The associations between gut microbiota and fecal metabolites with intelligence quotient in preschoolers.

BACKGROUND: The awareness of the association between the gut microbiota and human intelligence levels is increasing, but the findings are inconsistent. Furthermore, few research have explored the potential role of gut microbial metabolites in this association. This study aimed to investigate the associations of the gut microbiota and fecal metabolome with intelligence quotient (IQ) in preschoolers. METHODS: The 16 S rRNA sequencing and widely targeted metabolomics were applied to analyze the gut microbiota and fecal metabolites of 150 children aged 3-6 years. The Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to assess the cognitive competence. RESULTS: The observed species index, gut microbiome health index, and microbial dysbiosis index presented significant differences between children with full-scale IQ (FSIQ) below the borderline (G1) and those with average or above-average (all P < 0.05). The abundance of Acinetobacter, Blautia, Faecalibacterium, Prevotella_9, Subdoligranulum, Collinsella, Dialister, Holdemanella, and Methanobrevibacter was significantly associated with preschooler's WPPSI-IV scores (P < 0.05). In all, 87 differential metabolites were identified, mainly including amino acid and its metabolites, fatty acyl, and benzene and substituted derivatives. The differential fecal metabolites carnitine C20:1-OH, 4-hydroxydebrisoquine, pantothenol, creatine, N,N-bis(2-hydroxyethyl) dodecanamide, FFA(20:5), zerumbone, (R)-(-)-2-phenylpropionic acid, M-toluene acetic acid, trans-cinnamaldehyde, isonicotinic acid, val-arg, traumatin, and 3-methyl-4-hydroxybenzaldehyde were significantly associated with the preschooler's WPPSI-IV scores (P < 0.05). The combination of Acinetobacter, Isonicotinic acid, and 3-methyl-4-hydroxybenzaldehydenine may demonstrate increased discriminatory power for preschoolers in G1. CONCLUSION: This study reveals a potential association between gut microbiome and metabolites with IQ in preschoolers, providing new directions for future research and practical applications. However, due to limitations such as the small sample size, unclear causality, and the complexity of metabolites, more validation studies are still needed to further elucidate the mechanisms and stability of these associations.

Association between maternal metal exposure during early pregnancy and intelligence in children aged 3-6 years: Results from a Chinese birth cohort.

OBJECTIVE: Maternal environmental metal exposure is common, but long-term prospective epidemiological evidence of its impact on children's intellectual development is still insufficient. METHODS: Data on maternal plasma metal levels and child intelligence were obtained for 211 3-6-year-old children from Guangxi Zhuang Birth Cohort. ICP-MS was employed to detect 17 metals, including 7 essential metals (Mn, Fe, Co, Ni, Cu, Zn, Mo) and 10 non-essential metals (As, Rb, Sr, Cd, Sb, Cs, Ba, W, Pb, U), in maternal plasma samples obtained before 13 weeks of gestation during the initial maternity checkup. Child intelligence was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. The GLM, RCS and mixture models were used to assess the associations of maternal plasma metal levels with child intelligence quotient (IQ) scores. RESULTS: The GLM analysis revealed that U had a significant adverse effect on child IQ scores in high-dose exposure groups (-9.236 [-18.644, -4.936], p = 0.006) after adjusting for covariates, while Sb showed a linear adverse effect on children's intelligence in the adjusted model (-4.028 [-7.432, -0.626], p = 0.021). BKMR modeling indicated that overall IQ scores decreased as concentrations of non-essential metals mixtures increased after adjusting for essential metal mixtures, consistent with findings from the WQS (ß [95% CI], -8.463 [-14.449, -2.476], p = 0.007) and Qgcomp models (-7.003 [-12.928, -1.078], p = 0.022). Among the non-essential metals, U had the highest negative weight at 37.96%, followed by Pb (23.35%) and Sb (16.91%). Furthermore, potential interactions were observed between metals (Pb and U) and Sb in the study findings. CONCLUSION: Reducing exposure to non-essential metal mixtures, especially U, Sb and Pb, during early pregnancy and ensuring adequate intake of specific essential metal elements could be a critical intervention in addressing childhood intellectual impairment.

A Novel lncRNA lncRNA-4045 Promotes the Progression of Hepatocellular Carcinoma by Affecting the Expression of AKR1B10.

BACKGROUND: Long noncoding RNAs (lncRNAs) have been shown to be related to the occurrence and development of a variety of cancers including hepatocellular carcinoma (HCC). However, a large number of potential HCC-related lncRNAs remain undiscovered and are yet to be fully understood. METHODS: Differentially expressed lncRNAs were first obtained from the tumor tissues and adjacent normal tissues of five HCC patients using high-throughput microarray chips. Then the expression levels of 10 differentially expressed lncRNAs were verified in 50 pairs of tissue samples from patients with HCC by quantitative real-time PCR (qRT-PCR). The oncogenic effects of lncRNA-4045 (ENST00000524045.6) in HCC cell lines were verified through a series of in vitro experiments including CCK-8 assay, plate clone formation assay, transwell assay, scratch assay, and flow cytometry. Subsequently, the potential target genes of lncRNA-4045 were predicted by bioinformatics analysis, fluorescence in situ hybridization assay, and RNA sequencing. The mechanism of lncRNA-4045 in HCC was explored by WB assay as well as rescue and enhancement experiments. RESULTS: The results from microarray chips showed 1,708 lncRNAs to have been significantly upregulated and 2725 lncRNAs to have been significantly downregulated in HCC tissues. Via validation in 50 HCC patients, a novel lncRNA lncRNA-4045 was found significantly upregulated in HCC tissues. Additionally, a series of in vitro experiments showed that lncRNA-4045 promoted the proliferation, invasion, and migration of HCC cell lines, and inhibited the apoptosis of HCC cell lines. The results of qRT-PCR in HCC tissues showed that the expression levels of AKR1B10 were significantly positively correlated with lncRNA-4045. LncRNA-4045 knockdown significantly down-regulated AKR1B10 protein expression, and overexpression of lncRNA-4045 led to significant up-regulation of AKR1B10 protein in HCC cell lines. Lastly, down-regulation of AKR1B10 could partially eliminate the enhancement of cell proliferation induced by lncRNA-4045 overexpression, while up-regulation of AKR1B10 was shown to enhance those effects. CONCLUSION: LncRNA-4045 may promote HCC via enhancement of the expression of AKR1B10 protein.

Association between prenatal exposure to alkylphenols and intelligence quotient among preschool children: sex-specific effects.

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) (ß = -2.38; 95% CI: -4.59, -0.16) and working memory index (WMI) (ß = -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 (ß = 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 < 0.05). The combined effect primarily driven by NP, of maternal AP mixtures at concentrations above the 50th percentile exhibited an inverse trend on FSIQ in total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to various APs affects IQ in preschool children, and there may be nonmonotonic and sex-specific effects. Further investigation across the population is required to elucidate the potential neurotoxic effects of APs.

High prevalence of hyperuricemia and the association with metabolic syndrome in the rural areas of Southwestern China: A structural equation modeling based on the Zhuang minority cohort.

BACKGROUND AND AIMS: The prevalence of hyperuricemia (HUA) and metabolic syndrome (MetS) in the Zhuang minority had not been examined. We aimed to determine the prevalence of HUA and MetS, and explore the interrelationship among the serum uric acid to creatinine (SUA/Cr) ratio, MetS, and its components. METHODS AND RESULTS: A cross-sectional study was conducted with structured questionnaire and physical examination based on the Zhuang minority cohort. A Structural Equation Model was performed to examine the hypothesis link between the SUA/Cr ratio, MetS, and its components. 10,902 aged 35-74 years Zhuang minority adults were included. The total prevalence of HUA and MetS was 17.5% and 23.7%, respectively. The SUA/Cr ratio had a positive effect on MetS (the standardized coefficient ßr was 0.311 in males and 0.401 in females). The SUA/Cr ratio was positively associated with obesity (ßr = 0.215), dyslipidemia (ßr = 0.177), and high blood pressure (ßr = 0.034) in males and was positively associated with obesity (ßr = 0.303), dyslipidemia (ßr = 0.162), and hyperglycemia (ßr = 0.036) in females. CONCLUSIONS: The prevalence of HUA in the aged 35-74 years Zhuang minority adults was high while the prevalence of MetS was relatively low. As HUA is an earlier-onset metabolic disorder and the SUA/Cr ratio had a positive effect on MetS and its components, the prevention measures of MetS should be strengthened. And the SUA/Cr ratio can be used as an early warning sign to implement the intervention measures of MetS.

Relationship of urinary glyphosate concentrations with glycosylated hemoglobin and diabetes in US adults: a cross-sectional study.

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 < 0.001) and the prevalence of diabetes (OR: 1.45; 95% CI: 1.24, 1.68; P < 0.001) were found after adjustment. Compared with the lowest quartile of glyphosate levels, the highest quartile was positively associated with HbA1c levels (percentage change: 4.19; 95% CI: 2.54, 5.85; P < 0.001) and the prevalence of diabetes (OR: 1.89; 95% CI: 1.37, 2.63; P < 0.001). The RCS curves demonstrated a monotonically increasing dose-response relationship between urinary glyphosate levels and the prevalence of diabetes and HbA1c levels. CONCLUSIONS: Urinary glyphosate concentrations are positively associated with HBA1c levels and the prevalence of diabetes. To verify our findings, additional large-scale prospective investigations are required.

Associations of prenatal exposure to PM2.5 and its components with offsprings' neurodevelopmental and behavioral problems: A prospective cohort study from China.

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.

Associations of prenatal exposure to per- and polyfluoroalkyl substances and fetal sex hormones in the Guangxi Zhuang Birth Cohort Study: Greater effect of long-chain PFAS.

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.

Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study.

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.

Identification and verification of novel ferroptosis biomarkers predicts the prognosis of hepatocellular carcinoma.

BACKGROUND: Big data mining and experiments are widely used to mine new prognostic markers. METHODS: Candidate genes were identified from CROEMINE and FerrDb. Kaplan-Meier survival and Cox regression analysis were applied to assess the association of genes with Overall survival time (OS) and Disease-free survival time (DFS) in two HCC cohorts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Immunohistochemistry were performed in HCC samples. RESULTS: 21 and 15 genes that can predict OS and DFS, which had not been reported before, were identified from 719 genes, respectively. Survival analysis showed elevated mRNA expression of GLMP, SLC38A6, and WDR76 were associated with poor prognosis, and three genes combination signature was an independent prognostic factor in HCC. RT-qPCR and Immunohistochemistry confirmed the results. CONCLUSIONS: We established a novel computational process, which identified the expression levels of GLMP, SLC38A6, and WDR76 as potential ferroptosis-related biomarkers indicating the prognosis of HCC.

Nucleus-localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription.

Accumulating evidence indicates that circular RNAs (circRNAs) are inextricably linked to cancer development. However, the function and mechanism of nucleus-localized circRNAs in hepatocellular carcinoma (HCC) still require investigation. Here, qRT-PCR and receiver-operating characteristic curve were used to detect the expression and diagnostic potential of circSLC39A5 for HCC. The biological function of circSLC39A5 in HCC was investigated in vitro and in vivo. Nucleoplasmic separation assay, fluorescence in situ hybridization, RNA pulldown, RNA immunoprecipitation, the HDOCK Server, the NucleicNet Webserver, crosslinking-immunoprecipitation, MG132 treatment, and chromatin immunoprecipitation were utilized to explore the potential molecular mechanism of circSLC39A5 in HCC. The results showed that circSLC39A5 was downregulated in both HCC tissues and plasma and was associated with satellite nodules and lymph node metastasis/vascular invasion. CircSLC39A5 was stably expressed in plasma samples under different storage conditions, showing good diagnostic potential for HCC (AUC = 0.915). CircSLC39A5 inhibited proliferation, migration, and invasion, facilitated the apoptosis of HCC cells, and was associated with low expression of Ki67 and CD34. Remarkably, circSLC39A5 is mainly localized in the nucleus and binds to the transcription factor signal transducer and activator of transcription 1 (STAT1), affecting its stabilization and expression. STAT1 binds to the promoter of thymine DNA glycosylase (TDG). Overexpression of circSLC39A5 elevates TDG expression and reverses the increase of proliferating cell nuclear antigen (PCNA) expression and the overactive cell proliferation caused by TDG silencing. Our findings uncovered a novel plasma circRNA, circSLC39A5, which may be a potential circulating diagnostic marker for HCC, and the mechanism by which nucleus-localized circSLC39A5 exerts a transcriptional regulatory role in HCC by affecting STAT1/TDG/PCNA provides new insights into the mechanism of circRNAs.

Association between perfluoroalkyl and polyfluoroalkyl substances exposure and fetal overgrowth: A prospective birth cohort study conducted in China.

BACKGROUND: Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been associated with gestational diabetes mellitus, obesity or overweight in childhood, but data on fetal overgrowth outcomes including macrosomia and large for gestational age (LGA) and among gestational age diverse infants remain scarce. OBJECTIVE: To evaluate the association between maternal PFASs exposure and macrosomia and LGA, with exploration of the interaction between PFASs exposure and gestational age on fetal overgrowth. METHODS: A total of 1441 mother-infants pairs from Guangxi Zhuang Birth Cohort of China were analyzed. Nine PFASs were measured in maternal serum using ultra-high liquid performance chromatographytandem mass spectrometry. Multivaraible logistical regression and generalized additive models were performed for individual PFAS exposures, piecewise regression analysis was used to estimate the breakpoint values for the non-linear dose-response relationships. Bayesian Kernel Machine Regression was performed for PFASs mixture. RESULTS: In single pollutant models, maternal PFDA and PFOA exposure showed U-shaped relationship with macrosomia and LGA. When PFDA concentration exceeded 0.32 ng/mL was significantly positively associated with risks of LGA and macrosomia (OR=4.66, 95%CI: 1.26, 17.17; OR=14.43, 95%CI: 2.64, 79.02; respectively), while a negatively association was observed when level below 0.32 ng/mL. When PFOA concentration exceeded 1.20 ng/mL was significantly associated with increased risk of macrosomia (OR=7.75, 95%CI: 1.36, 44.06). In mixed exposure models, mixture of PFASs was positively associated with macrosomia, as well as associated with LGA when all the PFASs were at their 30th percentile or below. The maximum risk of LGA was reached when concentrations of PFUnA, PFDA, or PFBS were at the highest concentrations and the gestational age at the minimum of this study. CONCLUSIONS: Maternal exposure to PFDA, PFOA and PFASs mixture were non-monotonically associated with macrosomia and LGA, the direction of the associations depends on the level of exposure.

Associations of dietary, sociodemographic, and anthropometric factors with anemia among the Zhuang ethnic adults: a cross-sectional study in Guangxi Zhuang Autonomous Region, China.

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 (< 55%) was negatively related to anemia (OR = 0.68, 95% CI: 0.53-0.86, p = 0.0014). Conversely, a body water percentage above normal (> 65%) was positively correlated with anemia in men (OR = 1.73, 95% CI: 1.38-2.17, p < 0.0001). CONCLUSIONS: Anemia remains a moderate public health problem for premenopausal women and the elderly population in the Guangxi Zhuang minority region. The prevention of anemia at the population level requires multifaceted intervention measures according to sex and age, with a focus on dietary factors and the control of body composition.

Liver-specific LINC01146, a promising prognostic indicator, inhibits the malignant phenotype of hepatocellular carcinoma cells both in vitro and in vivo.

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.

Liver-specific lncRNA FAM99A may be a tumor suppressor and promising prognostic biomarker in hepatocellular carcinoma.

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.

Single and mixed effects of prenatal exposure to multiple bisphenols on hemoglobin levels and the risk of anemia in pregnant women.

INTRODUCTION: Bisphenols have endocrine-disrupting effects, which may disrupt hemoglobin (Hb) homeostasis and lead to anemia. However, the effects of bisphenols on anemia remain unknown. Therefore, we assessed the effects of single- and multiple-exposure to bisphenols on Hb levels and anemia of pregnant women. METHODS: The study involved 2035 pregnant women from Guangxi Zhuang Birth Cohort in China. Generalized linear regression, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were performed to examine the effects of serum bisphenols on Hb levels and the risk of anemia. RESULTS: After adjustment, elevated bisphenol A (BPA) levels were correlated with decreased Hb concentrations (ß = -0.51; 95%CI: -0.92, -0.10) in the first trimester, and these correlations were more sensitive in mothers of males. Compared with the low-exposure group, bisphenol B (BPB) levels in the high-exposure group led to a 1.52 g/L (95%CI: -3.01, -0.03) decrease in Hb levels in the second trimester; tetrabromobisphenol A (TBBPA) levels in the high-exposure group led to a higher the risk of anemia in the third trimester (OR = 1.46; 95%CI: 1.07, 1.99); bisphenol F (BPF) in the high-exposure group led to lower Hb levels (ß = -2.42; 95%CI:-4.69, -0.14) in mothers of male fetuses in the third trimester. Qgcomp showed that elevated levels of bisphenol mixture was correlated with (ß = -1.42; 95%CI: -2.61, -0.24) decrease in Hb levels in the second trimester. PCA revealed a negative association between PC2 and Hb levels in the first trimester (ß = -0.89; 95%CI: -1.61, -0.17). Similarly, a negative relationship was observed between PC1 and Hb levels in the third trimester among mothers with male fetuses (ß = -1.00; 95%CI: -1.94, -0.06). CONCLUSIONS: Prenatal exposure to single and mixed bisphenols may decrease Hb levels and increase the risk of anemia during pregnancy, the associations may be greater in mothers with male fetuses than those with female fetuses.

Association of maternal perfluoroalkyl substance exposure with postpartum haemorrhage in Guangxi, China.

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) (ß: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (ß: 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.

Identification of a tumor microenvironment-related gene signature to improve the prediction of cervical cancer prognosis.

BACKGROUND: Previous studies have found that the microenvironment of cervical cancer (CESC) affects the progression and treatment of this disease. Thus, we constructed a multigene model to assess the survival of patients with cervical cancer. METHODS: We scored 307 CESC samples from The Cancer Genome Atlas (TCGA) and divided them into high and low matrix and immune scores using the ESTIMATE algorithm for differential gene analysis. Cervical cancer patients were randomly divided into a training group, testing group and combined group. The multigene signature prognostic model was constructed by Cox analyses. Multivariate Cox analysis was applied to evaluate the significance of the multigene signature for cervical cancer prognosis. Prognosis was assessed by Kaplan-Meier curves comparing the different groups, and the accuracy of the prognostic model was analyzed by receiver operating characteristic-area under the curve (ROC-AUC) analysis and calibration curve. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between the multigene signature and immune cell infiltration. RESULTS: We obtained 420 differentially expressed genes in the tumor microenvironment from 307 patients with cervical cancer. A three-gene signature (SLAMF1, CD27, SELL) model related to the tumor microenvironment was constructed to assess patient survival. Kaplan-Meier analysis showed that patients with high risk scores had a poor prognosis. The ROC-AUC value indicated that the model was an accurate predictor of cervical cancer prognosis. Multivariate cox analysis showed the three-gene signature to be an independent risk factor for the prognosis of cervical cancer. A nomogram combining the three-gene signature and clinical features was constructed, and calibration plots showed that the nomogram resulted in an accurate prognosis for patients. The three-gene signature was associated with T stage, M stage and degree of immune infiltration in patients with cervical cancer. CONCLUSIONS: This research suggests that the developed three-gene signature may be applied as a biomarker to predict the prognosis of and personalized therapy for CESC.

Prenatal exposure to bisphenols and risk of preterm birth: Findings from Guangxi Zhuang birth cohort in China.

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.

Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma.

BACKGROUND: Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione S-transferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown. METHODS: Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients. RESULTS: Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367-0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342-0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways. CONCLUSIONS: In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis.