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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.05.022 Byline: Yanqiu Zhou, Hong-Xiang Liu, Charlotte M. Mistretta Keywords: Taste papilla; Bone morphogenetic protein; Noggin; Follistatin; Pattern formation; Fungiform papilla; Sonic hedgehog signaling; Embryonic tongue culture; Ectodermal specialization; Cyclopamine Abstract: Fungiform papillae are epithelial specializations that develop in a linear pattern on the anterior mammalian tongue and differentiate to eventually contain taste buds. Little is known about morphogenetic and pattern regulation of these crucial taste organs. We used embryonic rat tongue, organ cultures to test roles for bone morphogenetic proteins, BMP2, 4 and 7, and antagonists noggin and follistatin, in development of papillae from a stage before morphological initiation (E13) or from a stage after the pre-papilla placodes have formed (E14). BMPs and noggin proteins become progressively restricted to papilla locations during tongue development. In E13 cultures, exogenous BMPs or noggin induce increased numbers of fungiform papillae, in a concentration-dependent manner, compared to standard tongue cultures; BMPs, but not noggin, lead to a decreased tongue size at this stage. In E14 cultures, however, exogenous BMP2, 4 or 7 each inhibits papilla formation so that there is a decrease in papilla number. Noggin substantially increases number of papillae in E14 cultures. Using beads for a highly localized protein delivery, papillae are inhibited in the surround of BMP-soaked beads and induced in large clusters around noggin-soaked beads. Follistatin, presented in culture medium or by bead, does not alter papilla formation or number. In all fungiform papillae that form under various culture conditions, the molecular marker, sonic hedgehog, is within each papilla. However, the BMP inhibitory effect on papillae is not prevented by disrupting sonic hedgehog signaling through addition of cyclopamine to cultures. BMPs and noggin alter cell proliferation in tongue epithelium in opposite ways, demonstrated with Ki67 immunostaining. We propose that the BMPs and noggin, colocalized within papilla placodes and the fungiform papillae per se, have opposing inhibitory and activating or inducing roles in papilla development in linear patterns. We present a model for these effects. Author Affiliation: Department of Biologic and Materials Sciences, Room 6217, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA Article History: Received 6 January 2006; Revised 13 May 2006; Accepted 17 May 2006

Maternal exposure to phthalates may cause some adverse health effects on both mother and fetus, but variations of phthalate exposure and metabolism during pregnancy have not been thoroughly characterized. A total of 946 participants were selected from a cohort study conducted in Wuhan between 2014 and 2015 through which they had provided a complete set of urine samples at three trimesters. Eight phthalate metabolites were analyzed in 2838 urine samples. Based on urinary concentrations, various parameters (i.e. phthalate metabolite concentrations, ratios of metabolites of bis(2-ethylhexyl) phthalate (DEHP) in DEHP, and percentages of individual metabolites in total phthalates) were compared over three visits. We observed that levels of phthalate metabolites showed a U-shaped trend across three trimesters. The significant variations in the ratios of DEHP metabolites indicated that the efficiency in metabolizing DEHP declined during pregnancy and less recent exposure occurred in mid-pregnancy. The changes of percentages of individual compound in total phthalates suggested the inconsistent pattern over trimesters. This longitudinal study found that the exposure pattern, exposure timing and metabolic susceptibility varied by trimesters, which suggests that urine samples should be collected at multiple time points and mothers should be especially careful in the early pregnancy. Image 1 • Phthalate metabolite concentrations demonstrated U-trend over three trimesters. • The efficiency in metabolizing di-2-ethylhexyl phthalate decreased during pregnancy. • More recent exposure occurred on early and late gestational periods. • Mothers were more susceptive to DEHP in the early stages of pregnancy. • Multiple samples were needed to evaluate phthalate exposure throughout pregnancy. Urinary concentrations of phthalate metabolites showed a U-shaped trend across three trimesters. Mothers were more susceptive to phthalate exposure in the early stages of pregnancy. [ABSTRACT FROM AUTHOR]

Abstract Background Widespread exposure to parabens has been a concern, especially among pregnant women. Only one study reported that parabens are associated with glucose levels among pregnant women. However, studies on parabens exposure and gestational diabetes mellitus (GDM) are lacking. Objectives This study investigated whether exposure to parabens in early pregnancy is related to GDM. Methods We conducted a prospective study of 1087 pregnant women from a single tertiary medical center between 2014 and 2015 in Wuhan, China. Parabens [methyl paraben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and benzylparaben (BzP)] concentrations were measured in spot urine samples collected between 8 and 16 gestational weeks. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups Consensus Panel (IADPSG) recommendations. We used the Poisson regression with a robust error variance with generalized estimating equations (GEE) estimation analyses to evaluate associations between parabens exposure and GDM risk. Results A total of 103 (9.5%) women were diagnosed with GDM. We evaluated the associations of GDM risk with urinary MeP, EtP, and PrP (detection rate: >90%), but not with BuP and BzP due to the relatively low detection rate (<50%). After adjustment for potential confounders, urinary EtP was associated with GDM. The risk ratios (RRs) = 1.12 (95% CI: 0.63, 2.01) for the second quartile, RRs = 1.11 (95% CI: 0.64, 1.93) for the third quartile, and RRs = 1.70 (95% CI: 1.02, 2.82) for the highest quartile, compared with the lowest quartile. There was no evidence of associations between urinary MeP or PrP and GDM. Conclusions To the best of our knowledge, this is the first report of an association between urinary paraben levels in early pregnancy and GDM. Our findings suggest that exposure to EtP may increase the risk of GDM. Highlights • 2 parabens out of 5 were not studied because they were detected in <43% of the population. • Higher urinary ethylparaben levels were associated with increased risks of GDM. • Age and pre-pregnancy BMI might modify the association of ethylparaben with GDM. [ABSTRACT FROM AUTHOR]

Abstract Background Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with high production volume worldwide, which exhibit potential health risk to human. To date, little is known about the exposure of BTRs and BTHs (BTs) on human, especially in the context of pregnancy. Objectives We aimed to characterize the exposure profiles, temporal variability, and potential predictors of urinary BTs during pregnancy. Methods Between 2014 and 2015, we recruited 856 pregnant women in Wuhan who provided urine samples at three trimesters (13.1 ± 1.1, 23.7 ± 3.2, and 35.7 ± 3.4 gestational weeks). We measured the urinary concentrations of five BTRs (1‑H‑benzotriazole, 1‑hydroxy‑benzotriazole, xylyltriazole, tolyltriazole, 5‑chloro‑1‑H‑benzotriazole) and five BTHs (benzothiazole, 2‑hydroxy‑benzothiazole, 2‑methylthio‑benzothiazole, 2‑amino‑benzothiazole, 2‑thiocyanomethylthio‑benzothiazole) to characterize the exposure profiles of BTs. We calculated the intra-class correlation coefficients (ICCs) to assess the temporal variability and investigated potential predictors of urinary BTs by using the mixed models. Results Most of the targeted BTs were detected in over 50% of urine samples, except for 5‑chloro‑1‑H‑benzotriazole (9.3%) and 2‑thiocyanomethylthio-benzothiazole (1.4%). The predominant BTRs in urine was 1‑hydroxy‑benzotriazole [Geometric Mean (GM): 0.77 ng/mL]. Benzothiazole was the major derivative in urine samples with a GM concentration of 1.6 ng/mL. Correlations among BTHs (r = 0.04–0.39) were higher than that among BTRs (r = 0.02–0.14). The exposure pattern was constant at low level and co-exposure to all the targeted compounds was infrequent during pregnancy. Urinary concentrations of BTRs exhibited considerable within-subject variation (ICCs: 0.12–0.56) during pregnancy. Relatively high temporal reliability was observed for urinary concentrations of BTHs with ICCs ranging from 0.42 to 0.85. It was found that parity, household income, pregnancy occupational status, sampling season and menstrual cycle were associated with urinary concentrations of BTs in pregnant women (P < 0.05). Conclusions To the best of our knowledge, this is the first study to report the exposure profiles, variability and predictors of urinary BTs among pregnant women. Exposure assessment using multiple samples is essential in reducing measurement errors and identifying susceptible window of exposure in etiological studies. The potential predictors of urinary BTs raised concerns on tracing exposure routes and eliminating confounding variables in future studies. Highlights • Gestational exposure to BTs was investigated in 2568 urine samples collected from 856 pregnant women at three trimesters. • The exposure pattern was constant at low level and co-exposure to all the targeted compounds was infrequent. • Urinary BTRs exhibited substantial variation, while urinary BTHs were relatively stable during pregnancy. • Urinary BTs were associated with parity, household income, occupational status, sampling season and menstrual cycle. [ABSTRACT FROM AUTHOR]

Many studies have shown that aflatoxin B1 (AFB1) can cause cytotoxicity in numerous cells and organs induced by oxidative stress. However, the toxic effects and related mechanism of AFB1 on the microglia cells in the spinal cords have not been studied yet. Our results showed that AFB1 significantly reduced the number of microglia cells, increased the oxidants (malonaldehyde and hydrogen peroxide) but decreased the anti-oxidants (superoxide dismutase and total antioxidant capacity) in a dose dependent manner in mice spinal cords. In addition, AFB1 significantly increased the oxidative stress, promoted apoptosis and cell cycle arrest in G2-M phase, and activated NF-κB phosphorylation in BV2 microglia cells. However, the addition of active oxygen scavenger N-acetylcysteine can significantly reduce the ROS production, improve cell cycle arrest, reduce apoptosis, and the expression of phosphorylated NF-κB in BV2 microglia cells. These results indicate that AFB1 induces microglia cells apoptosis through oxidative stress by activating NF-κB signaling pathway. [Display omitted] • AFB1 induced microglia cells apoptosis in mice spinal cords. • AFB1 caused oxidative stress response in mice spinal cords. • AFB1 promoted NF-kB phosphorylation in mice spinal cords. • AFB1 caused oxidative stress in BV2 microglia cells through NF-kB pathway. • AFB1 induce BV2 miroglia cells apoptosis by oxidative stress through NF-kB pathway. [ABSTRACT FROM AUTHOR]

Abstract: Critical gerontology views aging as a social construction that reflects the intersections of micro-processes with the macro-level forces of individual aging experiences. In the contexts of immigration and transnationalism, however, the macro-structural conditions, dynamics and experiences of aging have become further diversified and complicated. The dearth of empirical and explanatory knowledge in this area has inhibited us from comprehending aging in a changing world. Drawing on data from a study of Chinese grandparents'' experiences of transnational caregiving in Canada, this article examines the impacts of such experiences on three interconnected dimensions – spatial, temporal and cognitive – of aging. Although the practice of transnational caregiving allows skilled immigrant families to mobilize care resources outside Canada, it has not only ruptured the traditional trajectories of aging for their elderly parents, but also complicated the inequalities that they have to bear on individual, familial and transnational levels. I argue that the critical examination of aging in the context of transnational caregiving helps us take into consideration those dimensions (such as place, space, time, and knowledge) that are changed by immigration processes, and rethink aging from a broader perspective that links seniors'' experiences with their relationship with their adult immigrant children''s families and macro-structures outside national borders. [Copyright &y& Elsevier]

In order to construct a unified permeability prediction model for multi-stage tight gas sandstones with permeability across 6 orders of magnitude and changeable porosity-permeability relationship, Bayesian regularization neural network is properly configured with core porosity, conventional logs and a few derivates of them as input items. With high accuracy and excellent generalization, it is promising to be stably and reliably popularized in the study area. The way of model construction, optimization and evaluation may provide underlying insights needed for permeability prediction of similar reservoirs and application of machine learning in reservoir evaluation. • No consistent porosity-permeability relation exists in channel sandstones. • Universal permeability model is built with Bayesian regularization neural network. • Sufficient petrophysical-geological information is contained in logs. • Prior knowledges enhance interpretability, controllability and applicability. [ABSTRACT FROM AUTHOR]

Abstract: Recent AIDS research has documented the widespread discrimination toward people living with HIV/AIDS (PLWHA) in China. General ignorance and misconceptions about this disease have been identified as the two primary reasons for this prejudice. Yet, little attention has been paid to social constructions of HIV/AIDS in the Chinese context and to the processes by which such constructions are experienced, understood, reacted to, and, perhaps, reconstructed through social and interpersonal interactions. Based on a qualitative study of Chinese PLWHA''s illness experiences, this paper explores how HIV/AIDS, as a social construct, is understood by these individuals in the context of their daily encounters. It is discovered that, despite their knowledge of HIV/AIDS, PLWHA''s perceptions about and responses to this disease are greatly influenced by their experiences of interacting with others (e.g., their families, friends, and health workers). The conflicts between individuals’ mastery of knowledge pertaining to, and their overreactions in practice toward, HIV-infected bodies suggest that AIDS education should not be limited to the dissemination of knowledge per se, but that the interpersonal or interactive dimensions of discrimination and efforts to combat it must also be taken into account. [Copyright &y& Elsevier]

Bisphenol A and its alternatives are frequently detected in environmental and human samples, but studies associated with the pattern of combined health hazards from the exposure to the bisphenol mixtures are lacking, particularly for pregnant women. Here, we recruited 941 pregnant women with a full set of urine samples in the three trimesters collected under a cohort study project in Wuhan, China, between 2014 and 2015. We measured the concentrations of 8 bisphenols in 2823 urine samples, and calculated the average concentrations of bisphenols, which were detected in over 50% of samples, once during each trimester of pregnancy. We calculated the maximum cumulative ratio (MCR) on basis of estimated daily intake (EDI), hazard quotient (HQ), hazard index (HI) of three major bisphenols, including bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), to find which one or mixtures drive risks. Participants were categorized into four groups according to their maximum HQ, HI and MCR values. We found negative relationships between log(MCR-1) and log(HI) with the slope (−0.6431). Percentage of HQ of BPA in HI ranged from 37.1% (<25th percentiles of HI) to 75.5% (>95th percentiles of HI) indicating the upward trend of dominance by BPA at increasing HI ranges. The cumulative health risks of bisphenol exposures largely originated from the health hazards of BPA and BPS, particularly BPA. The intervention for regulation on the production and application of BPA and its alternatives are urgent, and China should consider national regulation on these chemicals based on its risk to human health. Image 1 • Inverse relationships between MCR and HI of bisphenol exposure were noted. • Major health hazard was induced by exposure to high dose of BPS or BPA. • BPA was dominating the combined health hazards of bisphenol exposure. • Regulation of BPS production and application should be considered in China. BPA still dominates the cumulative health risks induced by exposure to bisphenols, although the application of BPA has been restricted. [ABSTRACT FROM AUTHOR]

Permeability estimates from well logs are essential inputs for reservoir characterization and of great significance to almost all aspects of hydrocarbon development. Borehole image, with high resolution and coverage to highlight subtle heterogeneity of formation, is rarely used for permeability estimation, especially for clastic rocks. Here, we put forward a set of algorithms to automatically extract sand resistivity from microresistivity borehole image to effectively indicate and estimate the intrinsic permeability of porous clastic rocks, and then apply it to the tight sandstone reservoir of Middle Jurassic Shaximiao Formation in Qiulin gas field, central Sichuan Basin. First, equations are deduced, according to the measurement principle and combined with shallow lateral log, to scale borehole image data into resistivity or conductivity depth by depth. Then, based on the volume model and the parallel conductance theory, sand resistivity component R s d is separated from the scaled borehole image by sliding statistics and partitioning with cutoffs equal to the shale volume properly calculated from conventional logs. Subsequently, exponential functions, derived from significant negative correlations between R s d and core permeability K _ c o r e in double logarithmic coordinate, are used to estimate formation permeability. With their correlation coefficients between 0.617 and 0.861, the resultant K_est curves coincide better with subtle variations of K _ c o r e than those estimations derived from conventional logs. This study may also be helpful to the improvement of high-resolution micromodeling and water saturation quantification in shaly sandstones. • Permeability of shaly sandstones is better estimated using borehole image. • Equations to scale borehole image resistivity depth by depth are deduced. • Resistivity components partitioning algorithm of borehole image is provided. • Sand resistivity component is a good negative indicator for permeability variation. • Half coring interval as window length of image logs ensures optimum scale matching. [ABSTRACT FROM AUTHOR]

• First study on maternal urinary levels of BTRs and BTHs and newborn mtDNAcn. • Exposure to BTRs and BTHs during first and third trimester were associated with newborn mtDNAcn alternation. • Sex-specific associations were observed between BTRs and BTHs exposure and newborn mtDNAcn. Mitochondria are sensitive to environmental toxicants due to the limited repair capacity. Exposure to benzotriazoles (BTRs) and benzothiazoles (BTHs) may contribute to adverse health outcomes through oxidative stress, which may interfere with mitochondrial function. However, the mitochondrial effects of exposure to BTs (BTRs and BTHs) have not yet been elucidated, particularly in human investigations. We examined the associations between trimester-specific urinary BTRs and BTHs concentrations and cord blood mitochondrial DNA copy number (mtDNAcn) in a prospective birth cohort. The present study included 742 mother-infant pairs who participated in a birth cohort between 2014 and 2015 in Wuhan and had data on urinary concentrations of BTRs and BTHs and mtDNAcn in cord blood. Concentrations of BTs were repeatedly measured in maternal urine samples at different trimesters using high performance liquid chromatography-tandem mass spectrometry. Relative mtDNAcn in umbilical cord blood was analyzed by quantitative real-time polymerase chain reaction. Generalized estimating equations were used to evaluate the associations between BTs exposure across gestation and mtDNAcn in cord blood. In the present study, we observed a positive association between urinary 2-methylthio-benzothiazole (2-MeS-BTH) concentrations in the first trimester and cord blood mtDNAcn, with marginal significance [percent changes (%Δ) = 3.97, 95% confidence interval (CI): −0.05, 8.16, p = 0.05], while urinary 2-amino-benzothiazole concentrations in the third trimester were significantly negatively associated with cord blood mtDNAcn (%Δ = −5.89, 95% CI: −10.32, −1.24). Similar patterns of associations were demonstrated between urinary 1-H-benzotriazole (1-H-BTR) and xylyltriazole concentrations in the third trimester and cord blood mtDNAcn (%Δ = −4.18 to −3.23). In sex-specific analysis, we identified that maternal urinary 1-H-BTR in the first trimester and 2-MeS-BTH in the third trimester were positively associated with cord blood mtDNAcn among male infants but not female (P for interaction = 0.05 for 1-H-BTR, P for interaction = 0.05 for 2-MeS-BTH, respectively). We found evidence that prenatal exposure to BTRs and BTHs were associated with cord blood mtDNAcn alternation, and these associations were modified by infant gender. Further investigations are needed to corroborate these findings. [ABSTRACT FROM AUTHOR]

• The associations of urinary BTs with the blood glucose levels were investigated. • Urinary levels of 2-OH-BTH were positively associated with 2-hour blood glucose. • Higher urinary levels of 2-OH-BTH were associated with increased risk of GDM. Benzotriazoles (BTRs) and benzothiazoles (BTHs) are emerging contaminants with potential insulin modulation activities. Pregnancy exposure to BTs (BTRs and BTHs) may be a risk factor for the development of gestational diabetes mellitus (GDM). However, epidemiological studies are limited. We prospectively investigated the associations of exposure to BTs at early pregnancy with the blood glucose levels and the risks of GDM. A prospective cohort of 1770 pregnant women who were free of diabetes at baseline was established between 2013 and 2015 in Wuhan, China. Urine samples collected at 13.1 ± 1.1 weeks of gestation were analyzed to estimate the exposure level of BTs. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) conducted at 26.4 ± 2.4 weeks of gestation. We examined the associations between urinary concentration of BTs and blood glucose levels by linear regression models. The associations of urinary BTs concentrations with the relative risk (RR) of GDM were evaluated by generalized estimating equations with Poisson regression. Effect modifications by fetus sex and pre-pregnancy body mass index (BMI) were further evaluated in the sensitivity analysis. Results: A total of 147 (8.31%) pregnant women were diagnosed with GDM. Median concentrations of urinary BTs did not differ significantly between pregnant women with and without GDM. It was found that urinary levels of benzothiazole and 2-hydroxy-benzothiazole (2-OH-BTH) were positively associated with 2-hour blood glucose (p for trend < 0.050). Comparing the high exposure group with the low exposure group of 2-OH-BTH, the adjusted RR of GDM was 1.79 (95% CI = 1.18 to 2.69, p for trend = 0.012). Sensitivity analysis indicated that the positive association of the urinary 2-OH-BTH level with the RR of GDM remained significant among pregnant women who had a male fetus (RR = 1.76, 95% CI = 1.02 to 3.03, p for trend = 0.041) and those with a normal pre-pregnancy BMI (RR = 1.85, 95% CI = 1.09 to 3.11, p for trend = 0.034). These findings suggested that higher urinary level of 2-OH-BTH in early pregnancy was associated with impaired glucose homeostasis and the increased risk of GDM. The results underscore the need of follow-up studies to validate the findings and elucidate the underlying biological mechanism. [ABSTRACT FROM AUTHOR]

Benzotriazole (BTR) and benzothiazole (BTH) derivatives are extensively applied in industrial processes and consumer products, and are thus frequently detected in the environmental matrices. Due to their potential estrogenic effects reported in animal studies, the assessment of human exposure to BTRs and BTHs is important. In this study, a method was developed and validated to determine six BTRs and five BTHs in human urine by using ultra-high performance liquid chromatography coupled with a triple quadrupole mass spectrometry (UHPLC-TQMS) in positive electrospray ionization mode. After de-conjugation by β -glucuronidase, urine samples were liquid-liquid extracted for the measurement of total concentrations of BTRs and BTHs. The linearity, detection limit, precision, recovery, accuracy and matrix effect were evaluated. The limits of detection were less than 0.5 ng/mL. The validated method demonstrated good precision (RSD% < 15%), linearity (R 2 > 0.99), recovery (>80%) and accuracy (80–100%). The method was successfully applied for the analysis of 22 human urine samples. Four out of eleven targeted compounds were detected in more than half of participants at ng/mL levels. [ABSTRACT FROM AUTHOR]

Long-term exposure to high-level ambient PM 2.5 was associated with increased risks of brain disorders, while the associations remain uncertain when the exposure is lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM 2.5 exposure on the brain system in the population with annual mean concentrations ≤15 μg/m3. We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank. The geographical distribution of PM 2.5 in 2010 was estimated by a land use regression model and linked with individual residential address. We investigated associations of ambient PM 2.5 with incident neurological (dementia, Parkinson's diseases [PD], epilepsy, and migraine) and psychiatric (major depressive disorder [MDD] and anxiety disorder) diseases through Cox proportional hazard models. We further estimated the links with brain imaging phenotypes by neuroimaging analysis. Results showed that in the population with PM 2.5 concentrations ≤15 μg/m3, each interquartile range (IQR, 1.28 μg/m3) increment in PM 2.5 was related to incidence risks of dementia, epilepsy, migraine, MDD, and anxiety disorder with hazard ratios of 1.08 (95% confidence interval [CI]: 1.03, 1.13), 1.12 (1.05, 1.20), 1.07 (1.00, 1.13), 1.06 (1.03, 1.09), and 1.05 (1.02, 1.08), respectively. We did not observe a significant association with PD. The association with dementia was stronger among the population with poor cardiovascular health (measured by Life's Essential 8) than the counterpart (P for interaction = 0.037). Likewise, per IQR increase was associated with specific brain imaging phenotypes, including volumes of total brain (β = −0.036; 95% CI: −0.050, −0.022), white matter (−0.030; −0.046, −0.014), grey matter (−0.030; −0.042, −0.017), respectively. The findings suggest long-term exposure to ambient PM 2.5 at low-level still has an adverse impact on the neuro-psychiatric systems. The brain-relevant epidemiological assessment suggests that each country should update the standard for ambient PM 2.5 following the World Health Organization Air Quality Guidelines 2021. [Display omitted] • Low-level PM 2.5 exposure was related to risks of dementia. • Low-level PM 2.5 exposure was associated with risks of mental illness. • Males were more vulnerable to the effect of PM 2.5 on major depressive disorder. • Low-level PM 2.5 was associated with shrunken volumes of brain imaging traits. [ABSTRACT FROM AUTHOR]

Previous studies on environmental pollutant exposure during pregnancy have mostly focused on individual chemical substances or single urine measurements. Thus, our understanding of the potential cumulative or interactive effects of exposure is limited. We aimed to ascertain the characteristics and predictors of exposure to environmental chemicals over three trimesters among pregnant women. We measured the concentrations of 34 chemicals in spot urine samples provided by 745 participants in their early, middle, and late pregnancy. We calculated Spearman correlation coefficients (SCC) between exposure levels of multiple chemicals in each trimester. K -means clustering and principal components analysis (PCA) were applied to classify the populations and reduce data dimensionality. We used generalized linear models (GLM) to confirm predictors of each cluster and principal component. SCC showed that the correlations of chemical concentrations from the same classes were higher than those among concentrations of different classes. Cluster analysis categorized participants into three clusters, and each cluster represented different chemical concentrations. We restricted the principal components to six, which explained more than 50% of the data variations. Several physiological, socio-demographic factors, and behavior patterns were related to different clusters and principal components. Distinct exposure patterns and dominant exposure components of multiple environmental chemicals among pregnant women might help research the potential health effects of exposure to chemical mixtures and develop relevant public health interventions. Unlabelled Image • We profiled the characteristics of exposure to multiple environmental chemicals over three trimesters among pregnant women. • K -means clustering classified participants into the metal, the phthalates, and the lower chemicals exposure group. • We identified metals, phthalates, and benzophenones as main exposure components of 34 chemicals with PCA. • Maternal age, parity, pre-pregnancy BMI, education levels, and job type were associated with mixed chemicals exposure. [ABSTRACT FROM AUTHOR]

Abstract Phthalates are a group of high production volume chemicals widely detected in environment matrix and human specimens. Potential health risks due to the prevalence of their exposure through water consumption and the endocrine-disrupting activities have become an important issue. This work aims to compare the distributions of phthalate levels and potential health risks caused by phthalate exposure among three groups of participants ingesting different types of water. Here, a method with good performance was applied for the analysis of nine common phthalate metabolites in 125 human urine samples collected from Wuhan women. Seven analytes (mono‑ethyl, mono‑benzyl, mono‑ n ‑butyl, mono‑(2‑ethylhexyl), mono‑(2‑ethyl‑5‑oxohexyl), mono‑(2‑ethyl‑5‑hydroxyhexyl), and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate) were detected in over 80% of the samples. By measuring urinary concentrations of phthalate monoesters, the exposure levels of respective parent phthalates, exposure patterns, the estimated daily intakes and accumulative risk assessments were investigated in three groups of participants consuming water from different sources (bottled water, filtered water and boiled tap water). The results showed that the exposure patterns of phthalates varied among the population groups with different water intakes, and the health risk was higher for people ingesting the boiled tap water than that of the groups consuming bottled water (purified water) and filtered water with filter cartridge containing activated carbon. Graphical abstract Unlabelled Image Highlights • MnBP was the major phthalate metabolite in the studied populations. • DnBP in group drinking tap water was significantly higher than other two groups. • DiBP in tap water intake group was strongly higher than bottled water group. • DEHP in tap water group was much higher than that in filtered water group. • Population group drinking tap water had the highest health risk caused by PAEs [ABSTRACT FROM AUTHOR]

Abstract Background Previous studies have suggested that phthalates might disrupt fetal steroidogenesis. However, the evidence of the effects of prenatal phthalate exposure across pregnancy on fetal glucocorticoids was insufficient. Objective We investigated the associations between urinary phthalate metabolites across pregnancy and cord blood glucocorticoids in a prospective birth cohort. Methods Our study included 553 mother-infant pairs from a prospective birth cohort conducted in Wuhan, China. Maternal urine samples were collected at 14, 24 and 36 weeks of gestation (mean). Urinary phthalate metabolites and cord blood glucocorticoids (cortisol and cortisone) were measured. Generalized estimating equation models were conducted to explore the relationships of phthalate metabolite concentrations at each trimester and glucocorticoid levels. Results Among the participants, mono‑benzyl phthalate (MBzP) in the first trimester was associated with higher cortisol/cortisone ratio concentrations, and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate (MECPP) and mono‑(2‑ethyl‑5‑oxohexyl) phthalate (MEOHP) measured in the third trimester were associated with decreased cortisone. Moreover, the associations between phthalates and glucocorticoids varied by sex. Among the female infants, each 10-fold increase in several maternal urinary phthalate metabolite concentrations in 1st and 3rd trimester was associated with the increased glucocorticoid levels with percent changes ranged from 16.2%–55.9%. However, among male infants, each 10-fold increase in maternal urinary MECPP, mono‑(2‑ethyl‑5‑hydroxyhexyl) phthalate (MEHHP) and MEOHP in 3rd trimester was associated with 20.8%–36.3% decreased cortisol and cortisone levels, respectively. Conclusion We have shown that prenatal phthalate exposure during early and late trimester disrupted the infant steroidogenesis and these associations might be modified by infant sex. To the best of our knowledge, this is the first study to evaluate phthalate exposure at three trimesters during pregnancy in relation to infant glucocorticoids. Highlights • Association between maternal phthalate exposure during pregnancy and cord glucocorticoids was evaluated for the first time. • Prenatal phthalate exposure during early and late trimester might disrupt the fetal steroidogenesis. • Fetal sex might modify the relationship of phthalate exposure and glucocorticoid levels. [ABSTRACT FROM AUTHOR]

Exposure to chromium is increasing due to environmental pollution from industrial processes. Several epidemiological studies have investigated chromium exposure and reproductive outcomes, but few studies have investigated the association of chromium exposure and low birth weight (LBW). This study was designed to investigate whether maternal exposure to chromium during pregnancy is associated with an increased risk of LBW. Chromium concentrations in maternal urine samples collected at delivery were measured in 204 LBW cases and 612 matched controls recruited between 2012 and 2014 in Hubei Province, China. Risk of LBW was associated with higher levels of chromium in maternal urine [adjusted odds ratio (OR) = 1.77 for the medium tertile, 95% confidence interval (CI): 0.95, 3.29; adjusted OR = 2.48 for the highest tertile, 95% CI: 1.33, 4.61; P trend = 0.01]. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile, 95% CI: 1.50, 8.97) than among male infants (adjusted OR = 1.22 for the highest tertile, 95% CI = 0.48, 3.11) ( p heterogeneity = 0.06). Our findings suggest that maternal exposure to higher levels of chromium during pregnancy may potentially increase the risk of delivering LBW infants, particularly for female infants. [ABSTRACT FROM AUTHOR]

We investigated the association between prenatal exposure to lead (Pb) and the risk of preterm low birth weight (PLBW). Pb concentrations in maternal urine collected at birth from 408 subjects (102 cases and 306 matched controls) were analyzed and adjusted by creatinine. The median Pb concentration in the PLBW cases (10.60 μg Pb/g creatinine) was higher than that of the controls (7.28 μg Pb/g creatinine). An adjusted odds ratio (OR) of 2.96 (95% CI = 1.49–5.87) for PLBW was observed when the highest tertile was compared to the lowest tertile of Pb levels. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile; 95% CI = 1.35–9.93) than male infants (adjusted OR = 1.91 for the highest tertile; 95% CI = 0.74–4.95). Our study suggests that prenatal exposure to levels of Pb encountered today in China is associated with an elevated risk of PLBW. [ABSTRACT FROM AUTHOR]

• Non-monotonic relationships between BPA and estrogen were noted among mothers. • Gender-specific associations of BPA with estrogen were observed. • Trimester-specific associations between BPA and estrogen were observed. • BPA was non-linearly associated with estrogen even under the safety threshold. Bisphenol A (BPA) may cause some adverse effects on human health by mimicking estrogen activities. In vitro and animal studies have observed the non-monotonic associations between BPA and natural estrogens, but the evidence in human study is lacking, particularly at multiple points in time during pregnancy. We aimed to examine the relationships between BPA and estrogens in the three trimesters among Chinese pregnant women and their gender variations. This study included 851 participants from a birth cohort conducted in Wuhan, China between 2014 and 2015. We measured concentrations of BPA and three estrogens (estrone (E1), 17β-estradiol (E2) and estriol (E3)) in urine samples collected in the three trimesters of pregnancy (mean for each visit: 13.0, 23.6, and 35.9 weeks' gestation). We calculated the estimated daily intakes using urinary BPA concentrations and compared them with the tolerable intake value to assess potential health risks. We used multivariate linear regression models stratified by trimester and gender to explore trimester-specific and gender-specific associations of BPA with E1, E2, and E3. We found the decreased levels of estrogens (β < 0, P < 0.05) in the upper BPA quartiles over three trimesters, except for the elevated levels of E3 (β = 0.20, 95% CI: 0.02, 0.38) in the highest BPA quartile in the 2nd trimester. There were significant non-linear associations (overall associations P < 0.05, non-linear associations P < 0.05) between BPA and E3 in the three trimesters. In the gender-stratified analysis, we observed significant negative relationships (β < 0, P < 0.05) between BPA and E2 among mothers carrying male fetuses in the 1st trimester and significant associations between BPA and E3 among mothers carrying female fetuses in the 2nd trimester. However, we found no significant relationship between BPA and E2 among mothers carrying female fetuses over three trimesters. Our findings support experimental evidence of non-monotonic relationships between BPA and three major estrogens, even at low doses of BPA. Mothers delivering male fetuses may be more sensitive to E2 at early pregnancy, and those delivering female fetuses may be more susceptive to E3 at mid-pregnancy. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) and its substitute bisphenol S (BPS) are endocrine-disrupting chemicals and metabolized rapidly in human body. BPA exposure in late pregnancy has been suggested to be associated with preterm birth (PTB), but the associations of trimester BPA and BPS exposures with gestational age have been rarely studied. We aimed to examine maternal urinary BPA and BPS levels longitudinally measured across pregnancy in relation to gestational age and PTB. A prenatal cohort study was conducted between 2014 and 2015 in Wuhan, China. Maternal urinary BPA and BPS concentrations were measured in a complete series of urine samples collected in the 1st, 2nd and 3rd trimesters from 850 pregnant women and corrected by specific gravity. In comparison with the lowest tertile of maternal urinary BPA, higher levels of averaged BPA concentration across pregnancy was associated with a 1.97-day decrease in gestation (95% CI: 3.25, −0.68) and an adjusted odds ratio of 3.19 (95% CI: 1.00, 10.45) for PTB. Higher BPA concentrations in three trimesters were also negatively associated with gestational age and positively correlated with PTB. In contrast, only a positive association of third-trimester BPS with gestational age was found, but the significant association disappeared in the adjusted models. Both maternal trimester and averaged BPA exposure across pregnancy were significantly associated with shortened gestation and increased risk of PTB. However, the results showed little evidence of a relationship between BPS and PTB. • Urinary BPA and BPS were measured in each trimester from 850 pregnant women. • Both trimester and averaged BPA exposure were associated with decreased gestation. • BPA exposure was related to increased risk of preterm birth (PTB) across pregnancy. • BPS exposure across pregnancy was not related to pregnancy duration or PTB. [ABSTRACT FROM AUTHOR]

Phthalates are a family of endocrine disruptors with short elimination half-lives in the human body. To date, few epidemiological studies have examined repeated measures of maternal urinary phthalates and the combined effects of prenatal exposure to multiple phthalates on children's neurocognitive development. We aimed to investigate the association between children's neurocognitive development at 2 years of age and prenatal phthalate exposure, as assessed by repeated measurements during pregnancy, and to further examine the effects of co-exposure to multiple phthalates using cumulative risk assessment. Within a prenatal cohort in Wuhan, China, we measured five high-molecular-weight (HMW) phthalates and three low-molecular-weight (LMW) phthalate metabolites' concentrations in three urine samples collected in the 1st, 2nd, and 3rd trimester of pregnancy from each mother. We assessed neurocognitive development by Bayley Scales of Infant and Toddler Development (BSID) at 2 years of age (n = 476) to obtain the children's mental development index (MDI) and psychomotor development index (PDI). Higher exposure levels to LMW phthalates compared to HMW phthalates were observed in our population. Ln-transformed averaged concentration of mono- n -butyl phthalate (MnBP), a metabolite of the LMW phthalate di- n -butyl phthalate (DnBP) during pregnancy, was associated with decreased PDI scores in all children (β = −1.90, 95% CI: −3.43, −0.37). Similarly, the averaged sum concentration of ∑dibutyl phthalate (∑DBP) was associated with decreased PDI scores in all children (β = −1.89, 95% CI: −3.63, −0.15). A negative trend of association between exposure to HMW phthalates and PDI scores was observed in girls, while a positive association was found in boys. In cumulative risk assessment analyses, we consistently observed that the hazard quotient of DnBP (the parent compound of MnBP) was inversely associated with PDI scores in all children, whereas the hazard quotient of di-2-ethylhexyl phthalate (DEHP), an HMW phthalate, was positively associated with PDI scores in boys only. This study is the first to use repeated measurement of maternal urinary phthalates in all three trimesters to assess prenatal exposure in relation to children's neurodevelopment. Our study suggested a negative association between prenatal exposure to MnBP and children's psychomotor development, and potentially sex-specific associations between HMW phthalates and neurocognitive development among boys and girls. These findings warrant further confirmation. • We first evaluated the effect of repeated measurements of maternal urinary phthalates on child neurocognitive development. • Prenatal exposure to mono-n-butyl phthalate was negatively associated with children's psychomotor development. • The sex-specific effect may exist between phthalates and neurocognitive development. [ABSTRACT FROM AUTHOR]