Glucose-6-phosphate dehydrogenase alleviates epileptic seizures by repressing reactive oxygen species production to promote signal transducer and activator of transcription 1-mediated N-methyl-d-aspartic acid receptors inhibition.

The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.

Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.

[Technical Status and Development Trend of Medical Electron Linear Accelerators].

More than 70% of tumor patients require radiotherapy. Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy. With the application of artificial intelligence technology in medical electron linear accelerator, radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy. This study introduces the development history, working principles and system composition of medical electron linear accelerators. It outlines the key technologies for improving the performance of medical linear electron accelerators, including beam control, multi-leaf collimator, guiding technology and dose evaluation. It also looks forward to the development trend of major radiotherapy technologies, such as biological guided radiotherapy, FLASH radiotherapy and intelligent radiotherapy, which provides references for the development of medical electron linear accelerators.

Zinc Oxide Nanoparticles Exacerbate Epileptic Seizures by Modulating the TLR4-Autophagy Axis.

Background: Zinc oxide nanoparticles (ZnO NPs) has been widely used in various fields and has had an important impact on human public health. In addition, it inevitably damages human health, including neurological diseases. Therefore, this study explored the effect of ZnO NPs on epilepsy. Methods: The effect of ZnO NPs on epilepsy was observed by behavioral analysis. TLR4 expression and autophagy related pathways were detected by RNA-seq and Western blot. In addition, the cell types of autophagy were detected by immunofluorescence. Further, the electrophysiological changes of ZnO NPs induced autophagy were detected by whole-cell patch-clamp. Finally, the recovery experiment was carried out by TLR4 inhibitor (TAK-242). Results: We found that ZnO NPs enhanced epilepsy susceptibility and severity. Through RNA-seq analysis and Western blot, it was found that ZnO NPs affected the changes of TLR4 and autophagy related pathways. In addition, we found that ZnO NPs mainly affects autophagy of inhibitory neurons, resulting in excitation/inhibition imbalance. The autophagy and epileptic phenotypes were reversed with TAK-242. In general, ZnO NPs exacerbate epileptic seizures by modulating the TLR4-autophagy axis. Conclusion: ZnO NPs enhanced the susceptibility and severity of epilepsy. Mechanistically, ZnO NPs affected autophagy by changing the expression of TLR4. In particular, the ZnO NPs mainly affected the synaptic function of inhibitory neuron, leading to excitation/inhibition imbalances.

Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age.

BACKGROUND: Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors. METHODS: A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children's neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility. RESULTS: Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (ß = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (ß = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins. CONCLUSIONS: Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Prenatal exposure to poly- and perfluoroalkyl substances and postpartum depression in women with twin pregnancies.

BACKGROUND: Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. OBJECTIVE: To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. METHODS: Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. RESULTS: Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. CONCLUSIONS: The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.

Association between prenatal exposure to rare earth elements and the neurodevelopment of children at 24-months of age: A prospective cohort study.

The increasing consumption of rare earth elements (REEs) has resulted in a considerable risk of environmental exposure. However, the adverse effects of prenatal REEs exposure on children's neurodevelopment are not yet fully recognized. Therefore, we investigated the individual and joint effects of prenatal exposure to 13 REEs on children's neurocognitive development based on 809 mother-child pairs from a large birth cohort in Wuhan, China. Maternal urinary concentrations of 13 REEs were repeatedly measured by inductively coupled plasma mass spectrometry. Children's neurodevelopment [e.g., mental and psychomotor development index (MDI/PDI)] at 24-months was assessed using Bayley Scales of Infant Development of Chinese Revision. GEE and BKMR models were applied to estimate the individual and joint effects of prenatal REE exposure on child neurodevelopment level. After controlling for typical confounders, we observed that exposure to 9 REEs during the first trimester were significantly associated with decreased MDI scores [ßs and 95% confidence intervals (CIs) ranging from -2.24 (-3.86 âˆ¼ -0.63) to -1.44 (-2.26∼ -0.26)], and 7 REEs during third trimester were significantly associated decreased PDI scores [ß and 95% CIs ranging from -1.95 (-3.19 âˆ¼ -0.71) to -1.25 (-2.34 âˆ¼ -0.16)]. Higher quantiles of REE mixture in first and third trimester were associated with decreased MDI and PDI score. Thulium, erbium in the first trimester and cerium, lanthanum in the third trimester accounted most importance to joint effects on MDI and PDI, respectively. In conclusion, prenatal exposure to higher concentrations of REEs during the first and third trimester were negative associated with children's neurodevelopment.

A co-twin control study of in utero exposure to poly- and perfluoroalkyl substances and associations with neonatal thyroid-stimulating hormone.

Research quantifying associations between early-life exposure to poly- and perfluoroalkyl substances (PFAS) and neonatal thyroid hormone levels is limited and reports inconsistent results. This study aimed to examine the associations of in utero PFAS exposure with neonatal thyroid-stimulating hormone (TSH), and to verify whether genetic and familial factors contribute to these associations. Within Wuhan Twin Birth Cohort study, we included 148 mother-twin pairs recruited between March 2016 and January 2018. Maternal plasma PFAS concentrations were measured at three different trimesters and averaged. Additionally, we measured cord plasma PFAS concentrations for twin newborns and retrieved their TSH levels from the medical system. Multivariable linear regression, generalized estimation equation, and linear mixed models were used to examine the covariate-adjusted associations. For maternal PFAS analyses, a 2-fold increment of average maternal perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) concentrations was linked with a 15% (95% CI: 2.5%, 28%) and 14% (95% CI: 2.4%, 28%) increase in neonatal TSH, respectively. For twin newborns discordant for PFAS exposure, a 2-fold increment of cord plasma PFOA, PFDA, perfluoroundecanoic acid (PFUdA), and perfluorohexanesulfonic acid (PFHxS) concentrations was related to a 7.1% (95% CI: 0.31%, 14%), 12% (95% CI: 4.8%, 20%), 7.5% (95% CI: 0.30%, 15%), and 8.5% (95% CI: 3.0%, 14%) increase in TSH among twins as individuals, respectively. Although these associations were mainly observed between twin pairs, certain PFAS exposure might have an independent association with increased TSH. Our present study suggests that higher maternal and cord plasma PFAS concentrations are associated with increased neonatal TSH, and genetic and familial factors contribute to these associations.

[Progress in Development of Dose Verification System Software KylinRay-Dose4D].

Advanced radiotherapy technology enables the dose to more accurately conform to the tumor target area of the patient, providing accurate treatment for the patient, but the gradient of the patient's radiation dose at the tumor edge is getting larger, which putting forward higher requirements for radiotherapy dose verification. The dose verification system software KylinRay-Dose4D can verify the patient's pre-treatment plan and the in vivo/on-line dose during the patient's treatment, providing important reference for the physicist to modify the radiotherapy plan and ensuring that the patient receives accurate treatment. This study introduces the overall design and key technologies of KylinRay-Dose4D, and tests the pre-treatment plan dose checking calculation and 2D/3D dose verification through clinical cases. The test results showed that the 2D/3D gamma pass rate (3 mm/3%) of KylinRay-Dose4D reconstructed dose compared with TPS plan dose and measured dose is larger than 95%, which indicating that the reconstructed dose of KylinRay-Dose4D meets the requirement of clinical application.

[Structural Design and Penumbra Analysis of Dynamic Multi-leaf Collimator Leaf End].

Dynamic multi-leaf collimator, which has the function of radiation beam shaping, is a key executive component of tumor precise radiotherapy, and plays a core role in improving the accuracy, efficiency and quality of radiotherapy. A new type of collimator leaf end structure with circular arc and plane combination was studied, and collimator penumbra performance analysis model combining analytical expression and graphic analysis was developed. The influence of leaf end structure on penumbra was analyzed quantitatively, and a set of three-dimensional structure design of dynamic multi-leaf collimator was completed. The feasibility of the structural design and analysis model was verified through experimental measurements.

Prenatal exposure to phthalates and child growth trajectories in the first 24 months of life.

BACKGROUND: Phthalates are a class of environmental chemicals with endocrine-disrupting properties. Prenatal phthalate exposure has been associated with adverse developmental outcomes in childhood. However, data assessing the effects of prenatal phthalate exposure on postnatal infant growth trajectories are sparse. OBJECTIVES: To evaluate the associations of prenatal phthalate exposure with child growth trajectories from birth to 24 months old. METHODS: Within a Chinese birth cohort study, 1051 mother-offspring pairs were included. Seven phthalate metabolites were quantified in maternal urine collected between weeks 33 and 39 of gestation. The trajectories for weight-for-age z-score (WAZ), length-for-age z-score (LAZ), weight-for-length z-score (WLZ) and head-circumference-for-age z-score (HCZ) were determined by group-based trajectory modeling (GBTM). Multinomial logistic regression and the weighted quantile sum approach (WQS) were used to investigate the association between individual and phthalate mixture exposure and the growth trajectories of four anthropometric metrics. RESULTS: Five trajectory groups were identified for each anthropometric measure using GBTM. Higher prenatal exposure to several phthalate metabolites (MEHP, MEHHP, MEOHP, MECCP, summed DEHP metabolites, as well as MBP) was associated with child growth trajectories, especially for WAZ and LAZ in the first 24 months of life. The associations were further confirmed by a mixture analysis of phthalate metabolites and a sex-specific effect was observed in the WAZ and LAZ trajectories. CONCLUSION: Prenatal phthalate exposure had heterogeneous associations with postnatal growth trajectories. More studies are warranted to confirm and elucidate the meaning of our findings.

RLI2 regulates Arabidopsis female gametophyte and embryo development by facilitating the assembly of the translational machinery.

Eukaryotic protein translation is a complex process that requires the participation of different proteins. Defects in the translational machinery often result in embryonic lethality or severe growth defects. Here, we report that RNase L inhibitor 2/ATP-BINDING CASSETTE E2 (RLI2/ABCE2) regulates translation in Arabidopsis thaliana. Null mutation of rli2 is gametophytic and embryonic lethal, whereas knockdown of RLI2 causes pleiotropic developmental defects. RLI2 interacts with several translation-related factors. Knockdown of RLI2 affects the translational efficiency of a subset of proteins involved in translation regulation and embryo development, indicating that RLI2 has critical roles in these processes. In particular, RLI2 knockdown mutant exhibits decreased expression of genes involved in auxin signaling and female gametophyte and embryo development. Therefore, our results reveal that RLI2 facilitates assembly of the translational machinery and indirectly modulates auxin signaling to regulate plant growth and development.

Protein powder supplementation in early pregnancy and the risk of gestational diabetes mellitus: a prospective cohort study.

Objective: Protein powder has attracted attention due to its possible adverse effects. We aimed to investigate the association of protein powder supplementation in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: We included 6897 participants with singleton pregnancies from a prospective birth cohort. Protein powder supplementation and GDM relationships were examined by unadjusted and multivariable analysis, 1 : 2 propensity score matching, and inverse probability weighting (IPW). A multinomial logistic regression model was used to further explore the effects of protein powder supplementation on the risk of GDM subtypes. Results: Overall, 14.6% of pregnant women (1010) were diagnosed with GDM. In the crude and multivariable analysis before propensity score matching, participants who had received protein powder supplements were more likely to have GDM than women who did not (OR, 1.39 [95% CI: 1.07-1.79]; OR, 1.32 [95% CI: 1.01-1.72]). Protein powder supplementation was significantly associated with a higher GDM risk on IPW analysis (OR, 1.41 [95% CI, 1.08-1.83]), propensity score matching analysis (OR, 1.40 [95% CI, 1.01-1.93]) and multivariable analysis adjusted for propensity score (OR, 1.53 [95% CI, 1.10-2.12]). In the multinomial logistic regression model, protein powder supplementation was only positively associated with the risk of GDM with isolated fasting hyperglycaemia (IFH) in the crude and multivariable models (OR, 1.87 [95% CI: 1.29-2.73]; OR, 1.82 [95% CI: 1.23-2.68]). Conclusions: Protein powder supplementation in early pregnancy is significantly associated with a greater risk of GDM, especially for GDM-IFH. Additional comparative studies are needed to validate these findings.

The association between organophosphate esters exposure and body mass index in children and adolescents: The mediating effect of sex hormones.

Organophosphate esters (OPEs), used as flame retardants and plasticizers, have been indicated to impair growth and development in toxicological studies, but current epidemiological data on their associations with body mass index (BMI) are limited and the underlying biological mechanisms remain unclear. In this study, we aim to explore the association of OPE metabolites with BMI z-score, and assess whether sex hormones mediate the relationships between OPE exposure and BMI z-score. We measured weight and height, and determined OPE metabolites in spot urine samples and sex hormones in serum samples among 1156 children and adolescents aged 6-18 years in Liuzhou city, China. The results showed that di-o-cresyl phosphate and di-pcresyl phosphate (DoCP & DpCP) levels were associated with lower BMI z-score of all participants and a similar pattern of associations were presented in prepubertal boys stratified by sex-puberty groups and male children stratified by sex-age groups. In addition, sex hormone binding globulin (SHBG) were related to reduced BMI z-score among all subgroups including prepubertal boys, prepubertal girls, pubertal boys, and pubertal girls (all Ptrend<0.05). We also found that DoCP & DpCP showed positive associations with SHBG among prepubertal boys. Mediation analysis further showed that SHBG mediated 35.0% of the association between DoCP & DpCP and reduced BMI z-score in prepubertal boys. Our results indicated that OPEs may impair growth and development by disrupting the sex hormones in prepubertal boys.

Independent and combined effects of exposure to organophosphate esters on thyroid hormones in children and adolescents.

Toxicological studies suggest that organophosphate esters (OPEs) may impair thyroid function. Epidemiological evidence, related to children and adolescents, has not been reported, and little is known about the combined effects of exposure to OPE mixtures. In this study, we collected information of 1156 children and adolescents (aged 6-18 years, 48.4% males) from a cross-sectional study in Liuzhou, China, and measured the levels of 15 urinary OPE metabolites and 5 serum thyroid hormones. Multivariate linear regression and quantile g-computation (QGC) approach were used to examine the associations which adjusted for demographic and lifestyle characteristics. Few participants had levels of triiodothyronine (T3) and free thyroxine (FT4) outside age-specific pediatric ranges. QGC analyses showed that individuals in the second, third, and fourth quartiles (Q2-Q4) of exposure had 3.93% (2.14%, 5.75%), 8.01% (4.32%, 11.8%), and 12.3% (6.54%, 18.3%) higher T3 than those in the first quartile (Q1), with similar pattern for free triiodothyronine (FT3). Individuals in Q2 and Q3 had higher thyroid-stimulating hormone (TSH) than those in Q1, but no differences were observed in TSH between Q1-Q4. In contrast, compared to the lowest quartile, FT4 was lower for those in Q2 (- 1.54%; 95% CI: - 3.02%, -0.04%), Q3 (-3.07%; 95% CI: -5.95%, -0.09%), and Q4 (-4.56%; 95% CI: - 8.80%, - 0.13%). These associations were consistent with the results from multivariate linear regression. When stratified by sex, OPE exposure (individual or mixtures) was associated with increased T3 and FT3 in males and decreased FT4 in females. This study provides the first evidence to characterize the thyroid-disrupting effects of OPE exposure in children and adolescents.

Spatiotemporal formation of the large vacuole regulated by the BIN2-VLG module is required for female gametophyte development in Arabidopsis.

In Arabidopsis thaliana, female gametophyte (FG) development is accompanied by the formation and expansion of the large vacuole in the FG; this is essential for FG expansion, nuclear polar localization, and cell fate determination. Arabidopsis VACUOLELESS GAMETOPHYTES (VLG) facilitates vesicular fusion to form large vacuole in the FG, but the regulation of VLG remains largely unknown. Here, we found that gain-of-function mutation of BRASSINOSTEROID INSENSITIVE2 (BIN2) (bin2-1) increases VLG abundance to induce the vacuole formation at stage FG1, and leads to abortion of FG. Loss-of-function mutation of BIN2 and its homologs (bin2-3 bil1 bil2) reduced VLG abundance and mimicked vlg/VLG phenotypes. Knocking down VLG in bin2-1 decreased the ratio of aberrant vacuole formation at stage FG1, whereas FG1-specific overexpression of VLG mimicked the bin2-1 phenotype. VLG partially rescued the bin2-3 bil1 bil2 phenotype, demonstrating that VLG acts downstream of BIN2. Mutation of VLG residues that are phosphorylated by BIN2 altered VLG stability and a phosphorylation mimic of VLG causes similar defects as did bin2-1. Therefore, BIN2 may function by interacting with and phosphorylating VLG in the FG to enhance its stability and abundance, thus facilitating vacuole formation. Our findings provide mechanistic insight into how the BIN2-VLG module regulates the spatiotemporal formation of the large vacuole in FG development.

Exposure to bisphenols, parabens and phthalates during pregnancy and postpartum anxiety and depression symptoms: Evidence from women with twin pregnancies.

BACKGROUND: Women are vulnerable to suffer from the common mental disorders like anxiety and depression during the postpartum period. Exposure to bisphenols, parabens, and phthalates has been linked to anxiety and depression symptoms in the general population. However, little is known about their impacts on postpartum women. OBJECTIVE: To evaluate the effects of individual and joint exposure to 11 nonpersistent chemicals during pregnancy on postpartum anxiety and depression. METHODS: Among 278 mothers from the Wuhan Twin Birth Cohort (WTBC), bisphenols, parabens, and phthalate metabolites were measured in maternal urine samples from each trimester. Self-rating Anxiety Scale (SAS) and Edinburgh Postnatal Depression Scale (EPDS) were administrated at early pregnancy and 1 month and 6 months postpartum to determine anxiety and depression symptoms, respectively. Associations between urinary chemical biomarkers (individual or mixtures) and anxiety and depression symptoms were estimated using multiple informant model and quantile-based g-computation. RESULTS: With adjustment for confounders, one quartile increase in the overall chemical mixture (bisphenols, parabens and phthalate metabolites) during the second trimester was associated with 1.03-point (95% CI: 0.07, 1.99, P = 0.036) higher EPDS score at 1 month postpartum, in which bisphenol A (BPA) and bisphenol F (BPF) contributed the most to the positive association. Consistent effects were also observed in the multiple informant models. We found that second-trimester BPA and BPF exposure individually showed the strongest and significant associations with anxiety and depression symptoms, and some of associations differed across trimesters (Ptrimester-int < 0.05). CONCLUSIONS: Second-trimester nonpersistent chemical exposure was associated with increased postpartum anxiety and depression symptoms.

Maternal paraben exposure and intra-pair thyroid-stimulating hormone difference in twin neonates.

Thyroid hormones are essential for fetal growth and neurodevelopment. The recent frequent use of parabens has raised concerns about their endocrine-disrupting potential. However, the effects of maternal paraben exposure on neonatal thyroid hormone levels are still largely unknown. In our study, a co-twin control design was employed to analyze the relationships between maternal paraben exposure and neonatal thyroid-stimulating hormone (TSH) difference. We collected information from 252 mother-twin pairs from a twin birth cohort in Wuhan, China. Concentrations of six parabens were measured in maternal urine samples collected at < 16, 16-28, and > 28 weeks of gestation. Data of neonatal TSH levels were retrieved from medical records. Multiple informant models were applied to explore the time-specific relationships between paraben exposure and intra-twin TSH difference and to determine the susceptible window of exposure. We found that maternal urinary methyl paraben (MeP) during early pregnancy was positively associated with intra-twin TSH difference (%change = 5.96 %; 95 % confidant interval (CI): 0.04 %, 12.2 %). However, no significant differences were observed for exposure to ethyl paraben (EtP) and propyl paraben (PrP), and the associations between parabens and intra-twin TSH difference did not differ materially across pregnancy. Further, a stratified analysis based on twin zygosity and chorionicity and sex types indicated that the positive association between early pregnancy MeP exposure and intra-twin TSH difference was significant in monochorionic diamniotic (MCDA) twins of female-female fetuses and dichorionic diamniotic (DCDA) twins of opposite-sex. The prospective twin study provides first evidence that MeP exposure in early pregnancy was associated with an increased TSH difference in twin neonates, especially in female fetuses.

Dietary zinc intake and body mass index as modifiers of the association between household pesticide exposure and infertility among US women: a population-level study.

Clinical studies on the relationship between pesticide exposure at home and infertility in the general population are scarce. Whether the antioxidant nutrients or other health-related factors affect the pesticide-infertility relationship remains unknown. This nationwide study screened 29,400 participants of the National Health and Nutrition Examination Surveys conducted between 2013 and 2018. The participants were subdivided according to dietary zinc intake based on the recommended dietary allowances as the low-zinc and high-zinc groups (< 8 and ≥ 8 mg/day, respectively), and according to body mass index (BMI; cut-off 28 kg/m2) as the low-BMI and high-BMI groups. Participants who were exposed to pesticides at home had an increased risk of infertility (odds ratio [OR] = 1.56, 95% confidence intervals [CI]: 1.06-2.29). The incidence of infertility differed in low-zinc and high-zinc groups (OR, 95% CI: 2.38, 1.40-4.06 vs. 0.98, 0.53-1.79, respectively), indicating an interaction between pesticide exposure and zinc intake in households (P = 0.047), which suggests that a zinc-rich diet may reduce the risk of pesticide-induced infertility. Similarly, the relationship between pesticide exposure and infertility risk differed in the low-BMI and high-BMI groups (OR, 95% CI: 0.90, 0.42-1.93 vs. 2.23, 1.39-3.58, respectively; P = 0.045), suggesting that high BMI may intensify the infertility risk caused by pesticide exposure. These new findings reveal the antagonistic and synergistic effect of zinc and obesity, respectively, in pesticide-induced infertility risk and suggest that individuals who are obese and on a low-zinc diet may be more susceptible to infertility induced by household pesticide exposure.