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.

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.

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.

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.

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.

Associations of Ambient Fine Particulate Matter and Its Chemical Constituents with Birth Weight for Gestational Age in China: A Nationwide Survey.

This study examined the associations of fine particulate matter (PM2.5) and its chemical constituents with risks of small for gestational age (SGA) and large for gestational age (LGA). Based on the China Labor and Delivery Survey, we included 70,206 birth records from 24 provinces in China. Concentrations of PM2.5 mass and six main constituents were estimated using satellite-based models. Logistic regression analysis was used to examine the associations, adjusted for sociodemographic characteristics and time trends. We found that an interquartile range increase in PM2.5 exposure during pregnancy was associated with 16% (95% confidence interval [CI]: 3-30%) and 11% (95% CI: 1-22%) higher risk of SGA and LGA, respectively. Elevated risk of SGA was associated with exposure to black carbon [odds ratio (OR) = 1.15, 95% CI: 1.00-1.32], ammonium (OR = 1.12, 95% CI: 1.01-1.25), and sulfate (OR = 1.12, 95% CI: 1.04-1.21); while increased risk of LGA was associated with exposure to black carbon (OR = 1.13, 95% CI: 1.02-1.26), ammonium (OR = 1.13, 95% CI: 1.03-1.24), sulfate (OR = 1.08, 95% CI: 1.01-1.15), and nitrate (OR = 1.14, 95% CI: 1.03-1.27). Our findings provide evidence that PM2.5 exposure was associated with increased risks of SGA and LGA, and constituents related to emissions from anthropogenic sources may play important roles in these associations.

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.

Identifying the Strength Level of Objects' Tactile Attributes Using a Multi-Scale Convolutional Neural Network.

In order to solve the problem in which most currently existing research focuses on the binary tactile attributes of objects and ignores identifying the strength level of tactile attributes, this paper establishes a tactile data set of the strength level of objects' elasticity and hardness attributes to make up for the lack of relevant data, and proposes a multi-scale convolutional neural network to identify the strength level of object attributes. The network recognizes the different attributes and identifies differences in the strength level of the same object attributes by fusing the original features, i.e., the single-channel features and multi-channel features of the data. A variety of evaluation methods were used for comparison with multiple models in terms of strength levels of elasticity and hardness. The results show that our network has a more significant effect in accuracy. In the prediction results of the positive examples in the predicted value, the true value has a higher proportion of positive examples, that is, the precision is better. The prediction effect for the positive examples in the true value is better, that is, the recall is better. Finally, the recognition rate for all classes is higher in terms of f1_score. For the overall sample, the prediction of the multi-scale convolutional neural network has a higher recognition rate and the network's ability to recognize each strength level is more stable.

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.

Self-Calibration Method and Pose Domain Determination of a Light-Pen in a 3D Vision Coordinate Measurement System.

Light pens for 3D vision coordinate measurement systems are increasingly widely used due to their advantages, such as their small size, convenience of being carried, and widespread applicability. The posture of the light pen is an important factor that affects accuracy. The pose domain of the pen needs to be given so that the measurement system has a suitable measurement range to obtain more qualified parameters. The advantage of the self-calibration method is that the entire self-calibration process can be completed at the measurement site with no auxiliary equipment. After the system camera calibration was completed, we took several pictures of the same measurement point with different poses to obtain the conversion matrix of the picture and subsequently used spherical fitting, the generalized inverse method of least squares, and the principle of position invariance in the pose domain range. The combined stylus tip center self-calibration method calculates the actual position of the light pen probe. The experimental results verify the effectiveness of the method; the measurement accuracy of the system can satisfy basic industrial measurement requirements.

Comparative epidemiology of gestational diabetes in ethnic Chinese from Shanghai birth cohort and growing up in Singapore towards healthy outcomes cohort.

BACKGROUND: Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. METHODS: The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. RESULTS: Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. CONCLUSIONS: We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.

Comparations of major and trace elements in soil, water and residents' hair between longevity and non-longevity areas in Bama, China.

Natural environment is an important factor affecting longevity. Soil, water and hair samples from Bama were assayed to investigate the effects of elements on the regional longevity. The concentrations of Cd, Co and Mg in soil and Co in drinking water were significantly higher in longevity area than those in non-longevity area (p < 0.05). The concentrations of K, Mo, Na, Pb and V in soil, Mg, Na, Fe, Li and Mn in drinking water and I, K, Mg, Mn, Na and Sr in hair were significantly lower in longevity area than those in non-longevity area (p < 0.05). Mg, Mn, Na and Sr in hair were affected by soil and drinking water. Our results indicate that adequate concentration of Mg in soil might benefit longevity, excessive concentrations of Na in soil, Mg, Mn and Na in drinking water and Mg, Mn, Na and Sr in hair might reduce lifespan of local residents.

Association of liver and kidney functions with Klotho gene methylation in a population environment exposed to cadmium in China.

Exposure to the heavy metal cadmium has adverse effects on human health, including DNA methylation. This study aimed to investigate the effects of cadmium on liver and kidney functions and Klotho gene methylation and to explore the relationship of methylation level with indicators of liver and kidney functions. Graphite furnace atomic absorption spectrometry was conducted to determine urinary cadmium, and an automatic biochemical analyzer was used to detect indices of liver and kidney functions. PCR pyrosequencing was performed to detect the methylation rate of Klotho. One-way ANOVA was adopted to compare the differences between groups, and the linear correlation to variables was analyzed. Cadmium exposure was negatively correlated with albumin level (r=-0.143, p=0.021) and positively correlated with urinary ß2-microglobulin level (r=0.229, p<0.001). However, the methylation levels of Klotho gene was decreased and increased by low and high doses of cadmium exposure, respectively. And Klothomethylation levels were negatively correlated with albumin levels and positively correlated with ß2-microglobulin levels.In this study, cadmium exposure affects liver and kidney functions as well as Klotho methylation levels, but the effect on Klotho methylation levels is not linear. Klotho methylation levels also influence liver and kidney functions.

Spatial, temporal, and spatiotemporal analysis of mumps in Guangxi Province, China, 2005-2016.

BACKGROUND: The resurgence of mumps around the world occurs frequently in recent years. As the country with the largest number of cases in the world, the status of mumps epidemics in China is not yet clear. This study, taking the relatively serious epidemic province of Guangxi as the example, aimed to examine the spatiotemporal pattern and epidemiological characteristics of mumps, and provide a scientific basis for the effective control of this disease and formulation of related health policies. METHODS: Geographic information system (GIS)-based spatiotemporal analyses, including spatial autocorrelation analysis, Kulldorff's purely spatial and space-time scan statistics, were applied to detect the location and extent of mumps high-risk areas. Spatial empirical Bayesian (SEB) was performed to smoothen the rate for eliminating the instability of small-area data. RESULTS: A total of 208,470 cases were reported during 2005 and 2016 in Guangxi. Despite the fluctuations in 2006 and 2011, the overall mumps epidemic continued to decline. Bimodal seasonal distribution (mainly from April to July) were found and students aged 5-9 years were high-incidence groups. Though results of the global spatial autocorrelation based on the annual incidence largely varied, the spatial distribution of the average annual incidence of mumps was nonrandom with the significant Moran's I. Spatial cluster analysis detected high-value clusters, mainly located in the western, northern and central parts of Guangxi. Spatiotemporal scan statistics identified almost the same high-risk areas, and the aggregation time was mainly concentrated in 2009-2012. CONCLUSION: The incidence of mumps in Guangxi exhibited spatial heterogeneity in 2005-2016. Several spatial and spatiotemporal clusters were identified in this study, which might assist the local government to develop targeted health strategies, allocate health resources reasonably and increase the efficiency of disease prevention.

Impact of meteorological factors on mumps and potential effect modifiers: An analysis of 10 cities in Guangxi, Southern China.

BACKGROUND: In the current context of global climate change, understanding the impact of climate on respiratory infectious diseases such as mumps and the potential modified factors is crucial, especially in developing countries. However, research on the climate-related incidence of mumps is rare, inconsistent and mainly limited to a single city or region. METHODS: Daily mumps cases and meteorological variables of 10 cities in Guangxi, Southern China were collected for 2005-2017. Two-stage analyses were performed to assess the relationship between meteorological factors and mumps incidence during two time-periods: 2005-2012 and 2013-2017, separately. First, a Poisson regression model that allows over-dispersion was used to estimate the city-specific climate-related morbidity after controlling for temporal trends, day of week, and national statutory holidays. Then, we used a multivariate meta-analytical model to pool the city-specific effect estimates and conducted subgroup analyses. Multivariate meta-regression was applied to detect potential effect modifiers. RESULTS: Non-linear relationships were observed among mean temperature, wind speed, and mumps incidence in 2005-2012. The impact of high temperature on mumps incidence was short and rapid, whereas the impact of low temperature was long and slow. The total cumulative relative risk (RR) associated with hot temperature was 1.18 [95% Confidence Interval (CI): 0.93, 1.48], which was calculated by comparing the incidence of mumps above the 90th percentile of temperature with its incidence at the median temperature at lag of 0-30 days. Meanwhile, the RR associated with cold temperature was calculated to be 1.50 (95% CI: 1.08, 2.10) by comparing the incidence of mumps below the 10th percentile of temperature with its incidence at the median temperature. Similarly, the RRs associated with windless and windy conditions for the total population were 1.23 (95% CI: 1.04, 1.46) and 0.83 (95% CI: 0.67, 1.02), respectively. Effects based on extreme temperature and wind speed conditions were more prominent in males than in females. Compared with children and adults, adolescents (5-14 years old) were more sensitive to extreme weather conditions. Geographical latitude, Population density, GDP per capita, Number of health institutions, Highly educated population and Inoculation rate were considered the most likely associated modifiers. In addition, the correlation between meteorological factors and the incidence of mumps and modification of socioeconomic factors after 2013 showed similar curves compared with results in 2005-2012, but the cumulative effect was not statistically significant. CONCLUSIONS: Meteorological factors, such as temperature and wind speed, exert a significant impact on the incidence of mumps. The relationship varies depending on gender and age. Socioeconomic factors such as vaccination, GDP, geographical latitude, etc. may substantially affect the weather-related mumps incidence.

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.

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.

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.

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.