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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng gong Haiying Liang Tingting Chen Department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular Drug Target NantongJiangsu ProvinceChina Department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

The Mechanism of Heating Rate on the Secondary Recrystallization Evolution in Grain Oriented Silicon Steel

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 275-282页

作者： GAO Qian LI Jun WANG Xianhui CAO Laifu gong Jian LI Bo Central Iron and Steel Research Institute Group Beijing 100081China Shougang Zhixin Electromagnetic Material R&D(Beijing)Co. Ltd.Beijing 101300China Beijing Shougang Co. Ltd.Qian’an 064404China

Grain-oriented silicon steels were prepared at different heating rates during high temperature annealing,in which the evolution of magnetic properties,grain orientations and precipitates were *** illustrate the Zener factor,the diameter and number density of precipitates of interrupted testing samples were statistically *** effect of precipitate ripening on the Goss texture and magnetic property was *** indicated that the trend of Zener factor was similar under different heating rates,first increasing and then decreasing,and that the precipitate maturing was greatly inhibited as the heating rate *** recrystallization was developed at the temperature of 1010℃when a heating rate of 5℃/h was used,resulting in Goss,Brass and{110}oriented grains growing abnormally and a magnetic induction intensity of ***,increasing the heating rate to 20℃/h would inhibit the development of undesirable oriented grains and obtain a sharp Goss ***,when the heating rate was extremely fast,such as 40℃/h,poor secondary recrystallization was developed with many island grains,corresponding to a decrease in magnetic induction intensity to 1.87 *** a suitable heating rate of 20℃/h,the sharpest Goss texture and the highest magnetic induction of 1.94 T with an onset secondary recrystallization temperature of 1020℃were found among the experimental variables in this *** heating rate affected the initial temperature of secondary recrystallization by controlling the maturation of precipitates,leading to the deviation and dispersion of Goss texture,thereby reducing the magnetic properties.

关键词： high temperature annealing heating rate secondary recrystallization grain oriented silicon steel

Engine Misfire Fault Detection Based on the Channel Attention Convolutional Model

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Computers, Materials & Continua 2025年第1期82卷 843-862页

作者： Feifei Yu Yongxian Huang Guoyan Chen Xiaoqing Yang Canyi Du Yongkang gong School of Mechatronic Engineering Guangdong Polytechnic Normal UniversityGuangzhou510665China School of Automotive and Transportation Engineering Guangdong Polytechnic Normal UniversityGuangzhou510665China

To accurately diagnosemisfire faults in automotive engines,we propose a Channel Attention Convolutional Model,specifically the Squeeze-and-Excitation Networks(SENET),for classifying engine vibration signals and precisely pinpointing misfire *** the experiment,we established a total of 11 distinct states,encompassing the engine’s normal state,single-cylinder misfire faults,and dual-cylinder misfire faults for different *** collection was facilitated by a highly sensitive acceleration signal collector with a high sampling rate of 20,*** collected data were methodically divided into training and testing sets based on different experimental groups to ensure generalization and prevent overlap between the two *** results revealed that,with a vibration acceleration sequence of 1000 time steps(approximately 50 ms)as input,the SENET model achieved a misfire fault detection accuracy of 99.8%.For comparison,we also trained and tested several commonly used models,including Long Short-Term Memory(LSTM),Transformer,and Multi-Scale Residual Networks(MSRESNET),yielding accuracy rates of 84%,79%,and 95%,*** underscores the superior accuracy of the SENET model in detecting engine misfire faults compared to other ***,the F1 scores for each type of recognition in the SENET model surpassed 0.98,outperforming the baseline *** analysis indicated that the misclassified samples in the LSTM and Transformer models’predictions were primarily due to intra-class misidentifications between single-cylinder and dual-cylinder misfire *** delve deeper,we conducted a visual analysis of the features extracted by the LSTM and SENET models using T-distributed Stochastic Neighbor Embedding(T-SNE)*** findings revealed that,in the LSTMmodel,data points of the same type tended to cluster together with significant ***,in the SENET model,data points of various types were more widely and evenly dispersed,demonstra

关键词： Channel attention SENET model engine misfire fault fault detection

Bacterial indole-3-propionic acid inhibits macrophage IL-1β production through targeting methionine metabolism

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Science China Life Sciences 2025年

作者： Ziyi Han Jian Fu Aiyan gong Wenkai Ren State Key Laboratory of Livestock and Poultry Breeding College of Animal Science South China Agricultural University Animal Disease-resistant Nutrition Key Laboratory of Sichuan Province Sichuan Agricultural University China Institute of Veterinary Drug Control

The gut microbiota plays key roles in host health by shaping the host immune responses through their metabolites, like indole derivatives from tryptophan. However, the direct role of these indole derivatives in macrophage fate decision and the underlying mechanism remains unknown. Here, we found that bacterial indole-3-propionic acid(IPA) downregulates interleukin-1beta(IL-1β) production in M1 macrophages through inhibition of nuclear factor-kappa B(NF-κB) signaling. Mechanistically, IPA binds specifically with methionine adenosyltransferase 2A(MAT2A) to promote S-adenosylmethionine(SAM) synthesis, which facilitates the DNA methylation of ubiquitin-specific peptidase 16(USP16, a deubiquitinase), and in turn promotes Toll-like receptor 4(TLR4) ubiquitination and NF-κB inhibition. Furthermore,IPA administration attenuates sepsis in mouse models induced by lipopolysaccharides(LPS), showcasing its potential as a microbial-derived adjunct in alleviating inflammation. Collectively, our findings reveal a newly found microbial metabolite-immune system regulatory pathway mediated by IPA.

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Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2

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Neural Regeneration Research 2025年第6期20卷 1801-1815页

作者： Qing He Zhen Wang Yuchen Wang Mengjie Zhu Zhile Liang Kanghong Zhang Yuge Xu gong Chen GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina

Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors––NeuroD1, Ascl1, and Dlx2––in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore,we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4(astrocyte endfeet signal), CX43(gap junction signal), and S100β. Importantly, none of these changes could be attributed to transgene leakage into preexisting neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

关键词： aquaporin-4 Ascl1 astrocyte cortex Dlx2 gap junction glia-to-neuron conversion neural regeneration NeuroD1 reprogramming

Long-read sequencing reveals novel genetic polymorphisms in the major histocompatibility complex region and their impacts on the Han Chinese population

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Science China Life Sciences 2025年

作者： Cong Zhou Tingting gong Shuhang Li Li Jin Shaohua Fan State Key Laboratory of Genetic Engineering Lab for Evolutionary Synthesis School of Life Sciences Human Phenome Institute Fudan University Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences

Human leukocyte antigen(HLA) genes in the major histocompatibility complex(MHC) region are crucial for immunity and are associated with numerous diseases and phenotypes. The MHC region's complexity and high genetic diversity make it challenging to analyze using short-read sequencing(SRS) technology. We sequence the MHC region of 100 Han Chinese individuals using both long-read sequencing(LRS) and SRS platforms at approximately 30X coverage to study genetic alterations and their potential functional impacts. LRS provides significantly greater coverage of the MHC region and eight classical HLA genes, particularly at the HLA-DRB1 locus, compared with SRS. We detect 78,249 single nucleotide polymorphisms(SNPs) using LRS, with 26.0% undetectable by SRS. Based on SNP and inferred HLA allele types, we construct an LRS-based MHC reference panel for the Han Chinese, containing approximately 2.6 times more genetic variants than the SRS-based Han-MHC reference panel. A phenome-wide association study assessing 26,024 phenotypes across 15 categories identifies significant associations for 7,879 independent variants(including 809 LRS-specific SNPs) with 409 phenotypes in nine categories. This analysis reveals 24 unreported HLA allele associations in the bioelectric and cellular categories. The conditional analysis identifies 530independent signals across the 409 phenotypes, including 28 previously unreported signals of eight classical HLA genes associated with 33phenotypes. Of the top-associated SNPs, 191 are detected by LRS only. Fine-mapping identifies 126 independent candidate causal SNPs for three immune-related cellular phenotypes, with 17 detected exclusively by LRS. Our study reveals previously unreported variants and their functional impacts in the MHC region, enhancing our understanding of genetic diversity and its potential biological implications in the Han Chinese population.

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial Key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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硝酸铈对Calpain基因表达的影响

中国稀土学报 2002年第1期20卷 57-60页

作者：杨维东刘洁生王艇龚孟濂雷衡毅杨燕生暨南大学生物工程系广东广州510632 中山大学生命科学学院广东广州510275 中山大学化学化工学院广东广州510275

运用逆转录聚合酶链式反应研究了硝酸铈对大白鼠肝脏CalpainⅠ、CalpainⅡ基因表达的影响。腹腔注射高浓度硝酸铈可引起Calpain基因表达的变化。

关键词：稀土硝酸铈中性蛋白酶逆转录聚合酶链式反应肝细胞细胞损伤生物效应钙离子基因表达脂质过氧化

Ca2+ cation-mediated microenvironment for electrochemical hydrodimerization of furfural

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Science China Chemistry 2025年

作者： Wei Du Shuangshuang Cha Can Lei Mengxin Qu Zhongqiang Deng Ming gong Xinhe Bao Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Fudan University State Key Laboratory of Catalysis National Laboratory for Clean Energy Collaborative Innovation Center of Chemistry for Energy Materials Dalian Institute of Chemical Physics Chinese Academy of Sciences

Furfural is one of the most important biomass-based platform molecules as sustainable precursors for chemicals and fuels. The electrochemical hydrodimerization of furfural can generate hydrofuroin, which is a promising precursor for gasoline or jet ***, steering the selectivity toward hydrodimerization under near-neutral conditions that suppress polymerization and disproportionation of furfural remains challenging. Herein, we discovered that tuning the electrolyte cations could be an effective and alternative strategy for modulating furfural reduction to the traditional electrocatalyst design. Under the optimal Ca2+cations,hydrofuroin yield could be much improved from other cations with hydrofuroin selectivity of 95.5%. The systematic characterization of the ion-centered double layer reflected the suitable sizes and charges of hydrated Ca2+for suppressing the hydrogen evolution reaction from activation of surrounding water molecules as well as encouraging furfural accumulation via non-covalent interaction for directing the electron transfer to furfurals. Ions with smaller or larger sizes can either activate local water molecules or form a crowded ionic interface that casts an adverse effect on furfural enrichment. This work not only presents an effective strategy for facilitating biomass valorization via hydrodimerization but also emphasizes the essential role of the ion-centered microenvironment for steering the electrocatalytic pathways.

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