The escalating accumulation of nanoplastics in reproductive tissues poses an emerging threat to female fertility. While oxidative stress is a known hallmark of this toxicity, the specific upstream molecular initiators remain elusive, and targeted interventions to mitigate damage after internalization are currently unavailable. To address this challenge, we integrated in vivo toxicity assessment, multi-omics profiling, and computational drug discovery. Female mice were exposed to polystyrene nanoplastics (PS-NPs) to characterize the reproductive phenotype. By intersecting RNA-sequencing data with toxicology databases, we screened for core pathogenic targets. Subsequently, in silico screening, molecular docking, and molecular dynamics simulations identified eriodictyol as a lead compound. It demonstrated superior binding affinity and stability compared to other candidates. In vivo, PS-NP-exposure precipitated a premature ovarian failure-like phenotype, characterized by follicular depletion, hormonal dysregulation (suppressed E2 and AMH, elevated FSH), and oxidative stress-mediated apoptosis. Multi-omics integration identified Toll-like receptor 4 (TLR4) as the core upstream driver orchestrating this toxicity. Virtual screening distinguished Eriodictyol as the superior candidate, uniquely combining high oral bioavailability (>70%) with high-affinity binding to the TLR4. Experimental validation in human granulosa cells (KGN) confirmed that Eriodictyol significantly rescued cell viability and estradiol secretion against PS-NPs attack. Mechanistically, Eriodictyol functioned as a specific inhibitor, severing the TLR4/NF-κB/NLRP3 inflammatory axis and inhibiting the downstream oxidative-apoptotic cascade. PS-NPs induce ovarian failure via TLR4-dependent oxidative inflammation, and Eriodictyol serves as a precision intervention to block this pathway. These findings provide a theoretical foundation for utilizing dietary flavonoids as prophylactic agents to safeguard reproductive health against plastic pollution.

BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) pose significant health risks to vulnerable populations such as pregnant women and children. Evidence on prenatal PFAS exposure and childhood respiratory allergic diseases (RAD) is scarce, particularly regarding how this relationship might be modified by prenatal PM2.5 exposure. OBJECTIVE:To assess the association between prenatal PFAS exposure and the risk of childhood RAD and evaluate whether prenatal PM2.5 exposure modifies this association. METHODS:We conducted a population-based prospective cohort study of 4,166 mother-child pairs from the Shanghai Birth Cohort Consortium to investigate this relationship. Data on RAD (including asthma and allergic rhinitis) in children under 8 years of age were collected from medical records or validated questionnaires. Concentrations of seven PFAS were measured in maternal blood collected during early pregnancy using ultra-high performance liquid chromatography/triple quadrupole tandem mass spectrometry. Generalized linear regression models were used to assess the associations between PFAS and childhood RAD after adjusting for potential confounders. RESULTS:Among the participants, 1,003 (23.9%) children were diagnosed with RAD. PFOA exhibited the highest median concentration (11.97 ng/mL), followed by PFOS (9.68 ng/mL). A doubling increment in PFOA was associated with an increased adjusted odds ratio (aOR) for childhood RAD (1.21, 95% CI: 1.03 to 1.41). The molar sum of five carboxylate PFAS (∑PFCAs) were also significantly associated with elevated RAD risk (aOR = 1.21, 95% CI: 1.03 to 1.42). Additionally, we observed that higher prenatal PM2.5 exposure appeared to enhance the adverse effects of PFAS on RAD, with a significant interaction specifically noted for PFOA in relation to allergic rhinitis (aOR = 1.35, 95% CI: 1.07 to 1.72). CONCLUSION:Prenatal exposure to individual and PFAS mixture was associated with an increased risk of childhood RAD, particularly allergic rhinitis. Children born to mothers with high PM2. 5 levels during pregnancy were more susceptible. Reducing prenatal PFAS and PM2.5 exposure may reduce the public health burden of childhood RAD.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants; however, their long-term neurodevelopmental effects following prenatal exposure remain incompletely characterized. This study examined associations between prenatal PFAS exposure and longitudinal neurodevelopment from birth to age 7 years old, with attention to sex-specific effects and thyroid hormone-mediated pathways. Using data from the Laizhou Wan Birth Cohort, 221 mother-infant pairs with at least three neurodevelopmental assessments were included. PFAS concentrations were quantified in cord blood at delivery, and neurodevelopment was evaluated using validated instruments. Generalized Linear Mixed-Effects Models and Bayesian Kernel Machine Regression were applied. Prenatal exposure to perfluorohexanesulfonic acid (PFHxS) (OR = 3.76, 95% CI: 1.10-11.24) and perfluorooctanoic acid (PFOA) (OR = 2.15, 95% CI: 1.01-4.62) was associated with below-average neurodevelopment. Female offspring showed greater sensitivity to PFHxS exposure (OR = 6.73, 95% CI: 1.19-38.19). Mediation analyses indicated that thyroid hormone disruption may partially mediate these associations, with stronger effects observed in females. Associations were most evident at ages 1-2 years. These findings suggest that prenatal PFAS exposure is associated with adverse neurodevelopmental outcomes and highlight thyroid hormone disruption and sex-specific susceptibility during early childhood.

[Background]Attention-deficit/hyperactivity disorder(ADHD)is one of the most common neu-rodevelopmental disorders in children and adolescents.Current research suggests that environ-mental factors,such as per-and polyfluoroalkyl substances(PFAS),may be associated with an in-creased risk of ADHD in offspring.However,most epidemiological evidence originates from non-Chinese populations,with limited research investigating the association between prenatal PFAS and ADHD-like symptoms in Chinese school-aged children. [Objective]To examine the association between prenatal PFAS exposure and ADHD-like symptoms in 7-year-old children. [Methods]Based on the Shanghai Birth Cohort,this study included 488 mother-child pairs.PFAS were measured in maternal serum during the second trimester using ultra-performance liquid chromatography-tandem mass spectrometry.The analysis focused on eight specific compounds from three PFAS categories[perfluorooctanoic acid(PFOA),perfluorooctanesulfonic acid(PFOS),and perfluorohexanesulfonic acid(PFHxS)].The hyperactivity subscale of the Strengths and Difficulties Questionnaire(SDQ)was used to assess ADHD-like symptoms in children at age 7.Basic demographic information was collected via questionnaires and medical records.Negative binomial regression models were used to evaluate the relationship between individual exposures to the three typical PFAS categories(PFOA,PFOS,and PFHxS)and children's ADHD-like symptoms,while the bayesian kernel machine regression(BKMR)mixture model was employed to assess the overall effect of PFAS mixture exposure on ADHD-like symptoms. [Results]The detection rates of the eight target PFAS in maternal second-trimester serum were all above 85％,with PFOA exhibiting the highest median concentration(10.21 ng·mL-1).Overall,14.75％of the children exhibited ADHD-like symptoms.Results from the negative binomial regression models showed that second-trimester exposures to PFOA(IRR=1.15,95％CI:1.05,1.26),n-PFOS(IRR=1.08,95％CI:1.01,1.15),6m-PFOS(IRR=1.13,95％CI:1.05,1.21),and 1m-PFOS(IRR=1.11,95％CI:1.03,1.18)were associated with an increased risk of ADHD-like symptoms in 7-year-old children.Stratified analyses suggested potentially statistically significant associations in girls[e.g.,for PFOA,boys vs.girls:1.09(0.96,1.23)vs.1.25(1.09,1.44),P-int=0.31].The BKMR mixture model indicated that the risk of ADHD-like symptoms trended upward with increasing PFAS mixture concentrations,although this association was statistically significant only among girls(P<0.05). [Conclusion]Prenatal PFAS exposure may be associated with an increased risk of ADHD-like symptoms in 7-year-old children,and this adverse association appears to be more prominent in girls.

Previous studies indicate pesticides may disrupt female reproductive hormone levels. However, the combined effects of multiclass pesticides on these hormones and whether different types exert distinct effects in women undergoing assisted reproductive technology (ART) remain unclear. Thus, we examined associations between combined multiclass pesticide exposure and reproductive hormone levels in ART women. The study included 462 women enrolled in the sub-cohort of the China National Birth Cohort between July 2017 and December 2018. Blood and urine samples were collected before ART treatment. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone (AMH) were obtained from medical records. Urine was quantified for organophosphates (OPs), pyrethroids (PYRs), neonicotinoids (NEOs), and their metabolites. Using hierarchical bayesian kernel machine regression models we found combined exposure to multiclass pesticides was associated with increased FSH (-12.35%, 95% CI: -22.41%, -0.97% for 30th vs. 50th percentile) and decreased AMH (-15.74%, 95% CI: -28.83%, -0.25% for 75th vs. 50th percentile) levels. 4-fluoro-3-phenoxybenzoic acid (4F-3PBA, a PYR metabolite, condPIP = 0.79) and nitenpyram (NIT, a NEO metabolite, condPIP = 0.45) contributed most to elevated FSH and reduced AMH levels, respectively. Furthermore, OPs and PYRs were mainly associated with increased FSH, and NEOs with decreased AMH. Our study suggests that combined exposure to multiclass pesticides may adversely affect female reproductive function.

Hypochlorite (ClO- ) as a kind of highly toxic pollutant has garnered significant interest in detection methods, highlighting the pressing need to develop intelligent functional materials for the qualitative and quantitative analysis of ClO- in aqueous solutions. Herein, a ratiometric fluorescent sensor was prepared by the combination of acriflavine (Acr) and UIO-66 via a post-synthetic modification strategy. Acr/UIO-66 exhibited both high crystallinity typical of metal-organic frameworks and demonstrated good fluorescent and thermal stability. Additionally, Acr/UIO-66 functioned effectively as a dual-responsive fluorescent platform for detecting ClO- in domestic drinking and surface water samples. This material displayed high sensitivity, exceptional selectivity, and superior anti-interference capabilities, along with fast respond time (60 s), a wide pH range (4.0-7.0), high recoveries (94.46-118.00 %), a broad linear range (0-28 mu mol L- 1) and low detection limits (0.74 mu mol L- 1). This study broadened the potential applications of fluorescent metal-organic frameworks and presented a feasible solution for water quality monitoring.

BACKGROUND:Dietary intake, especially foods of animal-origin, is an important source of per- and polyfluoroalkyl substances (PFAS) exposure to the general population. However, the distribution of legacy and emerging PFAS in different food categories is unclear, as well as their potential health risk for children. OBJECTIVES:To investigate dietary sources of PFAS and evaluate the risk for 7-year-old children in Laizhou Wan, a region with high PFAS exposure in Shandong, China. METHODS:We sampled participants from the Laizhou Wan Birth Cohort study. We administered a dietary questionnaire to the parents of 7-year-old children and measured PFAS compounds in the serum of the children (n = 154) and meat and seafood samples (n = 45). We calculated the Mann-Whitney U test to compare serum PFAS levels between children who frequently consumed a specific type of marine fish or shrimp/shellfish and those who did not. Children's dietary PFAS intake was calculated through multiplying food consumption and PFAS concentrations, and health risks were assessed by comparing the intake of PFAS with health-based guideline values. RESULTS:In seafood, perfluorooctanic acid (PFOA) (0.52 ng/g wet weight (ww)), perfluoro-6-methylheptanesulfonic acid (iso-PFOS) (0.02 ng/g ww), and 6:2 chlorinated polyfluoroethersulfonic acid (0.06 ng/g ww) had the highest median concentrations among 10 linear PFAS, 8 branched isomers of PFOA and perfluorooctanesulfonic acid (PFOS), and 3 alternatives, respectively. Particularly, PFOA levels (median, 87.80 ng/g) in Zoarces slongatus (one type of marine fish), were approximately 10-100 times of those in other seafood species. Children who frequently consumed Zoarces slongatus had higher serum PFAS levels, especially PFOA, than those who did not. Seafood intake accounted for more than 80% of the total estimated daily intake of PFAS. The dietary estimated weekly intake values of four PFAS (PFOA, PFOS, perfluorononanoic acid, and perfluorohexanesulfonic acid) for children (7.4 ng/kg of body weight (bw)/week) exceeded the tolerable weekly intake (4.4 ng/kg bw/week) as recommended by the European Food Safety Authority. CONCLUSION:Seafood was widely contaminated by both legacy PFAS and their alternatives in Laizhou Wan area. Intake of seafood, especially Zoarces slongatus, may contribute greatly to PFAS exposure in 7-year-old children. Avoiding intake of high PFAS polluted seafood may be an important strategy to protect local children. https://doi.org/10.1289/EHP15157.

Breastfeeding is an important source of Per- and polyfluoroalkyl substances (PFAS) exposure for breastfed infants. However, compared to prenatal exposures, health effects related to postnatal exposure to PFAS are less studied. In this study, we investigated PFAS exposure risk via breastfeeding and evaluate their associations with the physical growth of one-year-old infants in Laizhou Wan, a region with high PFAS exposure in Shandong, China. We included 117 mother-infant pairs who provided both human milk and maternal plasma samples for PFAS measurements. Among them, 99 one-year-old children were followed up for anthropometry measurement. We found that both legacy PFAS and their alternatives were widely detected in human milk samples. PFAS can be transferred from maternal serum to human milk. Perfluorooctanoic acid (PFOA) (median: 0.970 ng/mL) was the dominant PFAS compound in human milk, while perfluoro-6-methylheptanoic acid (6 m-PFOA) (0.013 ng/mL) and 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA) (0.018 ng/mL) had the highest median concentrations among branched isomers and alternatives, respectively. PFOA (77.35 ng/kg bw/d) had the highest median estimated daily intake (EDI) and contributed the most to the total median EDI of the Sigma 4PFAS (82.26 ng/kg bw/d). The daily exposure of infants to PFAS through breastfeeding has exceeded the health-based guidance value (HBGV) set by the European Food Safety Authority (EFSA) and the Agency for Toxic Substances and Disease Registry (ATSDR). Sex-specific effects might exist in the association between infants' physical growth and PFAS exposures via human milk, with the PFAS mixtures showing negative associations with heightfor-age z-score (HAZ) ((3 = -0.49, 95 % CI: -0.92, -0.06) and head circumference-for-age z-score (HCZ) ((3 = -0.61, 95 % CI: -1.02, -0.20), and a positive association with body mass index-for-age z-score (BMIZ) ((3 = 0.73, 95% CI: 0.02, 1.44) only in female infants. Further longitudinal studies are warranted to verify our results.

Bisphenol AF (BPAF), a widely used substitute for bisphenol A (BPA), has been widely detected in pregnant women, raising concerns about its potential effects on reproductive health. However, studies on the reproductive toxicity of BPAF in mammals remain limited. This study aimed to investigate the reproductive toxicity and underlying mechanisms of BPAF exposure during gestation and lactation. Pregnant Sprague-Dawley rats were randomly assigned to four groups (n = 10/group) and administered BPAF by oral gavage (0, 2, 10, or 50 mg/kg/d in corn oil) from gestational day (GD) 0 to postnatal day (PND) 21. Female offspring [first filial generation (F1)] were examined at PND21 and PND70 for reproductive outcomes and steroidogenic alterations. Gestational and lactational BPAF exposure significantly reduced anogenital distance (AGD) at PND21, from 12.05 +/- 0.59 mm in controls to 11.54 +/- 0.50 mm in the 50 mg/kg group (P < 0.001). At PND21, serum estradiol (E2) levels were decreased in the 2 and 10 mg/kg BPAF groups compared with controls (P < 0.05). By PND70, all BPAF-exposed offspring showed reduced E2 and testosterone (T) levels (P < 0.05). In addition, BPAF exposure increased follicular atresia and downregulated the mRNA expression of key steroidogenic genes (StAR, CYP11A1, 17 beta-HSD, and CYP19A1; P < 0.05) at PND70. Our findings indicate that BPAF exposure during gestation and lactation impairs reproductive function in F1 females and may exert long-term effects through disruption of ovarian steroidogenesis. Further research is warranted to confirm these outcomes.

IntroductionThe advanced maternal age (AMA) pregnancies escalate rapidly, which are frequently linked to higher risks of adverse outcomes. Advanced maternal age (AMA) placenta exhibited premature aging, presumably resulting in trophoblast dysfunction, inadequate placentation. However, the precise reasons and mechanisms of trophoblast aging in AMA placenta remain unclear, posing a significant limitation to provide effective guidance for prenatal healthcare in clinical settings. Notably, the organism shows heightened vulnerability to oxidative damage as it ages. YAP (Yes-associated protein) was reported to play a critical role in regulation of aging and resisting oxidative damage, yet these roles had not been elucidated in the placenta. Therefore, this study explored the relationship between trophoblast cell aging and oxidative injury and YAP in AMA pregnancy, which not only provided an insight into the mechanisms of trophoblast cell aging, but also provide valuable directions for healthcare during AMA pregnancy.MethodsIn this study, human term placentas were collected from AMA and normal pregnancies for the analysis of aging, oxidative damage and YAP level. HTR8/SVneo cells were manipulated with (hydrogen peroxide) H2O2 to explore the effects of oxidative damage on trophoblast cell senescence and YAP levels. YAP expression in HTR8/SVneo cells was manipulated to investigate its role in trophoblastic senescence and oxidative damage.ResultsCompared with the control group, the AMA placenta exhibits increased aging biomarkers, which is coupled with an elevation in oxidative damage within placental trophoblast cells and a notable decline in YAP levels. Cellular experiments demonstrated that oxidative damage from H2O2 triggered trophoblast cell senescence and resulted in a reduction of YAP levels. Furthermore, employing molecular modification to silence YAP expression in these cells led to an induction of aging. Conversely, overexpressing YAP ameliorated both trophoblast cell aging and the associated DNA oxidative damage that arised from H2O2.ConclusionThe decline of YAP in AMA pregnancy should be responsible for the increased oxidative injury and premature placenta aging, indicating that YAP plays a significant role in combating oxidative damage and delaying aging, thereby providing a new guidance for prenatal care in AMA pregnancies. Maintaining YAP levels or implementing anti-oxidative stress interventions could potentially mitigate the incidence of complications involved AMA pregnancy.

Prenatal PFAS exposure and maternal psychological distress may adversely affect child neurodevelopment through shared biological pathways, such as hypothalamic-pituitary-adrenal (HPA) axis disruption and pro-inflammatory responses. However, whether psychological distress modifies PFAS-related neurodevelopmental risks remains unclear. Using data from the Shanghai Birth Cohort including 1779 mother-child pairs, we measured maternal PFAS levels during the first trimester and assessed maternal psychological distress (perceived stress, depression, and anxiety) during the second trimester. Child neurodevelopment was evaluated at 6 months of age using the Ages & Stages Questionnaires-Third Edition (ASQ-3). Multivariable regression models and quantile g-computation were conducted to evaluate the associations of ASQ-3 scores with individual and mixture PFAS. Stratified analyses were conducted between the psychological distress positive group (experienced any one type of stressor) and negative group (experienced no stressors). We found that 41 % of pregnant women experienced at least one type of psychological distress. Among the overall participants, maternal PFAS exposure was associated with reduced gross motor scores in children. Maternal psychological distress status modified the association between PFAS and gross motor scores. Specifically, the adverse associations of PFAS with gross motor development were only observed in the psychological distress positive group, while no association was found in the negative group. Significant interaction effects were observed between maternal psychological distress and most PFAS compounds (all P for interaction <0.1). Furthermore, the adverse associations of prenatal PFAS exposure with gross motor development intensified in women experiencing multiple types of psychological stressors. This study indicates that maternal psychological distress may increase the risk of PFAS-related adverse gross motor development in six-month-old children. Investigating maternal psychological distress could be crucial for identifying vulnerable populations and guiding intervention measures.

[Objective]This nested case-control study,based on the Shanghai Birth Cohort(SBC),aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants(OPFRs)on attention deficit hyperactive disorder(ADHD)-like symptoms in 4-year-old children,so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children.[Methods]Strengths and Difficulties Questionnaire(SDQ)was used to assess ADHD like symptoms in 4-year-old children.Children with an SDQ hyperactivity subscale score≥6 points were defined as cases,while those with a score＜5 points were considered as controls.The case and control groups were matched at 1∶1 based on the child's age(±6 months),sex,and parental or primary caregiver's education level.A total of 105 cases and 112 controls were included eventually.Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS),including di-phenyl phosphate(DPHP),di-m-cresylphosphate(DmCP),di-o-cresylphosphate(DoCP),di-p-cresylphosphate(DpCP),di-n-butyl phosphate(DnBP),di-iso-butyl phosphate(DiBP),bis(2-butoxyethyl)phosphate(BBOEP),and bis(2-ethylhexyl)phosphate(BEHP).Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction.Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms,while a quantile g-computation(Qgcomp)regression model was employed to assess the effects of mixed OPFRs exposure(with detection rates＞75%)on ADHD-like symptoms in 4-year-old children.[Results]In this study,the detection rates of DPHP,DoCP,and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%,with DPHP having the highest detection rate(86.18%).The median concentrations of DPHP were highest in both the case and control groups(0.396 μg·L−1 and 0.305 μg·L−1,respectively).Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children(OR=1.262,95%CI:1.017-1.565).The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms(OR=1.508,95%CI:1.012-2.258),with DPHP being the primary contributor to the association.[Conclusion]Early pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children.Additionally,DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms.However,these findings require further validation through other large-scale prospective cohort studies.

This study utilized MAC-T cells cultured in vitro as a model to investigate the effects of varying concentrations of valine on α-casein synthesis and its underlying regulatory mechanisms. In this experiment, MAC-T cells were subjected to a 12 h starvation period, followed by the addition of valine in a range of concentrations (a total of seven concentrations: 0.000, 1.596, 3.192, 6.384, 12.768, 25.536, and 51.072 mM, as well as in 10% Fetal Bovine Serum). The suitable range of valine concentrations was determined using enzyme-linked immunosorbent assays (ELISAs). Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot analyses were employed to evaluate the expression levels and phosphorylation states of the casein alpha s1 gene (CSN1S1), casein alpha s2 gene (CSN1S2) and mTOR signaling pathway-related genes. The functionality of the mTOR signaling pathway was further validated through rapamycin (100.000 nM) inhibition experiments. Results indicated that 1× Val (6.384 mM), 2× Val (12.768 mM), 4× Val (25.536 mM), and 8× Val (51.072 mM) significantly enhanced α-casein synthesis (p < 0.01). Within this concentration range, valine significantly upregulated the expression of CSN1S1, CSN1S2, and mTOR signaling pathway-related genes including the RagA gene (RRAGA), RagB gene (RRAGB), RagC gene (RRAGC), RagD gene (RRAGD), mTOR, raptor gene (RPTOR), and 4EBP1 gene (EIF4EBP1), eukaryotic initiation factor 4E (EIF4E), and S6 Kinase 1 (S6K1) (p < 0.01). Notably, the expression of the eukaryotic elongation factor 2 (EEF2) gene peaked at 1× Val (6.384 mM), while the expression of other genes reached their maximum at 4× Val (25.536 mM). Additionally, valine significantly increased the phosphorylation levels of mTOR, S6K1, 4E-binding protein-1 (4EBP1), ribosomal protein S6 (RPS6), and eEF2 (p < 0.01), with the highest phosphorylation levels of mTOR, S6K1, and RPS6 observed at 4× Val (25.536 mM). Rapamycin treatment significantly inhibited mTOR phosphorylation and α-casein synthesis (p < 0.01); however, the addition of 4× Val (25.536 mM) partially mitigated this inhibitory effect. In conclusion, valine promotes α-casein synthesis by activating the mTOR signaling pathway, with an optimal concentration of 4× Val (25.536 mM).

[Background]Anxiety and depression are common perinatal mental health issues that often occur together and can have serious negative effects on both maternal and infant health. [Objective]To examine the relationships between lifestyle factors and comorbid anxiety and de-pression(CAD)among pregnant women in Shanghai. [Methods]The study estimated the prevalence of CAD during the first,second,and third trimesters of pregnancy using the Self-rating Anxiety Scale(SAS)and Center for Epidemiological Studies-Depression(CES-D)based on data from the China National Birth Cohort(CNBC)embryonic-derived diseases with assisted reproductive technology(ART)sub-cohort.Infor-mation on demographics,sleep status,nutritional intake,and exercise during each trimester was collected through self-made question-naires,the Pittsburgh Sleep Quality Index(PSQI),and the Food Frequency Questionnaire(FFQ).Lifestyle factors(such as sleep status,nu-tritional intake,and exercise during each trimester)were analyzed using logistic regression and generalized linear mixed models(GLMM)to determine their impacts on the prevalence of CAD(yes or no)among pregnant women. [Results]A total of 2876 pregnant women were included in this study.The prevalence of CAD was 10.6%(305),3.6%(103),and 5.5%(159)in the first,second,and third trimesters of pregnancy,respectively.The logistic regression analysis revealed that poor sleep quality throughout the entire pregnancy were statistically associated with an increased prevalence of CAD,and the odds ratios(OR)with 95%confidence intervals(CI)were 2.817(1.845,4.301),2.840(1.855,4.347),and 9.316(5.835,14.876)for the first,second,and third trimesters,respectively,when compared to good sleep quality.Additionally,compared to an intake frequency of 7 times per week,the frequency of egg intake≤3 times per week in the first trimester(OR=2.025,95%CI:1.197,3.425)and the frequency of egg intake of 4-6 times per week(OR=1.896,95%CI:1.117,3.216)or≤3 times per week(OR=1.906,95%CI:1.082,3.357)in the third trimester were asso-ciated with an increased risk of CAD(P<0.05).Moreover,when compared to a frequency of exercise>3 times per week,never or almost never exercising in the second trimester(OR=2.218,95%CI:1.220,4.035)was associated with an increased risk of CAD(P<0.05).The GLMM analysis also demonstrated a significant association between poor sleep quality,lower exercise frequency,or lower intake frequency of vegetables,eggs,or milk and an increased risk of CAD(P<0.05). [Conclusion]The prevalence of CAD among pregnant women in Shanghai follows a U-shaped distribution,with the highest rate occurring in early pregnancy and the lowest rate in mid-pregnancy.Factors such as poor sleep quality,inadequate intake of vegetables,eggs,or milk,and lack of exercise during pregnancy may increase the risk of CAD.Implementing lifestyle interventions during pregnancy could potentially reduce the risk of mental health problems and improve the overall health of both mothers and babies.

BackgroundPer- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. ObjectiveTo analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. MethodsBased on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable.ResultsPerfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). ConclusionAlthough differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.

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

MicroRNAs are small noncoding RNAs that regulate gene expression by targeting complementary mRNA molecules. Among them, microRNA408 (miR408) is an ancient microRNA influencing plant growth and aiding in abiotic stress adaptation. We proved that miR408 sliced uclacyanin7 ( UCL7 ) directly by degradome sequencing. However, the mechanisms underlying the balance between growth and stress response of rice ( Oryza sativa L.) controlled by miR408 remain unclear. We conducted a study comparing Nipponbare (wild -type, WT) plants with miR408 - 3p - overexpression (miR408 - 3p-OX) and UCL7 -overexpression (UCL7 - OX) plants under normal and heat stress conditions. Through RNA -sequencing, physiological measurements, and phenotype examination, we observed that miR408 overexpression resulted in increased dry weight and grain yield, higher levels of ATP and non-structural carbohydrates (NSC), improved photosynthesis, and reduced H 2 O 2 content, antioxidant enzyme activity, and ATPase activity in seedling plants compared to UCL7-OX plants. Additionally, the application of H 2 O 2 scavengers, such as ascorbic acid (ASA) and dimethylthiourea (DMTU), further enhanced dry weight and photosynthesis by reducing H 2 O 2 levels. Under heat stress conditions, miR408 overexpression sharply increased H 2 O 2 content, antioxidant enzyme activity, ATP levels, and ATPase activity compared to UCL7-OX plants, thereby enhancing heat tolerance in rice seedlings. These findings suggest that miR408 and its target gene UCL7 participate in regulating energy homeostasis to achieve a balance between growth and heat response. This regulation involves modulating H 2 O 2 levels and optimizing the relationship between the target of rapamycin (TOR) and SNF1-related protein kinase 1 (SnRK1) in rice.

Chinese children are exposed to broad environmental risks ranging from well-known hazards, such as pesticides and heavy metals, to emerging threats including many new man-made chemicals. Although anecdotal evidence suggests that the exposure levels in Chinese children are substantially higher than those of children in developed countries, a systematic assessment is lacking. Further, while these exposures have been linked to a variety of childhood diseases, such as respiratory, endocrine, neurological, behavioral, and malignant disorders, the magnitude of the associations is often unclear. This review provides a current epidemiologic overview of commonly reported environmental contaminants and their potential impact on children’s health in China. We found that despite a large volume of studies on various topics, there is a need for more high-quality research and better-coordinated regional and national data collection. Moreover, prevention of such diseases will depend not only on training of environmental health professionals and enhanced research programs, but also on public education, legislation, and networking.

BACKGROUND:Previous studies have suggested that prenatal exposure to organophosphate flame retardants (OPFRs) may have adverse effect on early neurodevelopment, but limited data are available in China, and the overall effects of OPFRs mixture are still unclear. OBJECTIVE:This study aimed to investigate the association between prenatal exposure to OPFR metabolites mixture and the neurodevelopment of 1-year-old infants. METHODS:A total of 270 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China. Ten OPFR metabolites were measured in maternal urine. Neurodevelopment of 1-year-old infants was assessed using the Gesell Developmental Schedules (GDS) and presented by the developmental quotient (DQ) score. Multivariate linear regression and weighted quantile sum (WQS) regression models were conducted to estimate the association of prenatal exposure to seven individual OPFR metabolites and their mixture with infant neurodevelopment. RESULTS:The positive rates of seven OPFR metabolites in the urine of pregnant women were greater than 70% with the median concentration ranged within 0.13-3.53 μg/g creatinine. The multivariate linear regression model showed significant negative associations between bis (1-chloro-2-propyl) phosphate (BCIPP), din-butyl phosphate (DnBP), and total OPFR metabolites exposure and neurodevelopment in all infants. Results from the WQS model consistently revealed that the OPFR metabolites mixture was inversely associated with infant neurodevelopment. Each quartile increased in the seven OPFR metabolites mixture was associated with a 1.59 decrease (95% CI: 2.96, -0.21) in gross motor DQ scores, a 1.41 decrease (95% CI: 2.38, -0.43) in adaptive DQ scores, and a 1.08 decrease (95% CI: 2.15, -0.02) in social DQ scores, among which BCIPP, bis (1, 3-dichloro-2-propyl) phosphate (BDCIPP) and DnBP were the main contributors. CONCLUSION:Prenatal exposure to a mixture of OPFRs was negatively associated with early infant neurodevelopment, particularly in gross motor, adaptive, and social domains.

Agarwood (Aquilaria malaccensis Lam.) is a resinous material from different geographical locations. The current evaluation of agarwood quality is usually based on its physical properties and chemical compounds, yet only a few studies have linked agarwood quality with its anxiolytic effect, as indicated by characteristic compounds. In this study, using solid-phase microextraction/gas chromatography–time-of-flight mass spectrometry (SPME/GC-TOFMS) and multivariate analysis, we found 116 significantly different compounds in agarwood samples from four locations in Southeast Asia with regard to their quality. Brunei and Nha Trang agarwood had abundant sesquiterpenoids, exhibiting notable pharmacological efficacy in relieving anxiety. Malaysian and Irian agarwood had abundant alcohols and aldehydes, qualifying them as high-quality spices. Compound–target–disease network and pathway enrichment analysis were further employed to predict 79 gene targets and 20 pathways associated with the anxiolytic effects based on the 62 sesquiterpenoids. The correlated relationships among the sesquiterpenoids and targets suggest that agarwood treats anxiety via multiple compounds acting on multiple targets. Varying levels of sesquiterpenes across agarwood groups might lead to differences in the anxiolytic effects via signaling pathways, such as neurotransmitter- and hormone-regulated pathways. Our study originally evaluates agarwood quality and its anxiolytic effect by linking the characteristic compounds to potential gene targets and pathways.