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Abstract 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

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.

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (

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.

Background: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. Objective: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. Methods: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. Results: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: −11.92%, −1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: −16.84%, −1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. Conclusion: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

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 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

Pineapple is a globally significant tropical fruit, but its cultivation faces numerous challenges due to abiotic and biotic stresses, affecting its quality and quantity. WRKY transcription factors are known regulators of stress responses, however, their specific functions in pineapple are not fully understood. This study investigates the role of AcWRKY31 by overexpressing it in pineapple and Arabidopsis. Transgenic pineapple lines were obtained using Agrobacterium-mediated transformation methods and abiotic and biotic stress treatments. Transgenic AcWRKY31-OE pineapple plants showed an increased sensitivity to salt and drought stress and an increased resistance to biotic stress from pineapple mealybugs compared to that of WT plants. Similar experiments in AcWRKY31-OE, AtWRKY53-OE, and the Arabidopsis Atwrky53 mutant were performed and consistently confirmed these findings. A comparative transcriptomic analysis revealed 5357 upregulated genes in AcWRKY31-OE pineapple, with 30 genes related to disease and pathogen response. Notably, 18 of these genes contained a W-box sequence in their promoter region. A KEGG analysis of RNA-Seq data showed that upregulated DEG genes are mostly involved in translation, protein kinases, peptidases and inhibitors, membrane trafficking, folding, sorting, and degradation, while the downregulated genes are involved in metabolism, protein families, signaling, and cellular processes. RT-qPCR assays of selected genes confirmed the transcriptomic results. In summary, the AcWRKY31 gene is promising for the improvement of stress responses in pineapple, and it could be a valuable tool for plant breeders to develop stress-tolerant crops in the future.

Exposure to bisphenols can affect bone mineral density (BMD) in animals and humans. However, the effects of maternal exposure to bisphenols during pregnancy on bone health in preschool children remain unknown. We aimed to assess the effects of prenatal exposure to single and multiple bisphenols on bone health in preschool children. A total of 230 mother–child pairs were included in this study. Generalized linear regression, restricted cubic spline (RCS), principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) were utilized to assess the relationship between bisphenol levels and bone health in preschool children. Each natural log (Ln) unit increase in tetrabromobisphenol A was related to a 0.007 m/s (95 % CI: –0.015, 0.000) decrease in Ln-transformed speed of sound (SOS) among girls. Decreased BMD Z scores in preschool children were found only in the high bisphenol S exposure group (β = -0.568; 95 % CI: –1.087, –0.050) in boys. The risk of low BMD (BMDL) was significantly higher in the middle-exposure group (OR = 4.695; 95 % CI: 1.143, 24.381) and high-exposure group of BPS (OR = 6.165, 95 % CI: 1.445, 33.789) compared with the low-exposure group in boys. In girls, the risk of BMDL decreased with increasing bisphenol A concentration (OR = 0.413, 95 % CI: 0.215, 0.721). RCS analysis revealed a U-shaped nonlinear correlation between BPB concentration and BMDL in girls (P-overall = 0.011, P-nonlinear = 0.009). In PCA, a U-shaped dose–response relationship was found between PC2 and the risk of BMDL (P-overall = 0.048, P-nonlinear = 0.032), and a significant association was only noted in girls when stratified by sex. The BKMR model revealed a horizontal S-shaped curve relationship between bisphenol mixtures and BMDL in girls. The results indicated that prenatal exposure to single and mixed bisphenols can affect BMD in preschool children, exerting nonmonotonic and child sex-specific effects.

Intrauterine growth restriction (IUGR) is an abnormal fetal growth pattern that can lead to neonatal morbidity and mortality. IUGR may be affected by prenatal exposure to environmental pollutants, including perfluoroalkyl substances (PFASs). However, research linking PFAS exposure to IUGR is limited, with inconsistent results. We aimed to investigate the association between PFAS exposure and IUGR by using nested casecontrol study based on Guangxi Zhuang Birth Cohort (GZBC), in Guangxi, China. A total of 200 IUGR cases and 600 controls were enrolled in this study. The maternal serum concentrations of nine PFASs were measured using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLCMS). The associations single and mixed effects of prenatal PFAS exposure on IUGR risk were assessed using conditional logistic regression (single-exposure), Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) models. In the conditional logistic regression models, the log10-transformed concentrations of perfluoroheptanoic acid (PFHpA, adjusted OR: 4.41, 95% CI: 3.03–6.41), perfluorododecanoic acid (PFDoA, adjusted OR: 1.94, 95% CI: 1.14–3.32), and perfluorohexanesulfonate (PFHxS, adjusted OR: 1.83, 95% CI: 1.15–2.91) were positively associated with risk of IUGR. In the BKMR models, the combined effect of PFASs was positively associated with IUGR risk. In the qgcomp models, we also found an increased IUGR risk (OR=5.92, 95% CI: 2.33–15.06) when all nine PFASs increased by one tertile as a whole, and PFHpA (43.9%) contributed the largest positive weights. These findings suggested prenatal exposure to single and mixtures of PFASs may increase IUGR risk, with the effect being largely driven by the PFHpA concentration.

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.

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.

Abstract Background Telomere length (TL) is variable at birth and is inversely associated with body mass index (BMI) in adulthood. A growing number of evidences suggested that a higher maternal pre-pregnancy BMI results in adverse offspring health outcomes, especially shorter newborn TL. However, a newborn’s genetic endowment is equally derived from both parents, the association between parental pre-pregnancy BMI and newborn TL has been rarely discussed. We aimed to determine the association between parental pre-pregnancy BMI and newborn TL. Methods A total of 1082 parent-newborn pairs were recruited from the Guangxi Zhuang Birth Cohort (GZBC). TL in cord blood was measured using quantitative real-time polymerase chain reaction (qPCR) and expressed as the ratio of telomere copy number to single-copy gene number (T/S). A series of linear regressions were performed to assess the associations between parental pre-pregnancy BMI and newborn TL. Results Mothers who were overweight before pregnancy had significantly shorter cord blood telomere length in their newborns than those who were normal weight before pregnancy [percentage change: − 7.96% (95% CI: − 14.49 to − 0.69%; P = 0.032)]. Further analysis of the combined effects of parental weight status on newborn TL showed that TL was significantly shortened among newborns whose mothers were overweight and fathers were of healthy weight when compared with those whose mothers and fathers were both of normal weight [percentage change: − 8.38% (95% CI: − 15.47 to − 0.92%; P = 0.028)]. Subgroup analysis indicated these effects were more pronounced among male newborns and those whose paternal age

Abstract 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.

Abstract Background Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. Methods Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2′-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC. Results The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency. Conclusion A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC. Graphic abstract

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.

Abstract Background Sepsis-associated encephalopathy (SAE) is epidemic in intensive care units and recognized as a fatal complication of sepsis. SAE is characterized by diffuse brain dysfunction and the correct diagnosis of SAE requires ruling out direct central nervous system (CNS) infection or other types of encephalopathy, such as hepatic encephalopathy, pulmonary encephalopathy, and other encephalopathy. Case presentation We reported a rare case of a 5-year-old girl who presented with abdominal pain, vomiting, recurrent seizures, and coma. Brain magnetic resonance imaging (MRI) showed diffuse white matter abnormalities in the brain on day 1. Cerebrospinal fluid (CSF) tests revealed that protein levels and glucose levels were normal without pleocytosis. CSF PCRs for pathogens were all negative. The electroencephalography examination demonstrated diffuse, generalized and slow background activity. The patient showed the symptom of hyperferritinemic sepsis with multiple organ dysfunction syndrome (MODS). SAE was also diagnosed by ruling out other encephalitis or encephalopathy. The patient made marked improvements of clinical symptoms and the lesions on brain imaging disappeared completely within two months after appropriate treatment including antibiotic treatments, methylprednisolone, intravenous immunoglobulin, membrane-based therapeutic plasma exchange (TPE), and continuous renal replacement therapy (CRRT). Conclusions SAE can be a fatal complication of sepsis which asks for immediate diagnosis and treatment. Few reports have focus on MRI imaging findings on the early onset of hyperferritinemic sepsis with MODS since these children were too ill to undergo an MRI scan. However, SAE might appear before other systemic features of sepsis are obvious, and MRI could show abnormal lesion in the brain during the early course. Therefore, MRI should be performed early to diagnose this fatal complication which would play important roles in improving the clinical outcomes by early initiation with appropriate treatments.

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.

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.

Resmethrin, a type I pyrethroid insecticide, can activate sodium channels, causing neurotoxicity in both mammals and insects. Possible routes of poisoning include inhalation, dermal contact and ingestion. There are no specific symptoms for resmethrin poisoning. Until now, no antidote has been available for resmethrin. Resmethrin poisoning is rarely reported in children. Here, we report a fatal case of resmethrin poisoning that might have been caused by accidental ingestion by a 26-month-old child. He presented with neurotoxic symptoms that included vomiting, recurrent seizures, and coma. The cranial CT showed extensive lesions of low intensity in the bilateral white matter, thalamus, brainstem, and cerebellum. Lumbar punctures showed increased intracranial pressure (ICP > 25 mmHg). Cerebrospinal fluid (CSF) tests revealed that protein was elevated to 289.2 mg/dL without pleocytosis. Resmethrin was detected in his blood by liquid chromatography-mass spectrometry, which confirmed the diagnosis of resmethrin poisoning. The child developed brain stem herniation and then was declared brain dead at the 77th h after admission. Resmethrin poisoning can be fatal, and it requires immediate diagnosis and treatment. Previous studies reported that cranial CT and CSF analyses were all normal in patients with pyrethroid poisoning. This case might extend the knowledge of neuroimaging and CSF analysis in children with resmethrin poisoning.

Pancreatic lipase is critical for the digestion and absorption of dietary fats. The most abundant lipolytic enzymes secreted by the pancreas are pancreatic triglyceride lipase (PTL or PNLIP) and its family members, pancreatic lipase-related protein 1 (PNLIPRP1or PLRP1) and pancreatic lipase-related protein 2 (PNLIPRP2 or PLRP2). Unlike the family’s other members, PNLIPRP2 plays an elemental role in lipid digestion, especially for newborns. Therefore, if genetic factors cause gene mutation, or other factors lead to non-expression, it may have an effect on fat digestion and absorption, on the susceptibility to pancreas and intestinal pathogens. In this review, we will summarize what is known about the structure and function of PNLIPRP2 and the levels of PNLIPRP2 and associated various pathological states.

Utilizing sintered ore catalysts (SOC), which are used in the sintering industry for NH3-SCR denitration, is a feasible and economical way to reduce NOx emission in sintering flue gas. Therefore, in order to enhance the denitration efficiency of SOC, sintered ore modified by sulfuric acid and sulfated sintered ore catalysts (SSOC-5) were prepared. Kinetic analyses of these two catalysts for denitration were carried out in this study. On the basis of eliminating the influence of internal and external diffusion, the relationship between reactants and reaction rate was studied by a power function kinetic model. This clarified that the adsorption ability of the acid-modified catalyst for reaction gas adsorption was stronger than that of sintered ore catalysts, and the reaction rate was also accelerated. The NO, NH3 and O2 reaction orders of SOC were 1, 0.3 and 0.16 at 250~300 °C, while these values of SSOC-5 were 0.8, 0.06 and 0.09, respectively. The apparent activation energy of SOC was 83.66 kJ/mol, while the value of SSOC-5 decreased to 59.93 kJ/mol.

Our study aimed to investigate the prevalence and associated factors of sarcopenia in the disabled elderly in communities in Shanghai, China. A cross-sectional study was conducted in 2018. Five hundred and seventy two participants (≥60 years) were recruited through cluster sampling from Putuo District of Shanghai. Sarcopenia was defined according to the updated consensus of the European Sarcoma Working Group in 2019. The sarcopenia, depression, and nutrition status were assessed by using SARC-F, the Short Version of the Center for Epidemiological Studies Depression Scale (CES-D-10), and the Mini Nutritional Assessment-Short form (MNA-SF), respectively Physical activity was also assessed. Our results showed the prevalence of sarcopenia was 0.5%, but the prevalence of low handgrip strength was 37.2% (male, 5.5%; female, 39.1%). The modified Poisson regression model was used to evaluate the relationship among related variables and low handgrip strength. The risk for low handgrip strength was higher in the physically disabled subjects than in the visually disabled ones (aPR: 1.69, 95% CI: 1.88-2.42). Depressive symptoms (aPR: 1.31, 95% CI: 1.04-1.62) and PASE score (aPR: 0.99, 95% CI: 0.99-1.00) were independently associated with low handgrip strength. In summary, the prevalence of EWGSOP2-defined sarcopenia is low and the prevalence of declined muscle strength is high in the disabled elderly. The elderly participants with a physical disability had a higher prevalence of low hand handgrip strength than those with a visual disability. More studies with a larger sample size and longitudinal follow-up are needed to confirm our findings.

BackgroundThis study searched for immune-related long noncoding RNAs (lncRNAs) to predict the prognosis of patients with cervical cancer.MethodWe obtained immunologically relevant lncRNA expression profiles and clinical follow-up data from cervical cancer patients from The Cancer Genome Atlas database and the Molecular Signatures Database. Cervical cancer patients were randomly divided into a training group, testing group and combined group. The immune prognostic signature was constructed by Least Absolute Shrinkage and Selection Operator Cox regression, prognosis was analyzed by Kaplan–Meier curves between different groups, and the accuracy of the prognostic model was assessed by receiver operating characteristic-area under the curve (ROC-AUC) analysis.ResultsA six-lncRNA immune prognostic signature (LIPS) was constructed to predict the prognosis of cervical cancer. The six lncRNAs are as follows: AC009065.8, LINC01871, MIR210HG, GEMIN7-AS1, GAS5-AS1, and DLEU1. A ROC-AUC analysis indicated that the model could predict the prognosis of cervical cancer patients in different subgroups. A Kaplan–Meier analysis showed that patients with high risk scores had a poor prognosis; these results were equally meaningful in the subgroup analyses. Risk scores differed depending on the clinical pathology and tumor grade and were independent risk factors for cervical cancer prognosis. Gene set enrichment analysis revealed an association between the LIPS and the immune response, Wnt signaling pathway, and TGF beta signaling pathway.ConclusionOur study shows that the six-LIPS can predict the prognosis of cervical cancer and contribute to decisions regarding the immunotherapeutic strategy.

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.

Abstract Background Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and highly aggressive NK cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with NK/T cell lymphoma (NKTL), which has a very different prognosis. Here, we present a case with nasal and bone marrow involvement, provide a literature review and make a differential diagnosis. Case presentation A 41-year-old male presented nasal congestion pharyngalgia, palatal perforation, high fever and multiorgan dysfunction. Our diagnosis primarily relied on clinical features, the morphology and immunophenotype of the neoplastic cells and imaging studies. Characteristic large granular lymphocytes with azurophilic granules were visible in the bone marrow smears. In addition, the neoplastic cells expressed a typical immunophenotype, and the T cell receptor γ (TCR-γ) gene rearrangement analysis and presence of Epstein-Barr virus (EBV) were negative. The patient’s symptoms and signs were temporarily relieved after chemotherapy treatment, but after a short time, he underwent a rapid clinical decline and died 8 weeks later after admission due to multiorgan function failure. Conclusion Our case demonstrates that to avoid a misdiagnosis, bone marrow analyses and other examinations should be performed early when a patient initially presents nasal lesions and other systemic symptoms. To the best of our knowledge, this may be the first reported case of ANKL with sternal tenderness.

The characteristic brain pathology and motor and nonmotor symptoms of Parkinson’s disease (PD) are well established. However, the details regarding the causes of the disease and its course are much less clear. Animal models have significantly enriched our current understanding of the progression of this disease. Among various neurotoxin-based models of PD, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most commonly studied model. Here, we provide an overview of the dynamic changes in the nigrostriatal pathway in the MPTP mouse model of PD. Pathophysiological events, such as reductions in the striatal dopamine (DA) concentrations and levels of the tyrosine hydroxylase (TH) protein, depletion of TH-positive nerve fibers, a decrease in the number of TH-positive neurons in the substantia nigra pars compacta (SNpc), and glial activation, are addressed. This article will assist with the development of interventions or therapeutic strategies for PD.

The safety of food additives has been widely concerned. Using single additives in the provisions of scope is safe, but the combination of additives, may induce additive, synergy, antagonism and other joint effects. This study investigated the cytotoxicity of aspartame (AT) together with potassium sorbate (PS). Thiazolyl Blue Tetrazolium Bromide (MTT) assay indicated that AT and PS had IC50 values of 0.48 g/L and 1.25 g/L at 24 h, respectively. High content analysis (HCA) showed that both AT and PS had a negative effect on mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and DNA damage while the joint group behaved more obviously. The biochemical assays revealed typical cell morphological changes and the activation of cytochrome c and caspase-3 verified apoptosis induced by AT together with PS. With dissipation of MMP and increase of cell membrane permeability (CMP), it indicated AT together with PS-induced apoptosis was mediated by mitochondrial pathway. Meanwhile, p53 were involved in DNA damage, and the ratio of Bax/Bcl-2 was increased. Moreover, excessive ROS induced by AT together with PS is a key initiating factor for apoptosis. All these results proved that p53 was involved in apoptosis via mitochondria-mediated pathway and the process was regulated by ROS.