Maternal concentrations of environmental phenols during early pregnancy and behavioral problems in children aged 4 years from the Shanghai Birth Cohort.

BACKGROUND: Prenatal exposure to environmental phenols such as bisphenol (BPs), paraben (PBs), benzophenone (BzPs), and triclosan (TCS) is ubiquitous and occurs in mixtures. Although some of them have been suspected to impact child behavioral development, evidence is still insufficient, and their mixed effects remain unclear. OBJECTIVES: To explore the association of prenatal exposure to multiple phenols with child behavioral problems. METHOD: In a sample of 600 mother-child pairs from the Shanghai Birth Cohort, we quantified 18 phenols (6 PBs, 7 BPs, 4 BzPs, and TCS) in urine samples collected during early pregnancy. Parent-reported Strengths and Difficulties Questionnaires were utilized to evaluate child behavioral difficulties across four subscales, namely conduct, hyperactivity/inattention, emotion, and peer relationship problems, at 4 years of age. Multivariable linear regression was conducted to estimate the relationships between single phenolic compounds and behavioral problems. Additionally, weighted quantile sum (WQS) regression was employed to examine the overall effects of the phenol mixture. Sex-stratified analyses were also performed. RESULTS: Our population was extensively exposed to 10 phenols (direction rates >50 %), with low median concentrations (1.00 × 10-3-6.89 ng/mL). Among them, single chemical analyses revealed that 2,4-dihydroxy benzophenone (BP1), TCS, and methyl 4-hydroxybenzoate (MeP) were associated with increased behavior problems, including hyperactivity/inattention (BP1: ß = 0.16; 95 % confidence interval [CI]: 0.04, 0.30), emotional problems (BP1: ß = 0.11; 95 % CI: 0.02, 0.20; TCS: ß = 0.08; 95 % CI: 0.02, 0.14), and peer problems (MeP: ß = 0.10; 95 % CI: 0.02, 0.18); however, we did not identify any significant association with conduct problems. Further phenol mixture analyses in the WQS model yielded similar results. Stratification for child sex showed stronger positive associations in boys. CONCLUSION: Our findings indicated that maternal phenol levels during early pregnancy, specifically BP1, TCS, and MeP, are associated with high behavioral problem scores in 4-year-old children.

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

Effect modification by maternal vitamin D status in the association between prenatal exposure to per- and polyfluoroalkyl substances and neurodevelopment in 2-year-old children.

BACKGROUND: Pregnant women in the Shanghai Birth Cohort (SBC) of China faced dual threats of per- and polyfluoroalkyl substances (PFAS) exposure and vitamin D (VD) insufficiency, potentially impacting offspring neurodevelopment. However, little is known about whether maternal VD status modifies PFAS-related neurodevelopment effect. OBJECTIVES: To explore the modifying role of maternal VD status in the effect of prenatal PFAS exposure on childhood neurodevelopment. METHODS: We included 746 mother-child pairs from the SBC. Ten PFAS congeners and VD levels were measured in maternal blood samples collected during the first and second trimester respectively. At 2 years of age, toddlers underwent neurodevelopment assessments using Bayley-III Scales. Multivariate linear, logistic regression, and weighted quantile sum approach were used to estimate associations of Bayley-III scores with individual and mixture PFAS. We stratified participants into VD sufficient and insufficient groups and further balanced PFAS differences between these groups by matching all PFAS levels. We fitted the same statistical models in each VD group before and after matching. RESULTS: Nearly half (46.5 %) of pregnant women were VD insufficient (<30 ng/mL). In the overall population, PFAS exposure was associated with lower language scores and an increased risk for neurodevelopmental delay, but higher cognitive scores. However, adverse associations with PFAS were mainly observed in the VD sufficient group, while the VD insufficient group showed positive cognitive score associations. Higher PFAS concentrations were found in the VD sufficient group compared to the VD insufficient group. Post-matching, adverse associations in the VD sufficient group were nullified, whereas in the VD insufficient group, positive associations disappeared and adverse associations becoming more pronounced. CONCLUSION: In this Chinese birth cohort, high prenatal PFAS exposure and low maternal VD levels collectively heighten the risk of adverse childhood neurodevelopment. However, disentangling PFAS and VD interrelationships is crucial to avoid paradoxical findings.

Associations of legacy perfluoroalkyl and polyfluoroalkyl substances, alternatives, and isomers with gestational diabetes mellitus and glucose homeostasis among women conceiving through assisted reproduction in Shanghai, China.

Prior research has reported that perfluoroalkyl and polyfluoroalkyl substances (PFAS) may be linked to impaired glucose homeostasis in pregnant women. However, few studies have investigated PFAS alternatives and isomers, and even less is known about the association among women conceiving through assisted reproductive technology (ART). The prospective cohort study aimed to explore associations of legacy PFAS, alternatives and isomers with gestational diabetes mellitus (GDM) and glucose homeostasis during pregnancy among 336 women conceiving through ART. Nineteen PFAS, including nine linear legacy PFAS, four short-chain alternatives, four branched isomers, and two emerging PFAS alternatives, were determined in first-trimester maternal serum. Fasting plasma glucose (FPG), 1-h and 2-h glucose concentrations following the oral glucose tolerance test (OGTT), and glycated hemoglobin (HbA1c) were measured during the second trimester. After adjusting for confounding variables, nearly half of individual PFAS (10/19) and PFAS mixtures were correlated with increased GDM risk or elevated 2-h glucose levels. Among PFAS congeners, emerging PFAS alternatives, chlorinated perfluoroalkyl ether sulfonic acids (Cl-PFESAs), showed a notable association with impaired glucose homeostasis. For example, 6:2 Cl-PFESA exhibited a correlation with GDM (OR = 1.31, 95% CI = 1.02, 1.68) and 2-h glucose concentrations (ß = 0.22, 95% CI = 0.08, 0.36), and contributed most to the overall association with 2-h glucose concentrations. Compared to those diagnosed with male factor infertility, the associations were more pronounced in infertile women with reproductive endocrine diseases. We provide evidence that exposure to PFAS, especially emerging PFAS alternatives, may impair glucose homeostasis and increase the risk of GDM among women conceiving through ART.

Associations of exposure to bisphenol A and its substitutes with neurodevelopmental outcomes among infants at 12 months of age: A cross-sectional study.

BACKGROUND: Bisphenol A (BPA) exposure has been linked to adverse childhood neurodevelopment, but little is known about whether BPA substitutes exposures are also related to childhood neurodevelopment. OBJECTIVES: To investigate the associations of exposure to BPA and its substitutes with infant neurodevelopment at 12 months. METHODS: A total of 420 infants at 12 months were included from the Laizhou Wan (Bay) Birth Cohort in Shandong, China. Urinary concentrations of BPA and its substitutes including bisphenol S (BPS), bisphenol B (BPB), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol P (BPP) and bisphenol Z (BPZ) were measured. Developmental quotient (DQ) scores based on the Gesell Development Schedules (GDS) were used to evaluate infant neurodevelopment. The multivariable linear regression and weighted quantile sum (WQS) regression were applied to estimate the associations of exposure to individual bisphenols and their mixtures with DQ scores, respectively. Sex-stratified analyses were also performed. RESULTS: BPA was detected in most infants (89.05%) and had the highest median concentration (0.709 ng/mL) among all bisphenols. BPA substitutes except BPZ were ubiquitous in infants' urine samples (>70%), and BPS showed the highest median concentration (0.064 ng/mL) followed by BPAP (0.036 ng/mL), BPAF (0.028 ng/mL), BPP (0.015 ng/mL) and BPB (0.013 ng/mL). In multivariable linear regression, only BPAF exposure was inversely associated with social DQ scores among all infants (ß = -0.334; 95% CI: -0.650, -0.019). After sex stratification, this inverse association was significant in girls (ß = -0.605; 95% CI: -1.030, -0.180). Besides, BPA exposure was negatively related to gross motor DQ scores in boys (ß = -1.061; 95% CI: -2.078, -0.045). WQS analyses confirmed these results. CONCLUSIONS: Our study suggests that bisphenol exposure during infancy may be associated with poor infant neurodevelopment, and BPAF as a commonly used BPA substitute contributing the most to this adverse association deserves more attention.

Maternal exposure to organophosphate flame retardants and neonatal anthropometric measures.

BACKGROUND: Organophosphate flame retardants (OPFRs) are widely used as flame retardants and plasticizers. Laboratory evidence has suggested that maternal OPFR exposure may adversely affect fetal growth, but the epidemiological data are limited. OBJECTIVES: To investigate the association of maternal OPFR exposure with neonatal anthropometric measures. METHODS: This study included 354 mother-newborn pairs from the Laizhou Wan Birth Cohort (LWBC), China. Ten OPFR metabolites were measured in maternal urine samples collected before delivery. Neonatal anthropometric data was collected from medical records and standardized into z-scores using the WHO standards (2007), including the weight-for-age (WAZ), length-for-age (LAZ), body mass index-for-age (BMIZ), weight-for-length (WLZ), and head circumference-for-age z-score (HCZ). Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of individual OPFR metabolites and their mixtures with neonatal anthropometrics, respectively. Stratified analysis by sex was performed. RESULTS: The detection rates of BCEP, DPHP, BCIPP, BDCIPP, BBOEP, DnBP and DiBP were above 60%, with median concentrations ranging from 0.14 to 3.60 µg/g creatinine. Most OPFR metabolites (i.e., BCIPP, BDCIPP, DiBP, DnBP, or BBOEP) were associated with decreased offspring WAZ and HCZ. When using WQS analysis, the OPFR metabolite mixture was inversely associated with the WAZ, BMIZ and HCZ, whereas DnBP had the highest weights. After stratified by gender, the negative associations were more pronounced among males. CONCLUSIONS: Maternal OPFR exposure was negatively associated with offspring WAZ, BMIZ, and HCZ, and males seemed to be more vulnerable to the developmental toxicity of certain OPFRs.

Urinary neonicotinoid insecticides and adiposity measures among 7-year-old children in northern China: A cross-sectional study.

BACKGROUND: Neonicotinoid insecticides (NEOs) are emerging synthetic insecticides used in various pest management regimens worldwide. Toxicology studies have indicated the obesogenic potential of NEOs, but their associations with adiposity measures are largely unknown. OBJECTIVES: We aimed to assess urinary levels of NEOs/metabolites and their associations with children's adiposity measures, and to further investigate the potential role of oxidative stress. METHODS: This study included 380 children who participated in the 7th year's follow-up of the Laizhou Wan Birth Cohort in northern China. Urinary levels of seven NEOs and two metabolites and a biomarker of lipid peroxidation named 8-iso-prostaglandin-F2α (8-iso-PGF2α) were detected. A total of nine indicators of adiposity were measured. Body mass index (BMI) z-score ≥85th percentile was defined as overweight/obesity, and waist-to-height ratio (WHtR) ≥0.5 was considered as abdominal obesity. Multiple linear regression, binary logistic regression and mediation analysis were performed. RESULTS: Six NEOs [imidacloprid (IMI, 99.7%), clothianidin (CLO, 98.9%), dinotefuran (DIN, 97.6%), thiamethoxam (THM, 95.5%), acetamiprid (ACE, 82.9%), thiacloprid (THD, 77.6%)] and two metabolites [N-desmethyl-acetamiprid (N-DMA, 100.0%), 6-chloronicotinic acid (6-CINA, 97.9%)] exhibited high detection rates. Multiple linear regressions showed positive associations of waist circumference with urinary levels of IMI and THM, of WHtR with IMI and THM levels, and of body fat percentage with 6-CINA levels. In contrast, exposure to N-DMA was negatively associated with body fat percentage and fat mass index. Binary logistic regressions further revealed that higher IMI levels were associated with overweight/obesity (OR = 1.556, 95% CI: 1.100, 2.201) and abdominal obesity (OR = 1.478, 95% CI: 1.078, 2.026) in children. 8-iso-PGF2α demonstrated 27.92%, 69.52% and 35.37% mediating effects in the positive associations of IMI, THD and THM with WHtR, respectively. Sex modified the associations of DIN with body fat mass (pint = 0.032), body fat percentage (pint = 0.009), fat mass index (pint = 0.037) and the overweight/obesity rate (pint = 0.046), with negative associations in girls and nonsignificant positive associations in boys. CONCLUSIONS: School-age children in northern China were widely exposed to NEOs/metabolites. Urinary levels of NEOs/metabolites were associated with adiposity measures through the mediating role of 8-iso-PGF2α. These associations were mixed, and a sex-specific effect might exist.

Effects of prenatal exposure to PM2.5 and its composition on cognitive and motor functions in children at 12 months of age: The Shanghai Birth Cohort Study.

BACKGROUND: Prenatal fine particulate matter (PM2.5) exposure has been linked to infant cognitive and motor functions, but the effects of PM2.5 chemical composition remain unclear. OBJECTIVES: We aimed to explore the associations of prenatal PM2.5 and its composition exposure with infant cognitive and motor functions. METHODS: We studied 2,435 mother-infant pairs in the Shanghai Birth Cohort Study. PM2.5 and its seven compositions [primary particles (black carbon, mineral dust and sea salts) and secondary particles (NH4+, NO3-, SO42- and organic matter)] during thethreetrimesters ofpregnancy were retrieved from the V4.CH.03 product developed by using a combined geoscience-statistical method. At the 12-month-old follow-up, infant cognitive and motor functions in five domains were assessed using the Ages and Stages Questionnaire (ASQ). We used multivariable linear regressions to estimate the effects of PM2.5 and its composition on the ASQ scores, for all infants and stratifying by sex and breastfeeding duration. RESULTS: PM2.5 exposure was negatively associated with gross motor, problem-solving and personal-social scores for all infants. PM2.5 compositions were inversely associated with ASQ scores in all five domains, and the effects of different compositions varied across domains. Specifically, all compositions except organic matter were correlated with lower problem-solving scores [e.g., ( [Formula: see text]  =  - 10.79, 95 % CI: -17.40, -4.18) ∼ ( [Formula: see text]  =  - 4.68, 95 % CI: -7.84, -1.53); for each 10 µg/m3 increase in PM2.5 compositions during the third trimester]. Primary and some secondary particles (organic matter, NO3-) were related to lower gross motor scores. Secondary particles were also inversely associated with communication (organic matter and NO3-), fine motor (NH4+, NO3-, SO42-) and personal-social (NH4+) scores. Additionally, boys and infants breastfed for < 6 months appeared to be more susceptible. CONCLUSIONS: We found negative associations of PM2.5 and its compositions with infant cognitive and motor functions over a range of domains, especially the problem-solving domain.

Prenatal exposure to per- and polyfluoroalkyl substances and childhood adiposity at 7 years of age.

BACKGROUND: An increasing number of studies have reported that prenatal per- and polyfluoroalkyl substances (PFAS) exposure may increase childhood adiposity. However, limited data is available in China, and the overall effects of PFAS mixture remain unclear. OBJECTIVE: To examine the association of prenatal exposure to individual PFAS and their mixture with childhood adiposity at 7 years of age. METHODS: A total of 206 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China between 2010 and 2013. Ten PFAS were measured in maternal serum. The measurements of fat mass, body fat percentage, body mass index, waist circumference, waist-to-height ratio and overweight/obesity were used to assess adiposity in children aged 7. We fitted logistic regression, linear regression and weighted quantile sum (WQS) regression models to estimate the association of prenatal exposure to individual PFAS and their mixture with childhood adiposity. RESULTS: We found negative associations of perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (PFOSA) exposure with adiposity measurements in all children. The result from the WQS model consistently revealed that the PFAS mixture was inversely related to adiposity measurements. Each quartile increase of the PFAS mixture was associated with a 1.14 kg decrease (95% CI: -2.27, -0.02) in fat mass and a 2.32% decrease (95% CI: -4.51, -0.14) in body fat. Moreover, significant sex differences were found. PFAS mixture was negatively associated with five adiposity measurements in boys, but positively associated with all adiposity measurements except body fat percentage in girls. PFOSA, PFHpA and perfluorobutanesulfonate (PFBS) with weights >0.300 were the main contributors to the overall effects observed among all children, boys and girls, respectively. CONCLUSION: This study suggests potential sex-specific associations of prenatal exposure to individual PFAS and their mixture with childhood adiposity, with the observed relationship being negative for boys but positive for girls.

Prenatal neonicotinoid insecticides Exposure, oxidative Stress, and birth outcomes.

BACKGROUND: An increasing number of studies have reported neonicotinoid insecticides (NEOs), the emerging alternatives to conventional insecticides, may increase oxidative stress and cause adverse health effects, but limited is known about the prenatal NEOs exposures and their impact on birth outcomes. OBJECTIVES: We investigated the levels of prenatal exposure to NEOs/metabolites, to assess their associations with birth outcomes, and investigate whether these associations could be mediated by oxidative stress using 8-OHdG as the biomarker. METHODS: We studied 296 mother-infant pairs recruited from Laizhou Wan Birth Cohort in 2010 - 2013. Two NEOs (IMI and ACE), three metabolites (6-CN, ND-ACE, and 2CTCA), and 8-OHdG were measured in maternal urine collected before delivery. Birth outcomes including birth weight, birth length, ponderal index (PI), head circumference, and gestational age, were acquired. We examined the associations between NEOs/metabolites and birth outcomes using multivariable linear regression. Mediation analysis was conducted to clarify the role of 8-OHdG on the association of NEOs/metabolites exposure and birth outcomes. RESULTS: Highest detection rate was observed for ACE (100.0%), followed by IMI (98.3%) and 6-CN (98.0%), suggesting the common exposure of pregnant women. The highest median concentration was observed for 6-CN with creatinine-adjusted median levels of 9.58 µg/g creatinine. A decrease in newborns' head circumference was observed with a 10-fold increase in IMI (ß = -1.83; 95% CI = -3.04, -0.62) and ACE (ß = -2.27; 95% CI = -3.56, -0.98). An increase in newborns' PI was observed with a 10-fold increase in IMI (ß = 0.40; 95% CI = 0.03, 0.75). Maternal 8-OHdG demonstrated 38.5-65.5% mediating effects in the negative association of IMI, ACE, 2-CTCA with head circumference. These associations might differ between boys and girls. CONCLUSIONS: Pregnant women were widely exposed to NEOs/metabolites in China. Results suggested the potential impacts of prenatal exposure to certain neonicotinoid insecticides on head circumference. Urinary 8-OHdG may partly mediate these associations.

Application of land use regression to map environmental noise in Shanghai, China.

BACKGROUND: Urban environment noise has been linked with wide adverse effects on health; however, noise epidemiological researches are hindered by the lack of large-scale population-based exposure assessment. OBJECTIVE: We aimed to measure noise levels over multiple seasons and to establish an LUR model to assess the spatial variability of intra-urban noise and identify its potential sources in Shanghai, China. METHODS: Forty-minute (LAeq, 40 min) measurements of environmental noise were collected at 144 fixed sites, and each was visited three times (morning, afternoon, and evening) in winter, spring, and summer in 2019. Noise measurements were then integrated with land-use types, road networks, socioeconomic variables, and geographic information systems to construct LUR models. Ten-fold cross-validation was used to test the model performance. RESULTS: A total of 1296 measurements and 29 predicting variables were used to estimate the spatial variation in environmental noise. The annual mean (±standard deviation) of LAeq, 40min, was 62 ± 8 dB (A). Significant variations were observed among monitoring sites but not between seasons or time of day. The LUR model explained 79% of the spatial variability of the noise, and the R2 of the ten-fold cross-validation was 0.75. The most contributory predictors of noise level were road-related variables all within the 50-m buffers, followed by urban area within a 50-m buffer, total area of buildings within a 1000-m buffer, and number of restaurant clusters within a 50-m buffer. Farmland area within a 100-m buffer was the only negative variable in the model. A 50-m resolution noise prediction map was produced and suggested high noise level in urban areas and near traffic arteries. CONCLUSION: LUR can be a robust method for reflecting noise variability in megacities such as Shanghai and may provide an efficient solution for noise exposure assessment in areas where noise maps are not available.

High spatial resolution land-use regression model for urban ultrafine particle exposure assessment in Shanghai, China.

BACKGROUND: Little is currently known about long-term health effects of ambient ultrafine particles (UFPs) due to the lack of exposure assessment metrics suitable for use in large population-based studies. Land use regression (LUR) models have been used increasingly for modeling small-scale spatial variation in UFPs concentrations in European and American, but have never been applied in developing countries with heavy air pollution. OBJECTIVE: This study developed a land-use regression (LUR) model for UFP exposure assessment in Shanghai, a typic mega city of China, where dense population resides. METHOD: A 30-minute measurement of particle number concentrations of UFPs was collected at each visit at 144 fixed sites, and each was visited three times in each season of winter, spring, and summer. The annual adjusted average was calculated and regressed against pre-selected geographic information system-derived predictor variables using a stepwise variable selection method. RESULT: The final LUR model explained 69% of the spatial variability in UFP with a root mean square error of 6008 particles cm-3. The 10-fold cross validation R2 reached 0.68, revealing the robustness of the model. The final predictors included traffic-related NOx emissions, number of restaurants, building footprint area, and distance to the nearest national road. These predictors were within a relatively small buffer size, ranging from 50 m to 100 m, indicating great spatial variations of UFP particle number concentration and the need of high-resolution models for UFP exposure assessment in urban areas. CONCLUSION: We concluded that based on a purpose-designed short-term monitoring network, LUR model can be applied to predict UFPs spatial surface in a mega city of China. Majority of the spatial variability in the annual mean of ambient UFP was explained in the model comprised primarily of traffic-, building-, and restaurant-related predictors.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid hormones, and infant neurodevelopment.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are believed to impair early neurodevelopment and disrupt thyroid hormone (TH) levels. However, there are limited epidemiological data on the neurodevelopmental effects in infancy of prenatal PFAS exposure and the potential mediating effects of TH. OBJECTIVES: To evaluate potential associations between prenatal PFAS exposure and early neurodevelopmental deficiencies, and assess mediator effects of TH. METHODS: From 2010 to 2013, 274 mother-infant pairs were recruited to the Laizhou Wan Birth Cohort in China. Ten PFAS and five TH were measured in cord serum. Developmental quotient (DQ) from 5 domains (adaptive, social, language, gross and fine motor) was assessed using Gesell Developmental Schedules for each child at 1 year of age. The associations between PFAS and DQs were evaluated using multivariable linear regressions. TH-mediated effects of PFAS on DQs were calculated by mediation analyses. RESULTS: Among our study population, PFAS exposures were common and associated with DQ decrement in infants. For each 10-fold increase in PFBS concentrations, gross motor and adaptive DQ decreased by 8.56 (95%CI: -15.15, -1.97) and 5.87 (95%CI: -8.07, -3.67) points, respectively. TSH mediated 12.90% of the association of PFBS with gross motor DQ and FT4 explained 19.63% of the association of PFBS with adaptive DQ. The negative association was also found between PFHxS exposure and gross motor DQ (ß = 8.14, 95%CI: -15.39, -0.98). CONCLUSIONS: PFBS and PFHxS were negatively associated with early neurodevelopment, especially consistent in gross motor domain. The associations were partly explained by TSH and FT4.

Personal exposure to fine particulate matter and blood pressure: Variations by particulate sources.

Fine particulate matter (PM2.5) is a complex mixture of components which has been associated with various cardiovascular effects, such as elevated blood pressure (BP). However, evidences on specific sources behind these effects remain uncertain. Based on 140 72-h personal measurements among a panel of 36 health college students in Shanghai, China, we assessed associations between source-apportioned PM2.5 exposure and BP changes. Based on personal filter samples, PM2.5 source apportionment was conducted using Positive Matrix Factorization (PMF) model. Linear mixed-effects models were applied to evaluate associations of source-specific PM2.5 exposure with BP changes. Seven sources were identified in PMF analysis. Among them, secondary sulfate (41%) and nitrate (24%) sources contributed most to personal PM2.5, followed by industrial emissions (15%), traffic-related source (10%), coal combustion (6.2%), dust (2.4%) and aged sea salt (1.1%). We found nitrate, traffic-related source and coal combustion were significantly associated with increased BP. For example, an interquartile range increase in PM2.5 from traffic-related source was significantly associated with increase in systolic BP [1.5 (95% CI: 0.26, 2.7) mmHg], diastolic BP [1.2 (95% CI: 0.10, 2.2) mmHg] and mean arterial pressure [1.2 (95% CI: 0.15, 2.2) mmHg]. This is the first investigation linking personal PM2.5 source profile and BP changes. This study provides evidence that several anthropogenic emissions (especially traffic-related emission) may be particularly responsible for BP increases, and highlights that the importance of development of health-oriented PM2.5 source control strategies.

Temperature changes between neighboring days and childhood asthma: a seasonal analysis in Shanghai, China.

Few evidences are available about the impact of temperature variation on childhood asthma in different seasons. This study aimed to assess the influence of temperature changes between neighboring days (TCN) on the exacerbation of asthma among children. Daily outpatient visits for childhood asthma (DOVCA) were collected from 17 main hospitals in Shanghai, China, from 2016 to 2018. A quasi-Poisson regression combined with distributed lagged nonlinear models was employed to estimate the association between TCN and asthma visits in cool or warm seasons, after controlling for short- and long-term trends, day of week, holidays, daily mean temperature, daily mean relative humidity, and air pollutants. The TCN varied from - 9.6 to 6.7 °C. The relationship between TCN and DOVCA greatly varied by season. In warm seasons, positive TCN (temperature rise) was associated with higher risks of asthma outpatient visits and negative TCN (temperature drop) was associated with lower risks; the associations were present on lag 1 day and lasted for 2 weeks; the cumulative relative risk of childhood asthma over 0 to 14 days was 1.98 (95% confidence interval: 1.42, 2.76) and 0.31 (95% confidence intervals: 0.21, 0.44) comparing a TCN of 2.5 °C (5th percentile) and - 3.2 °C (95th percentile) with 0 °C, respectively. In cool seasons, neither negative nor positive TCN showed significant risks. In conclusion, temperature rise might increase the risk of childhood asthma exacerbation and temperature drop might decrease the risks in warm seasons. There were no statistically significant influences in cool seasons.

Free Radical and Nicotine Yields in Mainstream Smoke of Chinese Marketed Cigarettes: Variation with Smoking Regimens and Cigarette Brands.

Free radicals and nicotine are components of cigarette smoke that are thought to contribute to the development of smoking-induced diseases. China has the largest number of smokers in the world, yet little is known about the yields of tobacco smoke constituents in different Chinese brands of cigarettes. In this study, gas-phase and particulate-phase free radicals as well as nicotine yields were quantified in mainstream cigarette smoke from five popular Chinese brands and two research cigarettes (3R4F and 1R6F). Mainstream smoke was generated under International Organization of Standardization (ISO) and Canadian Intense (CI) smoking regimens using a linear smoking machine. Levels of free radicals and nicotine were measured by electron paramagnetic resonance spectroscopy (EPR) and gas chromatography with flame-ionization detection, respectively. Under the ISO puffing regimen, Chinese brand cigarettes produced an average of 3.0 ± 1.2 nmol/cig gas-phase radicals, 118 ± 44.7 pmol/cig particulate-phase radicals, and 0.6 ± 0.2 mg/cig nicotine. Under the CI puffing regimen, Chinese brand cigarettes produced an average of 5.6 ± 1.2 nmol/cig gas-phase radicals, 282 ± 92.1 pmol/cig particulate-phase radicals, and 2.1 ± 0.4 mg/cig nicotine. Overall, both gas- and particulate-phase free radicals were substantially lower compared to the research cigarettes under both regimens, whereas no significant differences were observed for nicotine levels. When Chinese brands were compared, the highest free radical and nicotine yields were found in "LL" and "BS" brands, while lowest levels were found in "YY". These results suggested that the lower radical delivery by Chinese cigarettes compared to United States reference cigarettes may be associated with reductions in oxidant-related harm.

Necessity of personal sampling for exposure assessment on specific constituents of PM2.5: Results of a panel study in Shanghai, China.

Many epidemiological studies have evaluated the health risks of ambient fine particulate matter (PM2.5). However, few studies have investigated the potential exposure misclassification caused by using ambient PM2.5 concentrations as proxy for individual exposure to PM2.5 in regions with high-level of air pollution. This study aimed to compare the differences between personal and ambient PM2.5 constituent concentrations, and to predict the personal exposure of sixteen PM2.5 constituents. We collected 141 72-h personal exposure filter samples from a panel of 36 healthy non-smoking college students in Shanghai, China. We then used the liner mixed effects models to predict personal constituent-specific exposure using ambient observations and several possible influencing factors including time-activity patterns, temporal variables, and meteorological conditions. The final model of each component was further evaluated by determination coefficient (R2) and root mean square error (RMSE) from leave-one-out-cross-validation (LOOCV). We observed ambient concentrations were higher than personal concentrations for all PM2.5 components except for Mn, Fe, Ca, and V. Especially, ambient NH4+, As, and NO3- concentrations were 3.65, 5.65 and 7.33-fold higher than their corresponding personal concentrations, respectively. The ambient level was the strongest predictor of their corresponding personal PM2.5 components with the highest marginal R2 (RM2: 0.081 ~ 0.901), meteorological conditions (RM2: 0.000 ~ 0.357), time-activity pattern (RM2: 0.000 ~ 0.083) and temporal indicators (RM2: 0.031 ~ 0.562) were also important predictors. Our final models predicted at least 50% of the variance of all personal PM2.5 constituents and even over 90% for K, Pb, and SO42-. LOOCV analysis showed that R2 and RMSE ranged from 0.251 to 0.907 and 0.000 to 0.092 µg/m3, respectively. Our results showed that ambient concentration of most PM2.5 constituents along with time-activity patterns, temporal variables, and meteorological conditions, could adequately predict personal exposure concentration. Prediction models of individual PM2.5 constituent may help to improve the accuracy of exposure measurement in future epidemiological studies.

Heat stress interferes with chromosome segregation and cytokinesis during male meiosis in Arabidopsis thaliana.

In higher plants, male meiosis is a key process of microsporogenesis and is crucial for plant fertility. Male meiosis programs are prone to be influenced by altered temperature conditions. Studies have reported that an increased temperature (28°C) within a fertile threshold can affect the frequency of meiotic recombination in Arabidopsis. However, not much has been known how male meiosis responses to an extremely high temperature beyond the fertile threshold. To understand the impact of extremely high temperature on male meiosis in Arabidopsis, we treated flowering Arabidopsis plants with 36-38°C and found that the high-temperature condition significantly reduced pollen shed and plant fertility, and led to formation of pollen grains with varied sizes. The heat stress-induced unbalanced tetrads, polyad and meiotic restitution, suggesting that male meiosis was interfered. Fluorescence in situ hybridization (FISH) assay confirmed that both homologous chromosome separation and sister chromatids cohesion were influenced. Aniline blue staining of tetrad-stage pollen mother cells (PMCs) revealed that meiotic cytokinesis was severely disrupted by the heat stress. Supportively, immunolocalization of ɑ-tubulin showed that the construction of spindle and phragmoplast at both meiosis I and II were interfered. Overall, our findings demonstrate that an extremely high-temperature stress over the fertile threshold affects both chromosome segregation and cytokinesis during male meiosis by disturbing microtubular cytoskeleton in Arabidopsis.

The acute effects of fine particulate matter constituents on circulating inflammatory biomarkers in healthy adults.

BACKGROUND: Systemic inflammation is considered one of the key mechanisms in the development of cardiovascular diseases induced by fine particulate matter (PM2.5) air pollution. However, evidence concerning the effects of various PM2.5 constituents on circulating inflammatory biomarkers were limited and inconsistent. OBJECTIVES: To evaluate the associations of short-term exposure to a variety of PM2.5 constituents with circulating inflammatory biomarkers. METHODS: We conducted a panel study from May to October 2016 among 40 healthy adults in Shanghai, China. We monitored the concentrations of 27 constituents of PM2.5. We applied linear mixed-effect models to analyze the associations of PM2.5 and its constituents with 7 inflammatory biomarkers, and further assessed the robustness of the associations by fitting models adjusting for PM2.5 mass and/or their collinearity. Benjamini-Hochberg false discovery rate was used to correct for multiple comparisons. RESULTS: The associations of PM2.5 were strongest at lag 0 d with tumor necrosis factor-α (TNF-α), at lag 1 d with interleukin-6, interleukin-8, and interleukin-17A, at lag 02 d with monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1). After correcting for multiple comparisons in all models, Cl-, K+, Si, K, As, and Pb were significantly associated with interleukin-8; SO42- and Se were marginally significantly associated with interleukin-8; SO42-, As, and Se were marginally significantly associated with TNF-α; and Si, K, Zn, As, Se, and Pb were marginally significantly associated with MCP-1. CONCLUSIONS: Our results suggested that some constituents (SO42-, Cl-, K+, and some elements) might be mainly responsible for systemic inflammation triggered by short-term PM2.5 exposure.

Effects of personal nitrogen dioxide exposure on airway inflammation and lung function.

BACKGROUND: Few epidemiological studies have evaluated the respiratory effects of personal exposure to nitrogen dioxide (NO2), a major traffic-related air pollutant. The biological pathway for these effects remains unknown. OBJECTIVES: To evaluate the short-term effects of personal NO2 exposure on lung function, fractional exhaled nitric oxide (FeNO) and DNA methylation of genes involved. METHODS: We conducted a longitudinal panel study among 40 college students with four repeated measurements in Shanghai from May to October in 2016. We measured DNA methylation of the key encoding genes of inducible nitric oxide synthase (NOS2A) and arginase (ARG2). We applied linear mixed-effect models to assess the effects of NO2 on respiratory outcomes. RESULTS: Personal exposure to NO2 was 27.39 ±â€¯23.20 ppb on average. In response to a 10-ppb increase in NO2 exposure, NOS2A methylation (%5 mC) decreased 0.19 at lag 0 d, ARG2 methylation (%5 mC) increased 0.21 and FeNO levels increased 2.82% at lag 1 d; and at lag 2 d the percentage of forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow in predicted values decreased 0.12, 0.37 and 0.67, respectively. The model performance was better compared with those estimated using fixed-site measurements. These effects were robust to the adjustment for co-pollutants and weather conditions. CONCLUSIONS: Our study suggests that short-term personal exposure to NO2 is associated with NOS2A hypomethylation, ARG2 hypermethylation, respiratory inflammation and lung function impairment. The use of personal measurements may better predict the respiratory effects of NO2.