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Functional Investigation of a GRIN2A Variant Associated with Rolandic Epilepsy

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Neuroscience Bulletin 2018年第2期34卷 237-246页

作者： xing-xing xu Xiao-Rong Liu Cui-Ying Fan Jin-xing Lai Yi-Wu Shi Wei Yang Tao Su Jun-Yu xu Jian-Hong Luo Wei-Ping Liao Department of Neurobiology Key Laboratory of Medical Neurobiology (Ministry of Health of China) Collaborative Innovation Center for Brain Science Zhejiang University School of Medicine Institute of Neuroscience Department of the Second Affiliated Hospital of Guangzhou Medical University Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China

N-methyl-D-aspartate receptors（NMDARs）, a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2 A（a gene encoding the NMDAR GluN2A subunit） mutations in patients with epilepsy. Phenotypes of GRIN2 A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2 A mutation（c.1341 T[A, p.N447 K） from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizurefree with a combination of valproate and *** investigation was carried out using recombinant NMDARs containing a GluN2A-N447 K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293 T cells revealed that the N447 K mutation increased the NMDAR current density by;.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg;inhibition. These results indicated that N447 K is a gain-offunction mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue（N447 A and N447 E） did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447 K as a novel mutation associated with epilepsy and validated its functional consequences in *** of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.

关键词： Epilepsy NMDA receptors GRIN2A Mutation

Dyeing bacterial cellulose pellicles for energetic heteroatom doped carbon nanofiber aerogels

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Nano Research 2014年第12期7卷 1861-1872页

作者： Zhen-Yu Wu Hai-Wei Liang Chao Li Bi-Cheng Hu xing-xing xu Qing Wang Jia-Fu Chen Shu-Hong Yu Division of Nanomaterials and Chemistry Hefei National Laboratory for Physical Sciences at Microscale Collaborative InnovationCenter of Suzhou Nano Science and Technology Department of Chemistry University of Science and Technology of China HefeiAnhui 230026 China

The energy crisis and environmental pollution are serious challenges that humanity will face for the long-term. Despite tremendous efforts, the development of environmentally friendly methods to fabricate new energy materials is still challenging. Here we report, for the first time, a new strategy to fabricate various doped carbon nanofiber （CNF） aerogels by pyrolysis of bacterial cellulose （BC） pellicles which had adsorbed or were dyed with different toxic organic dyes. The proposed strategy makes it possible to remove the toxic dyes from waste-water and then synthesize doped CNF aerogels using the dyed BC pellicles as precursors. Compared with other reported processes for preparing heteroatom doped carbon （HDC） nanomaterials, the present synthetic method has some significant advantages, such as being green, general, low-cost and easily scalable. Moreover, the as-prepared doped CNF aerogels exhibit great potential as electrocatalysts for the oxygen reduction reaction （ORR） and as electrode materials for supercapacitors.

关键词： doped carbon nanofiberaerogels electrocatalysts oxygen reduction reaction supercapacitors organic dyes bacterial cellulose

Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study

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World Journal of Gastroenterology 2025年第2期31卷 85-101页

作者： Jun-Yi Zhan Jie Chen Jin-Zhong Yu Fei-Peng xu Fei-Fei xing De-Xin Wang Ming-Yan Yang Feng xing Jian Wang Yong-Ping Mu Cell Biology Laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Liver Diseases Shanghai Academy of Chinese MedicineShanghai 201203China Clinical Key Laboratory of Traditional Chinese Medicine of Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Key Laboratory of Liver and Kidney Disease of the Ministry of Education Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Gastroenterology and Hepatology Zhongshan Hospital Affiliated to Fudan UniversityShanghai 200032China Shanghai Institute of Liver Disease Fudan UniversityShanghai 200032China Evidence-Based Medicine Center Fudan UniversityShanghai 200032China Department of Gastrointestinal Endoscopy Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Hepatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and *** its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are *** To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal *** This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 *** least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic *** validation was performed with bootstrap *** assessed the discrimination,calibration and accuracy of the model,and performed patient risk *** Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)*** predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation ***,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both *** We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.

关键词： Esophagogastric variceal bleeding Variceal rebleeding Liver cirrhosis Prognostic model Risk stratification Secondary prophylaxis

热轧对搅拌摩擦加工制备CNTs/Al复合材料微结构与性能的影响

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材料导报 2017年第18期31卷 81-84页

作者：夏春汪云海黄春平邢丽夏星许冬南昌航空大学轻合金加工科学与技术国防重点学科实验室南昌330063

在搅拌摩擦加工制备碳纳米管增强铝基复合材料(CNTs/Al)的基础上,研究了热轧对复合材料微结构与性能的影响。结果表明,热轧使基体晶粒沿轧制方向拉长,同时有利于CNTs的取向并在一些CNTs-Al界面形成Al4C3相;基于CNTs取向等微结构的变化... 详细信息

在搅拌摩擦加工制备碳纳米管增强铝基复合材料(CNTs/Al)的基础上,研究了热轧对复合材料微结构与性能的影响。结果表明,热轧使基体晶粒沿轧制方向拉长,同时有利于CNTs的取向并在一些CNTs-Al界面形成Al4C3相;基于CNTs取向等微结构的变化以及界面反应引起界面结合力增强的因素,沿轧制方向复合材料的抗拉强度、导电性明显提高,热膨胀率降低。

关键词：热轧搅拌摩擦加工 CNTs/Al复合材料微结构性能

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轴肩过渡曲线设计及应力集中分析

舰船科学技术 2017年第5期39卷 38-41页

作者：屠星星徐勇杰上海船舶研究设计院上海201203

分析单曲率圆弧、双曲率圆弧、三曲率圆弧、椭圆和流线形等多种轴肩过渡曲线的设计方法,利用有限元软件Abaqus对这些曲线进行建模分析。对于单曲率圆弧,应力集中系数和应力集中角度随着过渡半径的增大而减小,但是应力集中系数减小的效... 详细信息

分析单曲率圆弧、双曲率圆弧、三曲率圆弧、椭圆和流线形等多种轴肩过渡曲线的设计方法,利用有限元软件Abaqus对这些曲线进行建模分析。对于单曲率圆弧,应力集中系数和应力集中角度随着过渡半径的增大而减小,但是应力集中系数减小的效果并不十分明显。流线形过渡曲线基本消除了应力集中,其应力集中系数仅为1.004。双曲率圆弧、三曲率圆弧和椭圆过渡曲线也都将应力集中系数降低到1.05以下,适于实际工程应用。

关键词：轴肩过渡曲线过渡半径应力集中系数

微织构车刀制备与SUS304钢高速微车削试验

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中国表面工程 2016年第6期29卷 1-7页

作者：于占江蔡倩倩王星星许金凯于化东长春理工大学吉林省精密微制造、检测及装备重点实验室长春130022

针对高速微切削过程中微型车刀表面摩擦磨损严重的问题,利用表面非光滑微织构减摩减阻原理,在高速微切削用车刀表面利用激光加工技术制备了微槽、微坑织构,研究了激光加工参数与微织构形貌之间的关系;分析了微织构的摩擦学特性;利用自... 详细信息

针对高速微切削过程中微型车刀表面摩擦磨损严重的问题,利用表面非光滑微织构减摩减阻原理,在高速微切削用车刀表面利用激光加工技术制备了微槽、微坑织构,研究了激光加工参数与微织构形貌之间的关系;分析了微织构的摩擦学特性;利用自行研制的高速微车削单元进行微织构刀具及无织构刀具的高速微切削SUS304不锈钢的对比试验,从切削力、切削温度、刀屑接触状态、切屑形态以及已加工表面粗糙度对微织构车刀性能进行评价。结果表明:微槽、微坑织构均可以有效降低刀具表面摩擦因数;在高速微切削过程中可以减小切削力、切削温度,降低刀屑接触长度,改善切屑形态,尤其是微坑织构可明显改善表面质量,可以应用到SUS304不锈钢的高速微加工。

关键词：微织构 SUS304 高速切削微车削车刀

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min xing Hai-Dong Qian Qiao Gao Sheng-Lan xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin xing xuyun Hua Yuwen Zhang Xin xue Jiajia Wu Mouxiong Zheng He Wang Jianguang xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

Insights into spinal muscular atrophy from molecular biomarkers

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Neural Regeneration Research 2025年第7期20卷 1849-1863页

作者： Xiaodong xing Xinzhu Liu Xiandeng Li Mi Li Xian Wu Xiaohui Huang Ajing xu Yan Liu Jian Zhang Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina College of Pharmacy Chongqing Medical UniversityChongqingChina

Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle *** is one of the most common genetic causes of mortality among infants aged less than 2 *** research is currently receiving more attention,and new candidate biomarkers are constantly being *** review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and *** also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific *** review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future ***,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.

关键词： biomarkers disease progression gene-targeting therapy neurofilaments Nusinersen spinal muscular atrophy(SMA) survival motor neuron therapeutic evaluation treatment outcomes