A prospects tool in virus research: Analyzing the applications of organoids in virus studies.

Organoids have emerged as a powerful tool for understanding the biology of the respiratory, digestive, nervous as well as urinary system, investigating infections, and developing new therapies. This article reviews recent progress in the development of organoid and advancements in virus research. The potential applications of these models in studying virul infections, pathogenesis, and antiviral drug discovery are discussed.

HIV/AIDS, SARS, and COVID-19: the trajectory of China's pandemic responses and its changing politics in a contested world.

The COVID-19 pandemic has revealed the contested politics of global health governance, though we still don't know enough about the dynamics of domestic pandemic responses, or about the relationship between the politics of those responses and the politics of global health governance, both of which have changed significantly in recent decades. Focusing on three cases (HIV/AIDS, SARS, and COVID-19) of cross-border infectious diseases, this article explores the trajectory of China's pandemic responses in the context of globalization. Attending to changing politics at domestic, international, and global levels, I argue that those responses have been a complex combination of China's domestic politics (e.g., priorities, institutions, leadership, and timing), its international relations (especially with the US), and its engagements with global health governance. It is concluded that the increasing divergence of pandemic responses in a time of ubiquitous global health crisis demands urgent attention to the connections (including contestations) between domestic pandemic responses and the evolvement of global health governance from a broader perspective that considers changes in geopolitics.

Vitamin D3 supplementation shapes the composition of gut microbiota and improves some obesity parameters induced by high-fat diet in mice.

PURPOSE: Individuals with vitamin D (VD) insufficiency have a greater tendency to develop obesity and have increased systemic inflammation. Gut microbiota are involved in the regulation of host inflammation and energy metabolism, which plays a role in the pathogenesis of obesity. Thus, we aimed to evaluate the effects of different doses of VD3 on body weight, serum lipids, inflammatory factors, and intestinal barrier function in obese mice and to explore the regulatory effect of VD3 on gut microbiota in obese mice. METHODS: Male C57BL/6 J mice received a normal chow diet (NCD, 10% fat) or high-fat diet (HFD, 60% fat) to induce obesity within 10 weeks. Then, HFD mice were supplemented with 5650, 8475, or 11,300 IU VD3/kg diet for 8 weeks. Finally, 16 s rRNA analysis was performed to analyze gut microbiota composition in cecal contents. In addition, body weight, serum lipids, inflammatory factors, and intestinal barrier function were analyzed. RESULTS: VD3 supplementation reduced body weight and the levels of TG, TC, HDL-C, TNF-α, IL-1ß and LPS, and increased ZO-1 in HFD-fed mice. Moreover, it increased α-diversity, reduced F/B ratio and altered microbiota composition by increasing relative abundance of Bacteroidetes, Proteobacteria, Desulfovibrio, Dehalobacterium, Odoribacter, and Parabacteroides and reducing relative abundance of Firmicutes and Ruminococcus. There were significant differences between HFD and NCD groups in several metabolic pathways, including endotoxin biosynthesis, tricarboxylic acid cycle, lipid synthesis and metabolism, and glycolysis. CONCLUSIONS: Low, medium, and high doses of VD3 inhibited weight gain, reduced levels of blood lipids and inflammatory factors, and improved endotoxemia and gut barrier function in obese mice. It also increased the α-diversity of gut microbiota in obese mice and reduced the relative abundance of some intestinal pathogenic bacteria, increased the relative abundance of some beneficial bacteria, and corrected the intestinal flora disorder of obese mice, with the low- and high-dose groups showing better effects than the medium-dose group.

Antibody-mediated spike activation promotes cell-cell transmission of SARS-CoV-2.

The COVID pandemic fueled by emerging SARS-CoV-2 new variants of concern remains a major global health concern, and the constantly emerging mutations present challenges to current therapeutics. The spike glycoprotein is not only essential for the initial viral entry, but is also responsible for the transmission of SARS-CoV-2 components via syncytia formation. Spike-mediated cell-cell transmission is strongly resistant to extracellular therapeutic and convalescent antibodies via an unknown mechanism. Here, we describe the antibody-mediated spike activation and syncytia formation on cells displaying the viral spike. We found that soluble antibodies against receptor binding motif (RBM) are capable of inducing the proteolytic processing of spike at both the S1/S2 and S2' cleavage sites, hence triggering ACE2-independent cell-cell fusion. Mechanistically, antibody-induced cell-cell fusion requires the shedding of S1 and exposure of the fusion peptide at the cell surface. By inhibiting S1/S2 proteolysis, we demonstrated that cell-cell fusion mediated by spike can be re-sensitized towards antibody neutralization in vitro. Lastly, we showed that cytopathic effect mediated by authentic SARS-CoV-2 infection remain unaffected by the addition of extracellular neutralization antibodies. Hence, these results unveil a novel mode of antibody evasion and provide insights for antibody selection and drug design strategies targeting the SARS-CoV-2 infected cells.

The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran's Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results. Results: We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy. Conclusions: Our study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.

Prenatal exposure to multiple environmental chemicals and birth size.

BACKGROUND: Epidemiological studies addressing the combined effects of exposure to chemical mixtures at different stages of pregnancy on birth size are scarce. OBJECTIVE: To evaluate the association between prenatal exposure to chemical mixtures and birth size. METHODS: Our previous study repeatedly measured the urinary concentrations of 34 chemical substances among 743 pregnant women and identified three distinct clusters of exposed population and six dominant principal components of exposed chemicals in each trimester. In this study, we assessed the associations of these exposure profiles with birth weight, birth length, and ponderal index using multivariable linear regression. RESULTS: We found that compared with women in cluster 1 (lower urinary chemical concentrations), women in cluster 2 (higher urinary concentrations of metals, benzothiazole, benzotriazole, and some phenols), and women in cluster 3 (higher urinary concentrations of phthalates) were more likely to give birth to children with higher birth length [0.23 cm (95% CI: -0.03, 0.49); 0.29 cm (95%CI: 0.03, 0.54), respectively]. This association was observed only in 1st trimester. In addition, prenatal exposure to PC3 (higher benzophenones loading) was associated with reduced birth length across pregnancy [-0.07 cm (95% CI: -0.18, 0.03) in 1st and 2nd trimester; -0.13 cm (95% CI: -0.24, -0.03) in 3rd trimester]. Exposure to PC6 (higher thallium and BPA loading in 2nd trimester) was associated with increased birth length [0.15 cm (95% CI: 0.05, 0.26)]. Compared with other outcomes, associations of both clusters and PCs with birth length were stronger, and these associations were more pronounced in boys. IMPACT STATEMENT: Exposure to multiple chemicals simultaneously, the actual exposure situation of pregnant women, was associated with birth size, indicating that chemical mixtures should be taken more seriously when studying the health effects of pollutants.

1,4,5,6,7,8­Hexahydropyrido[4,3­d]pyrimidine inhibits HepG2 cell proliferation, migration and invasion, and induces apoptosis through the upregulation of miR­26b­5p by targeting CDK8.

1,4,5,6,7,8-Hexahydropyrido[4,3-d]pyrimidine (PPM) promotes apoptosis of HepG2 cells and serves a role in tumor suppression. However, the role of microRNA (miRNA) regulation in initiating apoptosis remains unclear. Therefore, the present study performed reverse transcription-quantitative PCR to investigate the association between PPM and miRNA, which demonstrated that PPM upregulated the expression of miR-26b-5p. Wound healing and Transwell assays showed that PPM inhibited the migration and invasion of HepG2 cells, and EdU staining experiments showed that PPM inhibited the proliferation of HepG2 cells. Transfection with miR-26b-5p inhibitor reversed the effects of PPM on HepG2 cells. Flow cytometry results showed that PPM promoted apoptosis of HepG2 cells by upregulating miRNA (miR)-26b-5p, and Western blotting results showed that PPM promoted the expression of apoptosis-associated protein Bax and inhibited the expression of Bcl-2 by upregulating miR-26b-5p. Using a proteomic approach combined with bioinformatics analysis, CDK8 was identified as a potential target of miR-26b-5p and was downregulated by miR-26b-5p overexpression. However, PPM induced HepG2 cell cycle arrest without the involvement of miR-26b-5p. Western blotting results showed that PPM upregulation of miR-26b-5p suppresses NF-κB/p65 signaling pathway in HepG2 cells by targeting of CDK8. The present results suggested that miR-26b-5p may function as a target gene of PPM and may serve a role in hepatocellular carcinoma treatment.

Synthesis and Characterization of Random Block Hydroxyl-Terminated Polyfluoroether-Based Polyurethane Elastomers with Fluorine-Containing Side Chains.

Polype ntafluoropropane glycidyl ether (PPFEE), a new random block hydroxyl-terminated polyfluoroether, was synthesized successfully by cationic ring-opening polymerization of 2-(2,2,3,3,3-pentafluoropropoxymethyl) oxirane, and its molecular structure was confirmed by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectrometry, and gel permeation chromatography. The PPFEE-based polyurethane elastomers featuring fluorine in their side chains were prepared using PPFEE as soft segments, polyisocyanate polyaryl polymethylene isocyanate as hard segments, and dibutyltin dilaurate as catalysts under different curing conditions. The microphase separation, mechanical performance, and thermal behavior of the elastomers were investigated by differential scanning calorimetry, uniaxial tensile test, and thermal gravimetric analysis, respectively. Based on the results, the percentage of hard segments dissolved into the soft segments of elastomers was opposite to the change in breaking strength. The PPFEE-based polyurethane elastomer cured with 20 wt% PAPI at the curing temperature of 50 °C displayed the maximum tensile elongation of 2.26 MPa with an elongation at break of nearly 150%. The increased contents of PAPI can effectively strengthen the tensile strength, and the maximum tensile elongation was 3.04 MPa with an elongation at break of nearly 90% when the content of PAPI was 26 wt%. In addition, the PPFEE-based polyurethane elastomers exhibited excellent resistance to thermal decomposition and a sharp weight loss temperature at around 371 °C. All the results demonstrated that the PPFEE may be a potential polymeric binder as one of the ingredients applied to future propellant formulations.

VARS2 gene mutation leading to overall developmental delay in a child with epilepsy: A case report.

BACKGROUND: The mitochondrial respiratory chain defects have become the most common cause of neurometabolic disorders in children and adults, which can occur at any time in life, often associated with neurological dysfunction, and lead to chronic disability and premature death. Approximately one-third of patients with mitochondrial disease have biochemical defects involving multiple respiratory chain complexes, suggesting defects in protein synthesis within the mitochondria. We here report a child with VARS2 gene mutations causing mitochondrial disease. CASE SUMMARY: A girl, aged 3 years and 4 mo, had been unable to sit and crawl alone since birth, with obvious seizures and microcephaly. Brain magnetic resonance imaging showed symmetrical, flaky, long T1-weighted and low T2-weighted signals in the posterior part of the bilateral putamen with a high signal shadow. T2 fluid-attenuated inversion recovery imaging showed a slightly high signal and diffusion-weighted imaging showed an obvious high signal. Whole-exome gene sequencing revealed a compound heterozygous mutation in the VARS2 gene, c.1163(exon11)C>T and c.1940(exon20)C>T, which was derived from the parents. The child was diagnosed with combined oxidative phosphorylation deficiency type 20. CONCLUSION: In this patient, mitochondrial disorders including Leigh syndrome and MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) were ruled out, and combined oxidative phosphorylation deficiency type 20 was diagnosed, expanding the phenotypic spectrum of the disease.

Whole-genome sequencing combined RNA-sequencing analysis of patients with mutations in SET binding protein 1.

SET binding protein 1 (SETBP1) is essential for human development, and pathogenic germline variants in SETBP1 lead to a recognizable developmental syndrome and variable clinical features. In this study, we assessed a patient with facial dysmorphism, intellectual disability and delayed motor development. Whole genome sequencing identified a novel de novo variation of the SETBP1 (c.2631C > A; p. S877R) gene, which is located in the SKI domain, as a likely pathogenic variant for the proband's phenotype. RNA sequencing was performed to investigate the potential molecular mechanism of the novel variation in SETBP1. In total, 77 and 38 genes were identified with aberrant expression and splicing, respectively. Moreover, the biological functions of these genes were involved in DNA/protein binding, expression regulation, and the cell cycle, which may advance our understanding of the pathogenesis of SETBP1 in vivo.

Gender and Trajectories of Marital Breakdown: Accounts of Chinese Immigrant Women in Canada.

The relatively sparse literature has documented various challenges international migration poses to martial stability, yet we know little about immigrant women's experiences with marital breakdown. Drawing data from a qualitative study of Chinese economic immigrants to Canada, this article explores women's experiences of navigating the processes of this life circumstance, and of how gender-including their senses of changing gender roles in post-immigration and postmarital contexts-plays out in these trajectories. The results of this exploratory study illustrate the value of transcending dichotomous conceptions of the relationship between gender and migration, and of opening spaces in which to better understand immigrant women's increasingly diversified life trajectories and the range of barriers they encounter along the way. The study also reveals multiple opportunities for social work contributions: tackling systematic barriers to settlement, facilitating social support in the community, and recognizing individuals' diverse trajectory potentials (including the potential for this typically unwelcome event to be integrated as personal growth and transition).

Complex metabolic interactions between ovary, plasma, urine, and hair in ovarian cancer.

Ovarian cancer (OC) is the third most common malignant tumor of women accompanied by alteration of systemic metabolism, yet the underlying interactions between the local OC tissue and other system biofluids remain unclear. In this study, we recruited 17 OC patients, 16 benign ovarian tumor (BOT) patients, and 14 control patients to collect biological samples including ovary plasma, urine, and hair from the same patient. The metabolic features of samples were characterized using a global and targeted metabolic profiling strategy based on Gas chromatography-mass spectrometry (GC-MS). Principal component analysis (PCA) revealed that the metabolites display obvious differences in ovary tissue, plasma, and urine between OC and non-malignant groups but not in hair samples. The metabolic alterations in OC tissue included elevated glycolysis (lactic acid) and TCA cycle intermediates (malic acid, fumaric acid) were related to energy metabolism. Furthermore, the increased levels of glutathione and polyunsaturated fatty acids (linoleic acid) together with decreased levels of saturated fatty acid (palmitic acid) were observed, which might be associated with the anti-oxidative stress capability of cancer. Furthermore, how metabolite profile changes across differential biospecimens were compared in OC patients. Plasma and urine showed a lower concentration of amino acids (alanine, aspartic acid, glutamic acid, proline, leucine, and cysteine) than the malignant ovary. Plasma exhibited the highest concentrations of fatty acids (stearic acid, EPA, and arachidonic acid), while TCA cycle intermediates (succinic acid, citric acid, and malic acid) were most concentrated in the urine. In addition, five plasma metabolites and three urine metabolites showed the best specificity and sensitivity in differentiating the OC group from the control or BOT groups (AUC > 0.90) using machine learning modeling. Overall, this study provided further insight into different specimen metabolic characteristics between OC and non-malignant disease and identified the metabolic fluctuation across ovary and biofluids.

Clinical manifestations and gene analysis of Hutchinson-Gilford progeria syndrome: A case report.

BACKGROUND: This case report describes a child with Hutchinson-Gilford progeria syndrome (HGPS, OMIM: 176670) caused by LMNA (OMIM: 150330) gene mutation, and we have previously analyzed the clinical manifestations and imaging characteristics of this case. After 1-year treatment and follow-up, we focus on analyzing the changes in the clinical manifestations and genetic diagnosis of the patient. CASE SUMMARY: In April 2020, a 2-year-old boy with HGPS was found to have an abnormal appearance, and growth and development lagged behind those of children of the same age. The child's weight did not increase normally, the veins of the head were clearly visible, and he had shallow skin color and sparse yellow hair. Peripheral blood DNA samples obtained from the patient and his parents were sequenced using high-throughput whole-exosome sequencing, which was verified by Sanger sequencing. The results showed that there was a synonymous heterozygous mutation of C.1824 C>T (P. G608G) in the LMNA gene. CONCLUSION: Mutation of the LMNA gene provides a molecular basis for diagnosis of HGPS and genetic counseling of the family.

Heterogeneous logistic regression for estimation of subgroup effects on hypertension.

Personalized medicine has gained much attention in the past decades, and identifying the effects of factors is essential for personalized preventions and treatments. Hypertension is a major modifiable risk factor for cardiovascular disease and is influenced by complex factors. In order to decrease the incidence of hypertension effectively, the subjects should be divided into subgroups according to their characteristics. In this study, we proposed to use a heterogeneous logistic regression combined with a concave fusion penalty to analyze the population-based survey data, including common influencing factors of hypertension. The analytic steps include: (1) identifying the most important predictor; (2) estimating subgroup-based heterogeneous effects. In the present context of primary hypertension data, the modeling results showed that the calculated prediction accuracy under our method was greater than 99%, while zero under the classical logistic regression. The findings could provide a practical guide for further individualized measures implementation.

Associations of benzotriazoles and benzothiazoles with estrogens and androgens among pregnant women: A cohort study with repeated measurements.

People are extensively exposed to benzotriazoles (BTRs) and benzothiazoles (BTHs) derivatives, which are environmental pollutants that may possess endocrine-disrupting potential; however, no epidemiological evidence is available on the associations of BTRs and BTHs with estrogens and androgens. This study aimed at investigating the associations of BTRs and BTHs with estrogens and androgens among pregnant women. Based on a prospective cohort study, we included 459 pregnant women who donated a complete serial of urine samples at each trimester and had repeated measurements of four BTRs, four BTHs, three estrogens (estrone, 17ß-estradiol, and estrio), and two androgens (dehydroepiandrosterone and testosterone) in the urine samples. Associations of repeatedly measured BTRs and BTHs with maternal urinary estrogens and androgens were analyzed, and the cross-sectional associations were also analyzed. Tolyltriazole (TTR) (≥59.3%) and benzothiazole (BTH) (≥93.5%) had the highest detection rate among the BTRs and BTHs, respectively. Repeated measurement analysis and cross-sectional analysis consistently found the target BTRs and BTHs were positively associated with 17ß-estradiol, estriol, and testosterone, while the trend of the associations with estrone and dehydroepiandrosterone was inconsistent. Among the positive associations with 17ß-estradiol, estriol, and testosterone, the percent of change in estriol associated with TTR was the most prominent [28.5% (95% confidential interval: 24.2%, 32.9%) for each doubling in TTR]. The significant associations with estrone, estriol, testosterone, and dehydroepiandrosterone were stronger among pregnant women who gave birth to a boy than those who gave birth to a girl. These findings add epidemiological evidence on the endocrine-disrupting potential of BTRs and BTHs and highlight the importance of focusing on the health outcomes of BTRs and BTHs related to disturbed estrogens and androgens. Future studies are needed to validate these findings and explore the underlying mechanisms.

Small RNA Sequencing Revealed that miR4415, a Legume-Specific miRNA, was Involved in the Cold Acclimation of Ammopiptanthus nanus by Targeting an L-Ascorbate Oxidase Gene and Regulating the Redox State of Apoplast.

MicroRNAs (miRNAs) are small endogenous single-stranded RNAs that regulate plant growth, development, and environmental stress response posttranscriptionally. Ammopiptanthus nanus, a rare evergreen broad-leaved shrub in the temperate area of Central Asia, can tolerate freezing stress as low as -30 degrees centigrade in winter, and miRNA might be involved in the cold acclimation which enables A. nanus to obtain tolerance to freezing stress. Systematic identification and functional analysis of the miRNAs involved in the cold acclimation in A. nanus may promote understanding of the miRNA-mediated gene regulation network underlying cold acclimation. Here, based on small RNA and degradome sequencing, 256 miRNAs and 1,808 miRNA-target pairs were identified in A. nanus. A total of 39 cold-responsive miRNAs were identified, of which 29 were upregulated and ten were downregulated. These cold-responsive miRNAs may participate in the cold acclimation by regulating redox homeostasis (miR398, miR4415, and miR408), calcium signaling (miR5225 and miR5211), growth and development (miR159 and miR390), and small RNA-mediated gene silencing (miR168 and miR1515). We found that miR4415, a legume-specific miRNA, is involved in the cold acclimation of A. nanus by targeting an L-ascorbate oxidase gene and then regulating the redox state of the apoplast. Our study provides important data for understanding the regulatory role of miRNA in the cold acclimation of A. nanus.

Aflatoxin B1 induces microglia cells apoptosis mediated by oxidative stress through NF-κB signaling pathway in mice spinal cords.

Many studies have shown that aflatoxin B1 (AFB1) can cause cytotoxicity in numerous cells and organs induced by oxidative stress. However, the toxic effects and related mechanism of AFB1 on the microglia cells in the spinal cords have not been studied yet. Our results showed that AFB1 significantly reduced the number of microglia cells, increased the oxidants (malonaldehyde and hydrogen peroxide) but decreased the anti-oxidants (superoxide dismutase and total antioxidant capacity) in a dose dependent manner in mice spinal cords. In addition, AFB1 significantly increased the oxidative stress, promoted apoptosis and cell cycle arrest in G2-M phase, and activated NF-κB phosphorylation in BV2 microglia cells. However, the addition of active oxygen scavenger N-acetylcysteine can significantly reduce the ROS production, improve cell cycle arrest, reduce apoptosis, and the expression of phosphorylated NF-κB in BV2 microglia cells. These results indicate that AFB1 induces microglia cells apoptosis through oxidative stress by activating NF-κB signaling pathway.

Spatial distribution, partitioning, and ecological risk of short chain chlorinated paraffins in seawater and sediment from East China Sea.

Short chain chlorinated paraffins (SCCPs) have attracted increasing attention due to their potential risks to the ecosystem and human health. However, there is still a lack of systematic research on their environmental fate in the coastal marine environment. In this study, we collected paired seawater (n = 40) and surface sediment samples (n = 40) from East China Sea, and investigated their spatial distribution, partitioning behaviors and ecological risks. The total SCCP concentrations (∑SCCPs) in seawater and sediment samples were in the range of 12.2-430 ng/L and 89.6-351 ng/g (dry weight), respectively. C10-11 SCCPs and Cl5-7 SCCPs were the predominant homologues in all of the samples. This study first calculated the field-based logKOC values for ∑SCCPs in the marine environment, which ranged from 5.0 to 6.5 (mean 5.5). The logKOC values of SCCP homologues (range 3.6-8.0, mean 5.6) showed a weak correlation with their logKOW (R = 0.214, p < 0.05). A preliminary risk assessment indicated that SCCPs at current levels posed no significant ecological risk. Overall, this study contributes to the further understanding of environmental behaviors of SCCPs in the marine environment.

Machine Learning for Investigation on Endocrine-Disrupting Chemicals with Gestational Age and Delivery Time in a Longitudinal Cohort.

Endocrine-disrupting chemicals (EDCs) are widespread environmental chemicals that are often considered as risk factors with weak activity on the hormone-dependent process of pregnancy. However, the adverse effects of EDCs in the body of pregnant women were underestimated. The interaction between dynamic concentration of EDCs and endogenous hormones (EHs) on gestational age and delivery time remains unclear. To define a temporal interaction between the EDCs and EHs during pregnancy, comprehensive, unbiased, and quantitative analyses of 33 EDCs and 14 EHs were performed for a longitudinal cohort with 2317 pregnant women. We developed a machine learning model with the dynamic concentration information of EDCs and EHs to predict gestational age with high accuracy in the longitudinal cohort of pregnant women. The optimal combination of EHs and EDCs can identify when labor occurs (time to delivery within two and four weeks, AUROC of 0.82). Our results revealed that the bisphenols and phthalates are more potent than partial EHs for gestational age or delivery time. This study represents the use of machine learning methods for quantitative analysis of pregnancy-related EDCs and EHs for understanding the EDCs' mixture effect on pregnancy with potential clinical utilities.