pg/m 3 , respectively. Seasonal variation showed that the concentrations of PFCAs and PFSAs were higher in winter than in summer, whereas opposite seasonal trends were observed in PFAA precursors and PFAS alternatives. Estimated daily intake (EDI) and hazard quotient (HQ) were used to assess human inhalation-based exposure risks to PFAS. Although the health risks of PFAS via inhalation were insignificant (HQ far less than one), sufficient attention should be levied to ascertain the human exposure risks through inhalation, given that exposure to PFAS through air inhalation is a long term and cumulative process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glucocorticoid plays a key role in the growth and organ maturation of fetus. However, the effect of glucocorticoid on the association between per- and polyfluoroalkyl substance (PFAS) exposure and fetal growth is still unknown. We detected cord cortisol (active glucocorticoid in human) and 34 PFAS concentrations in the maternal serum samples, which were collected from 202 mother-fetus pairs in the Maoming Birth Cohort from 2015 to 2018. The mediation effect of cord cortisol on the association between maternal PFAS and the neonatal growth index (NGI) was estimated. We found that higher PFAS concentrations were associated with lower NGI in terms of ponderal index, birth weight (BW), head circumference (HC), and its z-scores (BWZ and HCZ) ( P < 0.05). Fetal cortisol could mediate 12.6-27.3% of the associations between PFAS and NGI. Specifically, cord cortisol mediated the association between branched perfluorooctane sulfonate (branched PFOS) and HCZ by 20.4% and between perfluorooctanoate (PFOA) and HCZ by 27.3%. Our findings provide the first epidemiological data evincing that fetal cortisol could mediate the association between prenatal PFAS exposure and fetal growth. Further investigations are recommended to elucidate the interactions among cord cortisol, PFAS, and fetal growth.

The sources, sizes, components, and toxicological responses of particulate matter (PM) have demonstrated remarkable spatiotemporal variability. However, associations between components, sources, and toxicological effects in different-sized PM remain unclear. The purposes of this study were to 1) determine the sources of PM chemical components, 2) investigate the associations between components and toxicology of PM from Guangzhou high air pollution season. We collected size-segregated PM samples (PM 10-2.5 , PM 2.5-1 , PM 1-0.2 , PM 0.2 ) from December 2017 to March 2018 in Guangzhou. PM sources and components were analyzed. RAW264.7 mouse macrophages were treated with PM samples for 24 h followed by measurements of toxicological responses. The concentrations of PM 10 - 2.5 and PM 1 - 0.2 were relatively high in all samples. Water-soluble ions and PAHs were more abundant in smaller-diameter PM, while metallic elements were more enriched in larger-diameter PM. Traffic exhaust, soil dust, and biomass burning/petrochemical were the most important sources of PAHs, metals and ions, respectively. The main contributions to PM were soil dust, coal combustion, and biomass burning/petrochemical. Exposure to PM 10 - 2.5 induced the most significant reduction of cell mitochondrial activity, oxidative stress and inflammatory response, whereas DNA damage, an increase of Sub G1/G0 population, and impaired cell membrane integrity were most evident with PM 1 - 0.2 exposure. There were moderate or strong correlations between most single chemicals and almost all toxicological endpoints as well as between various toxicological outcomes. Our findings highlight those various size-segregated PM-induced toxicological effects in cells, and identify chemical components and sources of PM that play the key role in adverse intracellular responses. Although fine and ultrafine PM have attracted much attention, the inflammatory damage caused by coarse PM cannot be ignored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother-child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal-social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.

Thallium (Tl) is a cumulative high toxicant in the environment, but few studies have investigated the comprehensive health effects underlying chronic Tl exposure at trace levels. This study aims to evaluate the liver, kidney, lung and other potential health effects associated with chronic Tl exposure at trace levels in rural areas of China. Urinary Tl concentrations of 2883 adults from rural areas of 12 provinces in China were measured and 2363 participants were involved in the final analysis. Indicators of liver and kidney functions in the serum, as well as the lung function indicators, were determined in the participants. General linear regression and restricted cubic spline regression were combined to study the associations between urinary Tl and health indicators or outcomes. In this study, the detected rate of Tl in the urine of the participants was 97.28 %. When the urinary Tl concentration was ranged at the fourth quintile, the risk of having liver function disorder was 70 % higher [Odds ratio (OR) = 1.70 (95 % confidence intervals (CI): 1.30, 2.22)] in all the participants, whereas the farmers were more likely to have the disorder [OR = 2.08 (95 % CI: 1.49, 2.92)] than the non-farmers [OR = 1.20 (95 % CI: 0.77, 1.88)]. Nonlinear associations between most of the liver health indicators and urinary Tl were identified, of which serum bilirubin was strongly associated with the elevation of urinary Tl when its concentration was >0.40 μg/g creatinine. Besides, urinary Tl was negatively associated with lung health indicators. Our study proposes the safety re-assessment of the current exposure level of Tl in the environment, especially in rural areas of China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Previous studies have indicated that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), when used as an alternative to per- and polyfluoroalkyl substances (PFASs), result in kidney toxicity. However, their co-exposure with heavy metals, has not yet been described., Objectives: To explore the joint effects of Cl-PFESAs and heavy metal exposure on renal health in Chinese adults, and identify specific pollutants driving the associations., Methods: Our sample consists of 1312 adults from a cross-sectional survey of general communities in Guangzhou, China. We measured Cl-PFESAs, legacy PFASs (perfluorooctanoic acid [PFOA] and perfluorooctane sulfonated [PFOS]), and heavy metals (arsenic, cadmium, and lead). The relationship between single pollutant and glomerular filtration rate (eGFR) and the odds ratio (OR) of chronic kidney disease (CKD) was studied using Generalized additive models (GAMs). Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint effects of Cl-PFESAs and heavy metals. Additionally, we conducted a sex-specific analysis to determine the modification effect of this variable., Results: In single pollutant models, CI-PFESAs, PFOA, PFOS and arsenic were negatively associated with eGFR. Additionally, PFOA and heavy metals were positively correlated with the OR of CKD. For example, the estimated change with 95% confidence intervals (CI) of eGFR at from the highest quantile of 6:2 Cl-PFESA versus the lowest quantile was -5.65 ng/mL (95% CI: -8.21, -3.10). Sex played a role in modifying the association between 8:2 Cl-PFESA, PFOS and eGFR. In BKMR models, pollutant mixtures had a negative joint association with eGFR and a positive joint effect on CKD, especially in women. Arsenic appeared to be the primary contributing pollutant., Conclusion: We provide epidemiological evidence that Cl-PFESAs independently and jointly with heavy metals impaired kidney health. More population-based human and animal studies are needed to confirm our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Perfluoroalkyl acids (PFAA) have been measured in ovarian follicular fluid from women using in vitro fertilization (IVF), although associations between follicular fluid PFAA and IVF outcomes have been inconsistent., Objectives: We investigated the association between follicular fluid PFAA and embryo quality in women undergoing IVF., Methods: We prospectively enrolled 729 women undergoing IVF treatment in Guangxi province, China, from July 2018 to December 2018. We measured 32 PFAA, including branched isomers, in follicular fluid using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We applied restricted cubic splines, linear regression, and log-binominal regression models to investigate associations between follicular fluid PFAA and embryo quality, adjusting for confounding variables and investigated oocyte maturity as an intervening variable using causal mediation analysis. We further estimated the overall effect of the PFAA mixture on outcomes using Bayesian kernel machine regression (BKMR)., Results: We detected 8 of 32 measured PFAA in > 85 % of follicular fluid samples. Higher PFAA concentrations were associated with fewer high-quality embryos from IVF. The high-quality embryo rates at the 50th percentile of linear perfluoro-1-octanesulfonate acid (n-PFOS), all branched PFOS isomers (Br-PFOS) and linear perfluoro- n -octanoic acid (n-PFOA) were - 6.34 % [95% confidence interval (CI): - 9.45 , - 3.32 % ], - 16.78 % (95% CI: - 21.98 , - 11.58 % ) and - 8.66 % (95% CI: - 11.88 , - 5.43 % ) lower, respectively, than the high quality embryo rates at the reference 10th percentile of PFAA. Oocyte maturity mediated 11.76% (95% CI: 3.18, 31.80%) and 14.28% (95% CI: 2.95, 31.27%) of the n-PFOS and n-PFOA associations, respectively. The results of the BKMR models showed a negative association between the PFAA mixture and the probability of high-quality embryos, with branched PFOS isomers having posterior inclusion probabilities of 1 and accounting for the majority of the association., Discussion: Exposure to higher PFAA concentrations in follicular fluid was associated with poorer embryo quality during IVF. Branched PFOS isomers may have a stronger effect than linear PFOS isomers. More studies are needed to confirm these findings and to directly estimate the effects on pregnancy and live-birth outcomes. https://doi.org/10.1289/EHP10857.

Background: Epidemiological studies suggest that both ambient ozone (O 3 ) and temperature were associated with increased risks of adverse birth outcomes. However, very few studies explored their interaction effects, especially for small for gestational age (SGA) and large for gestational age (LGA)., Objectives: To estimate the modification effects of ambient temperature on associations of ambient O 3 exposure before and during pregnancy with preterm birth (PTB), low birth weight (LBW), SGA and LGA based on multicity birth cohorts., Methods: A total of 56,905 singleton pregnant women from three birth cohorts conducted in Tianjin, Beijing and Maoming, China, were included in the study. Maximum daily 8-h average O 3 concentrations of each pregnant woman from the preconception period to delivery for every day were estimated by matching their home addresses with the Tracking Air Pollution in China (TAP) datasets. We first applied the Cox proportional-hazards regression model to evaluate the city-specific effects of O 3 exposure before and during pregnancy on adverse birth outcomes at different temperature levels with adjustment for potential confounders, and then a meta-analysis across three birth cohorts was conducted to calculate the pooled associations., Results: In pooled analysis, significant modification effects of ambient temperature on associations of ambient O 3 with PTB, LBW and LGA were observed (P interaction  < 0.05). For a 10 μg/m 3 increase in ambient O 3 exposure at high temperature level (> 75 th percentile), the risk of LBW increased by 28 % (HR: 1.28, 95% CI: 1.13-1.46) during the second trimester and the risk of LGA increased by 116% (HR: 2.16, 95%CI: 1.16-4.00) during the entire pregnancy, while the null or weaker association was observed at corresponding low (≤ 25 th percentile) and medium (> 25 th and ≤ 75 th percentile) temperature levels., Conclusion: This multicity study added new evidence that ambient high temperature may enhance the potential effects of ambient O 3 on adverse birth outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Particulate matter (PM) exposure is associated to the adverse change in blood lipids. Vitamin D is beneficial to lipid metabolism, but whether vitamin D levels modifies the impact of air pollutants on lipids is unclear. The purpose of the study was to investigate if vitamin D modifies the associations of PM and serum lipids in young healthy people. From December 2017 to January 2018, a panel study with five once weekly follow-ups was conducted on 88 healthy adults aged 21.09 (1.08) (mean (SD)) years on average in Guangzhou, China. We measured serum lipids, serum 25-hydroxyvitamin D (25(OH)D) concentrations (440 blood samples in total), mass concentrations of particulate matter with diameters ≤2.5 μm (PM 2.5 ), ≤1.0 μm (PM 1.0 ), and ≤0.5 μm (PM 0.5 ), and number concentrations of particulate matter with diameters ≤0.2 μm (PN 0.2 ) and ≤0.1 μm (PN 0.1 ) at each follow-up. Linear mixed-effect models were applied to assess the interaction of vitamin D and size-fractionated PM short-term exposure on four lipid metrics. We found the interactions between 25(OH)D and size-fractionated PM exposure on blood lipids in different lags (lag 3 days and 4 days). An interquartile range increase in PM 2.5 , PM 1.0 , PM 0.5 were significantly associated with increments of 12.30%, 12.99%, and 13.66% in triglycerides (TGs) at lag 4 days at vitamin D levels <15 ng/mL group, respectively. Similar results were found for PN 0.2 , PN 0.1 and low-density lipoprotein cholesterol (LDL-C). All the associations between size-fractionated PM and blood lipids were found null statistically significant in vitamin D levels ≥15 ng/mL group., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Little evidence exists concerning the associations of greenspace with childhood lipid profiles and dyslipidemias, especially in developing countries and regions. We aimed to investigate the associations of greenspace surrounding schools with lipid levels and dyslipidemia prevalence among Chinese children and teenagers. We obtained baseline information and health data of 10,408 children and teenagers (aged 6-18 years) who studied from 94 schools in China. We measured levels of four blood lipids: triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dyslipidemias were defined using standard recommendations. Greenness surrounding schools were assessed using two satellite-based greenness indices, Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) at 300-, 500-, and 1000-m circular buffers based on each school's latitude and longitude. We used random forest model combined with meteorological and remote sensing data to estimate air pollution levels surrounding each school. We used generalized linear mixed models to estimate the associations of greenness with lipid levels and dyslipidemias prevalence. We also performed sub-group and mediation analyses. An interquartile range (IQR) increase in NDVI 500m was significantly associated with a 0.064 mmol/L (95% confidence interval [CI]: 0.083, -0.045) and 0.049 mmol/L (95% CI: 0.065, -0.033) decreased TC and LDL-C levels, respectively, as well as a 0.13-fold (95% CI: 0.01, 0.23) and 0.17-fold (95% CI: 0.01, 0.30) decreased odds of hypercholesterolemia and hyperbetalipoproteinemia, respectively. Associations were stronger in students aged ≤12 years and born to parents having lower education levels compared to their counterparts. Particle with aerodynamic diameter ≤2.5 μm (PM 2.5 ) mediated 61.5% and 16.7% of the association of greenness with TG and LDL-C levels, respectively. In summary, higher school-based greenness exposure was beneficially associated with lipid levels among Chinese children and adolescents, and part of the association can be explained by lowed PM 2.5 levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Although ozone exposure has neurological toxicity, it remains unclear whether it was associated with an increased risk of attention-deficit/hyperactivity disorders (ADHD) among childhood., Methods: We matched the four-year average ozone concentration with questionnaire data for 35,103 children aged 3-12 years from seven cities in Liaoning, China, 2012-2013. Using mixed-effect logistic regression models, we assessed the association of ozone concentration with multiple ADHD indicators using the Conners Abbreviated Symptom Questionnaire (C-ASQ), including explicit attention-deficit/hyperactivity symptoms (ADHD; score ≥15), attention-deficit/hyperactivity disorder tendencies (ADHD-T; 11 ≤ score ≤14), and attention-deficit/hyperactivity problems (ADHP; score ≥11). Results were also stratified by sociodemongraphics., Results: After adjusting for covariates, we found that each interquartile range (IQR) increase in ozone concentration was associated with an increased risk of ADHD, ADHD-T, and ADHP (P < 0.001) with an odds ratio of 1.12 (95% confidence interval, 1.04-1.21), 1.08 (1.03-1.13), and 1.09 (1.05-1.14), respectively. Additionally, we found greater effect estimates in children who reported longer exercise time (vs those with limited exercise time) with odds ratio of 1.18 (1.07-1.31) vs 1.06 (0.96-1.17) for ADHD, 1.13 (1.06-1.21) vs 1.03 (0.96-1.10) for ADHD-T, and 1.15 (1.08-1.21) vs 1.04 (0.98-1.10) for ADHP. Non-breastfed children were also shown to be more vulnerable to ADHD with an odds ratio of 1.22 (1.09-1.36) compared with 1.06 (0.96-1.16) among the rest., Conclusions: Long-term ozone exposure may be associated with increased ADHD among children. Additional studies are needed to validate our findings and support policies and interventions to address this growing public health concern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 μg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Studies on the obesogenic effect of air pollution on children have been mixed and sparse. Moreover, due to insufficient air monitoring, few studies have investigated the role of more tiny but unregulated particles (ambient particles with a diameter of 0.1 μm or less, ultrafine particles)., Objective: We sought to explore the associations between long-term exposure to ambient ultrafine particles (UFPs) and childhood obesity in Chinese children., Methods: In this cross-sectional study, we randomly recruited 47,990 children, aged 6-18 years, from seven cities in Northeastern China between 2012 and 2013. Child age- and sex-specific z-scores for body mass index (BMI Z-score) and weight status were generated using the World Health Organization growth reference. Four-year average concentrations of UFPs and airborne particulates of diameter ≤ 1 μm (PM 1 ), ≤2.5 μm (PM 2.5 ), and ≤10 μm (PM 10 ) were estimated at home, using neural network simulated WRF-Chem model and spatiotemporal model, respectively. Confounder-adjusted generalized linear mixed models examined the associations between air pollution and BMI Z-score and the prevalence of childhood obesity., Result: We found that UFPs exposure was associated with greater childhood BMI Z-score and a higher likelihood of obesity. Compared with the lowest quartile, higher quartiles of UFPs were associated with greater odds for obesity prevalence in children (i.e., the adjusted OR was 1.25; 95 % CI, 1.12-1.39; 1.43; 95 % CI, 1.27-1.61; and 1.41; 95 % CI, 1.25-1.58 for the second, third, and fourth quartile, respectively). Similar associations were observed for PM 1 , PM 2.5 , and PM 10 , and were greater in boys and children living close to roadways., Conclusions: Long-term UFPs exposure was associated with a greater likelihood of childhood obesity, and stronger associations on BMI Z-score were observed in boys and children living close to roadways. This study indicates that more attention should be paid to the health effects of UFPs, and routinely monitoring of UFPs should be considered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The sources and chemical components of urban air particles exhibit seasonal variations that may affect their hazardousness to human health. Our aims were to investigate winter and spring variation in particulate matter (PM) sources, components and toxicological responses of different PM size fractions from samples collected in Guangzhou, China. Four size-segregated PM samples (PM 10 - 2.5 , PM 2.5 - 1 , PM 1 - 0.2 , and PM 0.2 ) were collected separately during winter (December 2017 and January 2018) and spring (March 2018). All PM samples were analyzed for chemical components and characterized by source. RAW 264.7 macrophages were exposed to four doses of PM samples for 24 h. Cytotoxicity, oxidation, cell cycle, genotoxicity and inflammatory parameters were tested. PM concentrations were higher in the winter samples and caused more severe cytotoxicity and oxidative damage than to PM in the spring samples. PM in winter and spring led to increases in cell cycle and genotoxicity. The trends of size-segregated PM components were consistent in winter and spring samples. Metallic elements and PAHs were found in the largest concentrations in winter PM, but ions were found in the largest concentrations in spring PM. metallic elements, PAHs and ions in size-segregated PM samples were associated with most toxicological endpoints. Soil dust and biomass burning were the main sources of PM in winter, whereas traffic exhaust and biomass burning was the main source with of spring PM. Our results suggest that the composition of PM samples from Guangzhou differed during winter and spring, which led to strong variations in toxicological responses. The results demonstrate the importance of examining a different particle sizes, compositions and sources across different seasons, for human risk assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Previous studies have separately linked either perfluoroalkyl acid (PFAA) or heavy metal exposure with kidney dysfunction. However, the relationships of co-exposure to PFAAs and heavy metals with kidney function are still unclear., Objectives: To explore the associations between exposure to PFAAs and heavy metals mixtures and kidney function in adults., Methods: We conducted a cross-sectional community-based population study in Guangzhou, China, enrolling 1312 adults from November 2018 to August 2019. We quantified 13 PFAAs in serum and 14 heavy metals in plasma. We chose estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) as outcomes of interest. Distributed lag non-linear models (DLNMs) were used to check nonlinearity of individual pollutant with kidney function. Joint associations of pollutant mixtures on kidney function were assessed by Bayesian Kernel Machine Regression (BKMR) models. We further explored modification effects of gender., Results: Most individual PFAA and heavy metal were associated with declined kidney function in single-pollutant models. We also observed significant dose-response relationships of pollutant mixtures with reduced eGFR levels and increased odds of CKD in BKMR models. Perfluoroheptanesulfonic acid (PFHpS), arsenic (As) and strontium (Sr) were the predominant contributors among pollutant mixtures. A change in log PFHpS, As and Sr concentrations from the 25th to the 75th percentile were associated with a decrease in eGFR of -5.42 (95% confidence interval (CI): -6.86, -3.98), -2.14 (95% CI: -3.70, -0.58) and -1.87 (95% CI: -3.03, -0.72) mL/min/1.73 m 2 , respectively, when other pollutants were at their median values. In addition, the observed associations were more obvious in females., Conclusions: We provided new evidence that co-exposure to PFAAs and heavy metals mixtures was associated with reduced kidney function in adults and PFHpS, As and Sr appeared to be the major contributors. Further studies are warranted to confirm our findings and elucidate the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Little evidence is available regarding the impact of different sizes of inhaled particulate matter (PM) on inflammatory responses in healthy young adults in connection with toxicological responses. We conducted a five-time repeated measurement panel study on 88 healthy young college students in Guangzhou, China from December 2017 to January 2018. Blood samples were collected from each participant and tested for tumor necrosis factor alpha (TNF-α) levels every week for 5 consecutive weeks. Mass concentrations of ambient PM 2.5 , PM 1 , PM 0.5 and number concentrations of ambient PM 0.1 were measured. RAW 264.7 macrophages were exposed to PM (PM 10 - 2.5 , PM 2.5 - 1 , PM 1 - 0.2 , PM 0.2 ) collected at the same time as the panel study. Cytotoxicity, oxidation and inflammatory parameters, cell cycle and genotoxicity were tested. Particles were characterized for their chemical composition. The trends of associations between PM 2.5 , PM 1 , PM 0.5 and TNF-α level were consistent in lag 0 and 3 days, and the relative risk decreased as the particle size decreased. All the ambient air pollutants had the similar change trends in lag 1, 4 and 5 days. Similar results in RAW 264.7 macrophages were found; PM 10 - 2.5 induced the greatest TNF-α and macrophage inflammatory protein 2 (MIP-2) productions and oxidative damage. PM 1 - 0.2 and PM 0.2 induced more significant dose-dependent increases of cell cycle and genotoxic response. In the component concentrations of PM samples, metal elements were PM 10 - 2.5 > PM 2.5 - 1 > PM 0.2 ≥ PM 1 - 0.2 ; ions and polycyclic aromatic hydrocarbons (PAHs) were PM 0.2 > PM 1 - 0.2 > PM 2.5 - 1 > PM 10 - 2.5 . Our results suggested that exposure to all particle sizes was significantly associated with inflammation among healthy young adults and toxicological responses in RAW 264.7 macrophages. Different human and toxicological reactions caused by PM samples indicated the importance of investigating various particle sizes., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Previous studies have indicated that outdoor light at night (LAN) is associated with a higher prevalence of overweight or obesity in adults. However, the association of LAN levels with overweight or obesity in children is still unknown. This study utilized data from the Seven Northeastern Cities study, which included 47,990 school-aged children and adolescents (ages 6-18 years). Outdoor LAN levels were measured using satellite imaging data. Weight and height were used to calculate age-sex-specific body mass index (BMI) Z-scores based on the World Health Organization (WHO) growth standards. Overweight status and obesity were defined using the Chinese standard. Information regarding socioeconomic status, sleep-related characteristics, and obesogenic factors were obtained using a questionnaire. A generalized linear mixed model examined the associations of outdoor LAN levels (in quartiles) with the outcomes of interest. Compared to children in the lowest quartile of outdoor LAN levels, children exposed to higher outdoor LAN levels had larger BMI Z-scores and higher odds of being overweight (including obesity) or obese, with the largest estimates in the third quartile [BMI Z-score: β = 0.26, 95% CI: 0.18-0.33; overweight (including obesity): OR = 1.40, 95% CI: 1.25-1.56; obesity: OR = 1.46, 95% CI: 1.29-1.65]. There was a significant sex difference (P interaction <0.001) in the association of outdoor LAN levels with BMI Z-scores, and the association was stronger in males. Results remained robust following multiple sensitivity analyses and the adjustment of sleep-related characteristics, obesogenic factors, and environmental exposures. Our findings suggest that higher outdoor LAN levels are associated with larger BMI Z-scores and greater odds of overweight (including obesity) and obesity in school-aged children and adolescents. Further, the association between outdoor LAN levels and BMI Z-scores is stronger in males. Future studies with exposure assessments that consider both outdoor and indoor LAN exposures are needed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ambient particles with aerodynamic diameter <0.1 μm (PM 0.1 ) have been suggested to have significant health impact. However, studies on the association between long-term PM 0.1 exposure and human blood lipid metabolism are still limited. This study was aimed to evaluate such association based on multiple lipid biomarkers and dyslipidemia indicators. We matched the 2006-2009 average PM 0.1 concentration simulated using the neural-network model following the WRF-Chem model with the clinical and questionnaire data of 15,477 adults randomly recruited from 33 communities in Northeast China in 2009. After controlling for social demographic and behavior confounders, we assessed the association of PM 0.1 concentration with multiple lipid biomarkers and dyslipidemia indicators using generalized linear mixed-effect models. Effect modification by various social demographic and behavior factors was examined. We found that each interquartile range increase in PM 0.1 concentration was associated with a 5.75 (95% Confidence interval, 3.24-8.25) mg/dl and a 6.05 (2.85-9.25) mg/dl increase in the serum level of total cholesterol and LDL-C, respectively. This increment was also associated with an odds ratio of 1.25 (1.10-1.42) for overall dyslipidemias, 1.41 (1.16, 1.73) for hypercholesterolemia, and 1.90 (1.39, 2.61) for hyperbetalipoproteinemia. Additionally, we found generally greater effect estimates among the younger participants and those with lower income or with certain behaviors such as high-fat diet. The deleterious effect of long-term PM 0.1 exposure on lipid metabolism may make it an important toxic chemical to be targeted by future preventive strategies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

It has been reported that exposure to perfluorooctane sulfonates (PFOS) causes behavioral abnormalities in zebrafish larvae, but the possible mechanisms underlying these changes remain unexplored. In this study, zebrafish embryos (2 h postfertilization, 2-hpf) were exposed to PFOS at different concentrations (0, 0.032, 0.32 and 3.2 mg/L) for 120 h. Developmental endpoints and the locomotion behavior of larvae were evaluated. Reactive oxygen species (ROS) levels, dopamine contents, several genes and proteins related to neurodevelopment and dopamine signaling were examined. Our results indicate that increased ROS levels in the zebrafish larvae heads may be causally associated with neurodevelopment damage. Meanwhile, brain-derived neurotrophic factor (BDNF) and alpha1-Tubulin (α1-Tubulin) protein contents were significantly increased, which may be a compensatory mechanism for the impaired central nervous system. PFOS-induced locomotor hyperactivity was observed in the first light phase and dark phase at the 0.32 and 3.2 mg/L of PFOS. Upregulation of dopamine-related genes tyrosine hydroxylase (th) and dopamine transporter (dat) associated with increased dopamine contents in the 3.2 mg/L of PFOS. In addition, protein expression of TH and DAT were noted at the 0.32 and 3.2 mg/L of PFOS concentrations. Our results suggested that PFOS induces neurobehavioral changes in zebrafish larvae, possibly by perturbing a dopamine signaling pathway. In addition, PFOS induced development damage, such as increased malformation rate and shorter body length., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (μIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.

Importance: Healthy sleep has an important role in the physical and mental health of children. However, few studies have investigated the association between outdoor artificial light at night (ALAN) and sleep disorders in children., Objective: To explore the associations between outdoor ALAN exposure and sleep disorders in children., Design, Setting, and Participants: This population-based cross-sectional study, part of the National Chinese Children Health Study, was conducted from April 1, 2012, to June 30, 2013, in the first stage and from May 1, 2016, to May 31, 2018, in the second stage in 55 districts of 14 cities in China. This analysis included 201 994 children and adolescents aged 2 to 18 years. Data were analyzed from February 20 to March 21, 2022., Exposures: Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's residential address obtained from the satellite imagery data, with a resolution of approximately 500 m., Main Outcomes and Measures: Sleep disorders were measured by the Chinese version of the Sleep Disturbance Scale for Children. Generalized linear mixed models were used to estimate the associations of outdoor ALAN with sleep scores and sleep disorders., Results: The study included 201 994 children and adolescents (mean [SD] age, 11.3 [3.2] years; 106 378 boys [52.7%]), 7166 (3.5%) of whom had sleep disorder symptoms. Outdoor ALAN exposure of study participants ranged from 0.02 to 113.48 nW/cm2/sr. Compared with the lowest quintile (Q1) of outdoor ALAN exposure, higher quintiles of exposure (Q2-Q5) were associated with an increase in total sleep scores of 0.81 (95% CI, 0.66-0.96) in Q2, 0.83 (95% CI, 0.68-0.97) in Q3, 0.62 (95% CI, 0.46-0.77) in Q4, and 0.53 (95% CI, 0.36-0.70) in Q5. Higher quintiles of exposure were also associated with odds ratios for sleep disorder of 1.34 (95% CI, 1.23-1.45) in Q2, 1.43 (95% CI, 1.32-1.55) in Q3, 1.31 (95% CI, 1.21-1.43) in Q4, and 1.25 (95% CI, 1.14-1.38) in Q5. Similar associations were observed for sleep disorder subtypes. In addition, greater effect estimates were found among children younger than 12 years., Conclusions and Relevance: The findings of this cross-sectional study suggest that sleep disorders are more prevalent among children residing in areas with high levels of outdoor ALAN and the associations are generally stronger in children younger than 12 years. These findings further suggest that effective control of outdoor ALAN may be an important measure for improving the quality of children's sleep.

Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Although the potential serious threat of anthropogenic heat on human health was receiving considerable attention worldwide, its long-term health effect on blood pressure (BP) remained unknown. We aimed to evaluate the associations of long-term anthropogenic heat exposure with different components of BP and hypertension., Methods: In this cross-sectional study (Liaoning province, China) conducted in 2009, we included a total of 24,845 Chinese adults (18-74 years). We estimated the anthropogenic heat exposure in 2008 using multisource remote sensing images and ancillary data. We measured systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), and defined hypertension. We used generalized linear mixed model to examine the associations., Results: In the adjusted model, the estimates indicated that the difference in SBP, MAP and PP for those in highest quartiles of total anthropogenic heat exposure was greater compared with the lowest quartile (highest quartile: β = 1.11 [95% CI: 0.28-1.94], 0.60 [95% CI: 0.04-1.17], 0.76 [95% CI: 0.17-1.35]). Compared with the lowest quartile, the odds of hypertension were higher among those in higher quartiles (second quartile: OR = 1.17 [95% CI: 1.05-1.30]; third quartile:1.10 [95% CI: 1.1.01-1.21]; highest quartile: 1.17 [95% CI: 1.06-1.28]). These associations were stronger in female participants., Conclusion: Our study showed that long-term exposure to anthropogenic heat was associated with elevated BP and higher odds of hypertension. These findings suggest that mitigation strategies to reduce anthropogenic heat should be considered., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The widely used Air Quality Index (AQI) has been criticized due to its inaccuracy, leading to the development of the air quality health index (AQHI), an improvement on the AQI. However, there is currently no consensus on the most appropriate construction strategy for the AQHI., Objectives: In this study, we aimed to evaluate the utility of AQHIs constructed by different models and health outcomes, and determine a better strategy., Methods: Based on the daily time-series outpatient visits and hospital admissions from 299 hospitals (January 2016-December 2018), and mortality (January 2017-December 2019) in Guangzhou, China, we utilized cumulative risk index (CRI) method, Bayesian multi-pollutant weighted (BMW) model and standard method to construct AQHIs for different health outcomes. The effectiveness of AQHIs constructed by different strategies was evaluated by a two-stage validation analysis and examined their exposure-response relationships with the cause-specific morbidity and mortality., Results: Validation by different models showed that AQHI constructed with the BMW model (BMW-AQHI) had the strongest association with the health outcome either in the total population or subpopulation among air quality indexes, followed by AQHI constructed with the CRI method (CRI-AQHI), then common AQHI and AQI. Further validation by different health outcomes showed that AQHI constructed with the risk of outpatient visits generally exhibited the highest utility in presenting mortality and morbidity, followed by AQHI constructed with the risk of hospitalizations, then mortality-based AQHI and AQI. The contributions of NO 2 and O 3 to the final AQHI were prominent, while the contribution of SO 2 and PM 2.5 were relatively small., Conclusions: The BMW model is likely to be more effective for AQHI construction than CRI and standard methods. Based on the BMW model, the AQHI constructed with the outpatient data may be more effective in presenting short-term health risks associated with the co-exposure to air pollutants than the mortality-based AQHI and existing AQIs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (β) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Background: Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives., Objectives: To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes., Methods: We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification., Results: After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models., Conclusions: Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children., Methods: In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems., Results: We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (β = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses., Conclusions: Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6-18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life., (© 2021. The Author(s).)

Background: Health effects of greenness perceived by residents at eye level has received increasing attention. However, the associations between eye-level greenness and respiratory health are unknown. The aim of the study was to investigate the associations between exposure to eye-level greenness and lung function in children., Methods: From 2012 to 2013, a total of 6740 school children in seven cities in northeast China were recruited into this cross-sectional study. Forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), peak expiratory flow rate (PEF), and maximum mid expiratory flow rate (MMEF) were measured to evaluate lung function and to define lung impairment. Eye-level greenness was extracted from segmented Tencent Map street view images, and a corresponding green view index (GVI) was calculated. Higher GVIs mean more greenness coverage. Mixed-effects logistic regressions were used to estimate the health effects on lung impairment per interquartile range (IQR) increase in GVI. Linear regressions were used to estimate the associations between GVI and lung function. The health effects of ambient air pollutants were also assessed, including particulate matter with an aerodynamic diameter <1.0 μm (PM 1 ), <2.5 μm (PM 2.5 ), <10 μm (PM 10 ) as well as nitrogen dioxide (NO 2 )., Results: An increase of GVI 800m was associated with lung impairment in FEV 1 , FVC, PEF and MMEF, with ORs ranging from 0.68 (95% CI: 0.59, 0.79) to 0.83 (95% CI: 0.74, 0.93). The associations between an IQR increase of GVI 800m and FEV 1 (48.15 ml, 95% CI: 30.33-65.97 ml), FVC (50.57 ml, 95% CI: 30.65-70.48 ml), PEF (149.59 ml/s, 95% CI: 109.79-189.38 ml/s), and MMEF (61.18 ml/s, 95% CI: 31.07-91.29 ml/s) were significant, and PM 1 , PM 2.5 , and PM 10 were found to be mediators of this relationship., Conclusion: More eye-level greenness was associated with better lung function and reduced impairment. However, eye-level greenness associations with lung function became non-significant once lower particulate matter air pollution exposures were considered., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the associations between childhood, parental, and grandparental asthma. Methods: We studied 59,484 children randomly selected from 94 kindergartens, elementary, and middle schools in seven Chinese cities from 2012 to 2013, using a cross-sectional survey-based study design. Information on their and their family members' (parents, paternal grandparents, and maternal grandparents) asthma status were reported by children's parents or guardians. Mixed effects logistic regressions were used to assess hereditary patterns of asthma and mediation analysis was performed to estimate the potential mediation effect of parents on the association between grandparental asthma and childhood asthma. Results: The magnitude of ORs for childhood asthma increased as the number of family members affected by asthma increased. Among children who had one family member with asthma, childhood asthma was associated with asthma in maternal grandmothers (OR: 2.08, 95% CI: 1.67-2.59), maternal grandfathers (OR: 2.08, 95% CI: 1.71-2.53), paternal grandmothers (OR: 2.40, 95% CI: 1.93-2.99), and paternal grandfathers (OR: 2.59, 95% CI: 2.14-3.13). Among children who had two family members with asthma, the highest asthma risk was found when both parents had asthma (OR: 15.92, 95% CI: 4.66-54.45). Parents had a small proportion of mediation effect (9-12%) on the association between grandparental asthma and childhood asthma. Conclusions: Grandparents with asthma were associated with childhood asthma and parents with asthma partially mediated the association., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Su, Wang, Hemminki, Dharmage, Bowatte, Bui, Qian, Vaughn, Aaron, Xiong, Shen, Zhou, Zhou, Zeng, Chen, Yang, Hu and Dong.)

Limitations of Normalized Difference Vegetation Index (NDVI) potentially contributed to the inconsistent findings of greenspace exposure and childhood asthma. The aim of this study was to use a novel greenness exposure assessment method, capable of overcoming the limitation of NDVI to determine the extent to which it was associated with asthma prevalence in Chinese children. During 2009-2013, a cross-sectional study of 59,754 children aged 2-17 years was conducted in northeast China. Tencent street view images surrounding participants' schools were segmented by a deep learning model, and streetscape greenness was extracted. The green view index (GVI) was used to assign exposure and higher value indicates more green coverage. Mixed-effects logistic regression models were used to calculate the adjusted odds of asthma per interquartile range (IQR) increase of GVI for trees and grass. Participants were further stratified to investigate whether particulate matter with an aerodynamic diameter <2.5 μm (PM 2.5 ) was a modifier. An IQR increase in GVI 800m for trees was associated with lower adjusted odds of doctor-diagnosed asthma (OR: 0.76; 95%CI: 0.72-0.80) and current asthma (OR: 0.82; 95%CI: 0.75-0.89). An IQR increase in GVI 800m for grass was associated with higher adjusted odds of doctor-diagnosed asthma (OR: 1.04; 95%CI: 1.00-1.08) and current asthma (OR: 1.08; 95%CI: 1.02-1.14). After stratification by PM 2.5 exposure level, the negative association between trees and asthma, and the positive association between grass and asthma were observed only in low PM 2.5 exposure levels (≤median: 56.23 μg/m 3 ). Our results suggest that types of vegetation may play a role in the association between greenness exposure and childhood asthma. Exposure to trees may reduce the odds of childhood asthma, whereas exposure to grass may increase the odds. Additionally, PM 2.5 may modify the associations of trees and grass with childhood asthma., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), a group of perfluorooctane sulfonate (PFOS) alternatives, can be widely observed in humans and environmental matrices. However, associations between exposure to Cl-PFESAs and serum lipid levels in adults are unknown., Objective: To explore the relationships between Cl-PFESA levels and serum lipid levels in adults., Methods: We analyzed 1238 adults from the Isomers of C8 Health Project, a cross-sectional study conducted in China from July 2015 to October 2016. The average age of the participants was 61.98 ± 14.40 years. We quantified two select legacy per- and perfluoroalkyl substances [perfluorooctanoic acid (PFOA) and PFOS] and their alternatives (6:2 and 8:2 Cl-PFESAs). We also measured four serum lipids: low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). We used generalized linear models to estimate the associations between PFASs and serum lipids, with PFASs defined as either a categorical variable divided into quartiles or as a continuous variable., Results: We found that 6:2 Cl-PFESA was positively associated with serum TC and LDL-C. For instance, LDL-C levels in the highest quartile of 6:2 Cl-PFESA exposure (Q4) were significantly higher than those in the lowest quartile (Q1) [β: 0.19, 95% confidence interval (CI): 0.08, 0.30]. Further analysis showed that one ln-ng/mL increase in 6:2 Cl-PFESA exposure corresponded to a 0.10 mmol/L (95% CI: 0.05, 0.16) LDL-C increase, and that exposure to 8:2 Cl-PFESA was negatively correlated with HDL-C (β: -0.03, 95% CI: -0.05, -0.01). TC had a similar relationship with both 6:2 Cl-PFESA and legacy PFASs. Participants with a BMI ≥ 25 kg/m 2 exhibited a stronger association between 6:2 Cl-PFESA and TC., Conclusions: Our findings make the novel suggestion that exposure to Cl-PFESAs are adversely associated with serum lipid levels, and that such associations are also observed in legacy PFASs. Increased investigation into the effects of Cl-PFESAs exposure on human health is warranted., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)