Search

Alzheimer's disease (AD) is a neurodegenerative disease, that accounts for 50-75% of all dementia cases. Evidence demonstrates the link between particulate matter (PM) exposure and AD. However, there are still considerable research gaps. This review aims to clarify the mechanism between PM and AD from different levels (subcellular/cellular/system/population) by using an adverse outcome pathway (AOP) framework. We applied a chemical-phenotype interaction network-based workflow to integrate diverse genes and phenotypes. The interactions among PM, genes, phenotypes, and AD were retrieved from the Comparative Toxicogenomics Database (CTD), DisGeNET, MalaCards, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), which are publicly available databases. The filtered genes and phenotypes were assembled as molecular initiating events (MIEs) and key events (KEs) according to the upstream and downstream relationships, generating a predictive PM-Gene-Phenotype-AD AOP network. According to the Organization for Economic Co-operation and Development handbook (OECD), a verified AOP network was assessed and applied to determine the effects of PM on AD. PM could increase APP and GSK3B, increase apoptosis, impair cognition and memory, and ultimately lead to AD. Overall, chemical-phenotype interactions are expressed in a formal structured notation using controlled terms for chemicals, phenotypes, taxons, and anatomical descriptors. To our knowledge, this is the first AOP framework focusing on the underlying mechanism of exposure to PM on AD. Our network-based approach not only fills mechanism gaps in PM and AD but sheds light 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 © 2025 Elsevier Ltd. All rights reserved.)

Research on epigenetic‒environmental interactions in the development of Alzheimer's disease (AD) has accelerated rapidly in recent decades. Numerous studies have demonstrated the contribution of ambient particulate matter (PM) to the onset of AD. Emerging evidence indicates that non-coding RNAs (ncRNAs), including long non-coding RNAs, circular RNAs, and microRNAs, play a role in the pathophysiology of AD. In this review, we provide an overview of PM-altered ncRNAs in the brain, with emphasis on their potential roles in the pathogenesis of AD. These results suggest that these PM-altered ncRNAs are involved in the regulation of amyloid-beta pathology, microtubule-associated protein Tau pathology, synaptic dysfunction, damage to the blood‒brain barrier, microglial dysfunction, dysmyelination, and neuronal loss. In addition, we utilized in silico analysis to explore the biological functions of PM-altered ncRNAs in the development of AD. This review summarizes the knowns and unknowns of PM-altered ncRNAs in AD pathogenesis and discusses the current dilemma regarding PM-altered ncRNAs as promising biomarkers of AD. Altogether, this is the first thorough review of the connection between PM exposure and ncRNAs in AD pathogenesis, which may offer novel insights into the prevention, diagnosis, and treatment of AD associated with ambient PM exposure., 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.)

Background: Exposure to fine particulate matter (PM 2.5 ) has been linked to visual impairment. Nevertheless, evidence associating PM 2.5 constituents with visual impairment in schoolchildren is sparse., Objectives: To explore the effects of long-term exposure to PM 2.5 and its constituents on visual impairment., Methods: We conducted a large cross-sectional population-based study to recruit 59,054 schoolchildren from four cities in Guangdong province, China, and used the ChinaHighAirPollutants (CHAP) dataset to estimate 3-year average concentrations of PM 2.5 and its constituents (black carbon (BC), organic matter (OM), nitrate (NO 3 - ), sulfate (SO 4 2- ) and ammonium (NH 4 + )) based on individuals' home addresses. Visual acuity was measured with a standardized logarithmic chart, and visual impairment was defined as visual acuity below 4.9 (Snellen 5/6 equivalent) in at least one eye. We utilized generalized linear mixed models and weighted quantile sum regression to assess the association between PM 2.5 constituents and visual impairment., Results: The observed associations typically displayed a nonlinear pattern. Compared to the lowest quartile of PM 2.5 and its constituents, the fourth quartile was associated with higher odds of visual impairment in schoolchildren (e.g., the adjusted odds ratio (OR) was 1.23 (95% CI: 1.13, 1.33) for PM 2.5 , 1.53 (95% CI: 1.40, 1.67) for OM, and 1.35 (95% CI: 1.27, 1.44) for BC), respectively. Similarly, joint exposure to PM 2.5 constituents was associated with visual impairment (OR = 1.17, 95% CI: 1.13, 1.22), while BC and OM contributed more to the observed associations., Conclusions: Long-term exposure to PM 2.5 and its constituents was significantly associated with higher rates of visual impairment in schoolchildren, with combustion-related BC and OM potentially driving the observed associations., 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 © 2025. Published by Elsevier Ltd.)

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.)

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.)

Chlorinated polyfluorinated ether sulfonate (F-53B), a chromium-fog depressant widely utilized as an alternative to perfluorooctanesulfonate, can transfer from mother to fetus. Recent research has demonstrated that prenatal exposure to F-53B results in synaptic damage in weaning mice. However, the mechanism underpinning F-53B-triggered synaptic damage during fetal development remains unclear. This study aims to investigate the role of the protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, a crucial signaling mechanism known as "synaptic switch", in the early neurotoxicity of F-53B exposure both in vivo and in vitro . Here, C57BL/6 fetal mice were subjected to exposure to F-53B (0, 4, and 40 μg/L) from gestation days (GD) 0 to 14 to evaluate nerve injury prior to delivery. HT22 neurons exposed to F-53B (0, 0.016, 0.08, 0.4, 2, and 10 μmol/L) for 24 h were utilized to elucidate the underlying mechanism. Our results demonstrated that F-53B significantly increased the fluorescence intensity of Nestin (a neural stem cell marker) in the fetal brain hippocampus (GD14). Subsequently, we found that F-53B downregulated the expression of synaptic plasticity markers (SYP, GAP43, and BDNF) in the fetal brain and HT22 neurons. Further molecular docking analysis revealed that F-53B fits into the ligand-binding pockets of PKA and CREB1. Results showed that F-53B inhibited the translocation of PKA protein from the cytoplasm to the neuronal nuclei and reduced the levels of PKA, CREB1, p-PKA(α/β/γ)-Thr197, and p-CREB1-S133 in the nucleus. Furthermore, the expression of synaptic plasticity markers altered by F-53B could be reversed by a PKA agonist and was intensified by a PKA antagonist. In summary, our findings suggest that intrauterine exposure to F-53B can weaken the expression of synaptic plasticity markers in the fetal brain, with this neurotoxicity being mediated by the cytoplasmic retention of PKA., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and American Chemical Society.)

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.)

Purpose: Sleep disorders are becoming more prevalent in hospitalized patients with acute myocardial infarction (AMI). We aimed to investigate the risk factors for sleep disorders in hospitalized patients with AMI, then develop and validate a prediction nomogram for the risk of sleep disorders., Methods: Clinical data were collected from patients with AMI hospitalized in our hospital from January 2020 to June 2023. All patients were divided into the training group and the validation group with a ratio of 7:3 in sequential order. The LASSO regression analysis and multivariate logistic regression analysis were used to screen potential risk factors for sleep disorders. The concordance index (C-index), calibration curves, and decision curve analysis (DCA) were plotted., Results: A total of 256 hospitalized patients with AMI were enrolled. Patients were divided into the training group (180) and the validation group (76) according to a scale of 7:3. Of the 256 patients, 90 patients (35.16%) suffered from sleep disorders, and 33 patients (12.89%) needed hypnotics. The variables screened by LASSO regression included age, smoking, NYHA class, anxiety status at admission, depression status at admission, and strangeness of environment. A nomogram model was established by incorporating the risk factors selected. The C-index, calibration curve, and DCA showed good predictive performance., Conclusions: We identified six clinical characteristics as predictors of sleep disorders in hospitalized patients with AMI. It helps nurses make appropriate decisions in clinical practice., (© 2024. The Author(s).)

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: Healthcare workers (HCWs) are at increased risk of contracting coronavirus disease 2019 (COVID-19) as well as worsening mental health problems and insomnia. These problems can persist for a long period, even after the pandemic. However, less is known about this topic., Aim: To analyze mental health, insomnia problems, and their influencing factors in HCWs after the COVID-19 pandemic., Methods: This multicenter cross-sectional, hospital-based study was conducted from June 1, 2023 to June 30, 2023, which was a half-year after the end of the COVID-19 emergency. Region-stratified population-based cluster sampling was applied at the provincial level for Chinese HCWs. Symptoms such as anxiety, depression, and insomnia were evaluated by the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index. Factors influencing the symptoms were identified by multivariable logistic regression., Results: A total of 2000 participants were invited, for a response rate of 70.6%. A total of 1412 HCWs [618 (43.8%) doctors, 583 (41.3%) nurses and 211 (14.9%) nonfrontline], 254 (18.0%), 231 (16.4%), and 289 (20.5%) had symptoms of anxiety, depression, and insomnia, respectively; severe symptoms were found in 58 (4.1%), 49 (3.5%), and 111 (7.9%) of the participants. Nurses, female sex, and hospitalization for COVID-19 were risk factors for anxiety, depression, and insomnia symptoms; moreover, death from family or friends was a risk factor for insomnia symptoms. During the COVID-19 outbreak, most [1086 (76.9%)] of the participating HCWs received psychological interventions, while nearly all [994 (70.4%)] of them had received public psychological education. Only 102 (7.2%) of the HCWs received individual counseling from COVID-19., Conclusion: Although the mental health and sleep problems of HCWs were relieved after the COVID-19 pandemic, they still faced challenges and greater risks than did the general population. Identifying risk factors would help in providing targeted interventions. In addition, although a major proportion of HCWs have received public psychological education, individual interventions are still insufficient., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. 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: 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.

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.)

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.)

Aim: To observe the changes in the thickness of peripapillary retinal nerve fiber layer (pRNFL) and peripapillary vessel density (pVD) in patients with different stages of Parkinson's disease (PD)., Methods: Totally 47 patients (47 eyes) with primary PD were divided into the mild group and the moderate-to-severe group according to Hoehn & Yahr (H&Y) stage. Among them, there were 27 cases (27 eyes) in mild group and 20 cases (20 eyes) in moderate-to-severe group. And 20 cases (20 eyes) who were included in the control group were healthy people who came to our hospital for health screening at the same time. All participants underwent optical coherence tomography angiography (OCTA) examinations. The pRNFL thickness, total vessel density (tVD) and capillary vessel density (cVD) of the optic disc in average, superior half, inferior half, superior nasal (SN), nasal superior (NS), nasal inferior (NI), inferior nasal (IN), inferior temporal (IT), temporal inferior (TI), temporal superior (TS), and superior temporal (ST) were measured. One-way ANOVA was used to compare the differences of optic disc parameters among the three groups, and Pearson and Spearman correlations were used to analyze the correlation between pRNFL, pVD and the disease duration, H&Y stage and UPDRS-III score in patients with PD, respectively., Results: There were significant differences in pRNFL thickness in average, superior half, inferior half, SN, NS, IN, IT and ST quadrants among the three groups ( P <0.05). In PD group, the pRNFL thickness in average, superior half, inferior half, NS and IT quadrants were negatively correlated with H&Y stage and UPDRS-III score, respectively ( P <0.05). There were statistically significant differences in the cVD of whole image, inferior half, NI and TS quadrants, the tVD of the whole image, inferior half, and peripapillary among the three groups ( P <0.05). In PD group, the tVD of whole image and the cVD of NI and TS quadrants were negatively correlated with the H&Y stage, respectively ( P <0.05); the cVD of TS quadrant was negatively correlated with UPDRS-III score ( P <0.05)., Conclusion: The thickness of pRNFL in PD patients is significantly decreased, and it is negatively correlated with H&Y stage and UPDRS-III score. With the increase of the severity of the disease, the pVD parameters in PD patients increase at first in the mild group, and then decrease in the moderate-to-severe group, and negatively correlate with H&Y stage and UPDRS-III score., (International Journal of Ophthalmology Press.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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.)

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).)

Low temperature remarkably limits rubber tree ( Hevea brasiliensis Muell. Arg.) growth, latex production, and geographical distribution, but the underlying mechanisms of Hevea brasiliensis cold stress response remain elusive. Here, we identified HbSnRK2.6 as a key component in ABA signaling functions in phytohormone abscisic acid (ABA)-regulated cold stress response in Hevea brasiliensis . Exogenous application of ABA enhances Hevea brasiliensis cold tolerance. Cold-regulated (COR) genes in the CBF pathway are upregulated by ABA. Transcript levels of all five HbSnRK2.6 members are significantly induced by cold, while HbSnRK2.6A , HbSnRK2.6B , and HbSnRK2.6C can be further activated by ABA under cold conditions. Additionally, HbSnRK2.6s are localized in the cytoplasm and nucleus, and can physically interact with HbICE2, a crucial positive regulator in the cold signaling pathway. Overexpression of HbSnRK2.6A or HbSnRK2.6B in Arabidopsis extensively enhances plant responses to ABA and expression of COR genes, leading to increased cold stress tolerance. Furthermore, HbSnRK2.6A and HbSnRK2.6B can promote transcriptional activity of HbICE2, thus, increasing the expression of HbCBF1 . Taken together, we demonstrate that HbSnRK2.6s are involved in ABA-regulated cold stress response in Hevea brasiliensis by regulating transcriptional activity of HbICE2.

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.)

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.)

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.)

Multiple systematic reviews on greenspace and health outcomes exist, but the overall evidence base remains unclear. Therefore, we performed an umbrella review to collect and appraise all relevant systematic reviews of epidemiological studies on greenness exposure and health. We searched PubMed, Embase, and Web of Science from inception to June 28, 2021, and screened references of relevant articles. Systematic reviews with or without meta-analyses of epidemiological studies that examined the associations of greenness with any health outcome were included. Two independent investigators performed study selection and data extraction. We also evaluated the methodological quality of the included systematic reviews using the "Assessing the Methodological Quality of Systematic Reviews 2" checklist. A total of 40 systematic reviews and meta-analyses were included, of which most were cross-sectional studies conducted in high-income countries. Greenspace exposure was estimated with various objective and subjective parameters. Beneficial associations of greenspace with all-cause and stroke-specific mortality, CVD morbidity, cardiometabolic factors, mental health, low birth weight, physical activity, sleep quality, and urban crime were observed. No consistent associations between greenspace and other health outcomes (e.g., cancers) were observed. Most of the included systematic reviews and meta-analyses had one or more limitations in methodology. Our findings provide supportive evidence regarding the beneficial effects of greenspace exposure on some aspects of human health. However, the credibility of such evidence was compromised by methodological limitations. Better performed systematic reviews and meta-analyses as well as longitudinal designed primary studies are needed to validate this conclusion., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Numerous studies have demonstrated that exposure to ambient ozone (O 3 ) could have adverse effects on children's respiratory health. However, previous studies mainly focused on asthma and wheezing. Evidence for allergic rhinitis and bronchitic symptoms (e.g., persistent cough and phlegm) associated with O 3 is limited, and results from existing studies are inconsistent. This study included a total of 59,754 children from the seven northeastern cities study (SNEC), who were aged 2 to 17 years and from 94 kindergarten, elementary and middle schools. Information on doctor-diagnosed allergic rhinitis (AR), persistent cough, and persistent phlegm was collected during 2012-2013 using a standardized questionnaire developed by the American Thoracic Society (ATS). Information for potential confounders was also collected via questionnaire. Individuals' exposure to ambient ozone (O 3 ) during the four years before the investigation was estimated using a satellite-based random forest model. A higher level of O 3 was significantly associated with increased risk of AR and bronchitic symptoms. After controlling for potential confounders, the OR (95% CI) were 1.13 (1.07-1.18), 1.10 (1.06-1.16), and 1.12 (1.05-1.20) for AR, persistent cough, and persistent phlegm, respectively, associated with each interquartile range (IQR) rise in O 3 concentration. Interaction analyses showed stronger adverse effects of O 3 on AR in children aged 7-17 years than those aged 2-6 years, while the adverse association of O 3 with cough was more prominent in females and children aged 7-12 years than in males and children aged 2-6 and 13-17 years. This study showed that long-term exposure to ambient O 3 was significantly associated with higher risk of AR and bronchitic symptoms in children, and the association varies across age and gender. Our findings contribute additional evidence for the importance of controlling O 3 pollution and protecting children from O 3 exposure.

Background: Urban greenness may protect against obesity, but very few studies have assessed 'street view' (SV) greenness metrics, which may better capture people's actual exposure to greenness compared to commonly-used satellite-derived metrics. We aimed to investigate these associations further in a Chinese adult study., Methods: Our analysis included 24,845 adults in the 33 Chinese Community Health Study in 2009. SV images from Tencent Map, segmented by machine learning algorithms, were used to determine the average proportion of green vegetation in SV images at community level in 800m road network buffer. Sensitivity analyses were performed with an alternative buffer size. Overall greenness was assessed as normalized difference vegetation index (NDVI) in 800 m buffer. We used predicted PM 2.5 and monitored NO 2 as proxies of air pollution. Body mass index (BMI), waist circumference (WC) and hip circumference (HC) were regressed on SV greenness by generalized linear mixed models, with adjustment for covariates. Mediation analyses were performed to assess the mediation effects of air pollution., Results: Each interquartile range (IQR = 3.6%) increase in street view greenness was associated with a 0.15 kg/m 2 (95% CI: -0.22, -0.09) decrease in BMI and 0.23 cm (95% CI: -0.35, -0.11) reduction in HC, and was associated with 7% lower odds of overweight (OR = 0.93, 95% CI:0.90, 0.96) and 18% lower odds of obesity (OR = 0.82, 95% CI:0.76, 0.89). Similar effect estimation was observed compared with commonly-used NDVI measures. PM 2.5 and NO 2 mediated 15.5% and 6.1% of the effects of SV greenness with BMI, respectively., Conclusions: Our findings suggest beneficial associations between community-level SV greenness and lower body weight in Chinese adults. The effects were observed in women but not in men. Air pollution may partially mediate the association. These findings may have implications to support efforts to promote greening in urban areas., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) exposure has been linked to diabetes, but evidence on the association of isomers of PFAS with type 2 diabetes (T2D) remains scant. This population based cross-sectional study aimed to investigate associations between serum PFAS isomers, glucose-homeostasis markers and T2D, adjusted for multiple potential confounders. We used data from "Isomers of C8 Health Project in China" from July 2015 to October 2016. A total of 10 PFAS including isomers of PFOS and PFOA were measured in serum of 1045 Chinese adults. Fasting blood glucose, fasting insulin, homeostasis model of insulin (HOMA-IR) and beta cell function (HOMA-β) were considered as markers of glucose-homeostasis. We found significant positive associations between serum PFAS isomers and glucose-homeostasis markers, namely, fasting blood glucose, fasting insulin and HOMA-IR. Per log-unit increase in branched (br)-PFOS concentration was associated with increased fasting blood glucose (β = 0.25, 95% CI: 0.18, 0.33), fasting insulin (β = 2.19, 95% CI: 1.44, 2.93) and HOMA-IR (β = 0.69, 95% CI: 0.50, 0.89). As compared to br-PFOS, linear (n)-PFOS and -PFOA showed lesser significant associations with glucose-homeostasis makers. Further, exposure to all PFAS including isomeric PFOS, PFOA and PFHxS increased the risk of T2D with br-PFOS exhibiting the highest risk (OR = 5.41, 95% CI: 3.68-7.96). The associations were stronger among women than men. In conclusion, chronic exposure to PFAS isomers was associated with impaired glucose-homeostasis and may increase the prevalence of T2D in Chinese adults. Given the ubiquity of PFAS in the environment and the public health burden of T2D, future studies are warranted to corroborate the findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Disturbance in the proteolytic process is one of the malignant signs of tumors. Proteolysis is highly orchestrated by cysteine cathepsin and its inhibitors. Cystatin-B (CSTB) is a general cysteine cathepsin inhibitor that prevents cysteine cathepsin from leaking from lysosomes and causing inappropriate proteolysis. Our study found that CSTB was downregulated in both oral squamous cell carcinoma (OSCC) tissues and cells compared with normal controls. Immunohistochemical analysis showed that CSTB was mainly distributed in the epithelial structure of OSCC tissues, and its expression intensity was related to the grade classification. A correlation analysis between CSTB and clinical prognosis was performed using gene expression data and clinical information acquired from The Cancer Genome Atlas (TCGA) database. Patients with lower expression levels of CSTB had shorter disease-free survival times and poorer clinicopathological features (e.g., lymph node metastases, perineural invasion, low degree of differentiation, and advanced tumor stage). OSCC cell models overexpressing CSTB were constructed to assess the effects of CSTB on malignant biological behaviors and upregulation of CSTB inhibited cell proliferation, migration, and invasion in vitro . Weighted gene correlation network analysis (WGCNA) and gene set enrichment analysis (GSEA) were performed based on the TCGA data to explore potential mechanisms, and CSTB appeared to correlate with squamous epithelial proliferation-differentiation processes, such as epidermal cell differentiation and keratinization. Moreover, in WGCNA, the gene module most associated with CSTB expression (i.e., the brown module) was also the one most associated with grade classification. Upregulation of CSTB promoted the expression levels of markers (LOR, IVL, KRT5/14, and KRT1/10), reflecting a tendency for differentiation and keratinization in vitro . Gene expression profile data of the overexpressed CSTB cell line were obtained by RNA sequencing (RNA-seq) technology. By comparing the GSEA enrichment results of RNA-seq data (from the OSCC models overexpressing CSTB) and existing public database data, three gene sets (i.e., apical junction, G2/M checkpoint, etc.) and six pathways (e.g., NOTCH signaling pathway, glycosaminoglycan degradation, mismatch repair, etc.) were enriched in the data from both sources. Overall, our study shows that CSTB is downregulated in OSCC and might regulate the malignant characteristics of OSCC via the epithelial proliferation/differentiation program., 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 Xu, Zeng, Wang, Yang, Luo and Yu.)

Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Evidence of maternal exposure to ambient air pollution on congenital heart defects (CHD) has been mixed and are still relatively limited in developing countries. We aimed to investigate the association between maternal exposure to air pollution and CHD in China., Method: This longitudinal, population-based, case-control study consecutively recruited fetuses with CHD and healthy volunteers from 21 cities, Southern China, between January 2006 and December 2016. Residential address at delivery was linked to random forests models to estimate maternal exposure to particulate matter with an aerodynamic diameter of ≤ 1 µm (PM 1 ), ≤2.5 µm, and ≤10 µm as well as nitrogen dioxides, in three trimesters. The CHD cases were evaluated by obstetrician, pediatrician, or cardiologist, and confirmed by cardia ultrasound. The CHD subtypes were coded using the International Classification Diseases. Adjusted logistic regression models were used to assess the associations between air pollutants and CHD and its subtypes., Results: A total of 7055 isolated CHD and 6423 controls were included in the current analysis. Maternal air pollution exposures were consistently higher among cases than those among controls. Logistic regression analyses showed that maternal exposure to all air pollutants during the first trimester was associated with an increased odds of CHD (e.g., an interquartile range [13.3 µg/m 3 ] increase in PM 1 was associated with 1.09-fold ([95% confidence interval, 1.01-1.18]) greater odds of CHD). No significant associations were observed for maternal air pollution exposures during the second trimester and the third trimester. The pattern of the associations between air pollutants and different CHD subtypes was mixed., Conclusions: Maternal exposure to greater levels of air pollutants during the pregnancy, especially the first trimester, is associated with higher odds of CHD in offspring. Further longitudinal well-designed studies are warranted to confirm our findings., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To determine the related imaging findings and risk factors to refracture of the cemented vertebrae after percutaneous vertebroplasty (PVP) treatment., Methods: Patients who were treated with PVP for single vertebral compression fractures (VCFs) and met this study's inclusion criteria were retrospectively reviewed from January 2012 to January 2019. The follow-up period was at least 2 years. Forty-eight patients with refracture of the cemented vertebrae and 45 non-refractured patients were included. The following variates were reviewed: age, sex, fracture location, bone mineral density (BMD), intravertebral cleft (IVC), kyphotic angle (KA), wedge angle, endplate cortical disruption, cement volume, surgical approach, non-PMMA-endplate-contact (NPEC), cement leakage, other vertebral fractures, reduction rate (RR), and reduction angle (RA). Multiple logistic regression modeling was used to identify the independent risk factors of refracture., Results: Refracture was found in 48 (51.6%) patients. Four risk factors, including IVC (P = 0.005), endplate cortical disruption (P = 0.037), larger RR (P = 0.007), and NPEC (P = 0.006) were found to be significant independent risk factors for refracture., Conclusions: Patients with IVC or larger RR, NPEC, or endplate cortical disruption have a high risk of refracture in the cemented vertebrae after PVP.

Background Although several studies have focused on the associations between particle size and constituents and blood pressure, results have been inconsistent. Methods and Results We conducted a panel study, between December 2017 and January 2018, in 88 healthy university students in Guangzhou, China. Weekly systolic blood pressure and diastolic blood pressure were measured for each participant for 5 consecutive weeks, resulting in a total of 440 visits. Mass concentrations of particles with an aerodynamic diameter of ≤2.5 µm (PM 2.5 ), ≤1.0 µm (PM 1.0 ), ≤0.5 µm (PM 0.5 ), ≤0.2 µm (PM 0.2 ), and number concentrations of airborne particulates of diameter ≤0.1 μm were measured. Linear mixed-effect models were used to estimate the associations between blood pressure and particles and PM 2.5 constituents 0 to 48 hours before blood pressure measurement. PM of all the fractions in the 0.2- to 2.5-μm range were positively associated with systolic blood pressure in the first 24 hours, with the percent changes of effect estimates ranging from 3.5% to 8.8% for an interquartile range increment of PM. PM 0.2 was also positively associated with diastolic blood pressure, with an increase of 5.9% (95% CI, 1.0%-11.0%) for an interquartile range increment (5.8 μg/m 3 ) at lag 0 to 24 hours. For PM 2.5 constituents, we found positive associations between chloride and diastolic blood pressure (1.7% [95% CI, 0.1%-3.3%]), and negative associations between vanadium and diastolic blood pressure (-1.6% [95% CI, -3.0% to -0.1%]). Conclusions Both particle size and constituent exposure are significantly associated with blood pressure in the first 24 hours following exposure in healthy Chinese adults.

Importance: Few studies have investigated the association between the exposure window (prenatal, early postnatal, and current period) of secondhand smoke (SHS) and attention-deficit/hyperactivity disorder (ADHD) symptoms and subtypes in children., Objective: To evaluate the associations of prenatal, early postnatal, or current SHS exposure with ADHD symptoms and subtypes among school-aged children., Design, Setting, and Participants: In this cross-sectional study, 48 612 children aged 6 to 18 years from elementary and middle schools in Liaoning province, China, between April 2012 and January 2013 were eligible for participation. Data on SHS exposure and ADHD symptoms and subtypes for each child were collected via questionnaires administered to parents or guardians by school teachers. Data were analyzed from September 14 to December 2, 2020., Main Outcomes and Measures: The ADHD symptoms and subtypes (inattention, hyperactivity-impulsivity, and combined) were measured based on a validated tool developed from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Generalized linear mixed models were evaluated to estimate the association of SHS exposure with ADHD symptoms and subtypes., Results: A total of 45 562 participants completed the questionnaires and were included in this study (22 905 girls [50.3%]; mean [SD] age, 11.0 [2.6] years; 2170 [4.8%] with ADHD symptoms). Compared with their unexposed counterparts, children who were ever exposed (odds ratio [OR], 1.50; 95% CI, 1.36-1.66) or always exposed to SHS (OR, 2.88; 95% CI, 2.55-3.25) from pregnancy to childhood had higher odds of having ADHD symptoms and subtypes (ORs ranged from 1.46 [95% CI, 1.31-1.62] to 2.94 [95% CI, 2.09-4.13]). Compared with their unexposed counterparts, children with SHS exposure had higher odds of having ADHD symptoms when exposed in the prenatal period (OR, 2.28; 95% CI, 2.07-2.51), early postnatal period (OR, 1.47; 95% CI, 1.29-1.68), or current period (OR, 1.20; 95% CI, 1.09-1.31). Compared with their unexposed counterparts, children whose fathers smoked 10 or more cigarettes/d on both weekdays and weekends had higher odds of having ADHD symptoms and subtypes (ORs ranged from 1.48 [95% CI, 1.28-1.70] to 2.25 [95% CI, 1.29-3.93])., Conclusions and Relevance: Being exposed to SHS from pregnancy to childhood was associated with higher odds of having ADHD symptoms and subtypes among school-aged children, and the associations were somewhat stronger for SHS exposure during prenatal and early postnatal periods. Our findings highlight the important public health implications of reducing SHS exposure, which may decrease the health and economic burdens of individuals with ADHD.

Background: Exposure to perfluoroalkyl acids (PFAAs) is known to be associated with metabolic disorders. However, whether PFAAs isomers are associated with metabolic syndrome (MetS) still remains unknown., Objectives: To explore the associations between serum PFAAs isomers and MetS., Methods: We recruited 1,501 adults from a cross-sectional study, the "Isomers of C8 Health Project in China" to investigate the associations between PFAAs isomers and MetS. A total of 20 PFAAs including the isomers of PFOS and PFOA were detected. Logistic regression models and restricted cubic spline models were used to evaluate the relationship of serum PFAAs isomers exposure with MetS and its components as well after adjusting for covariates., Results: The MetS prevalence in our study was 43.0%. The serum levels of both PFOS and PFOA isomers were higher in participants with MetS than that with non-MetS (p < 0.05). We found positive associations for per natural log-transformed ng/mL of branched perfluorooctane sulfonate (br-PFOS) (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.01, 1.38)) linear perfluoronanoic acid (n-PFOA) (OR = 1.35, 95% CI: 1.16, 1.58) and perfluoro-6-methylpheptanoic acid (6 m-PFOA) (OR = 1.32, 95% CI: 1.11, 1.57) with higher odds of MetS after covariates adjustment, while null association was observed for linear isomers of PFOS (OR = 1.09, 95% CI: 0.94, 1.25). We found a nonlinear dose-response relationship with a "threshold" effect in serum br-PFOS isomers with MetS, in which the odds of MetS increased quickly with increasing serum br-PFOS isomers under low exposure (p for nonlinearity = 0.030)., Conclusion: We report new evidence of associations between PFAAs isomers and MetS and the nonlinearity of dose-response relationship with br-PFOS isomers. Our findings indicate that more attention is needed to pay on the nonlinearity of dose-response relationship when investigate the association of PFAAs isomers with human health., (Copyright © 2020 Elsevier Inc. All rights reserved.)