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Abstract Background Glyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes. Methods A total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose–response relationship was examined using restricted cubic splines (RCS). Results Significantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P

Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14–1.18 per μg/m3 in the first trimester; 1.15, 1.12–1.17 in the second trimester; 1.06, 1.04–1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Abstract Background While prenatal exposure to alkylphenols (APs) has been demonstrated to be associated with neurodevelopmental impairments in animals, the evidence from epidemiological studies remains limited and inconclusive. This study aimed to explore the link between AP exposure during pregnancy and the intelligence quotient (IQ) of preschool children. Methods A total of 221 mother-child pairs from the Guangxi Zhuang Birth Cohort were recruited. Nonylphenol (NP), 4-tert-octylphenol (4-T-OP), 4-n-nonylphenol (4-N-NP), and 4-n-octylphenol were measured in maternal serum in early pregnancy. Childhood IQ was evaluated by the Fourth Edition of Wechsler Preschool and Primary Scale of the Intelligence at 3 to 6 years of age. The impact of APs on childhood IQ were evaluated by generalized linear models (GLMs), restricted cubic spline (RCS), and Bayesian kernel machine regression (BKMR). Results In GLMs, prenatal exposure to NP and the second tertile of 4-T-OP exhibited an inverse association with full-scale IQ (FSIQ) (β = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (β = -5.24; 95% CI: -9.58, -0.89), respectively. Prenatal exposure to the third tertile of 4-N-NP showed a positive association with the fluid reasoning index (β = 4.95; 95% CI: 1.14, 8.77) in total children, as well as in girls when stratified by sex. A U-shaped relationship between maternal 4-T-OP and WMI was noted in total children and girls by RCS (all P nonlinear

Background: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. Methods: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer’s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. Results: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00–2.02), ADHD (1.51, 1.15–1.98), schizophrenia (1.47, 1.15–1.87), and AD (1.57, 1.16–2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. Conclusions: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Abstract Background After decades of rapid economic development, anemia remains a significant public health challenge globally. This study aimed to estimate the associations of sociodemographic, dietary, and body composition factors with anemia among the Zhuang in Guangxi Zhuang Autonomous Region, China. Methods Our study population from the baseline survey of the Guangxi ethnic minority Cohort Study of Chronic Diseases consisted of 13,465 adults (6,779 women and 6,686 men) aged 24–82 years. A validated interviewer-administered laptop-based questionnaire system was used to collect information on participants’ sociodemographic, lifestyle, and dietary factors. Each participant underwent a physical examination, and hematological indices were measured. Least absolute shrinkage and selection operator (LASSO) regression was used to select the variables, and logistic regression was applied to estimate the associations of independent risk factors with anemia. Results The overall prevalences of anemia in men and women were 9.63% (95% CI: 8.94–10.36%) and 18.33% (95% CI: 17.42─19.28%), respectively. LASSO and logistic regression analyses showed that age was positively associated with anemia for both women and men. For diet in women, red meat consumption for 5–7 days/week (OR = 0.79, 95% CI: 0.65–0.98, p = 0.0290) and corn/sweet potato consumption for 5–7 days/week (OR = 0.73, 95% CI: 0.55–0.96, p = 0.0281) were negatively associated with anemia. For men, fruit consumption for 5–7 days/week (OR = 0.75, 95% CI: 0.60–0.94, p = 0.0130) and corn/sweet potato consumption for 5–7 days/week (OR = 0.66, 95% CI: 0.46–0.91, p = 0.0136) were negatively correlated with anemia. Compared with a normal body water percentage (55–65%), a body water percentage below normal ( 65%) was positively correlated with anemia in men (OR = 1.73, 95% CI: 1.38–2.17, p

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.

Abstract Background Many studies have shown that circular RNAs (circRNAs) are abnormally expressed in various tumor tissues and served as a key regulator in the occurrence and development of cancer. However, in hepatocellular carcinoma (HCC), the molecular mechanism of circRNAs in body fluids remains to be further explored. Methods The expression levels of genes and proteins were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting, respectively. Cell counting Kit‐8 (CCK‐8), 5‐Ethynyl‐2'‐deoxyuridine (EdU), wound healing assay, Transwell assays, flow cytometry, and tumor formation models in nude mice were conducted to investigate the effects of circFAM114A2 on HCC cells both in vitro and in vivo. RNA antisense purification (RAP), dual luciferase reporter assays and rescue assays were carried out to verify the interaction between circFAM114A2, miR‐630 and HHIP. Results CircFAM114A2 was significantly downregulated in HCC tissues and was associated with microvascular invasion and lymph node metastasis of HCC patients. We also observed that circFAM114A2 was lowly expressed in HCC plasma, which may serve as an effective biomarker to screen HCC patients from healthy controls (area under curve (AUC)=0.922). In vitro, circFAM114A2 overexpression significantly blunted HCC cell proliferation, migration, invasion, and promoted apoptosis, whereas circFAM114A2 silencing posed opposite effects. In vivo, circFAM114A2 overexpression inhibited the growth of HCC cells. Mechanistically, circFAM114A2 could increase the expression of the tumor suppressor HHIP via acting as a sponge for miR‐630. Conclusions CircFAM114A2 exerts a tumor suppressor role in HCC through miR‐630/HHIP axis, and may be served as a potential diagnostic and therapeutic biomarker for HCC patients.

BackgroundSugar-sweetened beverage (SSB) consumption has shown associations with cognitive function in preschool children, but effects of other ultraprocessed foods consumption are rarely discussed in China. This study aimed to investigate the relationship between ultraprocessed food consumption and cognitive function among preschool children in China.MethodsA total of 325 children aged 4–7 years were included from Guangxi Zhuang Birth Cohort in Guangxi Zhuang Autonomous Region, China. Face-to-face interviews with parents using the Food Frequency Questionnaire (FFQ) was conducted to investigate the status of seven ultraprocessed foods consumption (i.e., chocolate, biscuits, candy, fast-food, ice cream, SSBs, and sweet bakery products). The mandarin-language version of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI, Fourth Edition) was applied to assess the cognitive function of children. Multiple linear and logistic regression models were used to assess the associations between ultraprocessed food consumption and the full-scale intelligence quotient (FSIQ) and different domains and risk of cognitive deficit, respectively.ResultsWe found that frequent consumption of candy (β = −3.34, 95% CI: −5.62∼−1.06; p = 0.004) and sweet bakery products (β = −2.77, 95% CI: −5.58∼0.04; p = 0.054) were significant associated with decreased FSIQ scores in the linear regression models. However, only frequent consumption of candy was statistically significantly associated with an increased risk of cognitive deficit (OR = 2.05, 95% CI: 1.11∼3.79; p = 0.023) in the logistic regression models. For the different domains, we found frequent consumption of candy (β = −3.85, 95% CI: −6.28∼−1.43; p = 0.002) and sweet bakery products (β = −3.48, 95% CI: −6.47∼−0.49; p = 0.023) was also significantly associated with lower Verbal Comprehension Index (VCI). When combining the seven ultraprocessed foods, we found children who frequently consumed more than two kinds of ultraprocessed foods had a significant decrease of VCI scores (β = −2.66; 95% CI: −5.12∼−0.19; p = 0.035) too.ConclusionOur results suggested that frequent consumption of individual (candy and sweet bakery products) and multiple ultraprocessed foods may decrease VCI scores and thereby impact cognitive function in children aged 4–7 years.

Summary: Many circular RNAs (circRNAs) have been identified to be associated with hepatocellular carcinoma (HCC) progression. We aim to explore the diagnostic potential, functions, and mechanism of circELMOD3 in HCC. Differentially expressed circRNAs in HCC and its paired adjacent tissues were identified by RNA sequencing. circELMOD3 was downregulated in HCC tissues and was related to clinicopathological characteristics of HCC patients. Additionally, plasma circELMOD3 was shown to be a highly sensitive and non-invasive biomarker to distinguish HCC from healthy controls. Functional assays showed that circELMOD3 inhibited proliferation and induced apoptosis of HCC cells both in vitro and in vivo. Mechanistically, RNA antisense purification (RAP) and luciferase reporter assays verified that circELMOD3 functioned as a sponge for miR-6864-5p leading to increased expression of its target gene TRIM13. Interestingly, RNA stability test demonstrated that circELMOD3 overexpression led to enhanced stability of its directly bound TRIM13 mRNA, which in turn co-activated the p53 signaling pathway.

Abstract Background Increasing evidence shows that liver-specific long non-coding RNAs (lncRNAs) play important roles in the development of hepatocellular carcinoma (HCC). We identified a novel liver-specific lncRNA, FAM99A, and examined its clinical significance and biological functions in HCC. Methods The expression level and clinical value of FAM99A in HCC were examined using The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) databases, and were further verified using quantitative real-time polymerase chain reaction (qRT–PCR) in our HCC cohort. Univariate and multivariate Cox proportional hazards regression models were also applied to identify independent prognostic indicators for HCC patients. Cell counting kit-8, colony formation, and Transwell assays were performed to evaluate the effects of FAM99A on the proliferation, migration, and invasion abilities of HCC cells in vitro. A subcutaneous xenograft tumor model was implemented to determine the effect of FAM99A on the tumor growth of HCC cells in vivo. RNA pull-down and mass spectrometry assays were performed to reveal the potential molecular mechanisms of FAM99A in HCC. Results The three public online databases and qRT–PCR data showed that FAM99A was frequently downregulated in HCC tissues and inversely correlated with microvascular invasion and advanced histological grade of HCC patients. Kaplan–Meier survival analysis indicated that decreased FAM99A was significantly associated with poor overall survival of HCC patients based on TCGA database (P = 0.040), ICGC data portal (P < 0.001), and our HCC cohort (P = 0.010). A multivariate Cox proportional hazards regression model based on our HCC cohort suggested that FAM99A was an independent prognostic factor of overall survival for HCC patients (hazard ratio: 0.425, P = 0.039). Upregulation of FAM99A suppressed the proliferation, colony formation, migration, and invasion capacities of HCC cells in vitro, and knockdown of FAM99A had the opposite effects. A subcutaneous xenograft tumor model demonstrated that overexpression of FAM99A significantly inhibited the tumor growth of HCC cells in vivo. Seven tumor-related proteins (PCBP1, SRSF5, SRSF6, YBX1, IGF2BP2, HNRNPK, and HNRNPL) were recognized as possible FAM99A-binding proteins by the RNA pull-down and mass spectrometry assays. Conclusion Our results suggest that FAM99A exerts cancer-inhibiting effects on HCC progression, and it may be a promising prognostic indicator for HCC patients.

Abstract Background Long non-coding RNAs (lncRNAs) are involved in the development of hepatocellular carcinoma (HCC). We aimed to investigate the function of LINC01146 in HCC. Methods The expression of LINC01146 in HCC tissues was explored via The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and was verified using quantitative real-time polymerase chain reaction (qRT–PCR) in our HCC cohort. Kaplan–Meier analysis was used to assess the relationship between LINC01146 and the prognosis of HCC patients. Cell Counting Kit 8, colony formation assays, Transwell assays, flow cytometric assays, and tumour formation models in nude mice were conducted to reveal the effects of LINC01146 on HCC cells both in vitro and in vivo. Bioinformatic methods were used to explore the possible potential pathways of LINC01146 in HCC. Results LINC01146 was significantly decreased in HCC tissues compared with adjacent normal tissues and was found to be related to the clinical presentations of malignancy and the poor prognosis of HCC patients. Overexpression of LINC01146 inhibited the proliferation, migration, and invasion of HCC cells in vitro, while promoting their apoptosis. In contrast, downregulation of LINC01146 exerted the opposite effects on HCC cells in vitro. In addition, overexpression of LINC01146 significantly inhibited tumour growth, while downregulation of LINC01146 promoted tumour growth in vivo. Furthermore, the coexpressed genes of LINC01146 were mainly involved in the “metabolic pathway” and “complement and coagulation cascade pathway”. Conclusion LINC01146 expression was found to be decreased in HCC tissues and associated with the prognosis of HCC patients. It may serve as a cancer suppressor and prognostic biomarker in HCC.

Air gap thickness significantly affects the detonation reliability of explosive trains. This paper mainly studies the detonation reliability of explosive trains with a micro-sized air gap. First, the detonation process of the JO-9C mild detonation cord initiating the 1.7 g/cm3 JO-11C booster is simulated by the AUTODYN software, and the critical air gap thickness is obtained between 0.32 and 0.40 mm. Second, a test device for explosive trains with adjustable air gap thickness is designed based on the numerical simulation results, and the adjustable step length of the air gap thickness is 0.0625 mm. Finally, a small sample evaluation method that does not depend on the standard deviation of the sensitivity distribution is proposed, and only 86 test samples are needed to verify the detonation reliability of 0.9999 at 0.1 mm air gap thickness. The test device designed and the small sample evaluation method proposed can be referred to for the detonation reliability evaluation of explosive trains with a micro-sized air gap.

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (β: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (β: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage.

Background: Telomere length (TL) is an important biomarker of biological aging and disease that may be affected by prenatal exposure to environmental pollutants. Birth seasons have been linked to reproductive and immune-related diseases. Prenatal exposure to per- and polyfluoroalkyl substance (PFAS) has been associated with adverse birth outcomes, but the effects of PFAS and birth seasons on newborn TL are poorly understood. Objectives: To explore the individual and combined effects of maternal PFAS exposure on newborn TL, with exploration of the interaction between PFAS and birth seasons on newborn TL. Methods: Between June 2015 and May 2018, a total of 499 mother-newborn pairs were recruited for a birth cohort study in Guangxi, China. Maternal blood samples were collected during pregnancy. Nine PFASs were measured by ultraperformance liquid chromatography–mass spectrometry. Newborn TL was assessed using quantitative real-time polymerase chain reaction. Modeling newborn TL as the outcome, multivariable linear regressions were performed for individual PFAS exposures, and Bayesian Kernel Machine Regressions were performed for PFAS mixtures. Furthermore, interaction analyses were conducted to evaluate the effect modification by birth seasons in these relationships. Results: For both single and multipollutant models, PFASs exposure were inversely associated with newborn TL, although none of the relationships were significant. The mixture of PFASs showed a potential positive trend of combined effect on newborn TL but non-statistically significant. Each ln-transformed unit concentration increase in PFOA was related to a 20.41% (95% CI: −30.44%, −8.93%) shorter TL in spring-born infants but not in those born in other birth seasons. Mothers in the middle and highest tertiles of PFOA exposure had 11.69% and 10.71% shorter TLs in spring-born infants, respectively. Conclusion: Maternal PFAS exposure showed little association with newborn TL. The results suggested potential effect modification by birth season on the association between PFOA exposure and newborn TL.

Background: Circular RNAs (circRNAs) have been demonstrated to be closely related to the carcinogenesis of human cancer in recent years. However, the molecular mechanism of circRNAs in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. We aimed to identify critical circRNAs and explore their potential regulatory network in HCC.Methods: The robust rank aggregation (RRA) algorithm and weighted gene co-expression network analysis (WGCNA) were conducted to unearth the differentially expressed circRNAs (DEcircRNAs) in HCC. The expression levels of DEcircRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). A circRNA-miRNA-mRNA regulatory network was constructed by computational biology, and protein-protein interaction (PPI) network, functional enrichment analysis, survival analysis, and infiltrating immune cells analysis were performed to uncover the potential regulatory mechanisms of the network.Results: A total of 22 DEcircRNAs were screened out from four microarray datasets (GSE94508, GSE97332, GSE155949, and GSE164803) utilizing the RRA algorithm. Meanwhile, an HCC-related module containing 404 circRNAs was identified by WGCNA analysis. After intersection, only four circRNAs were recognized in both algorithms. Following qRT-PCR validation, three circRNAs (hsa_circRNA_091581, hsa_circRNA_066568, and hsa_circRNA_105031) were chosen for further analysis. As a result, a circRNA-miRNA-mRNA network containing three circRNAs, 17 miRNAs, and 222 mRNAs was established. Seven core genes (ESR1, BUB1, PRC1, LOX, CCT5, YWHAZ, and DDX39B) were determined from the PPI network of 222 mRNAs, and a circRNA-miRNA-hubgene network was also constructed. Functional enrichment analysis suggested that these seven hub genes were closely correlated with several cancer related pathways. Survival analysis revealed that the expression levels of the seven core genes were significantly associated with the prognosis of HCC patients. In addition, we also found that these seven hub genes were remarkably related to the infiltrating levels of immune cells.Conclusion: Our research identified three pivotal HCC-related circRNAs and provided novel insights into the underlying mechanisms of the circRNA-miRNA-mRNA regulatory network in HCC.

Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. A total of 138 shared DEGs were screened from two datasets. They were mainly enriched in the “Metabolic pathways” pathway (Padj = 8.21E-08) and involved in the carboxylic acid metabolic process (Padj = 0.0004). The top 10 hub genes were found by protein-protein interaction analysis and were upregulated in HCC tissues compared to normal tissues in The Cancer Genome Atlas database. Survival analysis distinguished 8 hub genes CENPE, SPDL1, Hyaluronan-mediated motility receptor, Rac GTPase activating protein 1, Thyroid hormone receptor interactor 13, cytoskeleton-associated protein (CKAP) 2, CKAP5, and Integrin subunit beta 3 binding protein (ITGB3BP) were considered as prognostic hub genes. Multivariate cox regression analysis indicated that all the prognostic hub genes were independent prognostic factors for HCC. Furthermore, the receiver operating characteristic curve revealed that the 8-hub genes model had better prediction performance for overall survival compared to the T stage (p = 0.008) and significantly improved the prediction value of the T stage (p = 0.002). The Human Protein Atlas showed that the protein expression of ITGB3BP was upregulated in HCC, so the expression of ITGB3BP was further verified in our cohort. The results showed that ITGB3BP was upregulated in HCC tissues and was significantly associated with lymph node metastasis.

Preterm birth (PTB), a serious adverse birth outcome, is the leading cause of perinatal mortality and morbidity. Bisphenols induce endocrine disruption that spreads across the placenta, which may affect fetal growth and development. However, the effects of bisphenols on PTB, particularly their combined effects, remain unknown. This study investigated the association between prenatal bisphenol exposure and PTB. Study participants were 2023 mother-infant pairs that were selected from the Guangxi Zhuang Birth Cohort. Maternal serum bisphenol levels were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry, and pregnancy outcomes were obtained from medical records. Multivariate logistic regression, restricted cubic spline, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were used to examine the association between serum bisphenol levels and PTB. Ln-transformed BPA concentrations were associated with an increased risk of PTB only in female infants (OR = 1.30, 95% CI: 1.02, 1.64). Ln-transformed bisphenol F (BPF) concentrations were positively associated with the risk of PTB (OR = 1.73, 95% CI: 1.18, 2.55). Inverse U-shaped relationships were observed between bisphenol B (BPB), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) levels and the risk of PTB (P-overall < 0.05, P-non-linear < 0.05). After sex stratification, the association between BPA analogs and PTB was only observed in males. In Qgcomp analysis, bisphenol mixtures were related to an increased risk of PTB (OR = 1.52, 95% CI: 1.04, 2.21), with BPF (43.7%), BPS (29.6%) and BPA (26.8%) having the greatest positive contribution. Results indicate that prenatal exposure to bisphenol mixtures might increase the risk of PTB, which might be primarily driven by BPA, BPF and BPS. There may also be sex-specific and nonmonotonic dose-dependent effects.

At present, the barrier to HIV-1 functional cure is the persistence of HIV-1 reservoirs. The “shock (reversing latency) and kill (antiretroviral therapy)” strategy sheds light on reducing or eliminating the latent reservoir of HIV-1. However, the current limits of latency-reversing agents (LRAs) are their toxicity or side effects, which limit their practicability pharmacologically and immunologically. Our previous research found that HSF1 is a key transcriptional regulatory factor in the reversion of HIV-1 latency. We then constructed the in vitro HSF1-knockout (HSF1-KO) HIV-1 latency models and found that HSF1 depletion inhibited the reactivation ability of LRAs including salubrinal, carfizomib, bortezomib, PR-957 and resveratrol, respectively. Furthermore, bortezomib/carfizomib treatment induced the increase of heat shock elements (HSEs) activity after HSF1-KO, suggesting that HSEs participated in reversing the latent HIV-1. Subsequent investigation showed that latent HIV-1-reversal by H2O2-induced DNA damage was inhibited by PARP1 inhibitors, while PARP1 was unable to down-regulate HSF1-depleted HSE activity, indicating that PARP1 could serve as a replaceable protein for HSF1 in HIV-1 latent cells. In summary, we succeeded in finding the mechanisms by which HSF1 reactivates the latent HIV-1, which also provides a theoretical basis for the further development of LRAs that specifically target HSF1.

Aflatoxin B1 (AFB1) is a common toxic mycotoxin and is detectable in pregnant women. Animal studies have revealed that AFB1 caused the lysis of erythrocytes and a decrease in hemoglobin. We conducted a prospective cohort study in Guangxi, China, in order to evaluate the association between AFB1 exposure and anemia in pregnant women during the entire pregnancy. A total of 616 pregnant women from the Guangxi Zhuang Birth Cohort were included in the study. Serum AFB1-albumin (AFB1-ALB) adduct levels were measured. The effect of AFB1-ALB adducts on hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed by using multivariable linear regression. The risks of anemia from AFB1-ALB adduct exposure were assessed by multivariable logistic regression. We found that the AFB1-ALB adduct was significantly associated with a decrease in Hb (β = −4.99, 95% CI: −8.42, −1.30), MCV (β = −4.58, 95% CI: −7.23, −1.94), MCH (β = −1.86, 95% CI: −2.87, −0.85), and MCHC (β = −5.23, 95% CI: −8.28, −2.17) in the first trimester with the third tertile of AFB1-ALB adducts when compared with the first tertile. Furthermore, the third tertile of the AFB1-ALB adduct significantly increased the risk of anemia by 2.90 times than compared to the first tertile in the first trimester (OR = 3.90, 95% CI: 1.67, 9.14). A significant positive does–response relationship existed between AFB1-ALB adduct levels and anemia risk (Ptrend = 0.001). When dividing anemia types, we only found that the third tertile of AFB1-ALB adduct increased the risk of microcytic hypochromic anemia (MHA) in the first trimester (OR = 14.37, 95% CI: 3.08, 67.02) and second trimester (OR = 4.75, 95% CI: 1.96, 11.51). These findings demonstrate the correlation between maternal AFB1 exposure during early pregnancy and risk of anemia, especially MHA, and during different trimesters in Southern China. More efforts should be made to diminish AFB1 exposure for pregnant women.

Objective: Little is known about the association between maternal history of dysmenorrhea and perinatal outcomes. The aim of this study was to investigate the association between maternal history of dysmenorrhea and low birth weight (LBW). Methods: A total of 6754 pregnant women were recruited from the ongoing prospective cohort study in Guangxi, China, in 2015–2018. Information on the maternal history of dysmenorrhea was obtained by questionnaires including visual analog scale (VAS) questions during the first antenatal care visit. The association of maternal history of dysmenorrhea and LBW was evaluated using logistic regression analyses adjusted for confounding factors (infant sex, maternal age, parity, pre-pregnancy body mass index (BMI) (kg/m² ), gestational age, alcohol use during pregnancy, passive smoking, and occupational status). Results: Mothers with a history of dysmenorrhea were more likely to give birth to LBW infants (adjusted odds ratio (OR)=1.44; 95% confidence interval (CI): 1.12, 1.83). Among women with a history of dysmenorrhea, women 29 years old (adjusted OR 1.46; 95% CI 1.02, 2.10), multiparous (adjusted OR 1.59, 95% CI 1.12, 2.25), and women gave birth to female infant (adjusted OR = 1.53, 95% CI = 1.11, 2.11) had a higher risk of LBW. Conclusions: As the first cohort study to investigate the association between maternal history of dysmenorrhea and LBW, our study shows that dysmenorrhea may increase the risk of LBW. [ABSTRACT FROM AUTHOR]