Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

AIM To establish a UPLC-ESI-MS/MS method for analyzing the toxic material basis of 95％ethanol cold soaked ultrasonic extract(EC),95％ethanol heated reflux extract(EH)and water decoction extract(WD)from Dryopteris crassirhizoma Nakai.METHODS The analysis was performed on a 25 ℃ thermostatic agilent ZORBAX RRHD StableBond C18 column(2.1 mm×150 mm,1.8 μm),with the mobile phase comprising of methanol-0.2％formic acid flowing at 0.30 mL/min,and heated electrospray ion source was adopted in positive and negative ion scanning.Compounds were identified by Compound Discover 3.3 software combined with the database and related literature,and the main differential components were screened by Heatmap cluster analysis and partial least squares discriminant analysis.RESULTS 72 compounds were identified(22 phloroglucinols,19 flavonoids,8 phenylpropanoids,6 terpenoids and 17 other components).The main toxic differential components were phloroglucinols such as flavaspidic acid AB,didemethylpseudoaspidin AA and filixic acid PBP,flavonoids such as(-)-epicatechin,(-)-epigallocatechin,cianidanol,and other compounds such as indole-3-carboxaldehyde.CONCLUSION This method can rapidly,effectively and comprehensively characterize the main chemical composition of D.crassirhizoma,and provide a reference for the study of its pharmacological mechanism.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

MicroRNAs(miRNAs)are small non-coding RNAs that are closely associated with the occur-rence and progression of tumors and other diseases.However,miRNAs require high-sensitivity and high-specificity detection due to their low abundance,high sequence homology,and rapid degradation.The RNA-cleaving deoxyribozyme(RCD)is a functional single-stranded DNA molecule that enables specific cleavage of substrates to release miRNAs that can be recycled with the assistance of metal ions,prompting cyclic signal amplification.Recently,developing new methods based on RCD catalytic amplification for miRNA high-sensitivity detection has become the focus of researchers.Based on combing with the various new technologies and materials in miRNA biosensors,this study classifies and reviews the new methods for detecting miRNAs based on deoxyribozyme catalytic amplification developed in recent years.We sepa-rate these miRNA detection strategies into three categories:RCDs combined with DNA self-assembly,i-sothermal amplification,and nanomaterials.We explore the basic principles of each approach,the latest research advancements,and application scenarios in biomedical sensors and medical detection.This re-view provides a foundation and reference for further research of highly sensitive and accurate miRNA de-tection strategies.

Objective:To investigate the correlation between peripheral blood T lymphocyte level and nerve function in patients with acute cerebral infarction.Methods:A total of 100 patients with acute cerebral infarction admitted to the First People′s Hospital of Xianyang from May 2020 to May 2023 were selected as the observation group. According to the degree of neurological impairment, they were divided into mild injury (33 cases), moderate injury (39 cases) and severe injury (28 cases). Another 60 healthy subjects in hospital during the same period were included as the control group. The levels of peripheral blood T lymphocyte subsets, including CD3 +, CD4 +, CD8 +, CD4 + /CD8 +, were detected. Spearman correlation coefficient was used to analyze the correlation between the level of peripheral blood T lymphocyte subsets and the degree of neurological impairment. Receiver operating characteristic (ROC) curve was drawn to analyze the value of T lymphocyte subsets in peripheral blood in the assessment of moderate and severe neurological impairment in acute cerebral infarction. Multivariate logistic stepwise regression was used to analyze the influencing factors of severe neurological impairment in acute cerebral infarction. Results:The levels of CD3 +, CD4 +, CD4 + /CD8 + in observation group were lower than those in control group, and CD8 + levels were higher than those in control group (all P<0.05). The levels of CD3 +, CD4 +, CD4 + /CD8 + were gradually decreased and CD8 + levels were gradually increased in patients with mild, moderate and severe neurological impairment (all P<0.05). Spearman correlation analysis showed that the levels of CD3 +, CD4 +, CD4 + /CD8 + were negatively correlated with the degree of neurological impairment in patients with acute cerebral infarction, and CD8 + was positively correlated with the degree of neurological impairment (all P<0.05). According to ROC curve analysis, area under the curve (AUC) of CD3 +, CD4 +, CD8 + and CD4 + /CD8 + in evaluating severe neurological impairment in acute cerebral infarction was 0.808, 0.874, 0.833 and 0.782, respectively, and the sensitivity was 0.791, 0.821, 0.806 and 0.716, respectively. The specificity was 0.758, 0.818, 0.788, 0.727 (all P<0.05), respectively. Compared with mild defect patients, the proportion of patients with moderate and severe defect complicated with diabetes mellitus, cardioembolism in Toast classification and infarct size >3 cm 2 was higher (all P<0.05). Multivariate logistic regression analysis showed that combined diabetes, Toast classification, infarct size, CD3 +, CD4 +, CD8 +, CD4 + /CD8 + levels were the influential factors for moderate and severe neurological impairment in acute cerebral infarction (all P<0.05). Conclusions:Compared with the normal population, the levels of CD3 +, CD4 +, CD4 + /CD8 + in patients with acute cerebral infarction are lower, and the level of CD8 + is higher, and the level of T lymphocytes is correlated with the degree of neurological impairment in patients, which has certain reference value for evaluating the severity of the disease.

Objective:To investigate the correlation between peripheral blood T lymphocyte level and nerve function in patients with acute cerebral infarction.Methods:A total of 100 patients with acute cerebral infarction admitted to the First People′s Hospital of Xianyang from May 2020 to May 2023 were selected as the observation group. According to the degree of neurological impairment, they were divided into mild injury (33 cases), moderate injury (39 cases) and severe injury (28 cases). Another 60 healthy subjects in hospital during the same period were included as the control group. The levels of peripheral blood T lymphocyte subsets, including CD3 +, CD4 +, CD8 +, CD4 + /CD8 +, were detected. Spearman correlation coefficient was used to analyze the correlation between the level of peripheral blood T lymphocyte subsets and the degree of neurological impairment. Receiver operating characteristic (ROC) curve was drawn to analyze the value of T lymphocyte subsets in peripheral blood in the assessment of moderate and severe neurological impairment in acute cerebral infarction. Multivariate logistic stepwise regression was used to analyze the influencing factors of severe neurological impairment in acute cerebral infarction. Results:The levels of CD3 +, CD4 +, CD4 + /CD8 + in observation group were lower than those in control group, and CD8 + levels were higher than those in control group (all P<0.05). The levels of CD3 +, CD4 +, CD4 + /CD8 + were gradually decreased and CD8 + levels were gradually increased in patients with mild, moderate and severe neurological impairment (all P<0.05). Spearman correlation analysis showed that the levels of CD3 +, CD4 +, CD4 + /CD8 + were negatively correlated with the degree of neurological impairment in patients with acute cerebral infarction, and CD8 + was positively correlated with the degree of neurological impairment (all P<0.05). According to ROC curve analysis, area under the curve (AUC) of CD3 +, CD4 +, CD8 + and CD4 + /CD8 + in evaluating severe neurological impairment in acute cerebral infarction was 0.808, 0.874, 0.833 and 0.782, respectively, and the sensitivity was 0.791, 0.821, 0.806 and 0.716, respectively. The specificity was 0.758, 0.818, 0.788, 0.727 (all P<0.05), respectively. Compared with mild defect patients, the proportion of patients with moderate and severe defect complicated with diabetes mellitus, cardioembolism in Toast classification and infarct size >3 cm 2 was higher (all P<0.05). Multivariate logistic regression analysis showed that combined diabetes, Toast classification, infarct size, CD3 +, CD4 +, CD8 +, CD4 + /CD8 + levels were the influential factors for moderate and severe neurological impairment in acute cerebral infarction (all P<0.05). Conclusions:Compared with the normal population, the levels of CD3 +, CD4 +, CD4 + /CD8 + in patients with acute cerebral infarction are lower, and the level of CD8 + is higher, and the level of T lymphocytes is correlated with the degree of neurological impairment in patients, which has certain reference value for evaluating the severity of the disease.

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.
Adult ; Animals ; Humans ; Brain/physiopathology* ; Hippocampus/physiopathology* ; Mammals/physiology* ; Neurogenesis/physiology* ; Brain Hemorrhage, Traumatic/therapy* ; Ischemic Stroke/therapy* ; Recovery of Function ; Spinal Cord/physiopathology*

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.
Lycium/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Structure-Activity Relationship ; Antioxidants/pharmacology* ; Antineoplastic Agents ; Polysaccharides/chemistry*