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Loss of CREST leads to neuroinflammatory responses and ALS-like motor defects in mice

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Translational Neurodegeneration 2019年第1期8卷 141-156页

作者： Cheng Cheng Kan Yang Xinwei Wu Yuefang Zhang shifang shan Aaron Gitler Anirvan Ghosh Zilong Qiu Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Xiangya Hospital Central South UniversityChangsha 410008China Department of Genetics Stanford University School of MedicineStanfordCA 94305USA Research and Early Development BiogenCambridgeMA 02142USA

Background:Amyotrophic lateral sclerosis(ALS)is a late onset neurodegenerative disease with fast *** has heavy genetic components in which a series of genetic mutations have been *** 2013,Mutations of the CREST gene(also known as SS18L1),which functions as a calcium-regulated transcriptional activator,were found in sporadic ALS ***,the pathogenic causality and mechanisms of ALS-associated mutations of CREST remain to be ***:In this study,we constructed CREST knockout and Q394X knock-in mice with CRISPR/Cas9 *** biochemical and imaging tools,we illustrated core pathological phenotypes in CREST mutant mice and claimed the possible pathogenic ***,we also observed locomotion defects in CREST mutant mice with behavioural ***:We demonstrate that ALS-related CREST-Q388X mutation exhibits loss-of-function ***,the microglial activation was prevalent in CREST haploinsufficiency mice and Q394X mice mimicking the human CREST Q388X ***,we showed that both CREST haploinsufficiency and Q394X mice displayed deficits in motor ***,we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons,via histone deacetylation,providing the molecular mechanisms underlying inflammatory responses within mice lack of ***:Our findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors,suggesting potential therapeutic methods through inflammation pathways.

关键词： ALS CREST Neuroinflammation Cytokine Microglia

Identification of CHMP4C as a new risk gene for inherited dilated cardiomyopathy

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Journal of Genetics and Genomics 2022年第2期49卷 169-172页

作者： Nianwei Zhou Lu Tang Yingying Jiang Xuejie Li shifang shan Bo Yuan Shengmei Qin Cuizhen Pan Xiaolin Wang Xianhong Shu Zilong Qiu Junbo Ge Department of Echocardiography Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseaseShanghai Institute of Medical ImagingShanghaiChina Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghaiChina Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseaseShanghaiChina Department of Interventional Radiology Zhongshan HospitalFudan UniversityShanghai Institute of Medical ImagingShanghaiChina

Dilated cardiomyopathy(DCM) is a primary myocardial disease of unknown cause that is characterized by ventricular enlargement and ventricular systolic dysfunction(Reichart et al., 2019). DCM exhibits obvious heterogeneity, and its outcomes extend from arrhythmia to heart failure. Early arrhythmia is a common condition that may progressively become aggravated, and death can occur at any stage of the disease. The most serious complications are heart failure and sudden death(Mc Nally et al., 2013).

关键词： cardiomyopathy ventricular

Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

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Protein & Cell 2023年第1期14卷 69-73页

作者： Dali Tong Mei Zhang Yunru Yang Han Xia Haiyang Tong Huajun Zhang Weihong Zeng Muziying Liu Yan Wu Huan Ma Xue Hu Weiyong Liu Yuan Cai Yanfeng Yao Yichuan Yao Kunpeng Liu shifang shan Yajuan Li Ge Gao Weiwei Guo Yun Peng Shaohong Chen Juhong Rao Jiaxuan Zhao Juan Min Qingjun Zhu Yanmin Zheng Lianxin Liu Chao shan Kai Zhong Zilong Qiu Tengchuan Jin Sandra Chiu Zhiming Yuan Tian Xue First Affiliated Hospital of USTC School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Hefei National Research Center for Physical Sciences at the Microscale Neurodegenerative Disorder Research CenterCAS Key Laboratory of Brain Function and DiseaseCAS Key Laboratory of Innate Immunity and Chronic DiseaseBiomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230026China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Hefei Institutes of Physical Science Chinese Academy of SciencesHefei 230031China Anhui Institute of Pediatric Research Anhui Provincial Children's HospitalHefei 230051China Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Clinical Laboratory First Affiliated Hospital of Anhui Medical UniversityHefei230022China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health *** disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).

关键词： respiratory acute

P2Y1 receptor in Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 440-453页

作者： shan Luo Yifei Wang Tatsuhiro Hisatsune Department of Integrated Biosciences The University of TokyoKashiwaJapan

Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated *** amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last ***,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic *** evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s *** receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s *** review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.

关键词： astrocytes neuroinflammation P2Y1 receptor purinergic receptor

Successful emergency surgical intervention in acute non-STsegment elevation myocardial infarction with rupture:A case report

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World Journal of Clinical Cases 2025年第4期13卷 41-47页

作者： Xing-Po Li Zi-shan Wang Hong-Xia Yu shan-shan Wang Department of Cardiovascular Medicine Huantai County Hospital of Traditional Chinese MedicineZibo 256400Shandong ProvinceChina Department of Cardiovascular Medicine Zibo Hospital of Integrated Traditional Chinese and Western MedicineZibo 255500Shandong ProvinceChina

BACKGROUND The incidence of acute myocardial infarction(AMI)is rising,with cardiac rupture accounting for approximately 2%of deaths in patients with acute ST-segment elevation myocardial infarction(STEMI).Ventricular free wall rupture(FWR)occurs in approximately 2%of AMI patients and is notably rare in patients with *** of cardiac rupture include left ventricular FWR,ventricular septal rupture,and papillary muscle *** FWR usually leads to acute cardiac tamponade or electromechanical dissociation,where standard resuscitation efforts may not be *** septal rupture and papillary muscle rupture often result in refractory heart failure,with mortality rates over 50%,even with surgical or percutaneous repair *** SUMMARY We present a rare case of an acute non-STEMI patient who suffered sudden FWR causing cardiac tamponade and loss of consciousness immediate before undergoing coronary *** resuscitation and emergency open-heart repair along with coronary artery bypass grafting resulted in successful patient *** This case emphasizes the risks of AMI complications,shares a successful treatment scenario,and discusses measures to prevent such complications.

关键词： Acute non-ST segment elevation myocardial infarction Cardiac rupture Acute myocardial infarction Free wall rupture Case report

Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： shan Ping Yu Emily Choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

Wave effect of gravitational waves intersected with a microlens field Ⅱ:An adaptive hierarchical tree algorithm and population study

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 241-254页

作者： Xikai shan Guoliang Li Xuechun Chen Wen Zhao Bin Hu Shude Mao Department of Astronomy Tsinghua University Purple Mountain Observatory Chinese Academy of Sciences Institute for Frontier in Astronomy and Astrophysics Beijing Normal University School of Physics and Astronomy Beijing Normal University School of Astronomy and Space Science University of Science and Technology of China CAS Key Laboratory for Researches in Galaxies and Cosmology Department of Astronomy University of Science and Technology of ChinaChinese Academy of Sciences

The gravitational lensing wave effect generated by a microlensing field embedded in a lens galaxy is an inevitable phenomenon in strong lensed gravitational waves （SLGWs）.This effect presents both challenges and opportunities for the detection and application of ***,investigating this wave effect requires computing a complete diffraction integral over each microlens in the *** is extremely time-consuming due to the large number of microlenses （10～3-10～6）.Therefore,simply adding all the microlenses is ***,the complexity of the time delay surface makes the lens plane resolution a crucial factor in controlling numerical *** this paper,we propose a trapezoid approximation-based adaptive hierarchical tree algorithm to meet the challenges of calculation speed and *** find that this algorithm accelerates the calculation by four orders of magnitude compared to the simple adding method and is one order of magnitude faster than the fixed hierarchical tree algorithm proposed for electromagnetic *** importantly,our algorithm ensures controllable numerical errors,increasing confidence in the *** with our previous work （***.66,239511,2023）,this paper addresses all numerical issues,including integral convergence,precision,and computational time1).Finally,we conducted a population study on the microlensing wave effect of SLGWs using this algorithm and found that the microlensing wave effect cannot be ignored,especially for Type II SLGWs （from saddle position of the time delay surface） due to their intrinsic geometric structures and their typical intersection with a denser microlensing ***,more than 33%（11%） of SLGWs have a mismatch larger than 1%（3%） compared to the unlensed ***,we found that the mismatch between signal pairs in a doubly imaged GW is generally larger than 10-3,and 61%（25%） of signal pairs have a mismatch larger than 1%（3%）.Therefo

关键词： gravitational lensing diffractional integral algorithm gravitational wave