Specific CpG sites methylation is associated with hematotoxicity in low-dose benzene-exposed workers.

Benzene is a broadly used industrial chemicals which causes various hematologic abnormalities in human. Altered DNA methylation has been proposed as epigenetic biomarkers in health risk evaluation of benzene exposure, yet the role of methylation at specific CpG sites in predicting hematological effects remains unclear. In this study, we recruited 120 low-level benzene-exposed and 101 control male workers from a petrochemical factory in Maoming City, Guangdong Province, China. Urinary S-phenylmercapturic acid (SPMA) in benzene-exposed workers was 3.40-fold higher than that in control workers (P < 0.001). Benzene-induced hematotoxicity was characterized by reduced white blood cells counts and nuclear division index (NDI), along with an increased DNA damage and urinary 8-hydroxy-2'-deoxyguanosine (all P < 0.05). Methylation levels of TRIM36, MGMT and RASSF1a genes in peripheral blood lymphocytes (PBLCs) were quantified by pyrosequencing. CpG site 6 of TRIM36, CpG site 2, 4, 6 of RASSF1a and CpG site 1, 3 of MGMT methylation were recognized as hot CpG sites due to a strong correlation with both internal exposure and hematological effects. Notably, integrating hot CpG sites methylation of multiple genes reveal a higher efficiency in prediction of integrative damage compared to individual genes at hot CpG sites. The negative dose-response relationship between the combined methylation of hot CpG sites in three genes and integrative damage enabled the classification of benzene-exposed individuals into high-risk or low-risk groups using the median cut-off value of the integrative index. Subsequently, a prediction model for integrative damage in benzene-exposed populations was built based on the methylation status of the identified hot CpG sites in the three genes. Taken together, these findings provide a novel insight into application prospect of specific CpG site methylation as epi-biomarkers for health risk assessment of environmental pollutants.

Moderate body lipid accumulation in mice attenuated benzene-induced hematotoxicity via acceleration of benzene metabolism and clearance.

Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.

Uterine-specific SIRT1 deficiency confers premature uterine aging and impairs invasion and spacing of blastocyst, and stromal cell decidualization, in mice.

A distinct age-related alteration in the uterine environment has recently been identified as a prevalent cause of the reproductive decline in older female mice. However, the molecular mechanisms that underlie age-associated uterine adaptability to pregnancy are not known. Sirtuin 1 (SIRT1), a multifunctional NAD+-dependent deacetylase that regulates cell viability, senescence and inflammation during aging, is reduced in aged decidua. Thus, we hypothesize that SIRT1 plays a critical role in uterine adaptability to pregnancy and that uterine-specific ablation of Sirt1 gene accelerates premature uterine aging. Female mice with uterine ablation of Sirt1 gene using progesterone receptor Cre (PgrCre) exhibit subfertility and signs of premature uterine aging. These Sirt1-deficient mothers showed decreases in litter size from their 1st pregnancy and became sterile (25.1 ± 2.5 weeks of age) after giving birth to the third litter. We report that uterine-specific Sirt1 deficiency impairs invasion and spacing of blastocysts, and stromal cell decidualization, leading to abnormal placentation. We found that these problems traced back to the very early stages of hormonal priming of the uterus. During the window of receptivity, Sirt1 deficiency compromises uterine epithelial-stromal crosstalk, whereby estrogen, progesterone and Indian hedgehog signaling pathways are dysregulated, hampering stromal cell priming for decidualization. Uterine transcriptomic analyses also link these causes to perturbations of histone proteins and epigenetic modifiers, as well as adrenomedullin signaling, hyaluronic acid metabolism, and cell senescence. Strikingly, our results also identified genes with significant overlaps with the transcriptome of uteri from aged mice and transcriptomes related to master regulators of decidualization (e.g. Foxo1, Wnt4, Sox17, Bmp2, Egfr and Nr2f2). Our results also implicate accelerated deposition of aging-related fibrillar Type I and III collagens in Sirt1-deficient uteri. Collectively, SIRT1 is an important age-related regulator of invasion and spacing of blastocysts, as well as decidualization of stromal cells.

Outdoor light at night, overweight, and obesity in school-aged children and adolescents.

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: ß = 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 (Pinteraction<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.

The association between anthropogenic heat and adult hypertension in Northeast China.

OBJECTIVES: Although the potential serious threat of anthropogenic heat on human health was receiving considerable attention worldwide, its long-term health effect on blood pressure (BP) remained unknown. We aimed to evaluate the associations of long-term anthropogenic heat exposure with different components of BP and hypertension. METHODS: In this cross-sectional study (Liaoning province, China) conducted in 2009, we included a total of 24,845 Chinese adults (18-74 years). We estimated the anthropogenic heat exposure in 2008 using multisource remote sensing images and ancillary data. We measured systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), and defined hypertension. We used generalized linear mixed model to examine the associations. RESULTS: In the adjusted model, the estimates indicated that the difference in SBP, MAP and PP for those in highest quartiles of total anthropogenic heat exposure was greater compared with the lowest quartile (highest quartile: ß = 1.11 [95% CI: 0.28-1.94], 0.60 [95% CI: 0.04-1.17], 0.76 [95% CI: 0.17-1.35]). Compared with the lowest quartile, the odds of hypertension were higher among those in higher quartiles (second quartile: OR = 1.17 [95% CI: 1.05-1.30]; third quartile:1.10 [95% CI: 1.1.01-1.21]; highest quartile: 1.17 [95% CI: 1.06-1.28]). These associations were stronger in female participants. CONCLUSION: Our study showed that long-term exposure to anthropogenic heat was associated with elevated BP and higher odds of hypertension. These findings suggest that mitigation strategies to reduce anthropogenic heat should be considered.

The effects of Cl-PFESAs exposure on blood lipids - A community-based large population study in Guangzhou.

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.

Improved morbidity-based air quality health index development using Bayesian multi-pollutant weighted model.

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 NO2 and O3 to the final AQHI were prominent, while the contribution of SO2 and PM2.5 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.

Exposure to second-hand smoke during early life and subsequent sleep problems in children: a population-based cross-sectional study.

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 (ß = 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.

The Asthma Family Tree: Evaluating Associations Between Childhood, Parental, and Grandparental Asthma in Seven Chinese Cities.

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.

Associations between trees and grass presence with childhood asthma prevalence using deep learning image segmentation and a novel green view index.

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 (PM2.5) was a modifier. An IQR increase in GVI800m 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 GVI800m 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 PM2.5 exposure level, the negative association between trees and asthma, and the positive association between grass and asthma were observed only in low PM2.5 exposure levels (≤median: 56.23 µg/m3). 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, PM2.5 may modify the associations of trees and grass with childhood asthma.

Association between eye-level greenness and lung function in urban Chinese children.

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 (FEV1), 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 (PM1), <2.5 µm (PM2.5), <10 µm (PM10) as well as nitrogen dioxide (NO2). RESULTS: An increase of GVI800m was associated with lung impairment in FEV1, 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 GVI800m and FEV1 (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 PM1, PM2.5, and PM10 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.

INO80 promotes H2A.Z occupancy to regulate cell fate transition in pluripotent stem cells.

The INO80 chromatin remodeler is involved in many chromatin-dependent cellular functions. However, its role in pluripotency and cell fate transition is not fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the transition toward and maintenance of the primed state. In the naïve state, INO80 pre-marked gene promoters that would adopt bivalent histone modifications by H3K4me3 and H3K27me3 upon transition into the primed state. In the primed state, in contrast to its known role in H2A.Z exchange, INO80 promoted H2A.Z occupancy at these bivalent promoters and facilitated H3K27me3 installation and maintenance as well as downstream gene repression. Together, our results identified an unexpected function of INO80 in H2A.Z deposition and gene regulation. We showed that INO80-dependent H2A.Z occupancy is a critical licensing step for the bivalent domains, and thereby uncovered an epigenetic mechanism by which chromatin remodeling, histone variant deposition and histone modification coordinately control cell fate.

Association of Prenatal, Early Postnatal, or Current Exposure to Secondhand Smoke With Attention-Deficit/Hyperactivity Disorder Symptoms in Children.

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.

Short-Term Effects of Particle Sizes and Constituents on Blood Biomarkers among Healthy Young Adults in Guangzhou, China.

Evidence of the effects of various particle sizes and constituents on blood biomarkers is limited. We performed a panel study with five repeated measurements in 88 healthy college students in Guangzhou, China between December 2017 and January 2018. Mass concentrations of particles with aerodynamic diameters ≤ 2.5 µm (PM2.5), PM1, and PM0.5 and number concentrations of particles with aerodynamic diameters ≤ 200 nm (PN0.2) and PN0.1 were measured. We used linear mixed-effect models to explore the associations of size-fractionated particulate matter and PM2.5 constituents with five blood biomarkers 0-5 days prior to blood collection. We found that an interquartile range (45.9 µg/m3) increase in PM2.5 concentration was significantly associated with increments of 16.6, 3.4, 12.3, and 8.8% in C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and endothelin-1(ET-1) at a 5-day lag, respectively. Similar estimates were observed for PM1, PM0.5, PN0.2, and PN0.1. For PM2.5 constituents, consistent positive associations were observed between F- and sVCAM-1 and CRP and between NH4+ and MCP-1, and negative associations were found between Na+ and MCP-1 and ET-1, between Cl- and MCP-1, and between Mg2+ and sVCAM-1. Our results suggested that both particle size and constituent exposure are significantly associated with circulating biomarkers among healthy Chinese adults. Particularly, PN0.1 at a 5-day lag and F- and NH4+ are the most associated with these blood biomarkers.

Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro.

Emerging evidence suggests associations between Perfluoroalkyl substances (PFASs) exposure and asthma, but the findings are inconsistent. The current study sought to investigate whether perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) could contribute to asthma exacerbation and to clarify the underlying biological mechanisms. The objectives are a) to determine whether PFOS or PFOA could aggravate the mouse asthma and pulmonary inflammation b) to investigate whether PFOS and PFOA regulate the balance of Th1/Th2 through the JAK-STAT signaling pathway and aggravated asthma. Ovalbumin (OVA) induced asthmatic mice were exposed to PFOS or PFOA by gavage. PFOS and PFOA serum level and toxicity in organs were assessed; and the impacts on respiratory symptoms, lung tissue pathology, T helper cell (Th2) response, and STAT6 pathway activity were also evaluated. In vitro Jurkat cells were used to study the mechanisms of PFOS and PFOA mediated Th1 and Th2 responses. Both PFOS and PFOA exacerbated lung tissue inflammation (greater number of eosinophils and mucus hyperproduction), upregulated Th2 cytokine production (IL-4 and IL-13), and promoted Th2 cells and STAT6 activation. Furthermore, PFOS and PFOA enhanced the Th2 response in Jurkat cells via STAT6 activation; and the effect of PFOS exposure on GATA-3, IL-4 and IFN-γ was blocked after the expression of STAT6 was suppressed in Jurkat cells, however, the effects of PFOA exposure were only partially blocked. PFOS and PFOA aggravated inflammation among OVA-induced asthmatic mice, by promoting the Th2 response in lymphocytes and disturbing the balance of Th1/Th2 through the JAK-STAT signaling pathway.

Greenness may improve lung health in low-moderate but not high air pollution areas: Seven Northeastern Cities' study.

INTRODUCTION: There is growing interest in the impact of greenness exposure on airway diseases, but the impact of greenness on lung function in children is limited. We aimed to investigate the associations between greenness surrounding schools and lung function in children and whether these associations are modified by air pollution exposure. METHODS: Between 2012 and 2013, a cross-sectional survey and spirometry were performed among 6740 school children. Lung function patterns were determined as obstructive forced expiratory volume 1 s/forced vital capacity (FEV1/FVC <0.8) or restrictive (FEV1/FVC ≥0.8 but FVC <80% of predicted). School greenness was defined by Normalized difference vegetation index (NDVI) and soil-adjusted vegetation index. Nitrogen dioxide, sulphur dioxide and particular matter concentrations were assessed using a spatiotemporal model and national monitoring data. Two-level generalised linear models were used to investigate associations and interactions. RESULTS: Overall, an IQR in NDVI within 500 m was associated with higher FEV1 (+57 mL 95% CI 44 to 70) and FVC (+58 mL 95% CI 43 to 73). NDVI was similarly associated with 25% reduced odds of spirometric restriction (OR: 0.75, 95% CI 0.65 to 0.86). However, among children exposed to the highest compared with the lowest quartile of particulate matter, increasing NDVI was paradoxically associated with lower -40 mL FVC (95% CI -47 to -33, p interaction <0.05). DISCUSSION: Our findings suggest that, in this study population, greening urban areas may promote lung health in low-moderate pollution areas but not in high air pollution areas. If the findings are replicated in other moderate-to-high pollution settings, this highlights a need to have a flexible green policy.

Associations of ambient particulate matter with homocysteine metabolism markers and effect modification by B vitamins and MTHFR C677T gene polymorphism.

Evidence concerning effects of ambient air pollution on homocysteine (HCY) metabolism is scarce. We aimed to explore the associations between ambient particulate matter (PM) exposure and the HCY metabolism markers and to evaluate effect modifications by folate, vitamin B12, and methylenetetrahyfrofolate reductase (MTHFR) C677T gene polymorphism. Between December 1, 2017 and January 5, 2018, we conducted a panel study in 88 young college students in Guangzhou, China, and received 5 rounds of health examinations. Real-time concentrations of PMs with aerodynamic diameter ≤2.5 (PM2.5), ≤1.0 (PM1.0), and ≤0.1 (PM0.1) were monitored, and the serum HCY metabolism markers (i.e., HCY, S-Adenosylhomocysteine [SAH], and S-Adenosylmethionine [SAM]) were repeatedly measured. We applied linear mixed effect models combined with a distributed lag model to evaluate the associations of PMs with the HCY metabolism markers. We also explored effect modifications of folate, vitamin B12, and the MTHFR C677T polymorphism on the associations. We observed that higher concentrations of PM2.5 and PM1.0 were associated with higher serum levels of HCY, SAH, SAM, and SAM/SAH ratio (e.g., a 10 µg/m3 increase in PM2.5 during lag 0 day and lag 5 day was significantly associated with 1.3-19.4%, 1.3-28.2%, 6.2-64.4%, and 4.8-28.2% increase in HCY, SAH, SAM, and SAM/SAH ratio, respectively). In addition, we observed that the associations of PM2.5 with the HCY metabolism markers were stronger in participants with lower B vitamins levels. This study demonstrated that short-term exposure to PM2.5 and PM1.0 was deleteriously associated with the HCY metabolism markers, especially in people with lower B vitamins levels.

Is PM1 similar to PM2.5? A new insight into the association of PM1 and PM2.5 with children's lung function.

Experimental data suggests that PM1 is more toxic than PM2.5 although the epidemiologic evidence suggests that the health associations are similar. However, few objective exposure data are available to compare the associations of PM1 and PM2.5 with children lung function. Our objectives are a) to evaluate associations between long-term exposure to PM1, PM2.5 and children's lung function, and b) to compare the associations between PM1 and PM2.5. From 2012 to 2013, we enrolled 6,740 children (7-14 years), randomly recruited from primary and middle schools located in seven cities in northeast China. We measured lung function including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF) utilizing two portable electronic spirometers. We dichotomized continuous lung function measures according the expected values for gender and age. The spatial resolution at which PM1 and PM2.5 estimated were estimated using a machine learning method and the temporal average concentrations were averaged from 2009 to 2012. A multilevel regression model was used to estimate the associations of PM1, PM2.5 exposure and lung function measures, adjusted for confounding factors. Associations with lower lung function were consistently larger for PM1 than for PM2.5. Adjusted odds ratios (OR) per interquartile range greater PM1 ranged from 1.53 for MMEF (95% confidence interval [CI]: 1.20-1.96) to 2.14 for FEV1 (95% CI: 1.66-2.76) and ORs for PM2.5 ranged from 1.36 for MMEF (95%CI: 1.12-1.66) to 1.82 for FEV1 (95%CI: 1.49-2.22), respectively. PM1 and PM2.5 had significant associations with FVC and FEV1 in primary school children, and on PEF and MMEF in middle school children. Long-term PM1 and PM2.5 exposure can lead to decreased lung function in children, and the associations of PM1 are stronger than PM2.5. Therefore, PM1 may be more hazardous to children's respiratory health than PM2.5 exposure.

Association Between Residential Greenness, Cardiometabolic Disorders, and Cardiovascular Disease Among Adults in China.

Importance: Living in areas with more vegetation (referred to as residential greenness) may be associated with cardiovascular disease (CVD), but little data are available from low- and middle-income countries. In addition, it remains unclear whether the presence of cardiometabolic disorders modifies or mediates the association between residential greenness and CVD. Objective: To evaluate the associations between residential greenness, cardiometabolic disorders, and CVD prevalence among adults in China. Design, Setting, and Participants: This analysis was performed as part of the 33 Communities Chinese Health Study, a large population-based cross-sectional study that was conducted in 33 communities (ranging from 0.25-0.64 km2) in 3 cities within the Liaoning province of northeastern China between April 1 and December 31, 2009. Participants included adults aged 18 to 74 years who had resided in the study area for 5 years or more. Greenness levels surrounding each participant's residential community were assessed using the normalized difference vegetation index and the soil-adjusted vegetation index from 2010. Lifetime CVD status (including myocardial infarction, heart failure, coronary heart disease, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, and subarachnoid hemorrhage) was defined as a self-report of a physician diagnosis of CVD at the time of the survey. Cardiometabolic disorders, including hypertension, diabetes, dyslipidemia, and overweight or obese status, were measured and defined clinically. Generalized linear mixed models were used to evaluate the association between residential greenness levels and CVD prevalence. A 3-way decomposition method was used to explore whether the presence of cardiometabolic disorders mediated or modified the association between residential greenness and CVD. Data were analyzed from October 10 to May 30, 2020. Main Outcomes and Measures: Lifetime CVD status, the presence of cardiometabolic disorders, and residential greenness level. Results: Among 24 845 participants, the mean (SD) age was 45.6 (13.3) years, and 12 661 participants (51.0%) were men. A total of 1006 participants (4.1%) reported having a diagnosis of CVD. An interquartile range (1-IQR) increase in the normalized difference vegetation index within 500 m of a community was associated with a 27% lower likelihood (odds ratio [OR], 0.73; 95% CI, 0.65-0.83; P < .001) of CVD prevalence, and an IQR increase in the soil-adjusted vegetation index within 500 m of a community was associated with a 26% lower likelihood (OR, 0.74; 95% CI, 0.66-0.84; P < .001) of CVD prevalence. The presence of cardiometabolic disorders was found to mediate the association between residential greenness and CVD, with mediation effects of 4.5% for hypertension, 4.1% for type 2 diabetes, 3.1% for overweight or obese status, 12.7% for hypercholesterolemia, 8.7% for hypertriglyceridemia, and 11.1% for high low-density lipoprotein cholesterol levels. Conclusions and Relevance: In this cross-sectional study, higher residential greenness levels were associated with lower CVD prevalence, and this association may be partially mediated by the presence of cardiometabolic disorders. Further studies, preferably longitudinal, are warranted to confirm these findings.