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Background: Obesity is major cause of heart failure (HF), but it is related with a better prognosis among the elderly. Therefore, we aimed to examine whether metabolically healthy obesity (MHO) in late life increases HF risk and is reflected in impaired left ventricular (LV) function., Methods: The participants were grouped into four metabolic phenotypes based on obesity and metabolic status: metabolically healthy non-obesity (MHN), MHO, metabolically unhealthy non-obesity (MUN), metabolically unhealthy obesity (MUO). Association of metabolic phenotypes with LV function was evaluated using multiple linear regression models. And association between metabolic phenotypes and risk of HF was assessed using multivariable logistic regression models. In addition, we validated the association of metabolic phenotypes and HF risk in a separate longitudinal cohort., Results: In the primary cohort of 6335 participant, there were 434 participants diagnosed with HF. Compared to MHN participants, the risk of HF was higher among older individuals with MUN (OR = 1.51 [95% CI: 1.14-1.99]) and MUO (OR = 2.01 [95% CI: 1.39-2.91]), but not older individuals with MHO (OR = 0.86 [95% CI: 0.30-2.43). Regarding to LV function, worse LV diastolic function was noted among MUN and MUO individuals rather than MHO individuals. Older adults with MHO were also not associated with risk of HF in the validation cohort., Conclusion: Among older individuals, the metabolic health status might modify the association of obesity with risk of HF and LV diastolic dysfunction. Worse LV diastolic function and higher risk of HF were just noted in individuals with MUO, but not in those with MHO., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Mental health problems among adolescents are a common concern globally. However, its relationship with childhood trauma is not clearly understood from the existing studies. Therefore, this study aims to explore the relationships among childhood trauma, mental health, self-control, and internet addiction in Chinese vocational high school students., Methods: A cross-sectional survey was conducted among vocational high school students in China from October 2020 to December 2020. Standardized questionnaires were used to collect basic information regarding childhood trauma, self-control, psychological state, and social demographics. A structural equation model was used to study the relationships among internet addiction, self-control, childhood trauma, and mental health., Results: A total of 3368 individuals participated in the study. The results revealed the mediating effects of poor self-control and internet addiction on the association between childhood trauma and mental health., Conclusions: Internet addiction and low self-control play mediating roles in childhood trauma and mental health. Clarifying these relationships will help formulate better-targeted interventions to improve the mental health of Chinese vocational high school students and aid in interventions to treat and prevent mental health problems., (© 2024. The Author(s).)

An original metal catalyzed CVD methodology assisted by hydrogen plasma for the direct deposition of few-layer graphene on a substrate is presented. Graphene is grown at 900 °C directly on the surface of the substrate of technological interest by carbon diffusion through a nickel film by using methane (CH 4 ) as the carbon precursor. Hydrogen atoms in the H 2 -plasma downstream are used to promote the solubilization of carbon atoms in Ni, thus favouring the growth of graphene at the Ni/substrate interface. Structural and transport properties of the as-grown multilayer graphene films on SiO 2 /Si and quartz substrates are provided. We demonstrate the peculiarity of this approach for controlling the thickness and transport properties of as-grown graphene films using process-step times. Finally, the potential of the proposed methodology for the bottom-up direct growth of patterned graphene is demonstrated., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The portrayed effects of olanzapine on brain development and neuronal response remain unclear under the genetic background of Homo sapiens . Here, we constructed therapeutic-dosage olanzapine-treated cerebral organoid (CO) models using induced pluripotent stem cells from human samples. We found that the activation of NODAL/FOXH1 axis mediated the early response to olanzapine up to day 15, which subsequently caused thicker cortical-like structures, cell identity maturation, higher stemness of neural progenitor cells (NPCs), and mature neuronal firing of early neurons in day 24. Transcriptomics and targeted metabolomics confirmed the upregulation of neurodevelopmental-related terms and glutamate production on day 24. Gene enrichment of transcriptomics into large-scale genome-wide association studies (GWAS) showed possible relationships with intelligence, major depressive disorder, schizophrenia. We did not observe the negative effects of in-utero exposure to olanzapine in mice. Collectively, we tended to conclude that olanzapine treatment had beneficial effects instead of harmful on early brain development., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Medications prescribed for chronic diseases can lead to short-term neuropsychiatric symptoms, but their long-term effects on brain structures and psychiatric conditions remain unclear., Methods: We comprehensively analyzed the FDA Adverse Event Reporting System database and conducted drug target Mendelian Randomization (MR) studies on six categories of common drugs, 477 brain imaging-derived phenotypes (IDPs) and eight psychiatric disorders. Genetic instruments were extracted from expression quantitative trait loci (eQTLs) in blood, brain, and other target tissues, protein quantitative trait loci (pQTLs) in blood, and genome-wide association studies (GWAS) of hemoglobin and cholesterol. Summary statistics for brain IDPs, psychiatric disorders, and gut microbiome were obtained from the BIG40, Psychiatric Genomics Consortium, and MiBioGen. A two-step MR and mediation analysis were employed to screen possible mediators of drug-IDP effects from 119 gut microbiota genera and identify their mediation proportions., Findings: Among 19 drug classes, six drugs were found to be associated with higher risks of psychiatric adverse events, while 11 drugs were associated with higher risks of gastrointestinal adverse events in the FAERS analysis. We identified ten drug-psychiatric disorder associations, 202 drug-IDP associations, 16 drug-microbiota associations, and four drug-microbiota-IDP causal links. For example, PPARG activation mediated HbA1c reduction caused a higher risk of bipolar disorder (BD) II. Genetically proxied GLP-1R agonists were significantly associated with an increase in the volume of the CA3-head of the right hippocampus and the area of the left precuneus cortex, both of which have been shown to correlate with cognition in previous studies., Interpretation: Common drugs may affect brain structure and risk of psychiatric disorder. Oral medications in particular may exert some of these effects by influencing gut microbiota. This study calls for greater attention to be paid to the neuropsychiatric adverse effects of drugs and encourages drug repurposing., Funding: National Natural Science Foundation of China (grant No. 82330035, 82130043, 82172685, and 82001223), National Natural Science Foundation of Hunan Province (grant No. 2021SK1010), and the Science Foundation for Distinguished Young Scholars of Changsha (grant No. kq2209006)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition., Methods: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test)., Results: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients., Conclusions: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients., (© 2024. The Author(s).)

Background: Psychiatric disorders are emerging as a serious public health hazard, influencing an increasing number of individuals worldwide. However, the effect of modifiable lifestyle factors on psychiatric disorders remains unclear., Methods: Genome-wide association studies (GWAS) summary statistics were obtained mainly from Psychiatric Genomics Consortium and UK Biobank, with sample sizes varying between 10,000 and 1,200,000. The two-sample Mendelian randomization (MR) method was applied to investigate the causal associations between 45 lifestyle factors and 13 psychiatric disorders, and screen potential mediator proteins from 2992 candidate plasma proteins. We implemented a four-step framework with step-by-step screening incorporating two-step, univariable, and multivariable MR., Results: We found causal effects of strenuous sports or other exercise on Tourette's syndrome (OR [95%CI]: 0.0047 [5.24E-04-0.042]); lifelong smoking index on attention-deficit hyperactivity disorder (10.53 [6.96-15.93]), anxiety disorders (3.44 [1.95-6.05]), bipolar disorder (BD) (2.25 [1.64-3.09]), BD II (2.89 [1.81-4.62]), and major depressive disorder (MDD) (2.47 [1.90-3.20]); and educational years on anorexia nervosa (AN) (1.47 [1.22-1.76]), and MDD (0.74 [0.66-0.83]). Five proteins were found to have causal associations with psychiatric disorders, namely ADH1B, GHDC, STOM, CD226, and TP63. STOM, a membrane protein deficient in the erythrocytes of hereditary stomatocytosis patients, may mediate the effect of educational attainment on AN., Limitations: The mechanisms underlying the effects of lifestyle factors on psychiatric disorders require further investigation., Conclusions: These findings could help assess the risk of psychiatric disorders based on lifestyle factors and also support lifestyle interventions as a prevention strategy for mental illness., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: An association between variability of cardiovascular risk factors and cardiovascular events has been reported. We examined whether intensive lifestyle intervention (ILI) for weight loss decreased variability of cardiovascular risk factors with a view to additional cardiometabolic benefits., Methods and Results: This study was a post hoc secondary analysis of the Look AHEAD (Action for Health in Diabetes) study. Cardiovascular risk factors were measured at 1-year intervals for 4 years in 4249 adults with overweight or obesity and type 2 diabetes who were randomly assigned to ILI or diabetes support and education. Long-term variability was defined as the SD of cardiovascular risk factors during 4-year follow-up. At multiple linear regression analysis, compared with the diabetes support and education group, the ILI group was associated with reduced variability of fasting blood glucose (β=-1.49 [95% CI, -2.39 to -0.59]), total cholesterol (β=-1.12 [95% CI, -1.75 to -0.48]), and low-density lipoprotein cholesterol (β=-1.04 [95% CI, -1.59 to -0.49]), as well as increased variability of systolic blood pressure (β=0.27 [95% CI, 0.00-0.54]). No significant effect of ILI was found on the variability of diastolic blood pressure (β=-0.08 [95% CI, -0.22 to 0.05])., Conclusions: Among adults with overweight or obesity and type 2 diabetes, ILI may reduce long-term variability of fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol. Our results support that ILI should be recommended to individuals with diabetes as part of management of long-term glycemic and blood lipid control.

Background: Patients with overweight/obesity and type 2 diabetes are encouraged to lose weight, but not all losing weight gain better cardiovascular health, especially old adults. The change in skeletal muscle mass (SMM) could be the key that explains the heterogenous cardiovascular effects of weight loss. This study aims to assess whether the cardiovascular effects of weight loss vary for those gaining skeletal muscle along with weight loss., Methods: The old adults with overweight/obesity and type 2 diabetes in the Look AHEAD study having muscle measurement from dual-energy X-ray absorptiometry were included. Based on the weight change (WC) and SMM change (SMMC) between baseline and the 4-year follow-up, participants were allocated into three groups-weight gain (WG) group, weight loss with muscle loss (WL-ML) group and weight loss with muscle gain (WL-MG) group. Cox proportional hazards regression was performed to evaluate the cardiovascular risk of those gaining or losing SMM with weight loss compared with those gaining weight. Among the participants with weight loss, the ratio of SMMC/WC was calculated, and the association of SMMC/WC with primary cardiovascular outcome was assessed., Results: A total of 491 participants were included in the study with an average age of 64.56 ± 3.81 years old. A total of 47.0% were male and 49.9% were from the intensive lifestyle intervention arm. Based on their WC and SMMC, 43 were assigned to the WG group, 373 to the WL-ML group and 75 to the WL-MG group. Over a follow-up of almost 10 years, 97 participants encountered the primary endpoint. The WG group had the highest incidence of 25.59%, the WL-MG group had the lowest incidence of 9.33% and the WL-ML group had 21.18% (P = 0.040). In the fourth adjusted Cox model, the WL-MG group achieved significantly decreased odds of the primary endpoint compared with the WG group (hazard ratio [HR] 0.33, 95% confidence interval [CI] [0.12, 0.87], P = 0.026), whilst the WL-ML group did not (HR 0.91, 95% CI [0.47, 1.78], P = 0.670). Among the participants with weight loss, when SMMC/WC reached around 50%, this HR soared to approximately two-fold., Conclusions: The participants gaining SMM along with weight loss achieved the lowest odds of adverse cardiovascular events, whilst those who lost SMM along with weight loss had comparable cardiovascular risk with those gaining weight. The more muscle lost during weight loss, the greater the harm. The cardiovascular effects of weight loss were modulated by whether the participants gained SMM meanwhile losing weight., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults., Methods: A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality., Results: We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75)., Conclusions: Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Heart rate variability (HRV) and resting heart rate (RHR) are usually analyzed and interpreted separately. We aimed to assess the interplay of HRV and RHR on mortality in type 2 diabetes., Methods: The study included 7,529 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. HRV metrics included standard deviation of all normal-to-normal intervals (SDNN) and root mean square of successive differences between normal-to-normal intervals (rMSSD). Abnormal values were defined based on <25th percentile for HRV and >75th percentile for RHR. Interactions of HRV status and RHR status were tested on multiplicative and additive scales. Results were validated in a subset of patients with type 2 diabetes (n = 745) from the Multi-Ethnic Study of Atherosclerosis., Results: Low SDNN was associated with increased all-cause mortality in the high RHR group (HR 1.60; 95% CI 1.29-1.97), but not in the normal RHR group. Compared with those who had neither low SDNN nor high RHR, the presence of either low SDNN or high RHR was not significantly associated with an increased risk of all-cause mortality. In contrast, the combination of low SDNN and high RHR was associated with a significantly increased risk of all-cause mortality (HR 1.68; 95% CI 1.43-1.97). Significant multiplicative and additive interactions were found between HRV status and RHR status on risk of all-cause mortality (all P interaction < 0.05). Similar findings were observed for cardiovascular mortality, in analyses using rMSSD, and in the Multi-Ethnic Study of Atherosclerosis., Conclusions: The association between HRV and mortality risk is modified by RHR levels. Furthermore, low HRV and high RHR have interdependent and synergistic associations with mortality risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalized therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Obesity is major cause of cardiovascular diseases. Metabolically healthy obesity (MHO) may increase heart failure risk early in life, and may be reflected in impaired cardiac structure and function. Therefore, we aimed to examine the relationship between MHO in young adulthood and cardiac structure and function., Methods: A total of 3066 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were included, who completed echocardiography in young adulthood and middle age. The participants were grouped by obesity status (body mass index ≥30 kg/m 2 ) and poor metabolic health (≥2 criteria for metabolic syndrome) into four metabolic phenotypes as follows: metabolically healthy non-obesity (MHN), MHO, metabolically unhealthy non-obesity (MUN), metabolically unhealthy obesity (MUO). The associations of the metabolic phenotypes (MHN serving as the reference) with left ventricular (LV) structure and function were evaluated using multiple linear regression models., Results: At baseline, mean age was 25 years, 56.4% were women, and 44.7% were black. After a follow-up 25 years, MUN in young adulthood was associated with worse LV diastolic function (E/é ratio, β [95% CI], 0.73 [0.18, 1.28]), worse systolic function (global longitudinal strain [GLS], 0.60 [0.08, 1.12]) in comparison with MHN. MHO and MUO were associated with LV hypertrophy (LV mass index, 7.49 g/m 2 [4.63, 10.35]; 18.23 g/m 2 [12.47, 23.99], respectively), worse diastolic function (E/é ratio, 0.67 [0.31, 1.02]; 1.47 [0.79, 2.14], respectively), and worse systolic function (GLS, 0.72 [0.38, 1.06]; 1.35 [0.64, 2.05], respectively) in comparison with MHN. These results were consistent in several sensitivity analyses., Conclusions: In this community-based cohort using data from the CARDIA study, obesity in young adulthood was significantly associated with LV hypertrophy, worse systolic and diastolic function regardless of metabolic status. Relationship of Baseline Metabolic Phenotypes with Young Adulthood and Midlife Cardiac Structure and Function. Adjusted for year 0 covariates: age, sex, race, educational level, smoking status, drinking status, and physical activity; metabolically healthy non-obesity was used as a reference category for comparison. † Criteria for metabolic syndrome are listed in Supplementary Table S6. MUN metabolically unhealthy non-obesity, MHO metabolically healthy obesity, LVMi left ventricular mass index, LVEF left ventricular ejection fraction, E/A early to late peak diastolic mitral flow velocity ratio, E/é mitral inflow velocity to early diastolic mitral annular velocity, CI confidence interval., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Coronavirus disease-19 (COVID-19) has been spreading all over the world for more than two years. Though several kinds of vaccines are currently available, emergence of new variants, spike mutations and immune escape have raised new challenges. Pregnant women are vulnerable to respiratory infections due to their altered immune defence and surveillance functions. Besides, whether pregnant persons should receive a COVID-19 vaccine is still under debate because limited data are available on the efficacy and safety of receiving a vaccine during pregnancy. Physiological features and lack of effective protection making pregnant women at high risk of getting infected. Another concern is that pregnancy may trigger the onset of underlying existing neurological disease, which is highly similar to those neurological symptoms of pregnant women caused by COVID-19. These similarities interfere with diagnosis and delay timely and effective management. Therefore, providing efficient emergency support for pregnant women suffering from neurological symptoms caused by COVID-19 remains a challenge among neurologists and obstetricians. To improve the diagnosis and treatment efficiency of pregnant women with neurological symptoms, we propose an emergency management framework based on the clinicians' experience and available resources. This emergency care system aimed at addressing the conundrums faced by the emergency guarantee system under COVID-19 pandemic and could serve as a potential multisystem project for clinical practice and medical education., Competing Interests: Competing interests All authors declare that there are no conflicts of interest., (copyright: © 2022 Yang et al.)

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Fan, Lv, Chen, Peng and Zhang.)

Background: Vocational education is an important part of high school education in China. However, there is little research on high school students' mental health. This study aimed to investigate the prevalence of suicidal behavior (SB) among this population and the mediating role of insomnia, depression, anxiety, and stress in the relationship between Internet addiction (IA) and SB using a structural equation model., Methods: A cross-sectional questionnaire survey was conducted among several vocational high school students in Hunan Province, and 7,968 valid questionnaires were obtained. General demographic data and data from the Dual-Mode Self-Control Scale, Athens Insomnia Scale, Depression Anxiety Stress scale-21, and Revised Chen Internet Addiction Scale were collected. A structural equation model was used to explore the different pathways from IA to SB., Results: Among the participants, 37.7, 15.7, and 21.8% reported suicidal ideation, plans, and attempts, respectively. The structural equation model confirmed that IA was indirectly related to SB and was mediated by insomnia and/or depression, anxiety, and stress., Limitations: First, we only recruited students from vocational schools in Hunan Province, therefore, the sample may not represent the entire population of vocational students in China. Second, self-report scales were used in this study, and clinical diagnosis required professional interviews. Third, since this study had a cross-sectional design, the causal relationship between the variables could not be determined., Conclusions: The prevalence of SB among vocational high school students in China was significantly high. The prevention of SB related to IA can be attributed to the improvement of insomnia and emotional problems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Teng, Zhang, Wei, Liu, Tang, Deng, Chen, Wu, Liu, Yang, Gao, Kun, Chen, Wu and Huang.)

Purpose: To construct a diversified and comprehensive network teaching model to provide highly qualified medical teaching in neurology under COVID-19 pandemic., Materials and Methods: Published studies on medical education were systematically reviewed and summarized. Based on previous studies and our experience, we constructed a novel online neurology teaching model and applied it to real scene. Students taking traditional in class lessons and online lessons were asked to finish the test, respectively, to compare the efficiency of learning. Questionnaires were designed and assigned to get the feedback from students., Results: The average test score of students who take online class (84.27 ± 4.64) was significantly higher than those who take in class lessons (82.08 ± 6.17) ( P < 0.01). According to the feedbacks from students, online classes were more attractive to students than the conventional one., Conclusion: Traditional single-mode teaching can no longer meet the needs of current medical education, especially under the rampant epidemic. This novel teaching mode, which orchestrates high-tech tools, diverse teaching methods and traditional teaching concepts, provides the solution to the challenge faced by traditional medical education. We believe that this novel online teaching mode will boost neurology education and inspire educators in other fields during this tough period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Fan, Chen, Zhang, Wu, Hu, Wu and Zhang.)

Background: Glioma is one of the most malignant brain tumors and diseases. N6-methyladenosine modification (m6A) is the most abundant and prevalent internal chemical modification of mRNA and long non-coding RNAs (lncRNAs) in eukaryotes. Nevertheless, the correlated pathways and clinical utilization of m6A-related lncRNAs have not been fully evaluated in glioma., Methods: Public RNA-sequencing and clinical annotation data were retrieved from TCGA, CGGA and GEO database. Differential expression analysis and univariate Cox regression analysis were performed to identify the m6A-related and differentially expressed lncRNAs with prognostic function (m6A-DELPF). The consensus clustering was performed to identify the expression pattern of m6A-DELPF. LASSO Cox regression analysis was performed to construct the lncRNA-based signature. The CIBERSORT and ESTIMATE algorithms were performed to analyze immune infiltration and tumor microenvironment, respectively. Immunotherapy sensitivity analysis was performed using data from TCIA. The small molecule drugs prediction analysis was performed using The Connectivity Map (CMap) database and STITCH database. A competing endogenous RNAs (ceRNA) network was constructed based on miRcode, miRDB, miRTarBase, TargetScan database., Results: Two clusters (cluster1 and cluster2) were identified after unsupervised cluster analysis based on m6A-DELPF. Additionally, a 15-gene prognostic signature namely m6A-DELPFS was constructed. Analyses of epithelial-mesenchymal-transition score, tumor microenvironment, immune infiltration, clinical characterization analysis, and putative drug prediction were performed to confirm the clinical utility and efficacy of m6A-DELPFS. The potential mechanisms including tumor immune microenvironment of m6A-DELPF influence the initiation and progression of glioma. A clinically accessible nomogram was also constructed based on the m6A-DELPF and other survival-relevant clinical parameters. Two miRNAs and 114 mRNAs were identified as the downstream of seven m6A-related lncRNAs in a ceRNA network., Conclusion: Our present research confirmed the clinical value of m6A related lncRNAs and their high correlation with tumor immunity, tumor microenvironment, tumor mutation burden and drug sensitivity in glioma., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Endothelial cells (ECs) play an important role in angiogenesis and vascular reconstruction in the pathophysiology of ischemic stroke. Previous investigations have provided a profound cerebral vascular atlas under physiological conditions, but have failed to identify new disease-related cell subtypes. We aimed to identify new EC subtypes and determine the key modulator genes., Methods: Two datasets GSE174574 and GSE137482 were included in the study. Seurat was utilized as the standard quality-control pipeline. UCell was used to calculate single-cell scores to validate cellular identity. Monocle3 and CytoTRACE were utilized in aid of pseudo-time differentiation analysis. CellChat was utilized to infer the intercellular communication pathways. The angiogenesis ability of ECs was validated by MTS, Transwell, tube formation, flow cytometry, and immunofluorescence assays in vitro and in vivo. A synchrotron radiation-based propagation contrast imaging was introduced to comprehensively portray cerebral vasculature., Results: We successfully identified a novel subtype of EC named "healing EC" that highly expressed pan-EC marker and pro-angiogenic genes but lowly expressed all the arteriovenous markers identified in the vascular single-cell atlas. Further analyses showed its high stemness to differentiate into other EC subtypes and potential to modulate inflammation and angiogenesis via excretion of signal molecules. We therefore identified X-box binding protein 1 (Xbp1) as a key modulator in the healing EC phenotype. In vitro and in vivo experiments confirmed its pro-angiogenic roles under both physiological and pathological conditions. Synchrotron radiation-based propagation contrast imaging further proved that Xbp1 could promote angiogenesis and recover normal vasculature conformation, especially in the corpus striatum and prefrontal cortex under middle cerebral artery occlusion (MCAO) condition., Conclusions: Our study identified a novel disease-related EC subtype that showed high stemness to differentiate into other EC subtypes. The predicted molecule Xbp1 was thus confirmed as a key modulator that can promote angiogenesis and recover normal vasculature conformation., (© 2022. The Author(s).)

Iron is one of the most crucial elements in the human body. In recent years, a kind of programmed, non-apoptotic cell death closely related to iron metabolism-called ferroptosis- has aroused much interest among many scientists. Ferroptosis also interacts with other pathways involved in cell death including iron abnormality, the cystine/glutamate antiporter and lipid peroxidation. Together these pathological pathways exert great impacts on intracerebral hemorrhage (ICH), a lethal cerebrovascular disease with a high incidence rate and mortality rate. Furthermore, the ferroptosis also affects different brain cells (neurons and neuroglial cells) and different organelles (mitochondria and endoplasmic reticulum). Clinical treatments for ferroptosis in ICH have been closely investigated recently. This perspective provides a comprehensive summary of ferroptosis mechanisms after ICH and its interaction with other cell death patterns. Understanding the role of ferroptosis in ICH will open new windows for the future treatments and preventions for ICH and other intracerebral diseases., Competing Interests: Disclosure Statement The authors have no conflicts of interest to declare., (copyright: © 2022 Lu et al.)

Recent evidence suggested that the mRNA vaccine has been effective for many tumors, but its progress in gliomas was slow. In this study, we screened potential tumor antigens and suitable populations for mRNA vaccine to develop mRNA vaccine for glioma. We integrated the normalized RNA sequencing expression data and somatic mutation data from TCGA-GBM, TCGA-LGG, and CGGA datasets. Putative antigens in glioma were identified by selecting highly mutated genes with intimate correlation with clinical survival and immune infiltration. An unsupervised partition around medoids algorithm was utilized to stably cluster the patients into five different immune subtypes. Among them, IS1/2 was cold tumor with low tumor mutation burden (TMB), immunogenic cell death (ICDs), and immune checkpoints (ICPs), and IS4/5 was hot tumor with high TMB, ICDs, and ICPs. Monocle3 package was used to evaluate the immune status similarity and evolution in glioma, which identified cluster IS2A/2B within IS2 subtype to be more suitable vaccination receivers. Weighted gene co-expression network analysis identified five hub immune genes as the biomarkers of patients' immune status in glioma. In conclusion, NAT1, FRRS1, GTF2H2C, BRCA2, GRAP, NR5A2, ABCB4, ZNF90, ERCC6L, and ZNF813 are potential antigens suitable for glioma mRNA vaccine. IS1/2A/2B are suitable for mRNA vaccination., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Central nervous system (CNS) diseases, such as multiple sclerosis, Alzheimer's disease (AD), and Parkinson's disease (PD), affect millions of people around the world. Great efforts were put in disease related research, but few breakthroughs have been made in the diagnostic and therapeutic approaches. Exosomes are cell-derived extracellular vesicles containing diverse biologically active molecules secreted by their cell of origin. These contents, including nucleic acids, proteins, lipids, amino acids, and metabolites, can be transferred between different cells, tissues, or organs, regulating various intercellular cross-organ communications and normal and pathogenic processes. Considering that cellular environment and cell state strongly impact the content and uptake efficiency of exosomes, their detection in biological fluids and content composition analysis potentially offer a multicomponent diagnostic readout of several human diseases. Recently, studies have found that aberrant secretion and content of exosomes are closely related to the pathogenesis of CNS diseases. Besides, loading natural cargoes, exosomes can deliver drugs cross the blood brain barrier, making them emerging candidates of biomarkers and therapeutics for CNS diseases. In this review, we summarize and discuss the advanced research progress of exosomes in the pathological processes of several CNS diseases in regarding with neuroinflammation, CNS repair, and pathological protein aggregation. Moreover, we propose the therapeutic strategies of applying exosomes to the diagnosis, early detection, and treatment of CNS diseases., (© 2022. The Author(s).)

Stroke is a leading cause of death worldwide. Vascular calcification (VC), defined as deposition of calcium-phosphate complexes in the vessels, is considered as the characteristic of vascular aging. Calcifications at different vessel layers have different implications. Intimal calcification is closely related to atherosclerosis and affects plaque stability, while medial calcification can cause arterial stiffening and reduce compliance. Accumulating evidence suggested that arterial calcifications, including calcifications in the intracranial artery, coronary artery, and carotid artery, are associated with the risk, prognosis, and treatment response of stroke. VC can not only serve as a marker of atherosclerosis, but cause cerebral hemodynamic impairment. In addition, calcifications in large arteries are associated with cerebral small vessel disease. In this review, we summarize the findings of recently published studies focusing on the relationship between large artery calcification and the risk, prognosis, treatment response, and prevention of stroke and also discuss possible mechanisms behind those associations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Chen, Chen and Zhang.)

As an important method to accurately and timely diagnose stroke and study physiological characteristics and pathological mechanism in it, imaging technology has gone through more than a century of iteration. The interaction of cells densely packed in the brain is three-dimensional (3D), but the flat images brought by traditional visualization methods show only a few cells and ignore connections outside the slices. The increased resolution allows for a more microscopic and underlying view. Today's intuitive 3D imagings of micron or even nanometer scale are showing its essentiality in stroke. In recent years, 3D imaging technology has gained rapid development. With the overhaul of imaging mediums and the innovation of imaging mode, the resolution has been significantly improved, endowing researchers with the capability of holistic observation of a large volume, real-time monitoring of tiny voxels, and quantitative measurement of spatial parameters. In this review, we will summarize the current methods of high-resolution 3D imaging applied in stroke., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Stroke is one of the leading causes of death and disability worldwide. However, there is a lack of effective medications to speed up the recovery process. Ischemic stroke, as the result of cerebral infarction or cerebral artery narrowing, is accompanied by hemiplegia or impaired consciousness. There are many transcription factors involved in the development of this condition, whose alterations can influence or signal the prognostic outcomes of ischemic stroke. Among them, the augmented expression of specificity protein 1 (SP1) can participate in the progression of the disease by binding DNA to regulate the transcriptions of many genes. Different studies have provided different answers as to whether SP1 plays a positive or a negative role in ischemic stroke. On the one hand, SP1 can play a cytoprotective role as both an antioxidant and anti-apoptotic agent for neurons and glial cells. On the other hand, it can also damage neuronal cells by promoting inflammation and exacerbating brain edema. In this review, we highlight the roles of SP1 in ischemic stroke and shed light on the underlying mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu, Liu, Chen and Zhang.)

Background: Glioma is the most common central nervous system tumor in adults, and a considerable part of them are high-degree ones with high malignancy and poor prognosis. At present, the classification and treatment of glioma are mainly based on its histological characteristics, so studies at the molecular level are needed., Methods: RNA-seq data from The Cancer Genome Atlas (TCGA) datasets (n = 703) and Chinese Glioma Genome Atlas (CGGA) were utilized to find out the differentially expressed RNA-binding proteins (RBPs) between normal cerebral tissue and glioma. A prediction system for the prognosis of glioma patients based on 11 RBPs was established and validated using uni- and multi-variate Cox regression analyses. STITCH and CMap databases were exploited to identify putative drugs and their targets. Single sample gene set enrichment analysis (ssGSEA) was used to calculate scores of specific immune-related gene sets. IC50 of over 20,000 compounds in 60 cancer cell lines was collected from the CellMiner database to test the drug sensitivity prediction value of the RBP-based signature., Results: We established a reliable prediction system for the prognosis of glioma patients based on 11 RBPs including THOC3, LSM11, SARNP, PABPC1L2B, SMN1, BRCA1, ZC3H8, DZIP1L, HEXIM2, LARP4B, and ZC3H12B. These RBPs were primarily associated with ribosome and post-transcriptional regulation. RBP-based risk scores were closely related to immune cells and immune function. We also confirmed the potential of the signature to predict the drug sensitivity of currently approved or evaluated drugs., Conclusions: Differentially expressed RBPs in glioma can be used as a basis for prognosis prediction, new drugs screening and drug sensitivity prediction. As RBP-based glioma risk scores were associated with immunity, immunotherapy may become an important treatment for glioma in the future., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: To investigate the knowledge, attitudes and anxiety toward COVID-19 among Chinese college students studying in China and abroad., Method: A structured questionnaire, comprised of demographic characteristics, knowledge and attitudes toward COVID-19 and the State-Trait Anxiety Inventory (STAI), was used to collect data for 566 domestic students and 126 students studying abroad., Results: Domestic students were better than students abroad in knowledge of epidemiology and manifestations. Domestic students showed a significant higher enthusiasm for voluntary services than students abroad, including medical science popularization, community services, traffic dispersion, logistics transportation and being volunteers for vaccine trials. The scores (Mean ± SD) of S-AI and T-AI among students abroad were 59.48 ± 8.63 and 54.10 ± 7.20, respectively, which were significantly higher than those of domestic students (39.46 ± 8.16 and 39.25 ± 7.72)., Conclusions: Our study showed a better understanding of knowledge, more positive attitudes and less anxiety toward COVID-19 among domestic students, compared with students studying abroad. In light of this information, more attention and appropriate psychological and social intervention should be paid to college students with anxiety, especially those studying abroad., (© The Author(s) 2021. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Central nervous system (CNS) diseases are responsible for a large proportion of morbidity and mortality worldwide. CNS diseases caused by intrinsic and extrinsic stimuli stimulate the resident immune cells including microglia and astrocyte, resulting in neuroinflammation that exacerbates the progression of diseases. Recent evidence reveals the aberrant expression patterns of long non-coding RNAs (lncRNAs) in the damaged tissues following CNS diseases. It was also proposed that lncRNAs possessed immune-modulatory activities by directly or indirectly affecting various effector proteins including transcriptional factor, acetylase, protein kinase, phosphatase, etc. In addition, lncRNAs can form a sophisticated network by interacting with other molecules to regulate the expression or activation of downstream immune response pathways. However, the major roles of lncRNAs in CNS pathophysiologies are still elusive, especially in neuroinflammation. Herein, we tend to review some potential roles of lncRNAs in modulating neuroinflammation based on current evidence in various CNS diseases, in order to provide novel explanations for the initiation and progression of CNS diseases and help to establish therapeutic strategies targeting neuroinflammation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Glioma is the most common primary malignant brain tumor with significant mortality and morbidity. Ferroptosis, a novel form of programmed cell death (PCD), is critically involved in tumorigenesis, progression and metastatic processes., Methods: We revealed the relationship between ferroptosis-related genes and glioma by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE16011, and the Repository of Molecular Brain Neoplasia Data (REMBRANDT) datasets. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a ferroptosis-associated gene signature in the TCGA cohort. Glioma patients from the CGGA, GSE16011, and REMBRANDT cohorts were used to validate the efficacy of the signature. Receiver operating characteristic (ROC) curve analysis was applied to measure the predictive performance of the risk score for overall survival (OS). Univariate and multivariate Cox regression analyses of the 11-gene signature were performed to determine whether the ability of the prognostic signature in predicting OS was independent. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify the potential biological functions and pathways of the signature. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Finally, seven putative small molecule drugs were predicted by Connectivity Map., Results: The 11-gene signature was identified to divide patients into two risk groups. ROC curve analysis indicated the 11-gene signature as a potential diagnostic factor in glioma patients. Multivariate Cox regression analyses showed that the risk score was an independent predictive factor for overall survival. Functional analysis revealed that genes were enriched in iron-related molecular functions and immune-related biological processes. The results of ssGSEA indicated that the 11-gene signature was correlated with the initiation and progression of glioma. The small molecule drugs we selected showed significant potential to be used as putative drugs., Conclusion: we identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Wu, Yan and Zhang.)

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms. Previous studies showed that MLH1, MSH2, MSH6, and PMS2 mutation in LS were associated with an elevated risk of colorectal, gastric, endometria, ovarian, and other cancers among family members. Patients of these kinds of cancers had high incidence of synchronous and metasynchronus. We describe the case of a 34-year-old female patient with 50 days of sudden dizziness and left limb weakness, whose head CT scan showed large infarction in the right frontal temporal parietal lobe and basal ganglia area. Imaging examinations and pathological biopsy indicated high-grade serous carcinoma (HGSC) IIIA1 of the right ovary. In addition, a novel frame-shift mutation in the MLH1 gene (c.1621dupG, p.A541Gfs*16) was found in the genetic panel sequence. It may render declining of MLH1 protein and also associate with the patient's progressive clinical manifestations of multiple systems. Therefore, the timely use of prenatal diagnosis to prevent unnecessary new cases of this severe genetic disease is available.

Background: Astrocyte activation promotes glutamate accumulation and secretion of inflammatory factors, mainly responsible for epilepsy. Long noncoding RNA (lncRNA) X-inactive-specific transcript (XIST) regulates inflammation; however, the biological role and regulatory mechanism of XIST during astrocyte activation remain unclear., Methods: In the present study, rat epilepsy model and lipopolysaccharide (LPS)-treated CTX-TNA2 were established. XIST and miR-29c-3p expression were evaluated using quantitative real-time polymerase chain reaction. Nuclear factor of activated T cells 5 (NFAT5) was measured using western blot analysis. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and L-glutamate levels in the culture supernatants were assessed using enzyme-linked immunosorbent assay. The binding between XIST and miR-29c-3p and between miR-29c-3p and the 3'-UTR of NFAT5 was analyzed using dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and Biotin pull-down assay. The proliferation and apoptosis were evaluated using CCK8 and flow cytometry, respectively., Results: XIST expression and NFAT5 protein level was increased, whereas miR-29c-3p expression was decreased in the epilepsy rat model and LPS-treated CTX-TNA2 cells. Silenced XIST expression, miR-29c-3p overexpression, or silenced NFAT5 expression inhibited the secretion of IL-1β, IL-6, and TNF-α and promoted glutamate transport in LPS-treated CTX-TNA2 cells. miR-29c-3p was the potential miRNA sponged by XIST. NFAT5 acted as a direct binding target of miR-29c-3p. Silenced miR-29c-3p expression or NFAT5 overexpression reversed the effect of silenced XIST expression on LPS-treated CTX-TNA2.XIST and miR-29c-3p treatment does not affect NFAT5 mRNA expression, but affects NFAT5 protein level. Furthermore, underexpressed XIST or overexpressed miR-29c-3p in LPS-stimulated CTX-TNA2 can attenuate neuronal apoptosis induced by LPS-stimulated CTX-TNA2., Conclusion: LncRNA XIST promotes the secretion of inflammatory cytokines in LPS- treated CTX-TNA2 via sponging miR-29c-3p and regulating NFAT5 expression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Yang, Chen, Hu, Wu and Liu.)

Background: Coronavirus disease 2019 (COVID-19) has a long incubation period and a high degree of infectivity. Patients may not show specific signs or symptoms of upper respiratory tract infection, and the age of onset is similar to that of stroke. Furthermore, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected. Providing emergency treatment for acute stroke in accordance with the strict epidemic control measures is currently one of the main challenges, as acute stroke is rapid onset and a major cause of death and disability globally. We aimed to evaluate the emergency treatment system for acute stroke during the epidemic control period to provide a reference and basis for informing government and medical institutions on improving patient treatment rates during this period. Methods: Difficulties faced in providing emergency treatment for stroke during an epidemic were investigated and combined with medical educational resources and clinical management experiences to construct an emergency treatment framework for acute stroke during the epidemic. Findings: Currently, emergency treatment measures for acute stroke during the epidemic control period are limited because the main focus is on identifying COVID-19 comorbidities during the critical period. Establishing standards for patients in the neurological outpatient consultation rooms and emergency observation and resuscitation zones; implementing a fast-lane system for the emergency treatment of patients with acute stroke, and strengthening ward management and medicine popularization, can improve the treatment efficiency for stroke patients during the epidemic and provide a reference for peers in clinical practice. Interpretation: Emergency treatment for acute stroke during COVID-19 epidemic control period requires a joint promotion of clinical, popularization, and teaching resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Yang, Chen, Fan, Xiang, Hu, Wu, Xiao, Feng, Zhao, Chi and Zhang.)

Importance: Corona virus disease 2019 (COVID-19) has long latent period, strong infectivity, and non-specific symptoms and signs in the upper respiratory tract. Some initial neurological symptoms appear, including dizziness, headache, seizures, slurred speech, disturbance of consciousness, and limb paralysis among a few COVID-19 patients, which share similar manifestations with central nervous system (CNS) infection. Improving the diagnostic efficiency of suspected CNS infection patients on the basis of preventing and controlling COVID-19 plays a key role in preventing nosocomial and cross infections. This study intends to formulate a hospital emergency management system of fastlane treatment of CNS infection for epidemic prevention and control, aiming at providing references and guidelines for the government and medical institutions to improve the efficiency of treating CNS infection patients in the clinical practice during COVID-19. Observations: This study formulated a framework of a fastlane treatment of CNS infection based on the cooperation of resources and experience, aiming at the key and difficult problems faced by the hospital emergency management system during the COVID-19 outbreak in Changsha, China. The main problem of formulating the hospital emergency management system is efficiently identifying whether CNS infection was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The framework improves the efficiency of diagnosing and treating CNS infections by standardizing the diagnosis and treatment process of patients in emergency observation and strengthening the management of inpatient wards, aiming at assisting medical staff during clinical practice. Conclusions and Relevance: The hospital emergency management system of a fastlane treatment of CNS infection for epidemic prevention and control of the COVID-19 outbreak is a professional and multisystem project, which needs the cooperation of various resources and the experience of clinical leadership., (Copyright © 2020 Yang, Chi, Chen, Fan, Wu, Hu, Wu, Xiao and Zhang.)

Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of lncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein l splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/XBP1s axis.

Thorough investigation of the three-dimensional (3D) configuration of the vasculature of mouse brain remains technologically difficult because of its complex anatomical structure. In this study, a systematic analysis is developed to visualize the 3D angioarchitecture of mouse brain at ultrahigh resolution using synchrotron-radiation-based propagation phase-contrast imaging. This method provides detailed restoration of the intricate brain microvascular network in a precise 3D manner. In addition to depicting the delicate 3D arrangements of the vascular network, 3D virtual micro-endoscopy is also innovatively performed to visualize randomly a selected vessel within the brain for both external 3D micro-imaging and endoscopic visualization of any targeted microvessels, which improves the understanding of the intrinsic properties of the mouse brain angioarchitecture. Based on these data, hierarchical visualization has been established and a systematic assessment on the 3D configuration of the mouse brain microvascular network has been achieved at high resolution which will aid in advancing the understanding of the role of vasculature in the perspective of structure and function in depth. This holds great promise for wider application in various models of neurovascular diseases.

There has been increasing interest in using high-resolution micro-tomography to investigate the morphology of neurovascular networks in the central nervous system, which remain difficult to characterize due to their microscopic size as well as their delicate and complex 3D structure. Synchrotron radiation X-ray imaging, which has emerged as a cutting-edge imaging technology with a high spatial resolution, provides a novel platform for the non-destructive imaging of microvasculature networks at a sub-micrometre scale. When coupled with computed tomography, this technique allows the characterization of the 3D morphology of vasculature. The current review focuses on recent progress in developing synchrotron radiation methodology and its application in probing neurovascular networks, especially the pathological changes associated with vascular abnormalities in various model systems. Furthermore, this tool represents a powerful imaging modality that improves our understanding of the complex biological interactions between vascular function and neuronal activity in both physiological and pathological states.

The type III transforming growth factor- β (TGF- β ) receptor (T β RIII), a coreceptor of the TGF- β superfamily, is known to bind TGF- β s and regulate TGF- β signaling. However, the regulatory roles of T β RIII in TGF- β -induced mesenchymal stem cell (MSC) chondrogenesis have not been explored. The present study examined the effect of T β RIII RNA interference (RNAi) on TGF- β 3-induced human MSC (hMSC) chondrogenesis and possible signal mechanisms. A lentiviral expression vector containing T β RIII small interfering RNA (siRNA) (SiT β RIII) or a control siRNA (SiNC) gene was constructed and infected into hMSCs. The cells were cultured in chondrogenic medium containing TGF- β 3 or control medium. T β RIII RNAi significantly enhanced TGF- β 3-induced chondrogenic differentiation of hMSCs, the ratio of type II (T β RII) to type I (T β RI) TGF- β receptors, and phosphorylation levels of Smad2/3 as compared with cells infected with SiNC. An inhibitor of the TGF- β signal, SB431542, not only inhibited T β RIII RNAi-stimulated TGF- β 3-mediated Smad2/3 phosphorylation but also inhibited the effects of T β RIII RNAi on TGF- β 3-induced chondrogenic differentiation. These results demonstrate that T β RIII RNAi enhances TGF- β 3-induced chondrogenic differentiation in hMSCs by activating TGF- β /Smad2/3 signaling. The finding points to the possibility of modifying MSCs by T β RIII knockdown as a potent future strategy for cell-based cartilage tissue engineering.