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Metabolic reprogramming: a new option for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第4期20卷 1042-1057页

作者： Jiangjie Chen Jinyang Chen Chao Yu Kaishun Xia Biao Yang Ronghao wang Yi Li Kesi Shi Yuang Zhang haibin Xu Xuesong Zhang Jingkai wang Qixin Chen Chengzhen Liang Department of Orthopedics The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Orthopedics Research Institute of Zhejiang University Zhejiang UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research Center of Motor System Disease of Zhejiang Province HangzhouZhejiang ProvinceChina Qiandongnan Prefecture People’s Hospital KailiGuizhou ProvinceChina Department of Orthopedics Fourth Medical CenterChinese PLA General HospitalBeijingChina

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they *** the ongoing development of various therapies for spinal cord injuries,their effectiveness remains ***,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic *** this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic *** spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic ***,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial *** metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of *** rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell *** available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord *** further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

关键词： axons glycolysis metabolic reprogramming metabolism mitochondria neural regeneration neuroprotection oxidative phosphorylation spinal cord injury therapy

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration Research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin Chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang dai Bing wang Department of Spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury

SensFL:Privacy-Preserving Vertical Federated Learning with Sensitive Regularization

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 385-404页

作者： Chongzhen Zhang Zhichen Liu Xiangrui Xu Fuqiang Hu Jiao dai Baigen Cai Wei wang School of Automation and Intelligence Beijing Jiaotong UniversityBeijing100044China Shuohuang Railway Development Co. Ltd.National Energy GroupCangzhou062350China Beijing Key Laboratory of Security and Privacy in Intelligent Transportation School of Computer Science and TechnologyBeijing Jiaotong UniversityBeijing100044China

In the realm of Intelligent Railway Transportation Systems,effective multi-party collaboration is crucial due to concerns over privacy and data *** Federated Learning(VFL)has emerged as a promising approach to facilitate such collaboration,allowing diverse entities to collectively enhance machine learning models without the need to share sensitive training ***,existing works have highlighted VFL’s susceptibility to privacy inference attacks,where an honest but curious server could potentially reconstruct a client’s raw data from embeddings uploaded by the *** vulnerability poses a significant threat to VFL-based intelligent railway transportation *** this paper,we introduce SensFL,a novel privacy-enhancing method to against privacy inference attacks in ***,SensFL integrates regularization of the sensitivity of embeddings to the original data into the model training process,effectively limiting the information contained in shared *** reducing the sensitivity of embeddings to the original data,SensFL can effectively resist reverse privacy attacks and prevent the reconstruction of the original data from the *** experiments were conducted on four distinct datasets and three different models to demonstrate the efficacy of *** results show that SensFL can effectively mitigate privacy inference attacks while maintaining the accuracy of the primary learning *** results underscore SensFL’s potential to advance privacy protection technologies within VFL-based intelligent railway systems,addressing critical security concerns in collaborative learning environments.

关键词： Vertical federated learning privacy defenses

Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： Xintian Ding Chun Chen Heng Zhao Bin dai Lei Ye Tao Song Shuai Huang Jia wang Tao You Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2

Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

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Neural Regeneration Research 2025年第2期20卷 518-532页

作者： Conglin wang Fangyuan Cheng Zhaoli Han Bo Yan Pan Liao Zhenyu Yin Xintong Ge dai Li Rongrong Zhong Qiang Liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina School of Medicine Nankai UniversityTianjinChina Tianjin Neurological Institute TianjinChina

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor ***-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system *** this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying *** results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral ***,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory *** sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier *** with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these *** summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

关键词： AKT astrocyte blood-brain barrier cerebral edema exosomes human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells neuroinflammation PI3K

Early identification of stroke through deep learning with multi-modal human speech and movement data

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Neural Regeneration Research 2025年第1期20卷 234-241页

作者： Zijun Ou Haitao wang Bin Zhang Haobang Liang Bei Hu Longlong Ren Yanjuan Liu Yuhu Zhang Chengbo dai Hejun Wu Weifeng Li Xin Li School of Computer Science and Engineering Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Emergency Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina

Early identification and treatment of stroke can greatly improve patient outcomes and quality of *** clinical tests such as the Cincinnati Pre-hospital Stroke Scale(CPSS)and the Face Arm Speech Test(FAST)are commonly used for stroke screening,accurate administration is dependent on specialized *** this study,we proposed a novel multimodal deep learning approach,based on the FAST,for assessing suspected stroke patients exhibiting symptoms such as limb weakness,facial paresis,and speech disorders in acute *** collected a dataset comprising videos and audio recordings of emergency room patients performing designated limb movements,facial expressions,and speech tests based on the *** compared the constructed deep learning model,which was designed to process multi-modal datasets,with six prior models that achieved good action classification performance,including the I3D,SlowFast,X3D,TPN,TimeSformer,and *** found that the findings of our deep learning model had a higher clinical value compared with the other ***,the multi-modal model outperformed its single-module variants,highlighting the benefit of utilizing multiple types of patient data,such as action videos and speech *** results indicate that a multi-modal deep learning model combined with the FAST could greatly improve the accuracy and sensitivity of early stroke identification of stroke,thus providing a practical and powerful tool for assessing stroke patients in an emergency clinical setting.

关键词： artificial intelligence deep learning diagnosis early detection FAST screening stroke

Surface-confined persistent luminescence with amplified FRET efficiency for cell-cell communication monitoring

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Science China Chemistry 2025年

作者： Ziyun Miao Wenjing dai Yubin Jin Bing Qi Jiayi Chen Lingling Qiu Yurong Wei Jie wang The Key Lab of Health Chemistry&Molecular Diagnosis of Suzhou College of ChemistryChemical Engineering&Materials ScienceSoochow University

Microbial communication monitoring is vital for understanding the mechanisms beneath gut microbiota equilibrium, infections,and biomanufacturing. Herein, we reported monitoring bacterial communication by surface-confined persistent ***, we constructed core-shell structured Zn1.4Ga1.2Ge0.4O4@Zn1.4Ga1.2Ge0.4O4:Cr（ZGGO@ZGGO:Cr） persistent luminescence nanoparticles（PLNPs） with amplified FRET efficiency for the detection of azoreductase（AzoR） that participates in bacterial communication. ZGGO@ZGGO:Cr nanoparticles were functionalized with an azo black hole quencher（ZGGO@ZGGO:Cr-BHQ-3）. Due to the proximity of surface-confined persistent luminescence with the surface-bound BHQ-3,ZGGO@ZGGO:Cr-BHQ-3 exhibited a FRET efficiency up to 1.6 times that of traditional ZGGO:Cr-BHQ-3. Further, the specific catalytic reduction of azo bonds in BHQ-3 by bacterial extracellular AzoR recovers the persistent luminescence of ZGGO@ZGGO:Cr. ZGGO@ZGGO:Cr-BHQ-3 displayed superior sensitivity and speed in detecting extracellular AzoR over ZGGO:Cr-BHQ-3, attributed to its surface-confined persistent luminescence. We found that the peak secretion of AzoR occurs during the exponential growth period of bacteria including S. aureus and E. coli based on the persistent luminescence recovery rate of ZGGO@ZGGO:Cr-BHQ-3. Furthermore, ZGGO@ZGGO:Cr-BHQ-3 was used to probe the communication between different bacterial species. R. palustris is a kind of lycopene-production bacteria. We found that the cohabitation of R. palustris and S. putrefaciens boosted both AzoR secretion and lycopene production. Moreover, the secretion and activity of AzoR positively correlated with lycopene production, suggesting that AzoR may participate in the communication between R. palustris and S. putrefaciens to promote lycopene production. This study offers a robust method to enhance PLNP-based biosensing sensitivity and provides a promising strategy for microbial communication monitoring.

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Dramatical enhancement of circular dichroism in chiral hybrid perovskites via carboxylic hydrogen bond engineering

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Science China Chemistry 2025年

作者： Hang Li Xinling Li Peng wang Tingting Zhu Ruiqing Li Huang Ye Yaru Geng Hongliang dai Junhua Luo State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences University of Chinese Academy of Sciences Fujian College University of Chinese Academy of Sciences College of Chemistry Fuzhou University College of Chemistry and Materials Key Laboratory of Fluorine and Silicon for Energy Materials and Chemistry of Ministry of EducationJiangxi Normal University

Chiral hybrid perovskites （CHPs） have been regarded as promising candidates for developing chiroptoelectronics ***,circular dichroism （CD）,as one of the most important characteristics to evaluate the chiroptical activity,remains at a comparatively low level in CHPs compared to other chiral materials,which hinders the successful applications of CHPs in stateof-the-art ***,exploring new methods for enhancing CD in CHPs is urgently needed and remains ***,enhanced CD response has been successfully realized via constructing carboxylic hydrogen bonding in chiralachiral mixed cations perovskites （R/S-PPA）2（ABA）PbBr5（2R/2S）(PPA=1-phenylpropylamine,ABA=4-aminobutyric acid).Compared with the prototype （R/S-PPA）PbBr3（1R/1S）,2R/2S provide intimate connections between organic units and inorganic parts via carboxylic hydrogen bonding N–H···O bridge,contributing new chirality transfer paths.A larger inorganic skeletons’helicity in 2R/2S predicts a high degree of chirality ***,2R/2S exhibit significantly enhanced CD response with an anisotropy factor amplified by an order of ***,bright blue circularly polarized luminescence applications are achieved in 2R/*** work systematically investigates the correlation between CD and hydrogen bonding interaction in CHPs,meanwhile providing a new avenue to develop the application potential of chiral materials in chiroptoelectronics.

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li Faqin Li Zhaoyi Chen Erwen Wu Xiaoxi dai Danni Li Haojie An Shiyi Zeng Chunyan wang Li Yang Cheng Long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission