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.

Chronic diseases and determinants of community health services utilization among adult residents in southern China: a community-based cross-sectional study.

BACKGROUND: The burden of chronic diseases has become a major public health concern, and high-efficiency use of community health services is essential in combating chronic diseases. This study described the status of chronic diseases in southern China and explored the determinants of health service utilization among adult residents. METHODS: Data were obtained from one part of community survey data from four counties in Ganzhou City, southern China. A multistage, stratified random sampling method was used to conduct a cross-sectional survey between 2018 and 2020. Overall, 7430 valid questionnaires were collected. A lasso-linear regression analysis was performed to explore the determinants of community health service utilization. RESULTS: According to the study, most participants (44.6%) reported having relatively good health, while 42.1% reported having moderate health. Chronic diseases were reported by 66.9% of the respondents. The three most prevalent self-reported chronic diseases were hypertension (22.6%), hyperlipidemia (5.9%), and diabetes (5.9%). Among residents with chronic diseases, 72.1% had one chronic disease, while the rest had multiple. Only 13.9% of residents frequently utilized community health services, while 18.9% never used them. Additionally, among residents who reported having chronic diseases, 14.1% had never attended community health services. Four categories of factors were the key determinants of community health service utilization: (1) personal characteristics, age, and sex; (2) health-related factors, such as family history, self-reported health conditions, and the number of chronic diseases; (3) community health service characteristics, such as satisfaction with and accessibility to community health services; and (4) knowledge of chronic diseases. Specifically, women tend to utilize healthcare services more frequently than men. Additionally, residents who are advanced in age, have a family history of chronic diseases, suffer from multiple chronic conditions, rate their self-reported health condition as poor, have a better knowledge about chronic diseases, have better accessibility to community health services, and have higher the satisfaction with community health services, tend to utilize them more frequently. CONCLUSIONS: Given the limited healthcare resources, the government should promote the effective utilization of community health facilities as a critical community-based strategy to combat the growing threat of chronic diseases in southern China. The priority measures involve enhancing residents' access to and satisfaction with community health services and raising awareness of chronic illnesses among older individuals with poor health status.

Effects of dietary copper intake on blood lipids in women of childbearing age and the potential role of gut microbiota.

Background: Copper (Cu) is a vital trace element involved in numerous physiological processes, including glycolysis and lipid metabolism. Imbalances in Cu homeostasis can contribute to various diseases. However, current research on the impact of Cu on lipid metabolism has yielded inconsistent findings. Moreover, studies investigating the effects of dietary Cu intake on blood lipids among women of childbearing age are rare. Understanding of this relationship could enhance lipid management, given that most women obtain Cu through their diet. Additionally, the gut microbiota may play a role in this process. This study aims to investigate the effects of dietary Cu intake on blood lipids in women of childbearing age and to analyze the role of gut microbiota in this process. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) to conduct a preliminary analysis of the correlation between dietary Cu levels and blood lipid indicators in women of childbearing age. Subsequently, an on-site research was conducted to further investigate this relationship, followed by animal experiments to verify the effect of different Cu doses on blood lipid levels. Multiple linear regression models, ANOVA, XGBOOST were employed to analyze the impact of Cu on blood lipids and the role of intestinal microbiota in this process. Results: In the population study, the NHANES results were consistent with on-site findings. The TG, and TC levels in women with childbearing were increased with higher dietary Cu intake. Animal experiments have shown that as Cu intake increases, TC levels increase. Furthermore, when the Cu intake reached 8 mg/day (the recommended dietary Cu intake limit of China, RDI), the TG levels in the research animals decrease, alongside a reduction in the abundance of Weissella cibaria (probiotics related to lipid metabolism), and the levels of LPS and IL-6 increase. Conclusion: The blood lipid levels of women of childbearing age increase with higher dietary Cu intake. RDI of 8 mg/day for women of childbearing age in China may need to be appropriately reduced. Regulating the gut microbiota, especially by increasing the abundance of Weissella cibaria may be an effective intervention for blood lipids.

Factors Associated with Intention to Use Telerehabilitation for Children with Special Needs: A Cross-Sectional Study.

Background: Children with special health care needs (CSHCN) require long-term and ongoing rehabilitation interventions supporting their development. Telerehabilitation can provide continuous rehabilitation services for CSHCN. However, few studies have explored the intention of CSHCN and their caregivers to use telerehabilitation and its impact on them. Objective: The objective of this study was to identify factors that influence the intention to use telerehabilitation among CSHCN and their caregivers. Methods: This study was a cross-sectional study. Based on the unified theory of acceptance and use of technology, extended with additional predictors (trust and perceived risk [PR]), this study developed a research model and proposed 10 hypotheses. A structured questionnaire was distributed to 176 caregivers. Data were analyzed and research hypotheses were tested using partial least squares structural equation modeling to better understand the factors influencing the use of telerehabilitation. Results: A total of 164 valid questionnaires were collected. CSHCN and their caregivers were overall satisfied with this telerehabilitation medical service. The results of the structural model analysis indicated that social influence (SI), facilitating conditions (FC), and trust had significant effects on behavioral intention (BI) to use telerehabilitation, while the paths between performance expectancy (PE), effort expectancy (EE), and PR and BI were not significant. PE, EE, and SI had a significant effect on trust. Moreover, EE and SI had indirect effects on BI, with trust as the mediator. Conclusions: The results indicated that SI, FC, and trust are significant factors influencing CSHCN and their caregivers' use of telerehabilitation. Trust is also an important mediator for the intention and highly influenced by PE, EE, and SI.

Factors associated with oral health service utilization among young people in southern China.

OBJECTIVES: To identify the patterns and influencing factors of oral health service utilization among college students, and further to provide scientific evidence for policy making on oral health education and behavioral interventions for the college population. METHODS: The study population was college students in Southern China. Totally 678 students participated in the survey. A self-designed questionnaire based on Anderson's model (predisposing factors, enabling factors, need factors) was used to survey college students. Descriptive statistics, χ2 test, and logistic regression were used to analyze influence factors of oral health service utilization among college students. RESULTS: The utilization rate of oral health service in the past 12 months was 30.2%. The primary type of oral health service was treatment (59.6%), and only 12.8% were for prevention. There were 39% of the participants having oral health diseases, of which dental caries (25.7%) and oral bleeding (22.2%) were the main problems. The results from logistic regression analysis revealed that students with better beliefs (OR = 1.84, 95% CI:=1.02-3.43), frequent consumption of sugary drinks (OR = 2.90, 95% CI:=1.90-4.47), teeth brushing frequency > = 2 times per day (OR = 2.09, 95% CI = 1.24-3.61), frequent floss utilization (OR = 2.63, 95% CI = 1.21-5.76), dental caries (OR = 2.07, 95% CI = 1.35-3.17) used oral health services higher, while those lived in rural areas (OR:0.52, 95% CI = 0.34-0.80), and had only a fair concern (OR = 0.48, 95% CI = 0.31-0.74) or no concern (OR = 0.26, 95% CI = 0.08-0.67) on oral health utilized oral health services lower. CONCLUSIONS: Chinese college students demonstrate some knowledge and attitudes towards oral health. However, they tend to neglect oral hygiene and have limited understanding of their own oral issues. Furthermore, the utilization of oral services, such as treatment, remains remarkably low, despite the availability of long-term and favorable health insurance policies. The utilization of oral health services among college students is influenced by various factors, including residing in rural areas, consuming sugary beverages on a daily basis, brushing teeth at least twice a day, and practicing flossing.

Prevalence of Hypertension and Associated Factors among Residents Aged ≥18 Years in Ganzhou, China: A Cross-Sectional Study.

Background: Reliable epidemiologic data on the present burden of hypertension are needed in developing region-specific strategies since previous studies have suggested that China is lagging in risk factor management. Objective: The study aimed at exploring the prevalence of hypertension and its associated factors among adult residents in Ganzhou, China. Methodology. A multistage, stratified, and cluster random sampling method was used to conduct the cross-sectional survey. The study selected four county-level districts in Ganzhou City, China, as the investigation area. Permanent residents aged ≥18 years who have settled in the area for 6 months or more were selected. A total of 7430 residents were involved in the study. Univariate and multivariate logistic regression analysis was carried out to identify predictors of hypertension. Results: The prevalence of hypertension in Ganzhou was 28.5%, and the age-standardized prevalence of hypertension was 22.4%. Univariate logistic regression analysis revealed that multiple variables have a statistically significant effect on the prevalence of hypertension. The elderly (odds ratio [95% CI]: 2.791 [2.594-3.004]), men (1.805 [1.583-2.058]), lower educated (0.848 [0.805-0.893]), a family history of hypertension (4.575 [3.900-5.368]), higher body mass index (1.344 [1.215-1.488]), central obesity (1.532 [1.304-1.799]), and less vegetable intake (1.150 [1.023-1.294]) were the major risk factors for hypertension. Conclusion: Hypertension is a major public health problem in Ganzhou and requires much effort to reduce its prevalence. An effective multifaceted implementation strategy is highly desirable to combat the emerging burden of hypertension.

Causal Paradigm Between Common Comorbidities of Cardiovascular and Metabolism-Related Diseases in Elderly: Evidence from Cross-Sectional and Mendelian Randomization Studies.

Background: Comorbidity is a common problem among elderly people, significantly damaging individuals' health and healthcare systems. However, observational studies may be susceptible to residual confounding factors and bias. The present study aimed to assess the causal effect of common chronic disease comorbidity using the Mendelian randomization (MR) approach. Methods: Data for the present study were obtained from a community survey conducted between 2018 and 2020 in four counties in Ganzhou City, southern China. A cross-sectional survey was conducted using a multi-stage stratified random sampling method. A total of 1756 valid questionnaires were collected to analyze common chronic disease comorbidities. Genetic variants associated with hypertension, diabetes, stroke, and hyperlipidemia-related factors were selected as instrumental variables for univariate and multivariate MR analyses. Results: The self-reported prevalence of chronic disease in the older adult population in Southern China was 68.1%, with hypertension (46.1%), diabetes (10.5%), and hyperlipidemia (8.5%) being the three most common conditions. The prevalence of chronic disease comorbidity was 20.7% among the 12 chronic diseases studied. Hypertension was identified as a predictor of diabetes (OR [95% CI]: 1.114 [1.049, 1.184], p < 0.001), and diabetes mellitus was equally identified as a risk factor for hypertension (OR [95% CI]: 1.118 [1.069, 1.187], p < 0.001). Furthermore, high triglyceride levels were identified as a risk factor for hypertension (OR [95% CI]: 1.262 [1.129, 1.411], p < 0.001). In contrast to intracranial hemorrhages, hypertension had a significant impact on ischemic stroke (OR [95% CI]: 1.299 [1.161, 1.454], p < 0.001). Conclusion: The causal association between multiple cardiovascular and metabolism-related diseases is mediated by hypertension, with a bidirectional cause-and-effect relationship between hypertension and diabetes. Hypertension is a risk factor for ischemic stroke, and the hyperlipidemia-related factor triglycerides (TG) influence hypertension. Therefore, prioritizing hypertension prevention and control in the elderly is critical for effective chronic disease management.

Internet addiction, loneliness, and academic burnout among Chinese college students: a mediation model.

Background: The dynamics of education and student life have changed since the COVID-19 pandemic. Our society, especially the education system, has become largely dependent on the Internet. This paradigm shifts largely took place in the last few decades. As such, there are various ways in which we cannot comprehend the impact that the Internet can have on student psychology, and how multiple other factors could influence that. Internet addiction and its relationship with academic burnout, along with the impact of loneliness, are all essential factors that must be discussed candidly in the post-COVID-19 era. Hence, the objective of this study was, therefore, to explore the relationship between Internet addiction, loneliness, and academic burnout among Chinese college students as well as the mediating role of loneliness. Methods: We conducted a cross-sectional questionnaire survey at a Chinese university from October to November 2022. In total, 810 valid respondents were selected via random cluster sampling using the well-established Internet Addiction, Loneliness, and Academic Burnout Scale. The primary approach of mediation analysis and structural equation modeling testing examined the relationships among the three components. Results: Internet addiction could be responsible for academic burnout among college students. Loneliness partially mediates the relationship between Internet addiction and academic burnout. In a mediated way, different types of loneliness contribute to different types of academic burnout. Conclusion: Psychological interventions for loneliness, especially emotional loneliness prevention, are the critical aspects of the problem of Internet addiction accompanied with academic burnout. The causal relationship between Internet addiction and academic burnout, possibly of a two-way nature, needs to be further explored in the next future.

Relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China.

BACKGROUND: With an increasing incidence of obesity, the relationship between obesity and body image has become a hot research topic worldwide. From high school to university, young people experience changes in their social environment. University students have a high incidence of eating disorders and insufficient physical activity. The purpose of this study was to explore the relationship between body dissatisfaction, insufficient physical activity, and disordered eating behaviors among university students in southern China. METHODS: In total, 1296 university students aged 18-23 years were recruited for this study. The participants completed anthropometric measurements, the Physical Activity Rating scale-3 (PARS-3), and the Chinese-Dutch Eating Behavior Questionnaire (C-DEBQ). The ideal weight and silhouette were reported by university students using a questionnaire. RESULTS: Compared with men, young women had a higher level of body dissatisfaction. For men, body mass index (BMI; ß = 0.76, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.10, P <  0.01) were the significant factors predictive of body dissatisfaction. For women, BMI (ß = 0.57, P <  0.01), muscle mass (ß = 0.12, P <  0.01), physical activity score (ß = - 0.11, P <  0.01), and restrained eating score (ß = 0.09, P <  0.01) were the significant factors predictive of body dissatisfaction. CONCLUSIONS: University students with high body dissatisfaction had lower physical activity scores and higher restrained eating scores. The data presented here highlight the impact of university students' body dissatisfaction on physical activity deficiency and disordered eating behaviors in China.

Configurations for positive public behaviors in response to the COVID-19 pandemic: a fuzzy set qualitative comparative analysis.

BACKGROUND: The COVID-19 crisis poses considerable threats to public health, and exploring the key configuration conditions of the public behavior response is very important for emergency risk management. OBJECTIVE: This study attempts to reveal differences in the conditional configuration and mechanism of public behavior based on the proposed framework, further make up for the deficiencies of existing research in explaining such issues as "How to promote the public's protective behavior or reduce the public's excessive behavior?" and finally provide new evidence and ideas for the government to improve the emergency management system. METHODS: A total of 735 valid cases were obtained using an online survey and revealed the conditional configuration and mechanism of public behavior differences through a fuzzy set qualitative comparative analysis based on the proposed public behavioral framework. RESULTS: The results show that critical factors including risk communication, trust, risk perception, and negative emotions alone did not constitute a necessary condition for public protective or excessive behavior. The different configurations of influencing factors reveal the complexity of public behavioral risk management, and taking adequate measures to increase public trust and reduce negative public emotions constitute the core path of risk management to enhance positive public behavior. CONCLUSIONS: The configurations of various influencing factors reveal the complexity of public behavioral risk management. For behavioral risk management, governments should focus on adapting to multiple conditions according to their situations and, under the "overall perspective," formulate policies based on local conditions and further form a differentiated risk management path. Practically speaking, for the government, taking adequate measures to increase public trust and reduce negative public emotions is the core path of risk management to enhance positive public behavior.

Analyzing Risk Communication, Trust, Risk Perception, Negative Emotions, and Behavioral Coping Strategies During the COVID-19 Pandemic in China Using a Structural Equation Model.

Objective: Risk communication and the degree of trust are major factors that affect the public's behavioral coping strategies and play an important role in emergency risk management. However, the internal formation mechanism involved in the public's psychological behavior remains unclear. This study aimed to investigate the association among risk communication, trust, risk perception, negative emotions, and behavioral coping strategies during the coronavirus disease 2019 (COVID-19) pandemic, and to identify and quantify the factors that influence public behavior. Methods: We launched an online survey through social media from April to July 2020 in China. Relevant data were elicited using a self-designed questionnaire that mainly examined respondent characteristics, risk communication, trust, risk perception, negative emotions, protective coping behavior, and excessive coping behavior in the context of the COVID-19 pandemic. A total of 735 valid responses were obtained. A structural equation model was then used to explore relationship pathways among the components. Results: The higher the degree of risk communication (ß = -0.10, p < 0.05) and trust (ß = -0.22, p < 0.001), the lower the public risk perception. Risk communication and trust had a direct effect on public behavioral coping strategies during the COVID-19 pandemic. The higher the level of risk communication (ß = 0.14, p < 0.001) or trust (ß = 0.48, p < 0.001), the more likely it was that this would encourage the public to adopt protective coping behaviors, while the public was less likely to engage in excessive coping behaviors as the degree of trust increased (ß = -0.12, p < 0.01). Risk perception influenced by poor risk communication and trust generated negative emotions (ß = 0.31, p < 0.001), and such negative emotions further positively influenced public behavioral coping strategies (whether protective [ß = 0.09, p < 0.05] or excessive [ß = 0.24, p < 0.001] behaviors). Conclusion: Risk communication, trust, risk perception, and negative emotions were significantly directly or indirectly related to public behavior. The findings provide useful information for emergency risk management and a theoretical basis for follow-up research on public coping behavior during the COVID-19 pandemic.

RyRs mediate lead-induced neurodegenerative disorders through calcium signaling pathways.

Heavy metal lead (Pb) is widely distributed in the environment and can induce neurodegeneration. Accumulating evidence has shown that ryanodine receptors (RyRs) play vital roles in neurodegenerative brain. However, whether aberrant RyRs levels contribute to Pb-induced neurodegeneration has largely remained unknown. In the present study, we report the important role of elevated levels of RyRs in Pb-induced neurodegeneration. Pb was found to upregulate the levels of RyRs in the rat hippocampal tissues and rat pheochromocytoma (PC12) cells. Furthermore, exposure to Pb induced neurodegenerative cognitive impairment in rats, depressed the long-term potentiation (LTP) in the rat brain slices, increased the neuronal intracellular free calcium concentration ([Ca2+]i), inhibited the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine 3',5'-monophosphate (cAMP) response element binding protein (CREB) as well as the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl2), and activated the phosphorylation of extracellular regulated protein kinases (Erk) protein both in vitro and in vivo. In addition, the knockdown of RyR3 in PC12 cells significantly decreased the [Ca2+]i levels, increased the CaMKIIα and CREB phosphorylation, decrease the phosphorylation of Erk, and elongated the cognitive function-related neurite outgrowth after exposure to Pb. Moreover, treatment with a RyRs agonist showed the involvement of RyRs in Pb-induced depression in LTP in the rat brain slices. In summary, we determined that Pb-mediated upregulation of RyRs led to neurodegeneration via high levels of free calcium, depression of the calcium-dependent CaMKIIα/CREB mnemonic signaling pathway, and activation of the calcium-dependent Erk/Bcl2 apoptotic signaling pathway. These findings on the impact of Pb on the levels of RyRs could further improve our understanding of Pb-induced neurotoxicity and provide a promising molecular target to antagonize Pb-induced neurodegenerative diseases.

Lead exposure-induced cognitive impairment through RyR-modulating intracellular calcium signaling in aged rats.

Lead is widely distributed in the environment and has become a global public health issue. It is well known that lead exposure induces not only neurodevelopmental toxicity but also neurodegenerative diseases, with learning and memory impairment in the later stage. However, the molecular mechanisms remain elusive. The present study investigated the effects of early life and lifetime lead exposure on cognition and identified the molecular mechanisms involved in aged rats. The results herein demonstrated that the lead concentration in peripheral blood and brain tissues in aged rats was significantly increased in a lead dose-dependent manner. High-dose lead exposure caused cognitive functional impairment in aged rats, concomitant with a longer escape latency and a lower frequency of crossing the platform via Morris water maze testing compared to those in the control and low-dose lead exposure groups. Importantly, neuron functional defects were still observed even in early life lead exposure during the prenatal and weaning periods in aged rats. The neurotoxicity induced by lead exposure was morphologically evidenced by a recessed nuclear membrane, a swollen endoplasmic reticulum, and mitochondria in the neurons. Mechanistically, the exposure of aged rats to lead resulted in increasing free calcium concentration, reactive oxygen species, and apoptosis in the hippocampal neurons. Lead exposure increased RyR3 expression and decreased the levels of p-CaMKIIα/CaMKIIα and p-CREB/CREB in the hippocampus of aged rats. These findings indicated that early life lead exposure-induced cognition disorder was irreversible in aged rats. Lead-induced neurotoxicity might be related to the upregulation of RyR3 expression and high levels of intracellular free calcium with increasing lead concentration in injured neurons.

Pb2+ modulates ryanodine receptors from the endoplasmic reticulum in rat brain.

Although the neurotoxic mechanism of lead (Pb2+) has been extensively studied, it is not well understood. The effects of Pb2+ on free cytosolic calcium (Ca2+) concentration and calcium-regulated events have been suggested to be major mechanisms in Pb2+ toxicity. Based on our previous findings that Pb2+ changes calcium release through ryanodine receptors (RyRs), the modulation of endoplasmic reticulum (ER) vesicular RyRs by Pb2+ was investigated further in the present study. The results of [3H]ryanodine binding assays showed that in the presence of a free Ca2+ concentration ([Ca2+]f) of 100µM, Pb2+ modulated the equilibrium of [3H]ryanodine binding to brain RyRs, with a U-type dose-response curve, where minimal binding was observed at a free Pb2+ concentration ([Pb2+]f) of 0.39µM. This modulation was also observed over a time course. Scatchard analysis indicated that both an increase in Kd and a possible decrease in Bmax were responsible for the decrease in binding induced by low [Pb2+]f. Moreover, the effects of Pb2+ on the function of ER RyRs in neurons might also be controlled by other RyR modulators. Whole-cell patch-clamp experiments revealed that dynamic calcium oscillations evoked by specific RyR agonists were depressed rapidly and reversibly by exposure to 10µM Pb2+. Our study indicates that RyRs are molecular targets of Pb2+, and this interaction disturbs Ca2+ signals and leads to neurotoxicity.

dbMDEGA: a database for meta-analysis of differentially expressed genes in autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) are hereditary, heterogeneous and biologically complex neurodevelopmental disorders. Individual studies on gene expression in ASD cannot provide clear consensus conclusions. Therefore, a systematic review to synthesize the current findings from brain tissues and a search tool to share the meta-analysis results are urgently needed. METHODS: Here, we conducted a meta-analysis of brain gene expression profiles in the current reported human ASD expression datasets (with 84 frozen male cortex samples, 17 female cortex samples, 32 cerebellum samples and 4 formalin fixed samples) and knock-out mouse ASD model expression datasets (with 80 collective brain samples). Then, we applied R language software and developed an interactive shared and updated database (dbMDEGA) displaying the results of meta-analysis of data from ASD studies regarding differentially expressed genes (DEGs) in the brain. RESULTS: This database, dbMDEGA ( https://dbmdega.shinyapps.io/dbMDEGA/ ), is a publicly available web-portal for manual annotation and visualization of DEGs in the brain from data from ASD studies. This database uniquely presents meta-analysis values and homologous forest plots of DEGs in brain tissues. Gene entries are annotated with meta-values, statistical values and forest plots of DEGs in brain samples. This database aims to provide searchable meta-analysis results based on the current reported brain gene expression datasets of ASD to help detect candidate genes underlying this disorder. CONCLUSION: This new analytical tool may provide valuable assistance in the discovery of DEGs and the elucidation of the molecular pathogenicity of ASD. This database model may be replicated to study other disorders.

The effect of lead exposure on expression of SIRT1 in the rat hippocampus.

Based on how the silent information regulator 2 homolog 1 (SIRT1) regulates the cyclic AMP response element binding protein (CREB), which is the molecular switch of long-term memory that maintains cognitive function, it is postulated that the impact of lead (Pb) on SIRT1 is one of the mechanisms leading to Pb-induced cognitive and learning deficits. Hence, the purpose of this study was to investigate the effect of Pb exposure on the expression of SIRT1, and the reversion effect of resveratrol, which is an activator of SIRT1. We examined the effects of maternal rat ingestion of Pb in drinking water during gestation and lactation on the expression of SIRT1 and CREB in the hippocampus of their offspring at postnatal week 3 (PNW3) and 52 (PNW52), and then reexamined these effects in offspring after intragastric administration of resveratrol for 4 weeks. Pb exposure decreased SIRT1 and CREB phosphorylation in a dose-dependent manner in the rat hippocampus at both PNW3 and 52, and resveratrol reversed those losses. These results indicated that SIRT1 might be a novel target to prevent Pb neurotoxicity.