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Four new transition metal borates have been successfully synthesized. Borate-based catalysts were prepared at different temperatures and their electrocatalytic properties were explored. 1-CoB5/600 and 2-CoSB/450 exhibited ideal ORR activities.

Three borates (1, 2, and 3) exhibit different interlinkage modes. 1, 2, and 3-based catalysts have shown the best ORR activity with a half-wave potential of 0.78 V for 1, 0.74 V for 2 and 0.79 V for 3.

Two new polyketides, pholiotones B and C (

Parabens, as suspected endocrine disruptors, are widely used in personal care products and pharmaceuticals. However, variability, predictors, and risk assessments of human exposure to parabens are not well characterized.To evaluate within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men.We measured four parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in repeated urine samples from 850 Chinese adult men. We examined the variability by intraclass correlation coefficients (ICCs) and identified the predictors by multivariable linear mixed models. We assessed risks of paraben exposures based on the estimated daily intake (EDI).The four parabens were detected in76% of urinary samples. We observed fair to good to high reproducibility (ICCs: 0.71 to 0.86) for urinary paraben concentrations within one day. Use of facial cleanser was associated with higher four urinary paraben concentrations. Increasing age, taking medicine, intravenous injection, and interior decoration in the workplace were related to higher urinary concentrations of specific parabens. Smoking and drinking were associated with lower urinary concentrations of specific parabens. The maximum EDIs for the four parabens ranged from 13.76 to 848.68 μg/kg bw/day, and 0.9% of participants had the hazard quotient values 1 driven by PrP exposure.Urinary paraben concentrations were less variable within one day. Several lifestyle characteristics including use of facial cleanser and pharmaceuticals may contribute to paraben exposures.

Two new polyketides, pholiotones B and C (1 and 2), and four known compounds, trichodermatide D (3), vermistatin (4), dehydroaltenuene A (5) and terpestacin (6) were isolated from the crude extract of Pholiota sp. Their structures were identified by NMR and MS spectroscopic data. The absolute configurations of compounds 1 and 2 were elucidated by modified Mosher’s method, electronic circular dichroism (ECD) calculations and 13C NMR calculations as well as DP4+ probability analyses. All the compounds were evaluated for their antifungal and cytotoxicity.

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend

Disinfection byproducts (DBPs) have been shown to alter ovarian steroidogenesis and cause estrous cyclicity disturbance and prolongation in experimental studies, however human studies are lacking. We aimed to evaluate the cross-sectional associations between drinking water DBPs and menstrual cycle characteristics. A total of 1078 women attending an infertility clinic in Wuhan, China were included between December 2018 and January 2020. Characteristics of menstrual cycle were collected by questionnaires. Concentrations of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were measured in urine as biomarkers of drinking water DBPs. Multivariate logistic and linear regression models were used to evaluate the associations between urinary DCAA and TCAA concentrations and menstrual cycle characteristics. Higher urinary DCAA concentrations were associated with increased odds ratios (ORs) of irregular menstrual cycle (OR = 1.80; 95% CI: 0.97, 3.33 for the highest vs. lowest quartile; P for trend = 0.05) and long menstrual cycle (OR = 1.62; 95% CI: 0.97, 2.70 for the highest vs. lowest quartile; P for trend = 0.06), as well as prolonged variation in cycle length (β = 1.27 days; 95% CI: -0.11, 2.66 for the highest vs. lowest quartile; P for trend = 0.04). Higher urinary TCAA concentrations were associated with prolonged bleeding duration (β = 0.23 days; 95% CI: -0.06, 0.51 for the highest vs. lowest quartile; P for trend = 0.07). These results suggest that exposure to drinking water DBPs is associated with menstrual cycle disturbances. These findings are warranted to confirm in other studies.

Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce.To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology.We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2-5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (EAfter adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: -0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 μg/L and 6.30 μg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: -0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones.Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

STUDY QUESTION Are sleep characteristics associated with outcomes of IVF/ICSI treatment? SUMMARY ANSWER Nocturnal sleep WHAT IS KNOWN ALREADY Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown. STUDY DESIGN, SIZE, DURATION This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years). MAIN RESULTS AND THE ROLE OF CHANCE Compared with women who slept 7 to LIMITATIONS, REASONS FOR CAUTION Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with WIDER IMPLICATIONS OF THE FINDINGS Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

The effects of disinfection by-products (DBPs) on adverse birth outcomes remain unsettled. Maternal genetic variants in relation to DBP metabolism may modify this effect. Pregnant women during late pregnancy (n=1306) were included from a Chinese cohort. Maternal urinary trichloroacetic acid (TCAA) was measured as a biomarker of DBP exposure. Maternal genotyping was conducted in Cytochrome P450 2E1 (CYP2E1; rs2031920, rs3813867, and rs915906) and Glutathione S-transferase zeta-1 (GSTZ1; rs7975). The associations between maternal urinary TCAA and birth outcomes and statistical interactions between maternal exposure and genetic polymorphisms were estimated. We found that maternal urinary TCAA levels were associated with decreased birth weight (P for trend = 0.003) and ponderal index (P for trend = 0.004). Interaction analyses showed that maternal urinary TCAA in association with decreased birth weight was observed only among subjects with CYP2E1 rs3813867 GC/CC vs. GG (Pint = 0.07) and associations with decr...

Background: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. Objective: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. Methods: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose–response associations between exposures and outcomes. Results: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: −0.44, −0.15 and −0.21 cm, 95% CI: −0.36, −0.07 comparing the extreme exposure groups, respectively, both p for trends

Organochlorine pesticides (OCPs) are endocrine-disrupting chemicals and may alter male reproductive hormone concentrations.To explore the associations between multiple OCP exposures and serum testosterone concentrations among Chinese men.We investigated 421 men who provided serum samples from an infertility clinic in Wuhan, China. Each man completed a questionnaire concerning demographic characteristics and lifestyle habits. Serum concentrations of 18 OCPs and total testosterone were measured. Linear regression models were used to explore whether serum OCP levels were associated with altered testosterone concentrations, and potential effect modifications by age and body mass index (BMI) were also examined.After adjusting for potential confounders, elevated dieldrin and p,p'-DDD levels had monotonically negative and positive exposure-response associations with testosterone concentrations, respectively (-30.98 ng/dL, 95% CI: -72.34, 10.37; P for trend = 0.12 and 41.31 ng/dL, 95% CI: -0.32, 82.93; P for trend = 0.06 for the highest vs. non-detectable exposure category, respectively). After stratification by age and BMI, dieldrin in relation to decreased testosterone concentrations was more pronounced among men aged30 years old, and p,p'-DDD in relation to increased testosterone concentrations was stronger among men aged ≥30 years old and among men with a BMI24 kg/mThe study found evidence that serum dieldrin and p,p'-DDD concentrations might be associated with altered serum testosterone concentrations.

Prenatal exposure to metals has been linked with adverse pregnancy outcomes. Oxidative stress and epigenetic changes are potential mechanisms of action.We aimed to examine the associations of individual and mixtures of metal exposures with oxidative stress and DNA methylation among pregnant women.We measured a panel of 16 metals and 3 oxidative stress biomarkers including 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-isoprostaglandin F2α (8-isoPGF2α) in urine from 113 pregnant women in a Chinese cohort. Biomarkers of global DNA methylation including Alu and long interspersed nucleotide element-1 (LINE-1) in cord blood were measured. Multivariable linear regression and Bayesian kernel machine regression (BKMR) models were separately applied to estimate the associations between individual and mixtures of metal exposures and biomarkers of oxidative stress and global DNA methylation.In single-metal analyses, we observed positive associations between 11 metals [arsenic (As), cadmium (Cd), thallium (Tl), barium (Ba), nickel (Ni), vanadium (V), cobalt (Co), zinc (Zn), copper (Cu), selenium (Se) and molybdenum (Mo)] and at least one of oxidative stress biomarkers (all FDR-adjusted P-values0.05). In mixture analyses, we found positive overall associations of metal mixtures with 8-OHdG and 8-isoPGF2α, and Se was the most important predictor. There was no evidence on associations of urinary metals as individual chemicals and mixtures with Alu and LINE-1 methylation.Urinary metals as individual chemicals and mixtures were associated with increased oxidative stress, especially Se.

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P ≤ 0.05). Meanwhile, we found that 8-isoPGF2α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P = 0.08). The mediation analysis indicated that 8-isoPGF2α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.

Nitrosamines, as a class of emerging frequently detected nitrogenous disinfection byproducts (N-DBPs) in drinking water, have gained increasing attention due to their potentially high health risk. Few studies focus on the occurrence variation and carcinogenic health risk of nitrosamines in drinking water systems. Our study aimed to investigate the spatial and temporal variability of nitrosamines in a drinking water system and to conduct a carcinogenic health risk assessment. Three types of water samples, including influent water, treated water and tap water, were collected monthly during an entire year in a drinking water system utilizing a combination of chlorine dioxide and chlorine in central China, and 9 nitrosamines were measured. The nitrosamine formation potentials (FPs) in influent water were also determined. N-nitrosodimethylamine (NDMA) was the most prevalent compound and was dominant in the water samples with average concentrations ranging from 2.5 to 67.4 ng/L, followed by N-nitrosodiethylamine (NDEA) and N-nitrosopiperidine (NPIP). Nitrosamine occurrence varied monthly, and significant seasonal differences were observed in tap water (p .05). The average and 95th percentile total lifetime cancer risks for the three main nitrosamines were 4.83 × 10−5 and 4.48 × 10−4, respectively, exceeding the negligible risk level (10−6) proposed by the USEPA. Exposure to nitrosamines in drinking water posed a higher cancer risk for children than for adults, and children aged 0.75 to 1 years suffered the highest cancer risk. These results suggest that nitrosamine occurrence in tap water varied temporally but not spatially. Exposure to drinking water nitrosamines may pose a carcinogenic risk to human health, especially to children.

Studies indicate that phthalates can disrupt spermatogenesis and lead to the reduction of semen quality. However, the underlying mechanisms remain unclear. This study aimed to examine the associations of phthalate exposures as individual chemicals and mixtures with spermatogenesis-related miRNA106a. We detected eight phthalate metabolites in repeated urine samples and a single seminal plasma specimen among 111 men from an infertility clinic in Wuhan, China. Spermatogenesis-related miRNA106a was measured in seminal plasma. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) models to separately evaluate the associations of phthalate metabolites as individual chemicals and mixtures with spermatogenesis-related miRNA106a. Elevated tertiles of urinary mono (2-ethylhexyl) phthalate (MEHP) was associated with decreased miRNA106a (−61.71%; 95%CI: 81.92, −18.93% for the highest vs. lowest tertile; P for trend = 0.01). Similarly, an inverse exposure-response relationship between seminal plasma MEHP concentrations and miRNA106a was also observed (−59.44%; 95%CI: 79.19, −20.95% for the highest vs. lowest tertile; P for trend = 0.01). The BKMR models showed that the mixtures of seminal plasma phthalate metabolites were associated with decreased miRNA106a when the chemical mixtures were ≥35th percentile compared to their medians. Nonlinear associations with miRNA106a were estimated for urinary and seminal plasma MEHP while fixing other phthalate metabolites at their medians. Our findings suggest that mixtures of phthalate metabolites in seminal plasma were negatively associated with spermatogenesis-related miRNA106a, and individual MEHP was the major contributor to the adverse effects.

Background Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. Methods Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) and ≤10 μm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. Results Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. Conclusions Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.

Experimental studies have demonstrated that disinfection byproducts (DBPs) can cause ovarian toxicity including inhibition of antral follicle growth and disruption of steroidogenesis, but there is a paucity of human evidence. We aimed to investigate whether urinary biomarkers of exposure to drinking water DBPs were associated with ovarian reserve. The present study included 956 women attending an infertility clinic in Wuhan, China from December 2018 to January 2020. Antral follicle count (AFC), ovarian volume (OV), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) were measured as indicators of ovarian reserve. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as potential biomarkers of drinking water DBP exposures. Multivariate linear and Poisson regression models were applied to estimate the associations of urinary DCAA and TCAA concentrations with indicators of ovarian reserve. Elevated urinary DCAA and TCAA levels were monotonically associated with reduced total AFC (− 5.98%; 95% CI: − 10.30%, − 1.44% in DCAA and − 12.98%; 95% CI: − 17.00%, − 8.76% in TCAA comparing the extreme tertiles; both P for trends ≤ 0.01), and the former was only observed in right AFC but not in left AFC, whereas the latter was estimated for both right and left AFC. Moreover, elevated urinary TCAA levels were monotonically associated with decreased AMH (− 14.09%; 95% CI: − 24.79%, − 1.86% comparing the extreme tertiles; P for trend = 0.03). These negative associations were still observed for the exposure biomarkers modeled as continuous variables. Our findings suggest that exposure to drinking water DBPs may be associated with decreased ovarian reserve.

Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes.To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort.Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother-infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis.We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood. For example, the molar sum of di-2-(ethylhexyl) phthalate (∑DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes.Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood.

Background Toxicological studies suggest that maternal exposure to disinfection by-products (DBPs) can impair fetal neurodevelopment. However, evidence from epidemiological studies is scarce and the underlying mechanisms remain unclear. Objective To explore the trimester-specific associations between maternal blood trihalomethane (THM) and urinary haloacetic acid (HAA) concentrations and neonatal neurobehavioral development, and the potential mediating role of oxidative stress (OS). Methods We included 438 pregnant Chinese women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort. Biospecimens were repeatedly collected across trimesters and measured for blood THMs, urinary HAAs, and urinary OS biomarker concentrations. On the third day after birth, the Neonatal Behavioral Neurological Assessment (NBNA) test was administered to newborns. Associations of trimester-specific DBP measurements and OS biomarkers with neonatal NBNA scores were assessed using linear regression models with generalized estimating equations. The potential mediating role of maternal OS biomarkers was also investigated using mediation analyses. Results After adjusting for potential confounders, blood bromodichloromethane (BDCM) concentrations in the first trimester were inversely associated with NBNA scores [percent change comparing the extreme BDCM tertiles = –28.1% (95% CI: –55.2%, –0.88%); p for trend = 0.043]. Besides, third-trimester urinary trichloroacetic acid (TCAA) concentrations were inversely associated with NBNA scores [percent change comparing the extreme TCAA tertiles = –32.9% (95% CI: –64.7%, –1.0%); p for trend = 0.046]. These inverse associations differed across pregnancy trimesters (Type 3 p-value = 0.066 and 0.053, respectively) and were stronger in male infants and mothers aged ≥25 years. There was no evidence of mediating effect by 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), or 8-iso-prostaglandin F2α (8-isoPGF2α). Conclusions Higher prenatal BDCM and TCAA concentrations during specific pregnancy trimesters were associated with lower NBNA scores. However, additional research is required to investigate underlying mechanisms.

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F

Background Exposure to bisphenol A (BPA) has been associated with various adverse health outcomes. Recently, an increasing concern on its alternatives such as bisphenol S (BPS) and bisphenol F (BPF) has been aroused due to the restriction use of BPA. Few studies have identified predictors of exposure to BPA alternatives and assessed their health risks. Objective The aim of this study was to identify predictors of BPA and its alternatives and to assess their health risks among pregnant women. Methods We detected first morning urinary concentrations of BPA and its alternatives (BPS and BPF) among 1097 pregnant women from an established Chinese cohort. A questionnaire was conducted to obtain demographic characteristics, dietary habits, and lifestyles. We examined the predictors of creatinine-adjusted urinary BPA and its alternatives concentrations using multivariable linear regression. Risk assessment of exposure to BPA and its alternatives was calculated based on the estimated of daily intake (EDI). Results Geometric means of creatinine-adjusted urinary BPA, BPF, and BPS were 0.92, 0.12, and 0.08 μg/g creatinine, respectively. Pregnant women from Wuhan had lower concentrations of BPA, BPF, and ∑BPs (sum of BPA, BPF, and BPS) than those from Xiaogan. Intake of fried food was related to higher concentrations of BPA, and intake of pickled food was associated with higher concentrations of BPF and ∑BPs. The maximum EDI values for exposure to BPA, BPF, BPS, and ∑BPs ranged from 5.6428 to 13.3356 nmol/kg body weight/day, which were below the tolerable daily intake (TDI) for BPA defined by the European Food Safety Authority (EFSA) (18 nmol/kg body weight/day). The maximum hazard index (HI) value was 0.7409. Conclusion Several predictors identified in this study may inform public recommendations to reduce exposure to BPA and its alternatives.

Background Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans. Objective To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men. Method Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers. Results Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend Conclusions Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

Epidemiological studies have suggested that phthalate exposures were associated with adverse reproductive outcomes, such as low oocyte yield and reduced embryo quality, but the underlying mechanisms remained largely unknown. Oxidative stress may be a potential contributor to phthalate-induced adverse reproductive outcomes. To explore the associations between phthalate exposure and levels of oxidative stress among women seeking in vitro fertilization (IVF), we measured the concentrations of eight phthalate metabolites and biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total antioxidant capacity (TAC), in follicular fluid (FF) samples collected from 332 women. Multivariable linear regression models were used to assess the associations between phthalate metabolites and biomarkers of oxidative stress in FF samples. The concentrations of most tested phthalate metabolites were positively associated with the 8-OHdG levels. The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were inversely associated with the TAC levels. The concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with the MDA levels. Our results revealed a positive association between phthalate metabolites and oxidative stress levels in FF, while more toxicological and epidemiological studies are required to confirm our findings.

Background Bisphenol A (BPA) has been shown to affect normal fetal growth, but human evidence on its analogues (BPF and BPS) is limited. Object To examine the associations between prenatal exposure to BPA and its analogues (BPF and BPS) and ultrasound parameters of fetal growth. Methods We measured urinary BPA, BPF, and BPS concentrations among 322 pregnant women during late pregnancy from a cohort study in Wuhan, China. Fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), and abdominal circumference (AC) were measured by ultrasonography. The associations of maternal urinary BPA, BPF, and BPS concentrations with ultrasound parameters of fetal growth were estimated by multivariable adjusted models. Results We observed a gender difference in association of maternal urinary BPA concentrations and fetal HC (P for interaction = 0.003); each ln-unit increase in maternal urinary BPA concentration was associated with a mean decrease of 0.10 cm (95%CI: 0.18, −0.02) among boys and a mean increase of 0.14 cm (95%CI: 0.00, 0.28) among girls for HC. The associations were robust for urinary BPA concentrations modeled as tertiles or including urinary BPA, BPF, and BPS into mutual adjustment models. We did not observe robust associations between maternal urinary BPF and BPS concentrations and ultrasound parameters of fetal growth, though an inverse association with AC and a positive association with FL were estimated for maternal urinary BPF concentrations modeled as continuous variables. Conclusions Prenatal exposure to BPA but not BPF and BPS was sex-specifically associated with certain fetal growth parameters.

Phthalates have been reported to affect the function and growth of thyroid. However, there is little data on the effect of phthalates on thyroid oncogenesis. Here we explored the associations between phthalates exposure and the risks of thyroid cancer and benign nodule. We sex-matched 144 thyroid cancer, 138 benign nodule patients and 144 healthy adults from Wuhan, China. Eight phthalate metabolites in spot urine samples were quantified using high-performance liquid chromatography and tandem mass spectrometry. The associations of creatinine-corrected urinary phthalate metabolites with the risks of thyroid cancer and benign nodule were assessed using multivariable logistic regression models. We found that urinary monomethyl phthalate (MMP), mono(2-ethyl-5hydroxyhexyl) phthalate (MEHHP) and mono(2-ethylhexyl) phthalate (MEHP) associated with increased risks of thyroid cancer and nodule, with adjusted odds ratios (ORs) ranging from 1.74 to 4.78 comparing the extreme tertiles, and urinary monobutyl phthalate (MBP) was associated with decreased risks of thyroid cancer and benign nodule (all P for trends 0.05). Male-specific positive associations of urinary monoethyl phthalate (MEP) with thyroid cancer and nodule as well as urinary mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) with thyroid cancer were also observed. Our results suggest that exposure to certain phthalates may contribute to increased risks of thyroid cancer and benign nodule.

Background Disinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. Objective To investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. Methods We included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. Results We found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: −0.35, −0.07; P for trend = 0.003), 0.46 cm (95% CI: −0.81, −0.10; P for trend = 0.01) and 0.17 cm (95% CI: −0.30, −0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. Conclusion The results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth.

Background: Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as alternatives to endocrine disrupting chemical bisphenol A (BPA). Evidence from in vitro and animal studies demonstrates that BPA, BPF and BPS induce oxidative stress, a proposed mechanism that is relevant to various adverse health effects. Evaluation in humans is hampered by the potentially high within-subject variability of urinary measurements. Objective: To evaluate the variability and associations of levels of BPA, BPS, BPF and 3 oxidative stress markers [i.e., 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine collected on multiple occasions over 3 months. Method: A total of 529 spot urine samples, including 88 first morning voids (FMVs) and 24-h specimens, were gathered from 11 adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analyzed for BPA, BPF, BPS, 8-OHdG, 8-isoPGF2α and HNE-MA. Intraclass correlation coefficients (ICCs) were estimated to characterize the reproducibility of urinary bisphenols and oxidative stress markers, and linear mixed models were applied to assess the associations between markers of exposure and response. Results: BPA and BPF were detected in ≥85% of the spot samples, while BPS in 13% of the samples. High degrees of within-subject variability were found for BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA in spot samples, FMVs and 24-h specimens (creatinine-corrected ICCs ≤ 0.37). The sensitivities were low-to-moderate (0.30–0.63) when using single spot samples or FMVs to predict high (>27th, or 36th percentile) 3-month average urinary levels of BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA. Collecting repeated specimens at different time points improved the accuracy of classification for markers of exposure and response. Elevated urinary BPA and BPF were associated with significantly higher levels of oxidative stress markers. Conclusions: Repeated urinary specimens are required to characterize bisphenol exposure levels and the oxidative stress status of individuals. Exposure to BPA and BPF may partly contribute to the elevated urinary levels of oxidative stress makers in adult men. Keywords: Associations, Bisphenols, Human, Oxidative stress, Urine, Variability