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Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

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Neural Regeneration research 2024年第12期19卷 2773-2784页

作者： Hui Zhu James D.Guest Sarah Dunlop Jia-Xin Xie Sujuan Gao Zhuojing Luo Joe E.Springer Wutian Wu Wise Young Wai Sang Poon Song Liu Hongkun Gao Tao Yu Dianchun Wang Libing Zhou Shengping Wu Lei Zhong fang Niu Xiaomei Wang Yansheng Liu Kwok-fai So Xiao-ming Xu Kunming Tongren Hospital KunmingYunnan ProvinceChina Neurological Surgery and the Miami Project to Cure ParalysisMiller School of MedicineUniversity of MiamiMiamiFLUSA School of Biological Sciences The University of Western AustraliaPerthWAAustralia minderoo foundation PerthWAAustralia Clinical center for Spinal Cord Injury Kunming General Hospital of Chengdu Military CommandKunmingYunnan ProvinceChina Department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisINUSA Department of Orthopedic Spinal Surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Spinal Cord and brain Injury research center Department of Physical Medicine and RehabilitationUniversity of Kentucky College of MedicineLexingtonKYUSA Guangdong-HongKong-macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina W.m.Keck center for Collaborative Neuroscience Rutgers UniversityPiscatawayNJUSA Neurosurgery Department Chinese University of Hong KongPrince of Wales HospitalHong Kong Special Administration RegionChina Spinal Cord and brain Injury research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA

for patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein *** is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury *** of effective therapies fo r chronic spinal co rd injury patients is *** conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive *** clinical trial was registered at ***(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord *** found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training ***,the surgical procedures and intensive rehabilitation were *** Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 *** combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

关键词： chronic spinal cord injury intensive rehabilitation locomotor training neurological recovery surgical intervention weightbearing walking training

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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational medical research in Cognitive Development and Learning and memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China center for medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical research center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAm10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAm10 and ADAm17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAm10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric medical research center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of magnetic Resonance imaging and brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical research center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Non-coding RNAs expression in SARS-CoV-2 infection:pathogenesis,clinical significance,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第1期9卷 55-78页

作者： Xiaoxing Liu Wandi Xiong maosen Ye Tangsheng Lu Kai Yuan Suhua Chang Ying Han Yongxiang Wang Lin Lu Yanping Bao Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)100191 BeijingChina Peking-Tsinghua center for Life Sciences and PKU-IDG/mcGovern Institute for brain research Peking University100871 BeijingChina Key Laboratory of Tropical Biological Resources of ministry of Education School of Pharmaceutical SciencesHainan University570228 HaikouChina Key Laboratory of Animal models and Human Disease mechanisms of the Chinese Academy of Sciences&Yunnan Province KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences650204 KunmingYunnanChina National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Peking UniversityBeijing 100191China Institute of brain Science and brain-inspired research Shandong First Medical University&Shandong Academy of Medical Sciences250117 JinanShandongChina Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina School of Public Health Peking University100191 BeijingChina

The coronavirus disease 2019(COVID-19)pandemic has been looming globally for three years,yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration,which holds paramount importance in mitigating future *** non-coding RNAs(ncRNAs)display aberrations in the context of ***,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)exhibit a close association with viral infection and disease *** this comprehensive review,an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development,encompassing viral invasion,replication,immune response,and multiorgan deficits which include respiratory system,cardiac system,central nervous system,peripheral nervous system as well as long ***,we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19,such as stratification biomarkers,prognostic biomarkers,and predictive biomarkers for treatment *** addition,we also discuss the therapeutic potential of ncRNAs for COVID-19,presenting ncRNA-based strategies to facilitate the development of novel *** an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis,we hope to offer valuable insights into the stratification,prognosis,and treatment of COVID-19.

关键词： invasion therapeutic infection

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High-resolution mid-infrared single-photon upconversion ranging

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Photonics research 2024年第6期12卷 1294-1302页

作者： SHUHONG JIANG KUN HUANG TINGTING YU JIANAN fANG BEN SUN YAN LIANG QIANG HAO E.WU mING YAN HEPING ZENG State Key Laboratory of Precision Spectroscopy East China Normal UniversityShanghai 200062China Chongqing Key Laboratory of Precision Optics Chongqing Institute of East China Normal UniversityChongqing 401121China Collaborative Innovation center of Extreme Optics Shanxi UniversityTaiyuan 030006China School of Optical Electrical and Computer Engineering University of Shanghai for Science and TechnologyShanghai 200093China Shanghai research center for Quantum Sciences Shanghai 201315China Guangyang Bay Laboratory Chongqing Institute for Brain and IntelligenceChongqing 400064China

Single-photon laser ranging has widespread applications in remote sensing and target ***,highly sensitive light detection and ranging(lidar)has long been restricted in the visible or near-infrared *** appealing quest is to extend the operation wavelength into the mid-infrared(mIR)region,which calls for an infrared photon-counting system at high detection sensitivity and precise temporal ***,we devise and demonstrate an mIR upconversion lidar based on nonlinear asynchronous optical ***,the infrared probe is interrogated in a nonlinear crystal by a train of pump pulses at a slightly different repetition rate,which favors temporal optical scanning at a picosecond timing resolution and a kilohertz refreshing rate ***,the cross-correlation upconversion trace is temporally stretched by a factor of 2×10^(4),which can thus be recorded by a low-bandwidth silicon *** combination with the time-correlated photon-counting technique,the achieved effective resolution is about two orders of magnitude better than the timing jitter of the detector itself,which facilitates a ranging precision of 4μm under a low detected flux of 8×10^(−5) photons per *** presented mIR time-of-flight range finder is featured with single-photon sensitivity and high positioning resolution,which would be particularly useful in infrared sensing and imaging in photon-starved scenarios.

关键词： resolution lidar repetition

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Probing the interseismic locking state of the Xianshuihe fault based on a viscoelastic deformation model

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Science China Earth Sciences 2024年第1期67卷 134-145页

作者： Yage ZHU faqi DIAO fei CHEN Yuebing WANG Zhigang SHAO Rongjiang WANG Xiong XIONG Hubei Subsurface multi-Scale imaging Key Laboratory School of Geophysics and GeomaticsChina University of GeosciencesWuhan 430074China China Earthquake Networks center Beijing 100045China Institute of Earthquake forecasting China Earthquake AdministrationBeijing 100036China

The interseismic locking state of tectonic faults is essential for regional seismic hazard ***,it is challenging to obtain this parameter reliably due to the weak deformation and complex model *** better probe the fault locking state,more reliable physical models and well-covered observations are *** we investigate the locking state of the Xianshuihe fault based on a new-developed viscoelastic deformation ***,we combine GPS velocities from 13 new near-field stations and existing stations in this region to improve the spatial *** to the theoretical predictions,our results indicate that the elastic model will clearly overestimate the fault locking depth and seismic moment accumulation rate,and the fault slip rate inferred from the elastic model is slightly lower than that from the viscoelastic *** on the locking distribution inferred from the viscoelastic model,we identify four potential asperities on the Xianshuihe *** importantly,we find a clear spatial correlation between the fault locking distribution and the rupture extent of historical earthquakes,which indicates that the fault locking state may control the rupture extent and thus the magnitude of *** addition,our results show that the 2022 m6.8 Luding earthquake only ruptured the south part of a potential asperity,and the accumulated energy in the northern unruptured area is equivalent to an mw6.9 earthquake,where the seismic hazard deserves special attention.

关键词： fault kinematics Viscoelastic relaxation effect GPS observations Seismic hazard The 2022 m6.8 Luding earthquake

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Individualized brain mapping for navigated neuromodulation

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Chinese medical Journal 2024年第5期137卷 508-523页

作者： Chaohong Gao Xia Wu Xinle Cheng Kristoffer Hougaard madsen Congying Chu Zhengyi Yang Lingzhong fan Sino–Danish College University of Chinese Academy of SciencesBeijing 100190China brainnetome center National Laboratory of Pattern RecognitionInstitute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100190China Department of Applied mathematics and Computer Science Technical University of DenmarkKongens Lyngby 2800Denmark Danish research Centre for magnetic Resonance Centre for Functional and Diagnostic Imaging and ResearchCopenhagen University Hospital Amager and HvidovreHvidovre 2650Denmark CAS center for Excellence in brain Science and Intelligence Technology Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdaoShandong 266000China

The brain is a complex organ that requires precise mapping to understand its structure and *** atlases provide a powerful tool for studying brain circuits,discovering biological markers for early diagnosis,and developing personalized treatments for neuropsychiatric *** techniques,such as transcranial magnetic stimulation and deep brain stimulation,have revolutionized clinical therapies for neuropsychiatric ***,the lack of fine-scale brain atlases limits the precision and effectiveness of these *** in neuroimaging and machine learning techniques have led to the emergence of stereotactic-assisted neurosurgery and navigation ***,the individual variability among patients and the diversity of brain diseases make it necessary to develop personalized *** article provides an overview of recent advances in individualized brain mapping and navigated neuromodulation and discusses the methodological profiles,advantages,disadvantages,and future trends of these *** article concludes by posing open questions about the future development of individualized brain mapping and navigated neuromodulation.

关键词： brain atlas Individualization Navigated neuromodulation multimodal magnetic resonance imaging Transcranial magnetic stimulation Deep brain stimulation

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通过USP7结合分子胶上调P53蛋白

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Science Bulletin 2024年第12期69卷 1936-1953页

作者：李朝阳王紫英钟超张航刘瑞安平马志强卢俊梅潘成芳张兆霖曹志远胡健一邢栋费一艳丁澦鲁伯埙 The State Key Laboratory of medical Neurobiology and mOE frontiers center for brain Science Huashan Hospitalthe Institutes of Brain ScienceSchool of Life SciencesFudan UniversityShanghai 200438China Department of Optical Science and Engineering Shanghai Engineering Research Center of Ultra-Precision Optical ManufacturingKey Laboratory of Micro and Nano Photonic Structures(Ministry of Education)Fudan UniversityShanghai 200438China Shanghai Engineering research center of molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241China

molecular glues are typically small chemical molecules that act at the interface between a target protein and degradation machinery to trigger ternary complex *** molecular glues is *** is a scarcity of target-specific upregulating molecular glues,which are highly anticipated for numerous targets,including P53.P53 is degraded in proteasomes through polyubiquitination by specific E3 ligases,whereas deubiquitinases(DUBs)remove polyubiquitination conjugates to counteract these ***,small-molecular glues that enhance P53 anchoring to DUBs may stabilize P53 through ***,using small-molecule microarray-based technology and unbiased screening,we identified three potential molecular glues that may tether P53 to the DUB,USP7,and elevate the P53 *** the molecular glues,bromocriptine(BC)is an fDA-approved drug with the most robust *** was further verified to increase P53 stability via the predicted molecular glue mechanism engaging *** with P53 upregulation in cancer cells,BC was shown to inhibit the proliferation of cancer cells in vitro and suppress tumor growth in a xenograft *** summary,we established a potential screening platform and identified potential molecular glues upregulating *** strategies could be applied to the identification of other types of molecular glues that may benefit drug discovery and chemical biology studies.

关键词： P53 USP7 Deubiquitination Upregulation

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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

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Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen Lu Ying Jing Chen Zhang Shuai ma Weiqi Zhang Daoyuan Huang Bin Zhang Yuesheng Zuo Yingying Qin Guang-Hui Liu Yang Yu Jing Qu Si Wang Advanced Innovation center for Human brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National center for Bioinformation Beijing 100101China The fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish center for Education and research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell research center Peking UniversityThird HospitalBeijing 100191China center for Reproductive medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of ***,the molecular basis of ovarian aging in higher vertebrates remains poorly ***,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate *** a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian ***,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated mT2(metallothionein 2)highly expressing spot(mT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ***,with advanced age,a subpopulation of mT2^(high)accumulates,likely disseminating and amplifying the senescent signal *** study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

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Improving the electrical performances of InSe transistors by interface engineering

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Chinese Physics B 2024年第4期33卷 153-158页

作者：曹天俊郝松吴晨晨潘晨戴玉頔程斌梁世军缪峰 Institute of brain-Inspired Intelligence National Laboratory of Solid State MicrostructuresSchool of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China Institute of Interdisciplinary Physical Sciences School of PhysicsNanjing University of Science and TechnologyNanjing 210014China

InSe has emerged as a promising candidate for next-generation electronics due to its predicted ultrahigh electrical ***,the efficacy of the InSe transistor in meeting application requirements is hindered due to its sensitivity to *** this study,we have achieved notable enhancement in the electrical performance of InSe transistors through interface *** engineered an InSe/h-BN heterostructure,effectively suppressing dielectric layer-induced ***,we successfully established excellent metal-semiconductor contacts using graphene ribbons as a buffer *** a methodical approach to interface engineering,our graphene/InSe/h-BN transistor demonstrates impressive on-state current,field-effect mobility,and on/off ratio at room temperature,reaching values as high as 1.1 mA/μm,904 cm^(2)·V^(-1)·s^(-1),and>10~6,*** computations corroborate that the graphene/InSe heterostructure shows significant interlayer charge transfer and weak interlayer interaction,contributing to the enhanced performance of InSe *** research offers a comprehensive strategy to elevate the electrical performance of InSe transistors,paving the way for their utilization in future electronic applications.

关键词： two-dimensional materials InSe van der Waals heterostructure electrical performances charge density difference

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