Healthy dietary patterns are associated with exposure to environmental chemicals in a pregnancy cohort.

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory efforts aimed at lowering environmental chemical exposure.

Perinatal exposure to perfluorooctane sulfonate and the risk of hepatic inflammation in rat offspring: Perturbation of gut-liver crosstalk.

Perfluorooctane sulfonate (PFOS) exposure is associated with harmful hepatic outcomes. Growing evidence indicates that crosstalk between the gut microbiome, immune system, and liver plays a vital role in the pathogenesis of liver diseases. However, the underlying mechanism is not fully understood. In the present study, we aimed to investigate the effects of PFOS exposure during pregnancy and lactation on hepatic inflammation in rat offspring. Features of hepatic inflammation and increased levels of aspartate-amino transferase (AST) were found in pups on postnatal day 28 (PND28) in PFOS-exposed groups. Gut microbiota analysis identified Chitinophaga, Ralstonia, and Alloprevotella as the key genera in distinguishing the PFOS-exposed group from the control group. Metabolic and transcriptomic analyses found that PFOS exposure resulted in 48 differentially expressed metabolites (DEMs) in the serum, 62 DEMs in the liver, and 289 differentially expressed genes (DEGs) in the liver of PND28 pups. The immune response is significantly enriched in PFOS-exposed liver on PND28; multi-omics analysis indicated that PFOS might lead to immune response perturbation by disturbing the metabolic profiling in the liver. The changed gut microbiota was significantly related to the serum level of the liver function index. Specifically, Alloprevotella, Chitinophage, Ruminococcus, and Allobaculum were significantly associated with the metabolic abundance changes of 4-Hydroxydebrisoquine, L-Norvaline, and Eremopetasinorol, and the gene expression changes of Acat211, Msmol, Idi1, Sqle, and Gadd45b in the liver. These findings suggest that early-life PFOS exposure may be associated with adverse hepatic inflammation in young offspring via disruption of the gut-liver crosstalk, which may provide mechanistic clues for clarifying the hepatotoxicity in offspring associated with perinatal PFOS exposure.

Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid.

Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3% starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including Gstm1, Kit, Adcy1, Gck, Ppp1r3c, Ppp1r3d, and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

ortho-Alkynyl Benzyl Alcohols as C6 Synthons in Regioselective Construction of Polysubstituted Naphthalenes.

A straightforward methodology for the assembly of polysubstituted naphthalenes from ortho-alkynyl benzyl alcohols, enabled by using catalytic amounts of Tf2O, has been developed. This transformation not only features transition-metal free and without using other bases and additives but also provides a new synthetic application for ortho-alkynyl benzyl alcohols, i.e., as C6 synthons for the construction of PAHs.

Enhanced bioavailability of curcumin amorphous nanocomposite prepared by a green process using modified starch.

Curcumin (Cur), a bioactive compound extracted from plants, has attracted widespread attention due to its multiple pharmacological activities. However, the low bioavailability due to the inherent limitations in water solubility, chemical stability, and permeability poses great challenges for realizing its clinical potentials. In the current study, octenyl succinic anhydride-modified starch (OSA-S), a renewable and biodegradable biopolymer, was employed to fabricate Cur amorphous composite nanoparticles (Cur/OSA-S NPs) through a solvent-free pH-driven method with the aim to enhance Cur's bioavailability by improving its solubility and stability. Cur/OSA-S NPs, with mean sizes of about 128.9 ± 8.6 nm, encapsulation efficiencies of about 90.0 %, and the drug loading capacities around 51.0 ± 0.2 %, were successfully prepared. Cur was found to be dispersed within the composite nanoparticles in amorphous state as confirmed by the XRD and DSC characterizations. In addition, Cur/OSA-S NPs offers excellent storage, thermal and light stability, excellent re-dispersibility, and approximately 92 times better solubility than the original Cur. Furthermore, studies of dissolution and the parallel artificial membrane permeability assay (PAMPA) confirmed enhanced dissolution rates and in vitro permeabilities of Cur/OSA-S NPs. Cancer cell viability and uptake experiments revealed that Cur/OSA-S NPs possessed more potent inhibitory effects on cancer cell proliferation compared to the raw Cur. The results obtained from the current study demonstrated the effectiveness of OSA-S for manufacturing Cur amorphous composite nanoparticles with enhanced solubility, stability, and permeability, which might be valuable for further development of Cur based products for treatment of various diseases.

Metabolomic Biomarkers of Dietary Approaches to Stop Hypertension (DASH) Dietary Patterns in Pregnant Women.

Objective: the aim of this study was to identify plasma metabolomic markers of Dietary Approaches to Stop Hypertension (DASH) dietary patterns in pregnant women. Methods: This study included 186 women who had both dietary intake and metabolome measured from a nested case-control study within the NICHD Fetal Growth Studies-Singletons cohort (FGS). Dietary intakes were ascertained at 8-13 gestational weeks (GW) using the Food Frequency Questionnaire (FFQ) and DASH scores were calculated based on eight food and nutrient components. Fasting plasma samples were collected at 15-26 GW and untargeted metabolomic profiling was performed. Multivariable linear regression models were used to examine the association of individual metabolites with the DASH score. Least absolute shrinkage and selection operator (LASSO) regression was used to select a panel of metabolites jointly associated with the DASH score. Results: Of the total 460 known metabolites, 92 were individually associated with DASH score in linear regressions, 25 were selected as a panel by LASSO regressions, and 18 were identified by both methods. Among the top 18 metabolites, there were 11 lipids and lipid-like molecules (i.e., TG (49:1), TG (52:2), PC (31:0), PC (35:3), PC (36:4) C, PC (36:5) B, PC (38:4) B, PC (42:6), SM (d32:0), gamma-tocopherol, and dodecanoic acid), 5 organic acids and derivatives (i.e., asparagine, beta-alanine, glycine, taurine, and hydroxycarbamate), 1 organic oxygen compound (i.e., xylitol), and 1 organoheterocyclic compound (i.e., maleimide). Conclusions: our study identified plasma metabolomic markers for DASH dietary patterns in pregnant women, with most of being lipids and lipid-like molecules.

Transcriptomic and metabolomic profile changes in the liver of Sprague Dawley rat offspring after maternal PFOS exposure during gestation and lactation.

Epidemiological and experimental research has indicated an association between perfluorooctane sulfonate (PFOS) exposure and liver disease. However, the potential hepatotoxic effects and mechanisms of low-level prenatal PFOS exposure in offspring remain ambiguous. The objective of this research was to examine the alterations in liver transcriptomic and metabolomic profiles in offspring rats at postnatal day (PND) 30 following gestational and lactational exposure to PFOS (from gestational day 1 to 20 and PND 1 to 21). Pregnant Sprague-Dawley rats were separated into a control group (3% starch gel solution, oral gavage) and a PFOS exposure group (0.03 mg/kg body weight per day, oral gavage). Histopathological changes in liver sections were observed by hematoxylin and eosin staining. Biochemical analysis was conducted to evaluate changes in glucose and lipid metabolism. Transcriptomic and metabolomic analyses were utilized to identify significant genes and metabolites associated with alterations of liver glucose and lipid metabolism through an integrated multi-omics analysis. No significant differences were found in the measured biochemical parameters. In total, 167 significant differentially expressed genes (DEGs) related to processes such as steroid biosynthesis, PPAR signaling pathway, and fat digestion and absorption were identified in offspring rats in the PFOS exposure group. Ninety-five altered metabolites were exhibited in the PFOS exposure group, such as heptaethylene glycol, lysoPE (0:0/18:0), lucidenic acid K, and p-Cresol sulfate. DEGs associated with steroid biosynthesis, PPAR signaling pathway, fat digestion and absorption were significantly upregulated in the PFOS exposure group (P < 0.05). The analysis of correlations indicated that there was a significant inverse correlation between all identified differential metabolites and the levels of fasting blood glucose, high-density lipoprotein, and triglycerides in the PFOS exposure group (P < 0.05). Our findings demystify that early-life PFOS exposure can lead to alterations in transcriptomic and metabolomic profiles in the offspring's liver, which provided mechanistic insights into the potential hepatotoxicity and developmental toxicity associated with environmentally relevant levels of PFOS exposure.

Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: findings from a multiracial cohort.

BACKGROUND: Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort. METHODS: We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using weighted correlation network analysis and common networks using consensus network analysis across four visits using linear mixed-effects models with the adjustment of false discover rate. FINDINGS: Multiple triglycerides (TG) were positively associated with birth weight (BW), BW Z-score, length and head circumference, while some cholesteryl ester (CE), phosphatidylcholine (PC), sphingomyelines (SM), phosphatidylethanolamines (PE), and lysophosphatidylcholines (LPC 20:3) families were inversely associated with BW, length, abdominal and head circumference at different GWs. Longitudinal trajectories of TG, PC, and glucosylcermides (GlcCer) were associated with BW, and CE (18:2) with BW z-score, length, and sum of skinfolds (SS), while some PC and PE were significantly associated with abdominal and head circumference. Modules of TG at GW 10-14 and 15-26 mainly were associated with BW. At GW 33-39, two networks of LPC (20:3) and of PC, TG, and CE, showed inverse associations with abdominal circumference. Distinct trajectories within two consensus modules with changes in TG, CE, PC, and LPC showed significant differences in BW and length. INTERPRETATION: The results demonstrated that longitudinal changes of TGs during early- and mid-pregnancy and changes of PC, LPC, and CE during late-pregnancy were significantly associated with neonatal anthropometry. FUNDING: National Institute of Child Health and Human Development intramural funding.

Transcriptomics integrated with metabolomics reveals perfluorobutane sulfonate (PFBS) exposure effect during pregnancy and lactation on lipid metabolism in rat offspring.

Emerging epidemiological evidence indicates potential associations between gestational perfluorobutane sulfonate (PFBS) exposure and adverse metabolic outcomes in offspring. However, the underlying mechanisms remain unclear. Our study aimed to investigate PFBS exposure effects during pregnancy and lactation on rat offspring lipid profiles and the possible underlying mechanisms. Although the biochemical index difference including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine amino transaminase (ALT), aspartate amino transferase (AST), and fasting blood glucose between exposed groups and the control group was not significant, transcriptome analyses showed that the differentially expressed genes (DEGs) in the 50 mg/kg/day PFBS exposure group were significantly related to protein digestion and absorption, peroxisome proliferator activated-receptor (PPAR) signaling pathway, xenobiotic metabolism by cytochrome P450, glycine, serine and threonine metabolism, ß-alanine metabolism, bile secretion, unsaturated fatty acid (FA) biosynthesis, and alanine, aspartate and glutamate metabolism. Untargeted metabolomics analyses identified 17 differential metabolites in the 50 mg/kg/day PFBS exposure group. Among these, phosphatidylserine [PS (18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))], lysoPE (18:1(11Z)/0:0), and PS (14:0/20:4(5Z,8Z,11Z,14Z)) were significantly correlated with phospholipid metabolism disorders. Correlation analysis indicated the DEGs, including FA binding protein (Fabp4), spermine oxidase (Smox), Fabp2, acyl-CoA thioesterase 5 (Acot5), sarcosine dehydrogenase (Sardh), and amine oxidase, copper-containing 3 (Aoc3) that significantly enriched in xenobiotic metabolism by cytochrome P450 and glycine, serine, and threonine metabolism signaling pathways were highly related to the differential metabolite pantetheine 4'-phosphate. Pantetheine 4'-phosphate was significantly negatively associated with non-high-density lipoprotein (non-HDL) and TC levels. Collectively, our study indicated that maternal PFBS exposure at a relatively low level could alter gene expression and metabolic molecules in lipid metabolism-related pathway series in rat offspring, although the effects on metabolic phenotypes were not significant within the limited observational period, using group-wise and trend analyses.

Exposure to multiple air pollutant mixtures and the subtypes of hypertensive disorders in pregnancy: A multicenter study.

BACKGROUND: Hypertensive disorders in pregnancy (HDP) have heterogeneous etiologies. Previous studies have linked individual air pollutants to overall HDP with inconsistent results. Moreover, it has not been explored how exposure to a mixture of multiple air pollutants may affect the risks of the subtypes of the disorders. OBJECTIVES: To investigate the associations of exposure to air pollutant mixture in the 1st and 2nd trimesters of pregnancy with the risks of HDP and its subtypes. METHODS: Pregnancy data were obtained from the China Labor and Delivery Survey, a nationwide cross-sectional survey in 2015 and 2016. Levels of air pollutants [including fine particulate matter (PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2)] in the 1st and 2nd trimesters were estimated based on the model developed by the Institution of Atmospheric Physics, Chinese Academy of Science. Generalized linear mixed models were built to assess the single-exposure effects of air pollutants in early gestation on HDP. The restricted cubic spline function was further applied to assess the potential non-linearity. The weighted quantile sum (WQS) regression was used to investigate the effects of co-exposure to multiple air pollutants. RESULTS: A total of 67,512 pregnancies were included, and 2,834 were HDP cases. The single-effect analysis showed that CO, PM2.5, and SO2 exposure in the 2nd trimester was positively associated with the risks of gestational hypertension (GH), with adjusted odds ratios (aORs) and 95% confidence intervals (CI) of 1.16 (1.04, 1.28), 1.19 (1.04, 1.37), and 1.13 (1.04, 1.22), respectively. The first-trimester O3 exposure was also associated with an increased preeclampsia/eclampsia (PE) risk (aOR = 1.17; 95%CI: 1.02, 1.33). WQS regression confirmed positive associations of air pollutant mixture with HDP subtypes, with PM2.5 as the main contributing pollutant to GH, and CO and O3 as the main pollutants to PE. CONCLUSIONS: Exposure to multiple air pollutant mixtures in early pregnancy was associated with increased risks of hypertensive disorders in pregnancy.

Extreme Temperature Exposure and Risks of Preterm Birth Subtypes Based on a Nationwide Survey in China.

BACKGROUND: Previous studies have reported that ambient temperature may affect perinatal outcomes. However, whether extreme temperature affects the risk of preterm birth (PTB) remains controversial. Studies on the associations of extreme temperature with PTB subtypes are lacking. OBJECTIVES: We aimed to investigate the associations of extreme climate events with the risks of PTB and its subtypes, discerning possible modifiers. METHODS: Data on all singleton deliveries were obtained from the China Labor and Delivery Survey (CLDS), a nationwide investigation implemented in 2015 and 2016. PTB was defined as gestational weeks <37 and then categorized as early (24-34 wk) and late PTBs (35-36 wk), and clinical subtypes [spontaneous PTB, preterm premature rupture of the fetal membranes (PPROM), iatrogenic PTB]. Ambient temperature data were provided by the China National Weather Data Sharing System. Five heat indexes and five cold indexes were used to define heat waves and cold spells. Generalized linear mixed models with a random term by hospital unit were used to assess the associations of short-term prenatal extreme temperature exposure. The Cox proportional hazard regression model was applied to assess the nonlinear associations of low- or high-temperature exposure at the whole and different trimesters of pregnancy with the risk of PTB. Stratified analyses were conducted to assess the possible modification by geographic region and fetal sex. RESULTS: A total of 70,818 singleton births from 96 hospitals in China were included, among which 4,965 (7.01%) were PTBs. Exposure to extreme cold events 1 wk before delivery was associated with an increased PTB risk, with an adjusted odds ratio (aOR) [95% confidence intervals (CIs)] of 1.07 (95% CI: 1.04, 1.10) and 1.06 (1.04, 1.09) for the total days when the daily average temperature below the fifth percentile (fifth-days) and the 10th percentile (10th-days), 1.18 (1.04, 1.34) for the cold spells when the daily average temperature below the fifth percentile for two consecutive days (fifth-2D), 1.09 (1.03, 1.16) and 1.12 (1.06, 1.19) for the cold spells when the daily average temperature below the 10th percentile for three and two consecutive days (10th-3D and 10th-2D), respectively. Results of extreme temperature exposure during 2 weeks before delivery showed similarly significant associations. The association between cold spells and PTB tended to be stronger for late PTB than for early PTB. Cold spells were mainly associated with spontaneous PTB and late PPROM. A stratified analysis indicated that pregnant women in western and northern regions tended to be more sensitive to cold spells, and pregnant women with a female fetus appeared to be at a higher risk of PTB when exposed to cold spells. Pregnant women in late pregnancy were more susceptible to extreme temperatures. No significant or stable association was found between heat waves and preterm birth. DISCUSSION: Exposure to cold spells was associated with an increased risk of PTB, especially late, spontaneous PTB and PPROM. The associations appeared to be more pronounced in the north and west regions and in pregnancies with female fetuses. https://doi.org/10.1289/EHP10831.

Effects of organic pollutants on struvite crystallization kinetics and the molecular mechanism of inhibition on crystal growth.

The abilities of improving phosphorus (P) resources sustainability and reducing water eutrophication make struvite crystallization technology attract increasing interest in wastewater treatment, but struvite crystallization process may be affected by various impurities in wastewater. In this study, the effects of nine representative ionic surfactants including three types (anionic, cationic and zwitterionic) on crystallization kinetics and product quality of struvite were investigated, and the influencing mechanism was further probed. The results demonstrated that anionic surfactants significantly inhibit crystal growth so as to reduce crystal size especially in a-axis direction, change crystal morphology and decrease P recovery efficiency, and also lead to a slight decline in product purity. In contrast, cationic and zwitterionic surfactants have no obvious influence on the formation of struvite. A series of experimental characterizations and molecular simulations collectively revealed that the inhibition of crystal growth by anionic surfactants is attributed to the adsorption of anionic surfactant molecules on struvite crystal surface and subsequent blockage of active growth sites. The binding ability of surfactant molecules with the Mg2+ exposed on struvite crystal surface was highlighted to be the most essential factor determining the adsorption behavior and adsorption capacity. Anionic surfactants with stronger binding ability with Mg2+ have more intense inhibitory effect, but a large molecular volume of anionic surfactants will weaken the adsorption capacity on crystal surface so as to reduce the inhibitory effect. Contrastively, cationic and zwitterion surfactants without binding ability with Mg2+ have no inhibitory effect. These findings enable us to have a clearer understanding of the impact of organic pollutants on struvite crystallization and make a preliminary judgment on the organic pollutants that may have the ability to inhibit the crystal growth of struvite.

Early life exposure to low-dose perfluorooctane sulfonate disturbs gut barrier homeostasis and increases the risk of intestinal inflammation in offspring.

Perfluorooctane sulfonate (PFOS), one of the legacy per- and poly-fluoroalkyl substances (PFAS), is associated with multiple adverse health effects on children. However, much remains to be known about its potential impacts on intestinal immune homeostasis during early life. Our study found that PFOS exposure during pregnancy in rats significantly increased the maternal serum levels of interleukin-6 (IL-6) and zonulin, a gut permeability biomarker, and decreased gene expressions of Tight junction protein 1 (Tjp1) and Claudin-4 (Cldn4), the tight junction proteins, in maternal colons on gestation day 20 (GD20). Being exposed to PFOS during pregnancy and lactation in rats significantly decreased the body weight of pups and increased the offspring's serum levels of IL-6 and tumor necrosis factor-α (TNF-α) on postnatal day 14 (PND14), and induced a disrupted gut tight junction, manifested by decreased expressions of Tjp1 in pup's colons on PND14 and increased pup's serum concentrations of zonulin on PND28. By integrating high-throughput 16S rRNA sequencing and metabolomics, we demonstrated that early-life PFOS exposure altered the diversity and composition of gut microbiota that were correlated with the changed metabolites in serum. The altered blood metabolome was associated with increased proinflammatory cytokines in offspring. These changes and correlations were divergent at each developmental stage, and pathways underlying immune homeostasis imbalance were significantly enriched in the PFOS-exposed gut. Our findings provide new evidence for the developmental toxicity of PFOS and its underlying mechanism and explain in part the epidemiological observation of its immunotoxicity.

Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis.

Emerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be linked to the disturbance of gestational glucolipid metabolism, but the toxicological mechanism is unclear, especially when the exposure is at a low level. This study examined the glucolipid metabolic changes in pregnant rats treated with relatively low dose perfluorooctanesulfonic acid (PFOS) through oral gavage during pregnancy [gestational day (GD): 1-18]. We explored the molecular mechanisms underlying the metabolic perturbation. Oral glucose tolerance test (OGTT) and biochemical tests were performed to assess the glucose homeostasis and serum lipid profiles in pregnant Sprague-Dawley (SD) rats randomly assigned to starch, 0.03 and 0.3 mg/kg·bw·d groups. Transcriptome sequencing combined with non-targeted metabolomic assays were further performed to identify differentially altered genes and metabolites in the liver of maternal rats, and to determine their correlation with the maternal metabolic phenotypes. Results of transcriptome showed that differentially expressed genes at 0.03 and 0.3 mg/kg·bw·d PFOS exposure were related to several metabolic pathways, such as peroxisome proliferator-activated receptors (PPARs) signaling, ovarian steroid synthesis, arachidonic acid metabolism, insulin resistance, cholesterol metabolism, unsaturated fatty acid synthesis, bile acid secretion. The untargeted metabolomics identified 164 and 158 differential metabolites in 0.03 and 0.3 mg/kg·bw·d exposure groups, respectively under negative ion mode of Electrospray Ionization (ESI-), which could be enriched in metabolic pathways such as α-linolenic acid metabolism, glycolysis/gluconeogenesis, glycerolipid metabolism, glucagon signaling pathway, glycine, serine and threonine metabolism. Co-enrichment analysis indicated that PFOS exposure may disturb the metabolism pathways of glycerolipid, glycolysis/gluconeogenesis, linoleic acid, steroid biosynthesis, glycine, serine and threonine. The key involved genes included down-regulated Ppp1r3c and Abcd2, and up-regulated Ogdhland Ppp1r3g, and the key metabolites such as increased glycerol 3-phosphate and lactosylceramide were further identified. Both of them were significantly associated with maternal fasting blood glucose (FBG) level. Our findings may provide mechanistic clues for clarifying metabolic toxicity of PFOS in human, especially for susceptible population such as pregnant women.

Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement.

Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits. Thus, targeting PDE4 may be a viable strategy for cognitive improvement. Currently, many PDE4 inhibitors have been discovered but with a great hurdle in clinical development due to adverse effects such as emesis. Analysis of PDE4 subtypes and discovery of subtype specific regulators indicate therapeutic benefits with improved safety in preclinical and clinical models. Herein, we summarize PDE4 structure, describe PDE4 mediated signaling pathways, review the role of individual PDE4 subtypes and discuss the development of PDE4 inhibitors for cognitive improvement, trying to give an insight into the strategy for cognitive improvement with PDE4 inhibitors in future.

Acute and chronic maternal exposure to fine particulate matter and prelabor rupture of the fetal membranes: A nation-wide survey in China.

BACKGROUND: Prelabor rupture of the fetal membranes (PROM) is a major contributor to adverse perinatal outcomes. Some epidemiologic studies explored the association between maternal PM2.5 exposure and PROM but failed to treat the labor induction and prelabor cesarean section as censored observations. OBJECTIVE: We aimed to evaluated whether acute and chronic maternal ambient PM2.5 exposure may increase the risk of PROM in China. METHODS: This study was based on the China Labor and Delivery Survey, a nationwide multicenter investigation. Included in the current analysis were 45,879 singleton spontaneous births in 96 hospitals in mainland China from 2015 to 2017. Outcomes were PROM, preterm PROM (<37 weeks' gestation) and term PROM (≥37 weeks' gestation). Daily concentration of PM2.5 at 1 km spatial resolution was estimated by gap-filling model. Generalized linear mixed model and mixed effects Cox model were applied to assess the associations of acute (from 0 to 4 days before delivery) and chronic (average gestational and trimester-specific) ambient PM2.5 exposure with outcomes, respectively. RESULTS: Significant associations were found between acute PM2.5 exposures (per interquartile range increase) and the risk of preterm PROM (OR = 1.11; 95 % CI: 1.03, 1.19 for PM2.5 on delivery day; OR = 1.10; 95 % CI: 1.02, 1.18 for PM2.5 1 day before delivery) but not for term PROM. An interquartile range increase in PM2.5 during the second trimester was associated with elevated risks of PROM (HR = 1.14; 95 % CI: 1.07, 1.22), preterm PROM (HR = 1.22; 95 % CI: 1.02, 1.45) and term PROM (HR = 1.13; 95 % CI: 1.06, 1.22), respectively. Women who were less educated, obese, or gave birth in a cold season appeared to be more sensitive to ambient PM2.5 exposure. CONCLUSION: Our findings suggest that both acute and chronic maternal exposures to ambient PM2.5 during pregnancy are risk factors for PROM.

Prenatal Exposure to PM2.5 and Its Specific Components and Risk of Hypertensive Disorders in Pregnancy: A Nationwide Cohort Study in China.

Hypertensive disorders in pregnancy (HDP) are a leading cause of maternal mortality and adverse birth outcomes. Fine particulate matter (PM2.5) has been linked to HDP risk; however, limited studies have explored the relationships between specific chemical constituents of PM2.5 and HDP risk. Based on maternal data from the China Labor and Delivery Survey (CLDS), this study included a total of 67,659 participants from 95 participant hospitals in 25 provinces of China between March 1, 2015, and December 31, 2016. Maternal exposure to total PM2.5 mass and six main components during pregestation and pregnancy were estimated using the Combined Geoscience-Statistical Method. Multilevel logistic regression models were applied to quantify the associations, controlling for sociodemographic characteristics. We found that an interquartile range (IQR) increase in PM2.5 exposure during the second trimester was associated with a 14% increase in HDP risk (95% CI: 2%, 29%). We observed that black carbon (BC) and SO42- had larger or comparable estimates of the effect than total PM2.5 mass. The association estimates were greater in the gestational hypertension group than in the group of pre-eclampsia and eclampsia. Our findings suggest that PM2.5 exposure and specific chemical components (particularly BC and SO42-) were associated with an increased HDP risk in China.

Exposure to perfluoroalkyl substances and neurodevelopment in 2-year-old children: A prospective cohort study.

BACKGROUND: Humans are widely exposed to per- and polyfluoroalkyl substances (PFAS). As fetal stage is a critical window for neurodevelopment, it is important to know if in utero exposure to PFAS affects fetal neurodevelopment. However, previous human studies are both limited and inconsistent. OBJECTIVES: To investigate the relationship between PFAS exposure during early pregnancy and the neurodevelopmental status at 2 years of age in a prospective cohort study. METHODS: We measured 10 PFAS in maternal plasma samples collected prior to 16 weeks of gestation in the Shanghai Birth Cohort Study between 2013 and 2016. Childhood neurodevelopment was assessed at 2 years of age using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Associations with domain specific scores for individual PFAS were assessed by multiple linear regression and binary logistic regression when scores were dichotomized. Quantile-based g-computation was used to estimate the joint effects of PFAS mixture. RESULTS: A total of 2257 mother-child pairs who had both PFAS and BSID measurements were included in our analyses. The means and standard deviations of comprehensive scores were 115 ± 22, 96 ± 15 and 108 ± 15 for cognition, language, and motor, respectively. In multiple linear regressions, we observed significant negative associations of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluoroundecanoic acid (PFUnDA) with cognitive scores; PFNA, PFDeA, PFUnDA and perfluorohexanesulfonate (PFHxS) negatively with language scores; and PFNA and PFUnDA negatively with motor scores. Quantile-based g-computation showed that PFAS mixture was significantly associated with decreased cognitive and language scores, with an estimated ß of -2.1 [95% confidence interval (CI): -3.5, -0.7)] and -2.0 (95% CI: -2.9, -1.0) per one quartile increase in PFAS mixture for cognitive and language domains, respectively. PFAS mixture was associated with increased odds of low cognition (adjusted odds ratio [OR] = 1.3, 95% CI:1.0, 1.6) and language scores (OR = 1.2, 95% CI: 1.1, 1.3). CONCLUSIONS: PFAS exposure during early pregnancy was significantly associated with the adverse neurodevelopmental status at 2 years of age, which raises a serious public health concern.

DPSSD: Dual-Path Single-Shot Detector.

Object detection is one of the most important and challenging branches of computer vision. It has been widely used in people's lives, such as for surveillance security and autonomous driving. We propose a novel dual-path multi-scale object detection paradigm in order to extract more abundant feature information for the object detection task and optimize the multi-scale object detection problem, and based on this, we design a single-stage general object detection algorithm called Dual-Path Single-Shot Detector (DPSSD). The dual path ensures that shallow features, i.e., residual path and concatenation path, can be more easily utilized to improve detection accuracy. Our improved dual-path network is more adaptable to multi-scale object detection tasks, and we combine it with the feature fusion module to generate a multi-scale feature learning paradigm called the "Dual-Path Feature Pyramid". We trained the models on PASCAL VOC datasets and COCO datasets with 320 pixels and 512 pixels input, respectively, and performed inference experiments to validate the structures in the neural network. The experimental results show that our algorithm has an advantage over anchor-based single-stage object detection algorithms and achieves an advanced level in average accuracy. Researchers can replicate the reported results of this paper.

Environmental exposure to per- and polyfluoroalkyl substances and sleep disturbance in pregnant women: A prospective cohort study.

Previous studies on the association between exposure to per- and polyfluoroalkyl substances (PFAS) and sleep patterns in pregnant women are limited. This cohort study aims to assess the associations between PFAS and sleep quality in pregnant women. Of the 4127 women who participated in the Shanghai Birth Cohort, 3174, 3070, and 2887 women in their first, second, and third trimesters of gestation, respectively, were included in our analysis. Sleep measures were taken using the Pittsburgh Sleep Quality Index questionnaire. Ten PFAS were measured in blood samples collected in early pregnancy. We first evaluate the associations between individual PFAS and sleep quality in the three trimesters. Weighted quantile sum (WQS) regression models were performed to test the overall effect of the PFAS mixture on sleep quality during the three trimesters. Longitudinal analyses throughout pregnancy were performed with generalized estimating equation models. Furthermore, the effect of the PFAS mixture on longitudinal sleep patterns was examined using longitudinal latent class analyses combined with WQS models. The single pollutant analysis suggested that most PFAS were associated with increased sleep disturbance risk, lower sleep efficiency, and shorter sleep duration in the three trimesters. Similarly, the WQS models revealed a significant association between the PFAS mixtures and elevated sleep disturbance risk in pregnant women, with perfluorobutane sulfonate acting as the predominant risk factor. Additionally, the longitudinal analysis confirmed the effects of PFAS exposure on increased sleep disturbance over time. The PFAS mixture was positively associated with higher risks of poor sleep quality and sleep medicine use [adjusted odds ratio (aOR) = 1.10; 95 % confidence interval (95%CI): 1.01, 1.20; and aOR = 1.25 (95%CI: 1.04, 1.50) respectively] throughout the three trimesters. Our study suggests that PFAS may increase the risk of sleep disturbance in pregnant women. Further studies are needed to confirm our results and elucidate potential mechanisms.