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Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen gu Hua Yan Dingding Shen xiaosong gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

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RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

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Neural Regeneration Research 2024年第8期19卷 1812-1821页

作者： Xinyang Zhou Yehua Lv Huimin Xie Yan Li Chang Liu Mengru Zheng Ronghua Wu songlin Zhou xiaosong gu Jingjing Li Daguo Mi Suzhou Medical College of Soochow University SuzhouJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Orthopedic Nantong Traditional Chinese Medicine HospitalNantongJiangsu ProvinceChina Nantong Stomatological Hospital Affiliated to Nantong University NantongJiangsu ProvinceChina Department of General Practice Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

关键词： ceRNA network exosomes fibroblast cells Gene Ontology(GO) Kyoto Encyclopedia of Genes and Genomes(KEGG) protein-protein interaction(PPI)networks RNA-seq Schwann cells

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Automatic velocity picking based on optimal key points tracking algorithm

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Petroleum Science 2024年第2期21卷 903-917页

作者： Yong-Hao Wang Wen-Kai Lu song-Bai Jin Yang Li Yu-Xuan Li xiao-Feng gu The Institute for Artificial Intelligence(THUAI) Tsinghua UniversityBeijing100084China State Key Laboratory of Intelligent Technology and Systems Tsinghua UniversityBeijing100084China Beijing National Research Center for Information Science and Technology(BNRist) Beijing100084China The Department of Automation Tsinghua UniversityBeijing100084China

Picking velocities from semblances manually is laborious and necessitates experience. Although various methods for automatic velocity picking have been developed, there remains a challenge in efficiently incorporating information from nearby gathers to ensure picked velocity aligns with seismic horizons while also improving picking accuracy. The conventional method of velocity picking from a semblance volume is computationally demanding, highlighting a need for a more efficient strategy. In this study, we introduce a novel method for automatic velocity picking based on multi-object tracking. This dynamic tracking process across different semblance panels can integrate information from nearby gathers effectively while maintaining computational efficiency. First, we employ accelerated density clustering on the velocity spectrum to discern cluster centers without the requirement for prior knowledge regarding the number of clusters. These cluster centers embody the maximum likelihood velocities of the main subsurface structures. Second, our proposed method tracks key points within the semblance volume. Kalman filter is adopted to adjust the tracking process, followed by interpolation on these tracked points to construct the final velocity model. Our synthetic data example demonstrates that our proposed algorithm can effectively rectify the picking errors of the clustering algorithm. We further compare the performances of the clustering method(CM), the proposed tracking method(TM), and the variational method(VM) on a field dataset from the gulf of Mexico. The results attest that our method offers superior accuracy than CM, achieves comparable accuracy with VM, and benefits from a reduced computational cost.

关键词： Velocity picking Multi-object tracking Density clustering Kalman filter

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Analysis of China's Electricity Price and Electricity Burden of Basic Industries under the Carbon Peak Target before 2030

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 481-491页

作者： Yue Qiu Suyang Zhou Wei gu xiao-Ping Zhang School of Electrical Engineering Southeast UniversityNanjingChina School of Electronic Electrical and System EngineeringUniversity of BirminghamU.K.

The Chinese government is deepening reformation of electricity prices during the 14th Five Year Plan period and has set a carbon emission reduction target of reaching carbon peak before 2030.In this context,will the carbon emission target influence electricity pricing and will electricity price influence competitiveness of Chinese main industries are two questions needing to be answered.This paper compares China's electricity price level with the selected major countries in the world,and four typical industries are selected to evaluate their electricity burden respectively.Then,the correlation between residential electricity price and industrial electricity price and the influencing factors is analyzed,from the perspectives of scale,structure and technology.According to the model obtained by regression analysis,the electricity price level and corresponding residential and industrial electricity burden in 2025 and 2030 are forecasted.Index Terms-Electricity burden,industrial electricity price,regression analysis,residential electricity price.

关键词： Electricity burden industrial electricity price regression analysis residential electricity price

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Transcriptional regulatory network during axonal regeneration of dorsal root ganglion neurons:laser-capture microdissection and deep sequencing

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Neural Regeneration Research 2023年第9期18卷 2056-2066页

作者： Li-Li Zhao Tao Zhang Wei-xiao Huang Ting-Ting guo xiao-song gu Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease Nanjing UniversityNanjingJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina School of Medicine and Life Sciences Nanjing University of Chinese MedicineNanjingJiangsu ProvinceChina

The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.

关键词： Arid5a Atf3 Crem dorsal root ganglion Fosl1 Klf6 laser-capture microdissection neuron smart-seq2 gene expression profile transcription factor

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Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

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Neural Regeneration Research 2022年第10期17卷 2185-2193页

作者： xiao-Lei Chu Xi-Zi song Qi Li Yu-Ru Li Feng He xiao-song gu Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Department of Rehabilitation Tianjin HospitalTianjinChina College of Exercise&Health Sciences Tianjin University of SportTianjinChina College of Precision Instruments&Optoelectronics Engineering Tianjin UniversityTianjinChina

Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous system,PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels.Therefore,the basic mechanisms of PNI have not been comprehensively understood.Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI,as well as to alleviate neuropathic pain,the specific mechanisms of successful PNI treatment are unclear.We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation.After PNI,activity in the central nervous system(spinal cord)is altered,which can limit regeneration of the damaged nerve.For example,cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission.The injured site of the peripheral nerve is also an important factor affecting post-PNI repair.After PNI,the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site.A slow speed of axon regeneration leads to low nerve regeneration.Therefore,it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site.From the perspective of target organs,long-term denervation can cause atrophy of the corresponding skeletal muscle,which leads to abnormal sensory perception and hyperalgesia,and finally,the loss of target organ function.The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping,addressing the excessive excitability of the dorsal root ganglion,alleviating neuropathic pain,improv

关键词： axonal transport brain-derived neurotrophic factor dorsal horn stimulation dorsal root ganglion stimulation electrical stimulation nerve regeneration neuropathic pain peripheral nerve injury spinal cord dorsal stimulation

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Graphene-anchored sodium single atoms:A highly active and stable catalyst for transesterification reaction

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Nano Research 2024年第6期17卷 4979-4985页

作者： song-song Peng Yao Nian Xing-Ru song Xiang-Bin Shao Chen gu Zhi-Wei Xing Shi-Chao Qi Peng Tan You Han xiao-Qin Liu Lin-Bing Sun State Key Laboratory of Materials-Oriented Chemical Engineering Jiangsu National Synergetic Innovation Center for Advanced Materials(SICAM)College of Chemical EngineeringNanjing Tech University30 South Puzhu RoadNanjing 211816China School of Chemical Engineering and Technology Tianjin UniversityTianjin 300072China Haihe Laboratory of Sustainable Chemical Transformations Tianjin 300192China

Solid strong base catalysts have received considerable attention in various organic reactions due to their facile separation,neglectable corrosion,and environmental friendliness.Although great progress has been made in the preparation of solid strong base catalysts,it is still challenging to avoid basic sites aggregation on support and active sites loss in reaction system.Here,we report a tandem redox strategy to prepare Na single atoms on graphene,producing a new kind of solid strong base catalyst(Na1/G).The base precursor NaNO_(3)was first reduced to Na2O by graphene(400℃)and successively to single atoms Na anchored on the graphene vacancies(800℃).Owing to the atomically dispersed of basicity,the resultant catalyst presents high activity toward the transesterification of methanol and ethylene carbonate to synthesize dimethyl carbonate(turnover frequency(TOF)value:125.7 h^(−1)),which is much better than the conventional counterpart Na2O/G and various reported solid strong bases(TOF:1.0-90.1 h^(−1)).Furthermore,thanks to the basicity anchored on graphene,the Na1/G catalyst shows excellent durability during cycling.This work may provide a new direction for the development of solid strong base catalysts.

关键词： solid strong base catalyst basic sites redox graphene single Na atoms

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Silencing the enhancer of zeste homologue 2,Ezh2,represses axon regeneration of dorsal root ganglion neurons

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Neural Regeneration Research 2022年第7期17卷 1518-1525页

作者： Ting-Ting guo Ying Zhao Wei-xiao Huang Tao Zhang Li-Li Zhao xiao-song gu song-Lin Zhou Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsJiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury RepairCo-Innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease Nanjing UniversityNanjingJiangsu ProvinceChina

Recovery from injury to the peripheral nervous system is different from that of the central nervous system in that it can lead to gene reprogramming that can induce the expression of a series of regeneration-associated genes.This eventually leads to axonal regeneration of injured neurons.Although some regeneration-related genes have been identified,the regulatory network underlying axon regeneration remains largely unknown.To explore the regulator of axon regeneration,we performed RNA sequencing of lumbar L4 and L5 dorsal root ganglion(DRG)neurons at different time points(0,3,6,12 hours,1,3 and 7 days)after rat sciatic nerve crush.The isolation of neurons was carried out by laser capture microscopy combined with NeuN immunofluorescence staining.We found 1228 differentially expressed genes in the injured sciatic nerve tissue.The hub genes within these differentially expressed genes include Atf3,Jun,Myc,Ngf,Fgf2,Ezh2,Gfap and Il6.We verified that the expression of the enhancer of zeste homologue 2 gene(Ezh2)was up-regulated in DRG neurons after injury,and this up-regulation differed between large-and small-sized dorsal root ganglion neurons.To investigate whether the up-regulation of Ezh2 impacts axonal regeneration,we silenced Ezh2 with siRNA in cultured DRG neurons and found that the growth of the newborn axons was repressed.In our investigation into the regulatory network of Ezh2 by interpretive phenomenal analysis,we found some regulators of Ezh2(including Erk,Il6 and Hif1a)and targets(including Atf3,Cdkn1a and Smad1).Our findings suggest that Ezh2,as a nerve regeneration-related gene,participates in the repair of the injured DRG neurons,and knocking down the Ezh2 in vitro inhibits the axonal growth of DRG neurons.All the experimental procedures approved by the Administration Committee of Experimental Animals of Jiangsu Province of China(approval No.S20191201-201)on March 21,2019.

关键词： axon regeneration dorsal root ganglion neurons Ezh2 IB4 laser capture microscopy NF160/200 quantitative reverse transcription-polymerase chain reaction sciatic nerve crush scRNA-seq siRNA

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PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines

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Chinese Chemical Letters 2024年第5期35卷 314-319页

作者： Wen xiao Fazhan Wang Yangzhuo gu Xi He Na Fan Qian Zheng Shugang Qin Zhongshan He Yuquan Wei Xiangrong song Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450000China

Dendritic cell(DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tumor vaccines.The targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mRNA delivery systems.Whether the PEG linker length influences the targeting delivery efficiency of mRNA nanocarrier in vivo remains unclear.Here,we designed and constructed DC-targeted mRNA delivery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP_(400)-LPX(the linker was PEG400)showed the optimal mRNA expression and antigen presentation owing to the highly efficient uptake by DCs.Furthermore,MP_(400)-LPX could better inhibited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse model.Collectively,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mRNA vaccines.Our findings provided a new platform for the rational design of targeted mRNA nanovaccines with shorter-length PEG.

关键词： Cancer immunotherapy mRNA vaccines DC-targeted delivery PEGylated liposomes Cellular uptake

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Long-term functional maintenance of primary hepatocytes in vitro using macroporous hydrogels engineered through liquid-liquid phase separation

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Nano Research 2024年第3期17卷 1725-1736页

作者： Yang Sun Sheng Yin Jian Cui Zhongxia Wang Yueying Han Ding Ma Shuo Wang Junhua Wu Yi Cao Chunping Jiang xiaosong gu Jinan Microecological Biomedicine Shandong Laboratory Jinan 250021China Collaborative Innovation Center of Advanced Microstructures National Laboratory of Solid State MicrostructureKey Laboratory of Intelligent Optical Sensing and ManipulationMinistry of EducationDepartment of PhysicsNanjing UniversityNanjing 210093China Department of Hepatobiliary Surgery The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210093China National Institute of Healthcare Data Science at Nanjing University Nanjing UniversityNanjing 210093China

Preserving the functionality of hepatocytes in vitro poses a significant challenge in liver tissue engineering and bioartificial liver,as these cells rapidly lose their metabolic and functional characteristics after isolation.Inspired by the macroporous structures found in native liver tissues,here we develop synthetic hydrogel scaffolds that closely mimic the liver’s structural organization through the phase separation between polyethylene glycol(PEG)and polysaccharides.Our hydrogels exhibit interconnected macroporous structures and appropriate mechanical properties,providing an optimal microenvironment conducive to hepatocyte adhesion and the formation of sizable aggregates.Compared to two-dimensional hepatocyte cultures,enhanced functionalities of hepatocytes cultured in our macroporous hydrogels were observed for 14 days,as evidenced by quantitative reverse-transcription–polymerase chain reactions(qRT-PCR),immunofluorescence,and enzyme linked immunosorbent assay(ELISA)analyses.Protein sequencing data further confirmed the establishment of cell–cell interactions among hepatocytes when cultured in our hydrogels.Notably,these hepatocytes maintained a protein expression lineage that closely resembled freshly isolated hepatocytes,particularly in the Notch and tumor necrosis factor(TNF)signaling pathways.These results suggest that the macroporous hydrogels are attractive scaffolds for liver tissue engineering.

关键词： liver tissue engineering phase separation hepatocytes macroporous hydrogel

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