Associations between maternal exposure to multiple metals and metalloids and blood pressure in preschool children: A mixture-based approach.

BACKGROUND: Exposure to metals during pregnancy can potentially influence blood pressure (BP) in children, but few studies have examined the mixed effects of prenatal metal exposure on childhood BP. We aimed to assess the individual and combined effects of prenatal metal and metalloid exposure on BP in preschool children. METHODS: A total of 217 mother-child pairs were selected from the Zhuang Birth Cohort in Guangxi, China. The maternal plasma concentrations of 20 metals [e.g. lead (Pb), rubidium (Rb), cesium (Cs), and zinc (Zn)] in early pregnancy were measured by inductively coupled plasmamass spectrometry. Childhood BP was measured in August 2021. The effects of prenatal metal exposure on childhood BP were explored by generalized linear models, restricted cubic spline and Bayesian kernel machine regression (BKMR) models. RESULTS: In total children, each unit increase in the log10-transformed maternal Rb concentration was associated with a 10.82-mmHg decrease (95% CI: -19.40, -2.24) in childhood diastolic BP (DBP), and each unit increase in the log10-transformed maternal Cs and Zn concentrations was associated with a 9.67-mmHg (95% CI: -16.72, -2.61) and 4.37-mmHg (95% CI: -8.68, -0.062) decrease in childhood pulse pressure (PP), respectively. The log10-transformed Rb and Cs concentrations were linearly related to DBP (P nonlinear=0.603) and PP (P nonlinear=0.962), respectively. Furthermore, an inverse association was observed between the log10-transformed Cs concentration and PP (ß =-12.18; 95% CI: -22.82, -1.54) in girls, and between the log10-transformed Rb concentration and DBP (ß =-12.54; 95% CI: -23.87, -1.21) in boys, while there was an increasing association between the log10-transformed Pb concentration and DBP there was an increasing in boys (ß =6.06; 95% CI: 0.36, 11.77). Additionally, a U-shaped relationship was observed between the log10-transformed Pb concentration and SBP (P nonlinear=0.015) and DBP (P nonlinear=0.041) in boys. Although there was no statistically signiffcant difference, there was an inverse trend in the combined effect of maternal metal mixture exposure on childhood BP among both the total children and girls in BKMR. CONCLUSIONS: Prenatal exposure to both individual and mixtures of metals and metalloids influences BP in preschool children, potentially leading to nonlinear and sex-specific effects.

Correlation between urinary rare earth elements and liver function in a Zhuang population aged 35-74 years in Nanning.

BACKGROUND: Animal studies have shown that exposure to REEs can cause severe liver damage, but evidence from population studies is still lacking. Therefore, we investigated the relationship between REEs concentrations in urine and liver function in the population. METHODS: We conducted a cross-sectional study on 1024 participants in Nanning, China. An inductively coupled plasma mass spectrometer (ICP-MS) was used to detect the concentrations of 12 REEs in urine. The relationship between individual exposure to individual REE and liver function was analyzed by multiple linear regression. Finally, the effects of co-exposure to 5 REEs on liver function were assessed by a weighted sum of quartiles (WQS) regression model and a Bayesian kernel machine regression (BKMR) model. RESULTS: The detection rate of 5 REEs, lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and dysprosium (Dy), is greater than 60%. After multiple factor correction, La, Ce, Pr, Nd, and Dy were positively correlated with serum ALP, Ce, Pr, and Nd were positively correlated with serum AST, while Ce was negatively correlated with serum TBIL and DBIL. Both WQS and BKMR results indicate that the co-exposure of the 5 REEs is positively correlated with serum ALP and AST, while negatively correlated with serum DBIL. There were potential interactions between La and Ce, La and Dy in the association of co-exposure of the 5 REEs with serum ALP. CONCLUSIONS: The co-exposure of the 5 REEs was positively correlated with serum ALP and AST, and negatively correlated with serum DBIL.

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.

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.

The role of liver enzymes in the association between ozone exposure and diabetes risk: a cross-sectional study of Zhuang adults in China.

Background: Growing evidence has demonstrated the role of ambient air pollutants in driving diabetes incidence. However, epidemiological evidence linking ozone (O3) exposure to diabetes risk has been scarcely studied in Zhuang adults in China. We aimed to investigate the associations of long-term exposure to O3 with diabetes prevalence and fasting plasma glucose (FPG) and estimate the mediating role of liver enzymes in Zhuang adults. Methods: We recruited 13 843 ethnic minority adults during 2018-2019 based on a cross-sectional study covering nine districts/counties in Guangxi. Generalized linear mixed models were implemented to estimate the relationships between O3 exposure and diabetes prevalence and FPG. Mediation effect models were constructed to investigate the roles of liver enzymes in the associations of O3 exposure with diabetes prevalence and FPG. Subgroup analyses were conducted to identify potential effect modifications. Results: Long-term exposure to O3 was positively associated with diabetes prevalence and FPG levels in Zhuang adults, with an excess risk of 7.32% (95% confidence interval [CI]: 2.56%, 12.30%) and an increase of 0.047 mmol L-1 (95% CI: 0.032, 0.063) for diabetes prevalence and FPG levels, respectively, for each interquartile range (IQR, 1.18 µg m-3) increment in O3 concentrations. Alanine aminotransferase (ALT) significantly mediated 8.10% and 29.89% of the associations of O3 with FPG and diabetes prevalence, respectively, and the corresponding mediation proportions of alkaline phosphatase (ALP) were 8.48% and 30.00%. Greater adverse effects were observed in females, obese subjects, people with a low education level, rural residents, non-clean fuel users, and people with a history of stroke and hypertension in the associations of O3 exposure with diabetes prevalence and/or FPG levels (all P values for interaction < 0.05). Conclusion: Long-term exposure to O3 is related to an increased risk of diabetes, which is partially mediated by liver enzymes in Chinese Zhuang adults. Promoting clean air policies and reducing exposure to environmental pollutants should be a priority for public health policies geared toward preventing diabetes.

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.

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.

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.

Low expression of GOT2 promotes tumor progress and predicts poor prognosis in hepatocellular carcinoma.

Background: To explore the biological function and the underlying mechanisms of GOT2 in hepatocellular carcinoma (HCC). Materials & methods: The expression level and prognostic value of GOT2 were examined using International Cancer Genome Consortium and International Cancer Proteogenome Consortium databases. The cell counting kit-8 method, clone formation, Transwell® assays and western blotting were used to evaluate the effects of GOT2 on the biological function and autophagy of HCC cells. Results: The expression of GOT2 was downregulated in HCC tissues and correlated with poor prognosis of HCC patients. Knockdown of GOT2 promoted proliferation, migration and invasion of HCC cells and promoted cells' proliferation by inducing autophagy. Conclusion: GOT2 plays a tumor-inhibitory role in HCC and may be a potential therapeutic target for HCC.

Associations between maternal serum phytoestrogens and liver function markers: a cross-sectional study from China.

Phytoestrogens (PEs) may harm liver function. However, studies in pregnant women are limited. Our study was conducted in pregnant women to assess the effect of serum PEs on liver function markers. We conducted a cross-sectional study focusing in the first trimester of pregnancy. A total of 352 pregnant women were enrolled in the study. We used generalized linear model (GLM) to explore the associations between each PE and each marker of liver function. We used Quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) models to explore the associations between mixed exposure to all PEs and liver function markers. The GLM results showed that equol (EQU), daidzein (DAD), genistein (GEN), enterolactone (ENT), and enterodiol (END) were negatively correlated with albumin (ALB). DAD and GEN were associated with elevated alanine aminotransferase (ALT). DAD, GEN, naringin (NAR), and glycitein (GLY) were related to elevated aspartate aminotransferase (AST). Mixed exposure model results showed that the mixture of PEs was associated with reduced ALB. Our results support the existence of associations between PEs and maternal liver function in the first trimester. Emphasizing the detrimental associations between serum PEs and liver function in pregnant women is essential to ensure maternal liver health during pregnancy.

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.

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.

Association of ultraprocessed foods consumption and cognitive function among children aged 4-7 years: a cross-sectional data analysis.

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

circELMOD3 increases and stabilizes TRIM13 by sponging miR-6864-5p and direct binding to inhibit HCC progression.

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

Effects of urinary barium exposure on bone mineral density in general population.

Previous studies have reported that exposures to metals are associated with bone health, but are mostly restricted to a few of the most frequent hazardous metals. The effects of barium (Ba) are not fully understood. A cross-sectional study involving 1532 adults from the National Health and Nutrition Examination Survey (NHANES, 2013-2016) was conducted. Generalized linear model (GLM) and restricted cubic spline (RCS) were applied to evaluate the relationship of urinary Ba exposure with BMDs. According to the GLM analyses, urinary Ba was adversely correlated with total BMD (percent change: -0.75; 95% CI: -1.21, -0.29) and lumbar BMD (percent change: -0.76; 95% CI: -1.47, -0.04). Compared with the lowest tertile of Ba levels, the percentage change of T3 was -2.06 (-3.36, -0.73) for total BMD and was -2.39 (-4.51, -0.24) for lumbar BMD, showing a significant linear trend (P trend = 0.014 and P trend = 0.047, respectively). The RCS models showed a monotonically decreasing relationship of urinary Ba with total BMD and lumbar BMD. Moreover, the positive joint effects were observed between Pb (lead) and Ba, and Cd (cadmium) and Ba on BMDs. According to our findings, exposure to Ba may lead to a decrease in BMDs. Possible positive joint effects of Ba and Pb, and Ba and Cd on BMDs were found. Exposure to Ba may contribute to poor skeletal health.

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.

Artificial Intelligence and Machine (Deep) Learning in Otorhinolaryngology: A Bibliometric Analysis Based on VOSviewer and CiteSpace.

BACKGROUND: Otorhinolaryngology diseases are well suited for artificial intelligence (AI)-based interpretation. The use of AI, particularly AI based on deep learning (DL), in the treatment of human diseases is becoming more and more popular. However, there are few bibliometric analyses that have systematically studied this field. OBJECTIVE: The objective of this study was to visualize the research hot spots and trends of AI and DL in ENT diseases through bibliometric analysis to help researchers understand the future development of basic and clinical research. METHODS: In all, 232 articles and reviews were retrieved from The Web of Science Core Collection. Using CiteSpace and VOSviewer software, countries, institutions, authors, references, and keywords in the field were visualized and examined. RESULTS: The majority of these papers came from 44 nations and 498 institutions, with China and the United States leading the way. Common diseases used by AI in ENT include otosclerosis, otitis media, nasal polyps, sinusitis, and so on. In the early years, research focused on the analysis of hearing and articulation disorders, and in recent years mainly on the diagnosis, localization, and grading of diseases. CONCLUSIONS: The analysis shows the periodical hot spots and development direction of AI and DL application in ENT diseases from the time dimension. The diagnosis and prognosis of otolaryngology diseases and the analysis of otolaryngology endoscopic images have been the focus of current research and the development trend of future.

Maternal exposure to neonicotinoid insecticides and fetal growth restriction: A nested case-control study in the guangxi Zhuang birth cohort.

BACKGROUND: Fetal growth restriction (FGR) is a major determinant of perinatal morbidity and mortality, with adverse long-term neurocognitive effects in childhood and adulthood. Prenatal exposure to environmental pollutants has been reported to be associated with FGR. Neonicotinoids (NEOs) are extensively used insecticides worldwide and are suggested to have embryonic and developmental neurotoxicity. However, the effects of NEOs exposure on FGR is unknown. OBJECTIVES: We aimed to quantify the single and combined associations of maternal exposure to NEOs and FGR. METHODS: We conducted a nested case-control study based on the Guangxi Zhuang Birth Cohort, China. A total of 387 with FGR cases and 1096 without- FGR controls were included between 2015 and 2018. Ten NEOs were measured by UPLC-MS from the maternal blood samples were pre-collected in the first trimester. After adjusting for potential confounders, multivariable logistic regressions, weighted quantile sum regression and quantile g-computation were performed for individual and NEOs mixtures. RESULTS: In the individual exposure models, each 1-standard deviation increment of the natural-log in dinotefuran and acetamiprid concentrations were significantly associated with odds ratios of 1.93 (95% CI: 1.69, 2.20) and 1.31 (95% CI: 1.07, 1.59) higher odds of FGR, respectively. However, the FGR risk was negatively associated with thiacloprid, sulfoxaflor, and nitenpyram (OR = 0.23, 95%CI: 0.15, 0.34; OR = 0.48, 95%CI: 0.41, 0.56; OR = 0.86, 95%CI: 0.80, 0.93; respectively). Similar findings were found in the combined exposure analysis. Dinotefuran was the most strongly attributable to increase FGR, while sulfoxaflor and thiacloprid contributed the highest negative weighted on FGR. Furthermore, each quintile increase in all ten NEOs exposures was associated with FGR (OR = 0.21, 95% CI: 0.08, 0.54). CONCLUSION: Our findings suggest that maternal single and combined exposures to NEOs were associated with varying FGR risks. They contribute to the mounting evidence on serum NEOs exposure impact on FGR. However, a replication of these associations in other populations is warranted.

Near Full-Length Genomic Characterization of Two Novel HIV Type 1 Second-Generation Recombinant Forms (CRF01_AE/CRF07_BC) from Guangxi, China.

CRF01_AE and CRF07_BC are the two predominant HIV-1 subtypes currently circulating in China. We identified here a novel CCR5-tropic HIV-1 second-generation recombinant form virus found in two individuals, (GX19017 and GX19032), which were isolated from two HIV-1-positive people in Guangxi, southwest China. Phylogenic analyses indicated that these two sequences were all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, with four recombinant breakpoints observed in the pol, vpu/env, and env gene regions, respectively. The recombinant CRF01_AE region was clustered with the previously described CRF01_AE subcluster 2 lineage, which was characterized by the susceptibility to phenotypic transfer. The genome structure is significantly different from other previously reported CRFs and unique recombination forms. The emergence of a series of novel recombinant strains is indicative of the burgeoning complexity of the HIV-1 epidemic among the sexually transmitted population. Meanwhile, it may furnish significant insights into the dynamics and intricacy of the HIV-1 epidemic in China.

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.