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Both gain-and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia

Journal of Genetics and Genomics 2024年第8期51卷 801-810页

作者： Wan-Bing Sun Jing-Xin fu Yu-Lan Chen Hong-fu Li Zhi-Ying wu Dian-fu Chen Department of Medical Genetics and Center for Rare Diseases and Department of Neurologyand Zhejiang Key Laboratory of Rare Diseases for Precision Medicine and Clinical Translation in Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Nanhu Brain-computer Interface Institute HangzhouZhejiang 314050China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310012China

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channelα*** variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia(PKD),but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD *** the whole exome sequencing followed by Sanger sequencing,we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese *** proband of one family(c.496G>A,p.A166T)manifests as episodic ataxia type 1,and the other two(c.877G>A,p.V293I and c.1112C>A,p.T371A)manifest as *** pathogenicity of these variants is confirmed by functional studies,suggesting that p.A166T and p.T371A cause a loss-of-function of the channel,while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic *** reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein,we find that these variants tend to cluster around the pore domain,which is similar to ***,our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype–phenotype correlations of KCNA1 channelopathy.

关键词： Paroxysmal kinesigenic dyskinesia KCNA1 Loss-of-function Gain-of-function Channelopathy Episodicataxiatype1

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Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

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Neural Regeneration Research 2024年第1期19卷 171-179页

作者： Weilin Tan jun Ma Jiayuanyuan fu Biying wu Ziyu Zhu Xuekang Huang Mengran Du Chenrui wu Ehab Balawi Qiang Zhou Jie Zhang Zhengbu Liao Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain ***,the precise mechanism of action remains unclea *** this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive *** sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular *** Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK *** competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and *** the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was ***6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro *** findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

关键词： axon guidance bioinformatics analysis competing endogenous RNA erythropoietin Gene Ontology Kyoto Encyclopedia of Genes and Genomes non-coding RNA RNA sequencing transcriptomics traumatic brain injury

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A buffer overflow detection and defense method based on RiSC-V instruction set extension

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Cybersecurity 2024年第2期7卷 28-43页

作者： Chang Liu Yan-jun wu Jing-Zheng wu Chen Zhao Intelligent Software Research Center Institute of SoftwareChinese Academy of SciencesBejingChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Computer Science Institute of SoftwareChinese Academy of SciencesBeijingChina

Buffer overflow poses a serious threat to the memory security of modern operating *** overwrites the con-tents of other memory areas by breaking through the buffer capacity limit,destroys the system execution environ-ment,and provides implementation space for various system attacks such as program control flow *** makes it a wide range of harms.A variety of security technologies have been proposed to deal with system security problems including buffer *** example,No eXecute(NX for short)is a memory management technology commonly used in Harvard *** can refuse the execution of code which residing in a specific memory,and can effectively suppress the abnormal impact of buffer overflow on control ***,in recent years,it has also been used in the field of system security,deriving a series of solutions based on NX technology,such as ExecShield,DEP,StackGuard,***,these security solutions often rely too much on the processor archi-tecture so that the protection coverage is insufficient and the accuracy is *** in the emerging system architecture field represented by RiSC-V,there is still a lack of effective solutions for buffer overflow *** the continuous rapid development of the system architecture,it is urgent to develop defense methods that are applicable to different system application environments and oriented to all executable memory spaces to meet the needs of system security ***,we propose BOP,A new system memory security design method based on RISC-V extended instructions,to build a RISC-V buffer overflow detection and defense system and deal with the buffer overflow threat in *** to this method,NX technology can be combined with program control flow analysis,and Nx bit mechanism can be used to manage the executability of memory space,so as to achieve a more granular detection and defense of buffer overflow attacks that may occur in RISC-V system

关键词： RISc-V Operating system security Buffer overflow Control flow hijacking Nx bit Xibop

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Achieving a superior Na storage performance of Fe-based Prussian blue cathode by coating perylene tetracarboxylic dianhydride amine

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Carbon Energy 2024年第5期6卷 53-64页

作者： Xin-Yuan fu Lu-Lu Zhang Zhao-Yao Chen Yunkai Xu junxiu wu Cheng-Cheng Wang Xiao-Kai Ding Xue-Lin Yang jun Lu Hubei Provincial Collaborative Innovation Center for New Energy Microgrid College of Electrical Engineering&New EnergyChina Three Gorges UniversityYichangHubeiChina College of Materials and Chemical Engineering China Three Gorges UniversityYichangHubeiChina College of Chemical and Biological Engineering Zhejiang UniversityHangzhouChina

Fe-based Prussian blue(Fe-PB)cathode material shows great application potential in sodium(Na)-ion batteries due to its high theoretical capacity,long cycle life,low cost,and simple preparation ***,the crystalline water and vacancies of Fe-PB lattice,the low electrical conductivity,and the dissolution of metal ions lead to limited capacity and poor cycling *** this work,a perylene tetracarboxylic dianhydride amine(PTCDA)coating layer is successfully fabricated on the surface of Fe-PB by a liquid-phase *** aminated PTCDA(PTCA)coating not only increases the specific surface area and electronic conductivity but also effectively reduces the crystalline water and vacancies,which avoids the erosion of Fe-PB by ***,the PTCA layer reduces the charge transfer resistance,enhances the Na-ion diffusion coefficient,and improves the structure *** PTCA-coated Fe-PB exhibits superior Na storage performance with a first discharge capacity of 145.2 mAh g^(−1) at 100 mA g^(−1).Long cycling tests exhibit minimal capacity decay of 0.027%per cycle over 1000 cycles at 1 A g^(−1).Therefore,this PTCA coating strategy has shown promising competence in enhancing the electrochemical performance of Fe-PB,which can potentially serve as a universal electrode coating strategy for Na-ion batteries.

关键词： cathode material coating Fe-based Prussian blue Na-ion batteries perylene tetracarboxylic dianhydride amine

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Paroxysmal Kinesigenic Dyskinesia:Genetics and Pathophysiological Mechanisms

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Neuroscience Bulletin 2024年第7期40卷 952-962页

作者： Jiao-Jiao Xu Hong-fu Li Zhi-Ying wu Department of Medical Genetics and Center for Rare Diseases The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Neurology in the Second Affiliated Hospital Key Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhou 310009China

Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary *** is mainly caused by mutations in the PRRT2 or TMEM151A *** exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last *** on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or *** addition,the cerebellum is regarded as the key pathogenic *** depolarization in the cerebellum is tightly associated with dyskinetic ***,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.

关键词： Paroxysmal kinesigenic dyskinesia PRRT2 TMEM151A Genetics Pathophysiological mechanisms

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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3585-3599页

作者： De-Gang Li Jia-Peng Jiang Fan-Ye Chen Wei wu jun fu Gong-He Wang Yu-Bo Li Department of Gastrointestinal and Anorectal Surgery The First Affiliated Hospital of Guangxi University of Chinese MedicineNanning 530023Guangxi Zhuang Autonomous RegionChina

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract *** is the first-line therapy for GIST *** resistance limits the long-term effectiveness of *** regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse *** To further investigate the mechanism of IGF2 specific to *** IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)*** IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry *** used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated *** injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of *** Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug *** cells with high expression of IGF2 had increased proliferation and migration,invasiveness and *** of IGF2 significantly inhibited those *** addition,OEIGF2 promoted GIST metastasis in vivo in nude ***2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver *** cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib ***,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in *** IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

关键词： Insulin-like growth factor 2 Gastrointestinal stromal tumors IGF1R Glycolysis Imatinib resistance

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Pion-photon and kaon-photon transition distribution amplitudes in the Nambu–Jona-Lasinio model

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Chinese Physics C 2024年第8期48卷 94-103页

作者： Jin-Li Zhang jun wu Department of Mathematics and Physics Nanjing Institute of TechnologyNanjing 211167China National Laboratory of Solid State Microstructures Department of PhysicsNanjing UniversityNanjing 210093China

The Nambu–Jona-Lasinio model is utilized to investigate the pion-and kaon-photon leading-twist transition distribution amplitudes using proper time ***,the properties of the vector and axial vector pion-photon transition distribution amplitudes are examined,and the results meet the desired *** study involves sum rule and polynomiality *** vector and axial vector pion-photon transition form factors that are present in theπ^(+)→γe^(+)νprocess are the first Mellin moments of the pion-photon transition distribution *** vector transition form factor originates from the internal structure of hadrons,the axial current can be coupled to a pion,this pion is virtual,and its contribution will be present independently of the external *** kaon transition form factors are *** vector form factor's value at zero momentum transfer is determined by the axial anomaly,while this is not the case for the axial *** vector and axial form factors,as well as the neutral pion vector form factor F_(πγγ)(t),are *** to our findings,the pion axial transition form factor is harder than the vector transition form factor and harder than the electromagnetic form *** also discuss the link betweenπ−γandγ−πtransitions distribution amplitudes.

关键词： transition form factors NJL model transition distribution amplitudes

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Diabetes remission and nonalcoholic fatty pancreas disease

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World Journal of Diabetes 2024年第7期15卷 1390-1393页

作者： Wen-jun wu Department of Endocrinology Jinshan Branch of Shanghai Sixth People’s HospitalShanghai 201500China

This editorial focuses on the relationship between nonalcoholic fatty pancreas disease(NAFPD)and the development and remission of type 2 diabetes(T2D).NAFPD is characterized by intrapancreatic fatty deposition associated with obesity and not associated with alcohol abuse,viral infections,and other *** fat deposition in the pancreas is associated with the development of T2D,and the underlying mechanism is lipotoxicβ-cell ***,the results on the relationship between intrapancreatic fat deposition(IPFD)andβ-cell function are *** of the therapeutic approach,weight loss improves IPFD,glycemia,andβ-cell *** imaging is valuable for clinically monitoring and evaluating the management of T2D.

关键词： Diabetes remission Type 2 diabetes Pancreatic fat content βcell function Weight loss

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Effect of intermittent joint distribution on the mechanical and acoustic behavior of rock masses

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1231-1244页

作者： Shuaiyang fu Haibo Li Liwang Liu Di wu Ben Wang State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China

The mechanical characteristics and acoustic behavior of rock masses are greatly influenced by stochastic *** this study,numerical models of rock masses incorporating intermittent joints with different numbers and dip angles were produced using the finite element method(FEM)with the intrinsic cohesive zone model(ICZM).Then,the uniaxial compressive and wave propagation simulations were *** results indicate that the joint number and dip angle can affect the mechanical and acoustic properties of the *** uniaxial compressive strength(UCS)and wave velocity of rock masses decrease monotonically as the joint number ***,the wave velocity grows monotonically as the joint dip angle *** the joint dip angle is 45°–60°,the UCS of the rock mass is lower than that of other dip *** wave velocity parallel to the joints is greater than that perpendicular to the *** the dip angle of joints remains unchanged,the UCS and wave velocity are positively *** the joint dip angle increases,the variation amplitude of the UCS regarding the wave velocity *** reveal the effect of the joint distribution on the velocity,a theoretical model was also *** to the theoretical wave velocity,the change in wave velocity of models with various joint numbers and dip angles was consistent with the simulation ***,a theoretical indicator(*** tensor)was adopted to analyze the variation of the wave velocity and UCS.

关键词： Stochastic joints Intrinsic cohesive zone model Uniaxial compressive strength(UCS) Wave propagation Fabric tensor

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Mechanism of action of cordycepin in the treatment of hepatocellular carcinoma via regulation of the Hippo signaling pathway

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Food Science and Human Wellness 2024年第2期13卷 1040-1054页

作者： Xiaomin Li Qing Liu Songyu Xie Xiaoping wu junsheng fu College of Life Sciences Mycological Research CenterFujian Agriculture and Forestry UniversityFuzhou 350002China

Hepatocellular carcinoma(HCC)is one of the common most malignant *** study aimed to determine the in vitro and in vivo anticancer activity of cordycepin and elucidate its mechanism of *** results of in vitro and in vivo studies revealed that cordycepin inhibited proliferation and migration in HepG-2 cells and inhibited the growth of HepG-2 xenograft-bearing nude mice by inducing *** sequencing analysis revealed a total of 403 differential genes,which revealed that cordycepin may play an anti-HCC role by regulating Hippo signaling *** regulatory effects of cordycepin on the Hippo signaling pathway was further investigated using a YAP1 *** results demonstrated that cordycepin upregulated the expression of MST1 and LAST1,and subsequently inhibited YAP1,which activated the Hippo signaling *** in turn downregulated the expression of GBP3 and ETV5,and subsequently inhibited cell proliferation and ***,YAP1 regulated the expression of Bax and Bcl-2,regulated the mitochondrial apoptotic pathway,and induced apoptosis by upregulating the expression of the caspase-3 *** summary,this study reveals that cordycepin exerts its anti-hepatocarcinoma effect through regulating Hippo signaling pathway,and GBP3 and ETV5 may be potential therapeutic targets for hepatocarcinoma.

关键词： Cordycepin Hepatocellular carcinoma Hippo signaling pathway GBP3 ETV5

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