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.

Five new Daphniphyllum alkaloids, daphmacropomines A-E (1-5), were isolated from Daphniphyllum macropodum Miq. and structurally characterized. Compound 1 is an unprecedented Daphniphyllum alkaloid that features a unique 6/9/7/5/5 ring with a rare N-nitroso group. Compound 2 is the second Daphniphyllum alkaloid featuring a highly rearranged 6/6/6/7/5/6-fused skeleton. Compounds 3 and 4 are new yuzurimine-type alkaloids, and their structures were determined by extensive techniques including HRESIMS, NMR, ECD, and single-crystal X-ray. A plausible biosynthetic pathway for 1-4 is proposed. Furthermore, compounds 3 and 4 can induce lysosomal biogenesis and promote autophagic flux.

Evidence regarding maternal per- and polyfluoroalkyl substances (PFAS) exposure on offspring physical development is inconsistent. This study included 937 mother-infant pairs from the Jiashan Birth Cohort. Thirteen PFAS congeners were quantified in maternal peripheral blood at the first prenatal visit (< 16 weeks of gestation). Data on offspring weight and length from birth to 24 months of age were extracted, and Z-scores for weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) were calculated. Group-based trajectory modeling (GBTM) was applied to fit growth trajectories. Maternal PFTrDA exposure was associated with higher likelihood of offspring in WAZ "rising" groups, specifically the "Low-start rapid-rise" (OR: 1.37, 95% CI: 1.09, 1.71), "High-start slow-rise" (OR: 1.29, 95% CI: 1.07, 1.56), and "High-start rapid-rise" (OR: 1.46, 95% CI: 1.10, 1.96) groups. PFHxS and PFNA were linked to the LAZ-"Low-start rapid-rise" group (OR: 1.48, 95% CI: 1.07, 2.05; OR: 1.24, 95% CI: 1.02, 1.51, respectively), while PFTrDA was associated with the LAZ-"High-start rapid-rise" group (OR: 1.23, 95% CI: 1.01, 1.51). Most PFAS were associated with elevated likelihood of offspring in the WLZ-"Medium-start rapid-rise" group (ORs: 1.26-1.43). Bayesian kernel machine regression further confirmed the joint effects of the PFAS mixture on rising WAZ/WLZ trajectories and PFTrDA as the key chemical driving the association with the WAZ-"High-start rapid-rise" group. These findings provide evidence for associations between maternal PFAS exposure and offspring growth trajectories during early life.

BACKGROUND:Early-life exposure to exogenous chemicals can disrupt neurodevelopment. Perfluorohexanesulfonic acid (PFHxS), a legacy PFAS widely used and detected globally, remains poorly studied for its neurotoxicity. METHODS:CD-1 mice (n = 90 dams) were exposed to human-relevant dose of PFHxS from gestational day (GD) 0-17. PFHxS levels were measured in maternal plasma and foetal/offspring medial prefrontal cortex (mPFC) (GD 18, postnatal weeks [PNW] 4 and 10) using liquid chromatography tandem mass-spectrometry (LC-MS/MS). Offspring social behaviour was assessed with the Three-Chamber social test. Neurotransmitters in mPFC of PNW 10 offspring were profiled by LC-MS/MS, transcriptomics was performed on GD 18 and PNW 4 mPFC, GABAergic neurons were quantified by immunofluorescence, and glutamate decarboxylase (GAD) expression by western blotting. PFHxS-GAD interactions were examined via molecular docking and microscale thermophoresis (MST). FINDINGS:Maternal plasma reached 5.1 ± 0.1 ng/mL, equivalent to human biomonitoring data, and PFHxS accumulated in foetal mPFC (68.1 ± 4.1 pg/g). PFHxS exposure induced social deficits at PNW 4 and 10, which were more pronounced in males. The mPFC of PFHxS exposed offspring exhibited an excitatory-tilted neurotransmitter profile, feature with reduced γ-aminobutyric acid (GABA, 90.6 ± 12.2 vs. 70.2 ± 4.3 μg/g, p = 0.008). The differentially expressed genes were enriched in GABAergic and synaptic signalling pathways. Despite unchanged percentage of GABAergic neuron and GAD expression, metabolite GABA/glutamate ratio was attenuated, suggesting impaired GAD function. Both molecular docking and MST suggested moderate-to-strong binding affinity between PFHxS and GAD, affecting GABA synthesis. INTERPRETATION:Gestational PFHxS exposure at human-relevant levels impairs offspring social behaviour, likely via disruption of GAD-mediated imbalance in excitation/inhibition. FUNDING:This work was provided by grants from the National Natural Science Foundation of China (82404221 and 82373586), Anhui Provincial Natural Science Foundation (2308085Y50 and 2408085QH275), Education Department of Anhui Province for Excellent Young Scientist (2022AH030076), and funding from Center for Big Data and Population Health of IHM (JKS2022020).

BACKGROUND:Gestational blood pressure (BP) is susceptible to exogenous exposures, including environmental chemicals. However, epidemiological evidence is lacking, particularly for the emerging contaminants. METHODS:We quantified 31 urinary chemicals in early-pregnancy among 815 women from the Jiashan Birth Cohort in Zhejiang Province, China. We applied logistic regression, generalized estimating equation and Bayesian kernel machine regression (BKMR) models to analyze associations between 16 frequently detected compounds and gestational hypertension (GH), trimester-specific BP levels, and BP trajectories throughout pregnancy. RESULTS:Bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE-H2O), bisphenol A-bis(2,3-dihydroxypropyl) ether (BADGE-2H2O), and N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) were consistently associated with an increased risk of GH, elevated BP levels across all trimesters, and a greater likelihood of belonging to BP trajectory groups with a rising pattern. BKMR confirmed that the mixture exposure was associated with higher BP values across all trimesters, identifying BADGE-H2O as the predominant contributor. Bisphenol A (BPA) and 2-methylthio-benzothiazole (2-Me-S-BTH) also showed associations with elevated BP levels and altered BP trajectory membership, whereas inverse associations were preliminarily observed for propyl paraben (PrP), benzyl paraben (BzP), and 2-(Isopropylamino)-5-(phenylamino) cyclohexa-2,5-diene-1,4-dione (IPPD-Q). CONCLUSION:This study reported novel associations between early-pregnancy exposure markers of non-persistent chemicals, especially emerging contaminants (BADGE-H2O, BADGE-2H2O, and 6PPD-Q), and adverse maternal BP outcomes. These findings highlight the potential public health concern posed by these widespread environmental exposures, and underscore the importance of considering real-world mixture exposures. Further research is needed to validate these associations and to elucidate the underlying biological mechanisms.

BackgroundPer- and polyfluoroalkyl substances (PFAS) are synthetic chemicals characterized by environmental persistence and have been ubiquitously detected in pregnant women. Although existing evidence suggests that PFAS may exert endocrine-disrupting effects, evidence remains limited regarding the associations of individual legacy and emerging PFAS congeners, as well as PFAS mixtures, with fetal hormonal homeostasis.ObjectiveBased on the Jiashan Birth Cohort in China, to investigate the associations between maternal plasma concentrations of legacy and emerging PFAS in the second trimester and levels of multiple hormones in fetal cord blood.MethodsA total of 336 women in the second trimester from the Jiashan Birth Cohort were enrolled. Concentrations of 53 legacy and emerging PFAS were measured in maternal plasma, and levels of eight key hormones were determined in fetal cord blood. Multiple linear regression, restricted cubic spline, and Bayesian kernel machine regression models were used to examine the linear, nonlinear, and joint associations of individual PFAS and PFAS mixtures with fetal cord blood hormone levels.ResultsMaternal plasma concentrations of perfluorononanoic acid, perfluorohexane sulfonic acid, perfluorooctanesulfonic acid, and 8:2 chlorinated perfluoroether sulfonic acid were positively associated with cord blood levels of insulin-like growth factor 1 (IGF1), with β values of 0.040, 0.050, 0.040, and 0.030, respectively (all P<0.05). In contrast, perfluoroheptanoic acid was negatively associated with prolactin levels (β=−0.060, P<0.01). Restricted cubic spline models revealed a nonlinear dose–response relationship between perfluorobutane sulfonic acid and growth hormone (likelihood ratio test P=0.045), with a positive association in the intermediate concentration interval (β=0.261, P=0.010) that turned negative at higher concentrations (β=−0.425, P=0.048), as well as a nonlinear trend between 6:2 fluorotelomer sulfonic acid and prolactin (likelihood ratio test P=0.074). Bayesian kernel machine regression analysis indicated a negative trend between PFAS mixture exposure and cord blood prolactin levels.ConclusionMaternal PFAS exposure in the second trimester is associated with higher insulin-like growth factor 1 levels and lower prolactin levels in fetal cord blood. Prolactin appears to be consistently associated with both individual PFAS congeners and PFAS mixtures. These findings suggest that maternal PFAS exposure may affect fetal endocrine homeostasis by disrupting the hypothalamic-pituitary-prolactin regulatory axis.

Perfluorinated/polyfluorinated substances(PFAS)are synthetic organic compounds widely used in over 200 industrial and consumer applications since the 1950s.

Covering: 1948 to 2025Ryanodane diterpenes (RDs) are a unique class of plant-derived natural products characterized by their complex, polyoxygenated pentacyclic frameworks. They have been primarily identified in plants from the Salicaceae and Lauraceae families. In recent years, RDs have garnered significant interest due to their notable bioactivities, particularly their modulation of ryanodine receptors (RyRs) and their insecticidal properties. Since the initial isolation of ryanodine from the shrub Ryania speciosa Vahl in 1948, a total of 135 natural RDs across nine subtypes have been discovered. These compounds exhibit a range of biological activities, including insecticidal, cardiac activity, and immunomodulatory effects. However, the limited natural abundance of RDs has posed challenges for their comprehensive biological evaluation. Fascinated by their high affinity for RyRs and their intricate polycyclic structures, synthetic chemists have pursued the total synthesis of RDs since the 1990s, with notable progress in recent decades. Advances in synthetic methodology have enabled the successful construction of key RD scaffolds, facilitating further exploration of their biological potential. This review provides a comprehensive overview of RDs from 1948 to May of 2025, highlighting their significance in drug discovery and development. It also emphasizes the need for interdisciplinary collaboration to fully harness the therapeutic potential of these complex natural products.

Maternal per- and polyfluoroalkyl substances (PFAS) exposure has been linked to adverse health effects on offspring, but the mechanisms remain unclear. The present study investigates the relationship between maternal PFAS exposure and the expression of placental cytochrome P450 enzymes (CYP19A1, CYP2J2, and CYP2E1), and explores the potential role of these enzymes in linking maternal PFAS exposure to offspring development. We included 350 mother-infant pairs from the Jiashan birth cohort. Thirteen PFAS compounds were measured in maternal plasma collected at 8–16 weeks of gestation, while the expression levels of the three CYP genes were quantified in placental tissues collected at delivery. Offspring weight and length were measured at birth and at 1, 3, 6, 8, 12, and 24 months of age, and their ponderal index (PI) was computed. Multivariable linear regression was used to examine associations between plasma concentrations of individual PFAS and placental CYP gene expression. Quantile-based g-computation was used to examine the association of the PFAS mixture with placental CYP gene expression. A linear mixed model was used to examine the associations of maternal PFAS and placental CYP expression levels with repeated PI measurements from birth to 24 months. Multilevel mediation analysis was conducted to explore the potential mediating role of CYP genes. Consistent inverse associations between maternal PFAS exposure and the three placental CYP genes expression in female placentas were observed. Specifically, statistically significant decreases were observed in the associations between all PFAS compounds and CYP2J2 expression with β- estimates for the highest exposure versus the lowest from -0.255 to -0.174, as well as between the highest exposure of perfluorotridecanoic acid (PFTrDA) and CYP19A1 expression (β = -0.279, 95

Prenatal exposure to organophosphate esters (OPEs) and polybrominated diphenyl ethers (PBDEs) has been linked to disrupted fetal thyroid hormone (TH), though the underlying mechanisms remain unclear. Based on the S-MBCS cohort, we analyzed OPE metabolite concentrations in maternal urine during early pregnancy and PBDE levels in cord plasma. Methylation of five TH regulatory genes, namely deiodinase type 3 (DIO3), solute carrier family 16 member 2 (SLC16A2), solute carrier organic anion transporter family member 1C1 (SLCO1C1), thyrotropin-releasing hormone (TRH), and transthyretin (TTR), was quantified in the placenta. We investigated the associations between prenatal exposure to PBDEs and OPEs and DNA methylation of placental TH-related genes, using samples from 240 and 327 mother-newborn pairs, respectively. We further examined sex-specific differences in these associations and assessed whether the observed epigenetic alterations mediated the relationship between exposures and TH disruption. Mediation analyses were conducted in a subset of mother-newborn pairs with available TH measurements in cord plasma. BDE-47 and ΣPBDE showed sex-specific relationships with DIO3 and SLC16A2 methylation, with a significant positive association in females and a non-significant inverse association in males. Both BDE-47 and ΣPBDEs were linked to SLCO1C1 hypermethylation. OPE metabolites were positively associated with DIO3 and TTR methylation, predominantly in females. Mediation analyses suggested that SLCO1C1 hypermethylation mediated 6.5-7.0 % of the association between ΣPBDE exposure and reduced free triiodothyronine. These findings highlight sex-specific epigenetic changes in placental TH-related genes in relation to PBDE and OPE exposure, providing novel insights into fetal thyroid disruption pathways.

Animal studies have indicated that prenatal depression may affect the reproductive development of offspring. The digit ratio has been proposed as a marker of in utero reproductive development. The aim of this study was to explore the association between prenatal depression and the digit ratio (2nd:4th digit ratio (2D:4D)) in children. This study involved 668 mother-child pairs enrolled in the Shanghai-Minhang birth cohort study (S-MBCS). Prenatal depressive symptoms among pregnant women were evaluated during recruitment and late pregnancy using the validated Chinese version of the Center for Epidemiological Studies Depression Scale (CES-D). Measurements of digit lengths of both hands were conducted during follow-up visits at 4 and 6 years. We observed that mothers with prenatal depressive symptoms tended to have offspring with higher digit ratios at 4 and 6 years of age. For children whose mothers experienced depressive symptoms in the second trimester, the digit ratio of the left hand (2D:4DL) at 4 years of age increased by 0.007 (95% CI: 0.000, 0.015) in the subthreshold group and 0.010 (95% CI: 0.001, 0.019) in the screen-positive group. For those with depressive symptoms in the third trimester, the 2D:4DL in the screen-positive group increased by 0.012 (95% CI: 0.001, 0.023) at 4 years of age and 0.014 (95% CI: 0.003, 0.024) at 6 years of age. A dose-response relationship was established for both the strength and duration of depressive symptoms. Our study suggests that prenatal depressive symptoms may perturb the reproductive development of offspring and predominantly exhibit a feminizing effect.

Studies suggested that per- and polyfluoroalkyl substances (PFAS) may have adverse effects on fetus by altering placental DNA methylation. In the study, we explored associations of maternal PFAS concentrations with placental DNA methylation of thyroid hormone (TH)-related genes and the potential mediating role of DNA methylation levels in PFAS-fetal TH associations. We measured PFAS concentrations in maternal plasma in early pregnancy and levels of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in cord plasma. We assessed DNA methylation in 345 placental samples for five TH-related genes, i.e., iodothyronine deiodinase 3 (DIO3), solute carrier family 16 member 2 (SLC16A2), solute carrier organic anion transporter family member 1C1 (SLCO1C1), thyrotropin-releasing hormone (TRH), and transthyretin (TTR). We found the associations of PFDA with increased SLC16A2 methylation, PFOA with decreased SLCO1C1 methylation, PFOS with increased TRH methylation, and PFDoA with decreased TRH methylation, and these associations showed sex-specific patterns. Mediation analyses suggested placental SLCO1C1 and SLC16A2 methylation as potential mediators in the associations of PFOA with FT3 and PFUdA with TT4, respectively. These findings provided evidence for associations between prenatal PFAS exposure and epigenetic changes in placental TH-related genes.

Further phytochemical investigation on the twigs of Trichilia connaroides led to the isolation of nine limonoids (1, 2, and 5-11), one 3,4-seco-homo-cycloartane (3), and two steroids (4 and 12). The structures of these obtained isolates were established by means of detailed analyses of their extensive spectroscopic information and ECD calculations, four of them were elucidated as undescribed compounds (1-4). It is noted that an unprecedented 7-oxabicyclo[2.2.1]-heptane moiety in trichilitin M (1) was proposed by the linkage of C-11 and C-14 via an oxygen atom. All compounds were evaluated for their anti-tobacco mosaic virus (TMV) activities by the conventional half-leaf method and RT-PCR assays. Compared with the positive control ningnanmycin, compounds 1, 6, 7, and 11 showed significant anti-TMV biological activities. Futhermore, qRT-PCR assays suggested that the expression level of the TMV CP gene in inoculated and systemic K326 leaves treated by both 1 and 6, was significantly lower than that for the control group. More importantly, compounds 1 and 6 could not only inhibit the accumulation of TMV CP gene, but also enhance the host plant's resistance to TMV infection.

Urinary exposome analysis faces analytical challenges due to the lack of reference standards for biotransformed products and the wide structural diversity of metabolites. This study developed a chemically labeled exposome analysis (CLEAN) strategy for nontargeted identification of urinary metabolites. The strategy uses dansyl chloride (DnsCl) and N-methylphenylethylamine (MPEA) to label exogenous and endogenous molecules with phenolic hydroxyl, primary amine, and carboxyl groups and develops an integrated screening workflow based on diagnostic fragment ion filtering and machine learning-assisted retention time prediction and structure annotation. We applied the CLEAN strategy to screen for key environmental chemicals in pregnant women associated with small vulnerable newborns (SVN) in a nested case-control study of 80 SVN cases and 160 matched controls. Among 97 identified exogenous substances, 29 were detected in more than 70% samples. The BKMR analysis revealed a significant and positive association between mixed exposure and the SVN risk and identified 1-hydroxypyrene, monoisopropyl phthalate and pentabromophenol as the key exposure markers. Among the identified endogenous metabolites, four amino acids exhibited the strongest mediation effects on the environmental exposure-SVN associations. Collectively, our work demonstrates the ability of CLEAN to achieve high-throughput and accurate urinary exposome characterization, supporting large-scale human biomonitoring and epidemiological studies.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with potential developmental toxicity, yet human evidence, particularly for emerging PFAS, remains scarce. This study examined maternal plasma concentrations of 48 PFAS using an Agilent UPLC system coupled with a SCIEX 5500+ triple quadrupole mass spectrometer, and explored their associations with fetal growth in a Chinese birth cohort (n = 377). Perfluorooctanic acid (PFOA) exhibited the highest median level (12.88 ng/ml), followed by 6:2 chlorinated perfluoroether sulfonic acid (6:2 Cl-PFESA, 5.96 ng/mL) and perfluorooctanesulfonic acid (PFOS, 4.35 ng/mL). Nonafluoro-3,6-dioxaheptanoic acid was also detected in maternal plasma (median: 0.16 ng/mL, detection rate: 98 %), providing additional human exposure evidence for this emerging PFAS, particularly in early pregnancy. Higher perfluorodecanoic acid levels were significantly associated with reduced birth weight (β = -2.71 g, 95 % CI: -5.02, -0.39) and abdominal circumference (β = -1.74 cm, 95 % CI: -3.15, -0.33). PFOA was linked to reduced head circumference (β = -0.75 cm, 95 % CI: -1.25, -0.25). Sex-stratified analysis revealed that PFOS was negatively associated with abdominal circumference in female infants and with birth weight in males. In contrast, 8:2 Cl-PFESA and 6:2 fluorotelomer sulfonic acid were positively associated with abdominal circumference and birth weight in males, respectively. These findings highlight the developmental risks of both legacy and emerging PFAS, particularly their sex-specific effects, and underscore the need for continued surveillance and mechanistic studies.

Emerging chemicals (ECs), including parabens, bisphenols, bisphenol diglycidyl ethers, N,N′-substituted p-phenylenediamines, and benzotriazoles/benzothiazoles (BTH/BTRs), are widely used in industrial and consumer products. This study aimed to determine the urinary concentrations of 33 ECs and three oxidative stress biomarkers in pregnant women from a large birth cohort in Jiashan, China. Among the detected compounds, methyl paraben (MeP), bisphenol A (BPA), bisphenol A bis(2,3-dihydroxypropyl) glycidyl ether (BADGE·2H2O), N-isopropyl-N′-phenyl-1,4-phenylenediamine quinone (IPPDQ), and 1H-benzotriazole (1-H-BTR) were the most prevalent, with median concentrations ranging from 0.51 to 9.02 ng/mL. Notably, BTH/BTRs exhibited the highest exposure levels, approximately 4–16 times greater than those of other ECs. Most ECs showed elevated concentrations in pregnant women who were exposed to secondhand smoke prior to pregnancy. After model analysis, we found that mixtures of ECs were positively associated with both 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 15(R)-prostaglandin F2α (15-PGF2α), while a negative trend was observed between ECs and 8-iso-prostaglandin F2α (8-PGF2α). Specifically, urinary benzyl paraben (BzP), BPA, bisphenol S (BPS), N-(1,3-dimethylbutyl)-N′-phenyl-1,4-phenylenediamine quinone (6PPDQ), IPPDQ, 2(3H)-benzothiazole (2-OH-BTH), and 2-methylthio-benzothiazole (2-Me-S-BTH) or 1-H-BTR were significantly (p < 0.05) associated with 8-OHdG. MeP, 6PPDQ, and 2-Me-S-BTH were linked to 15-PGF2α, while only bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE·H2O) showed a significant positive association with 8-PGF2α. This study provides a comprehensive evaluation of the exposure characteristics of ECs and their associations with oxidative stress biomarkers in pregnant women, offering new insights into the health risks associated with ECs exposure during critical periods of pregnancy.

This study presents a streamlined stereoselective synthesis strategy for constructing the highly congested cage-like tetracyclic core of cipadonoid A, employing visible-light photoredox catalysis to enable intramolecular Giese-type radical cyclization as a key step. Density Functional Theory (DFT) analysis revealed that the selective formation of the cis-fused AB bicyclic framework is controlled by intramolecular hydrogen bonding-mediated conformational stabilization. Notably, the synthesized B,D-seco-limonoid scaffold exhibited lysosomal biogenesis enhancing activity on par with its natural counterpart, with comparative bioassays demonstrating equivalent efficacy between the synthetic derivative and native cipadonoid A (1) in promoting lysosomal biogenesis.

Organic ultraviolet (UV) filters, chemicals protecting against harmful UV radiation, are extensively incorporated into personal care products and polymers. Evidence regarding the impacts of prenatal UV filter exposure on children's neurodevelopment remains limited. In this study, we included 393 mother-offspring pairs from the Shanghai-Minhang Birth Cohort Study. Maternal urinary concentrations of UV filters in the third trimester of pregnancy were quantified, and children's cognitive and neurobehavioral development was evaluated by the Wechsler Intelligence Scale and Child Behavior Checklist at six years of age. The effects of individual UV filters were examined using linear regression or negative binomial regression, and their combined effect was examined using Bayesian Kernel Machine Regression (BKMR) and Quantile G-Computation (QG-C) models. Our results showed that Oxybenzone (BP-3) exposure in the third tertile was significantly associated with decreased scores in Full Scale Intelligence Quotient (FSIQ), Perceptual Reasoning Index (PRI), and Verbal Comprehension Index (VCI). The BKMR model revealed a higher level of the UV filter mixture was inversely associated with FSIQ and PRI. Notably, the adverse effect of UV filters on cognitive development was modified by sex. In males, a higher level of the UV filter mixture was inversely associated with all three cognitive measures of neurodevelopment whereas no significant associations were observed in females. The results were further supported by the QG-C model. In terms of neurobehavior development, Bumetrizole (UV-326) was associated with higher scores on externalizing problems in the total population. However, no association was observed in BKMR or QG-C models. In conclusion, our results suggest that prenatal exposure to UV filters may be associated with impairment of both cognitive and neurobehavioral development at six years old. Further studies are required to confirm these associations and explore the underlying biological mechanisms, especially regarding sex-specific vulnerabilities.

Maternal exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with offspring adiposity; however, underlying mechanisms remain unclear. In this study, we quantified 11 PFAS in maternal plasma collected between 12 and 16 gestational weeks and 104 lipid metabolites in the cord blood of 525 mother-infant pairs. Principal components of multiple PFAS compounds, extracted by principal component analysis, were employed to investigate the effect of the PFAS mixture. Infant anthropometric indicators included weight, length, waist/arm circumference, and abdominal/triceps/subscapular skinfold thickness at birth and 6 and 12 months old. Multiple linear regression showed that maternal PFAS exposure was primarily associated with increased glycerophospholipids and decreased fatty acyls and bile acids in cord blood. Four glycerophospholipids (16:0 PI, 16:0-18:1 PI, 18:0-20:4 PI, and 18:0-18:1 PS), fatty acyls (5(S)-HETE, 15(S)-HETE, 13-HDoHE, and dhkPGF2), and bile acids (GCA, TCA, TCDA, and TDCA) partially mediated the positive associations of the first principle component of PFAS compounds (with positive loadings for all PFAS compounds), PFNA, and PFUdA with infant skinfold thickness with mediating proportions ranging from 15.24% to 33.39%. Our findings provide novel insights into mechanisms underlying the effects of maternal PFAS exposure on infant growth.

Accumulating evidence indicates that elevated maternal glucose concentrations during pregnancy are associated with adverse birth outcomes, but the mechanistic underpinnings remain unclear. This study aimed to evaluate the associations between maternal glucose concentrations and DNA methylation levels in genes related to the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the human placenta and explore the potential mediating role of placental DNA methylation in the relationship between maternal glucose concentrations and neonatal anthropometric measures. Maternal glucose concentrations were obtained from medical records, and neonatal anthropometric parameters were measured in 335 mother–infant pairs. DNA methylation levels of 14 genes related to the PPAR signaling pathway were analyzed in placental samples. Multiple linear regression models and mediation analyses were used to examine the associations and potential mediation effects. Higher maternal fasting plasma glucose (FPG) concentrations were generally associated with hypomethylation of genes related to the PPAR signaling pathway, with stronger effects in male neonates. Maternal 1-h plasma glucose concentrations after the glucose challenge test exhibited weaker but consistent patterns. Mediation analyses indicated that hypomethylation of ACAA1 mediated 29.00