Background: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated. Results: In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23–2. Conclusion: This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.

Background: Various risk factors influence obesity differently, and environmental endocrine disruption may increase the occurrence of obesity. However, most of the previous studies have considered only a unitary exposure or a set of similar exposures instead of mixed exposures, which entail complicated interactions. We utilized three statistical models to evaluate the correlations between mixed chemicals to analyze the association between 9 different chemical exposures and obesity in children and adolescents. Methods: We fitted the generalized linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) to analyze the association between the mixed exposures and obesity in the participants aged 6–19 in the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Results: In the multivariable logistic regression model, 2,5-dichlorophenol (2,5-DCP) (OR (95% CI): 1.25 (1.11, 1.40)), monoethyl phthalate (MEP) (OR (95% CI): 1.28 (1.04, 1.58)), and mono-isobutyl phthalate (MiBP) (OR (95% CI): 1.42 (1.07, 1.89)) were found to be positively associated with obesity, while methylparaben (MeP) (OR (95% CI): 0.80 (0.68, 0.94)) was negatively associated with obesity. In the multivariable linear regression, MEP was found to be positively associated with the body mass index (BMI) z-score (β (95% CI): 0.12 (0.02, 0.21)). In the WQS regression model, the WQS index had a significant association (OR (95% CI): 1.48 (1.16, 1.89)) with the outcome in the obesity model, in which 2,5-DCP (weighted 0.41), bisphenol A (BPA) (weighted 0.17) and MEP (weighted 0.14) all had relatively high weights. In the BKMR model, despite no statistically significant difference in the overall association between the chemical mixtures and the outcome (obesity or BMI z-score), there was nonetheless an increasing trend. 2,5-DCP and MEP were found to be positively associated with the outcome (obesity or BMI z-score), while fixing other chemicals at their median concentrations. Conclusion: Comparing the three statistical models, we found that 2,5-DCP and MEP may play an important role in obesity. Considering the advantages and disadvantages of the three statistical models, our study confirms the necessity to combine different statistical models on obesity when dealing with mixed exposures.

Background: Gut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood. Methods: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses. Results: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium. Conclusion: Glioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.

Objectives The incidence of bystander cardiopulmonary resuscitation (CPR) is low in China. CPR training could improve public attitudes and willingness, but at present, the attitudes of the public after online training are unclear. This study investigated individual attitudes towards CPR, the willingness to perform it in emergencies along with the main obstacles and the overall effects of online training. Design Questionnaires were distributed to investigate the public attitudes and willingness towards performing bystander CPR. Setting Questionnaires were accessible after the online course ‘First Aid’. Participants 1888 students who attended ‘First Aid’ from December 2019 to 1 January 2020 and then completed the questionnaire voluntarily. Results The majority understood CPR (96.7%) and displayed a willingness to learn (98.4%) and to disseminate CPR knowledge (82.0%). Characteristics associated with more positive attitudes included women, the 26–35-year olds and those in medical-related occupations (p<0.05). Only 34.8% had CPR training before. Most people would willingly perform CPR on a close family member. Compared with the standard CPR (S-CPR), the public preferred chest compression-only CPR (CO-CPR) (p<0.01). The top three obstacles to performing CO-CPR were lack of confidence (26.7%), fear of harming the victim (23.4%) and causing legal trouble (20.7%), while regarding S-CPR, fear of disease transmission (22.9%) ranked second. Women, those in poor health and in medical-related occupations, were more likely to perform CPR (p<0.05). The confidence to perform CPR was improved remarkably after online training (p<0.05). Conclusions The overwhelming majority of respondents showed positive attitudes and willingness towards CPR. In some cases, there is still reluctance, especially towards S-CPR. Obstacles arise mainly due to lack of confidence in administering CPR, while online CPR training can markedly improve it. Therefore, we should focus on disseminating CPR knowledge, targeting those who are less willing to perform CPR and helping overcome their obstacles by online training.

Traumatic brain injury (TBI) is a widespread central nervous system (CNS) condition and a leading cause of death, disability, and long-term disability including seizures and emotional and behavioral issues. To date, applicable diagnostic biomarkers have not been elucidated. MicroRNAs (miRNAs) are enriched and stable in exosomes in plasma. Therefore, we speculated that miRNAs in plasma exosomes might serve as novel biomarkers for TBI diagnosis and are also involved in the pathogenesis of TBI. In this study, we first isolated exosomes from peripheral blood plasma in rats with TBI and then investigated the alterations in miRNA expression in exosomes by high-throughput RNA sequencing. As a result, we identified 50 significantly differentially expressed miRNAs, including 31 upregulated and 19 downregulated miRNAs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most highly correlated pathways that were identified were the MAPK signaling pathway, regulation of actin cytoskeleton, Rap1 signaling pathway and Ras signaling pathway. This study provides novel perspectives on miRNAs in peripheral blood plasma exosomes, which not only could be used as biomarkers of TBI diagnosis but could also be manipulated as therapeutic targets of TBI.

Neurological diseases are a significant contributor to premature mortality and temporary or long-term disability among survivors. Asia serves as an essential region for assessing the shifting burden of these disorders. This study aims to calculate and evaluate the changes in burden of neurological diseases across Asia. The Global Burden of Disease database provided data on deaths, disability-adjusted life-years (DALYs), incidence, and prevalence from 1990 to 2021 across Asian subregions and countries. Twelve common neurological diseases were analyzed. Estimated Annual Percent Change were calculated to reveal trends in all the metrics. The Nordpred age-period-cohort model was employed to project the neurological disease burden. In 2021, the leading neurological disorders in DALYs were stroke (109,144.87, 95% uncertainty intervals (UI) 95,992.89–123,089.90), headache disorders (25,713.91, 95%UI 4,693.65–54,853.47), and Alzheimer’s disease and other dementias (19,156.46, 95% UI 9,137.72–41,421.18). Stroke and degenerative neurological disorder presented the most severe burden in East Asia, while headache disorders were prominent in South Asia. Between 1990 and 2021, Asia’s regions showed varying reductions in age-standardized DALYs and age-standardized death rates for neurological diseases, with the steepest decline observed in high-income Asia Pacific (DALYs -2.27, 95% confidence interval (CI) -2.4 to -2.13; ASDR -3.85, 95% CI -4.02 to -3.69). Neurological disease burden was higher in males, peaking at ages 65–74. Projections to 2045 indicate a decline in DALYs for stroke, infectious neurological diseases, Parkinson’s disease, and idiopathic epilepsy across most regions of Asia. In contrast, trends for other neurological diseases will vary regionally. Neurological diseases were the primary cause of DALYs in 2021, ranking second only to cardiovascular diseases as a leading cause of death. As the aging trend in Asia’s population continues to intensify, it is crucial to focus more on the prevention and management of neurological disorders.