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The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning shi Lv Qian Wang Yuzhen xu Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng xue Xiaokun xu Guannan Zhong Yuanyuan shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling shi Quan-Hong Ma Department of Neurology and Clinical Research Center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response

AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo Zhang Mengjie Li Chunyan Zuo Chengyuan Mao Zhongxian Zhang Mibo Tang Changhe shi Yuming xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei xu Chang Lin Xi shi Wei Chen shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells

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Science China Life Sciences 2025年

作者： shi Chen Yuanyuan He Lejun Lv Bei Liu Cheng Li Hongkui Deng Jun xu Department of Cell Biology School of Basic Medical Sciences Peking University Stem Cell Research Center Peking University Health Science Center Peking University Academy of Advanced Interdisciplinary Studies Peking University BeiCell Therapeutics School of Life Sciences Center for Bioinformatics Center for Statistical Science Peking University MOE Engineering Research Center of Regenerative Medicine School of Basic Medical Sciences State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University

Human primed pluripotent stem cells are capable of generating all the embryonic ***,their extraembryonic trophectoderm potentials are *** remains unclear how to expand their developmental potential to trophectoderm *** we show that transient treatment with a cocktail of small molecule epigenetic modulators imparts trophectoderm lineage potentials to human primed pluripotent stem cells while preserving their embryonic *** chemically treated cells can generate trophectoderm-like cells and downstream trophoblast stem cells,diverging into syncytiotrophoblast and extravillous trophoblast *** and CUT&Tag analyses reveal that these induced cells share transcriptional profiles with in vivo trophectoderm and cytotrophoblast,and exhibit reduced H3K27me3 modification at gene loci specific to trophoblast lineages compared with primed pluripotent *** exploration highlighted the critical roles of epigenetic modulators HDAC2,EZH1/2,and KDM5s in the activation of trophoblast lineage *** findings demonstrate that transient epigenetic resetting activates unrestricted lineage potential in human primed pluripotent stem cells,and offer new mechanistic insights into human trophoblast lineage specification and in vitro models for studying placental development and related disorders.

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Joint Feature Encoding and Task Alignment Mechanism for Emotion-Cause Pair Extraction

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Computers, Materials & Continua 2025年第1期82卷 1069-1086页

作者： shi Li Didi Sun College of Computer and Control Engineering Northeast Forestry UniversityHarbin150040China

With the rapid expansion of social media,analyzing emotions and their causes in texts has gained significant ***-cause pair extraction enables the identification of causal relationships between emotions and their triggers within a text,facilitating a deeper understanding of expressed sentiments and their underlying *** comprehension is crucial for making informed strategic decisions in various business and societal ***,recent research approaches employing multi-task learning frameworks for modeling often face challenges such as the inability to simultaneouslymodel extracted features and their interactions,or inconsistencies in label prediction between emotion-cause pair extraction and independent assistant tasks like emotion and cause *** address these issues,this study proposes an emotion-cause pair extraction methodology that incorporates joint feature encoding and task alignment *** model consists of two primary components:First,joint feature encoding simultaneously generates features for emotion-cause pairs and clauses,enhancing feature interactions between emotion clauses,cause clauses,and emotion-cause ***,the task alignment technique is applied to reduce the labeling distance between emotion-cause pair extraction and the two assistant tasks,capturing deep semantic information interactions among *** proposed method is evaluated on a Chinese benchmark corpus using 10-fold cross-validation,assessing key performance metrics such as precision,recall,and F1 *** results demonstrate that the model achieves an F1 score of 76.05%,surpassing the state-of-the-art by 1.03%.The proposed model exhibits significant improvements in emotion-cause pair extraction(ECPE)and cause extraction(CE)compared to existing methods,validating its *** research introduces a novel approach based on joint feature encoding and task alignment mechanisms,contributing to advancements in emotion-c

关键词： Emotion-cause pair extraction interactive information enhancement joint feature encoding label consistency task alignment mechanisms

Detection and Recognition of Spray Code Numbers on Can Surfaces Based on OCR

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Computers, Materials & Continua 2025年第1期82卷 1109-1128页

作者： Hailong Wang Junchao shi School of Computer Science Zhongyuan University of TechnologyZhengzhou450007China

A two-stage algorithm based on deep learning for the detection and recognition of can bottom spray codes and numbers is proposed to address the problems of small character areas and fast production line speeds in can bottom spray code number *** the coding number detection stage,Differentiable Binarization Network is used as the backbone network,combined with the Attention and Dilation Convolutions Path Aggregation Network feature fusion structure to enhance the model detection *** terms of text recognition,using the Scene Visual Text Recognition coding number recognition network for end-to-end training can alleviate the problem of coding recognition errors caused by image color distortion due to variations in lighting and background *** addition,model pruning and quantization are used to reduce the number ofmodel parameters to meet deployment requirements in resource-constrained environments.A comparative experiment was conducted using the dataset of tank bottom spray code numbers collected on-site,and a transfer experiment was conducted using the dataset of packaging box production *** experimental results show that the algorithm proposed in this study can effectively locate the coding of cans at different positions on the roller conveyor,and can accurately identify the coding numbers at high production line *** Hmean value of the coding number detection is 97.32%,and the accuracy of the coding number recognition is 98.21%.This verifies that the algorithm proposed in this paper has high accuracy in coding number detection and recognition.

关键词： Can coding recognition differentiable binarization network scene visual text recognition model pruning and quantification transport model

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艾滋病中药治疗现状分析

中国实验方剂学杂志 2016年第20期22卷 196-202页

作者：许前磊许二平谢世平徐立然郭会军河南中医药大学第一附属医院郑州450000 河南中医药大学艾滋病研究所郑州450008 河南省病毒性疾病中医药防治重点实验室郑州450008 河南中医药大学郑州450046

人类免疫缺陷病毒感染与获得性免疫缺陷综合征(艾滋病)作为一种新发的传染病,中医学没有明确的记载,经过近30年医家们运用中医药的临床实践,取得了显著的临床疗效,研发出了大量的有效方药,但在中药新药研发方面进展缓慢,目前治疗艾滋病... 详细信息

人类免疫缺陷病毒感染与获得性免疫缺陷综合征(艾滋病)作为一种新发的传染病,中医学没有明确的记载,经过近30年医家们运用中医药的临床实践,取得了显著的临床疗效,研发出了大量的有效方药,但在中药新药研发方面进展缓慢,目前治疗艾滋病的中药新药仅唐草片一个品种,在一定程度上限制了中医药防治艾滋病作用的发挥。笔者通过对治疗艾滋病中药研究现状的分析,探讨限制治疗艾滋病中药新药研发的瓶颈,如缺少理想的动物模型,艾滋病的中医临床研究混杂因素过多,提出在深入开展动物模型研究的基础上,注重中医复方作用机制研究,尤其体外抗病毒、免疫调节活性成分筛选,为更好的研发治疗艾滋病中药新药提供证据。

关键词：艾滋病中药研究现状分析