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Exosomes:the next-generation therapeutic platform for ischemic stroke

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Neural Regeneration research 2025年第5期20卷 1221-1235页

作者： Wenjing Yin Hongyin Ma Yang Qu Jiaxin Ren Yingying Sun Zhen-Ni Guo Yi Yang Stroke center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina Neuroscience research center Department of NeurologyFirst Hospital of Jilin UniversityChangchunJilin ProvinceChina

Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional ***,there is an urgent need to develop new methods for the treatment of this *** are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological *** have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain *** physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic *** rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages *** in technology have also driven clinical translational research on *** this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction ***,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified *** optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic ***,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.

关键词： blood–brain barrier electroacupuncture engineering exercise exosomes ischemic stroke mesenchymal stem cells microglia neuroprotection stents

Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong Department of Spine Surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)Key Laboratory for Quality research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial center for Quality Control of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial center for engineering and Technology research of Minimally Invasive Spine Surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

Self-assembled carbon monoxide nanoprodrug for chemiexcitationtriggered synergistic chemotherapy against breast cancer

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Science China Chemistry 2025年

作者： Shunfei Cui Yiyao Pan Chenzhe Ma Bin Qi Qingqiang Min Ming Li Huabing Chen Hengte Ke Xingyue Ji Jiangsu province engineering research center of Precision Diagnostics and Therapeutics Development College of Pharmaceutical ScienceSoochow University

Carbon monoxide（CO） has recently been well-established as a promising therapeutic modality against cancer. The development of transition-metal-free and tumor-targeted delivery platforms for CO is highly demanded but remains very sporadic. Herein, we developed a polyprodrug system for the co-delivery of CO and a chemotherapeutic agent combretastin A-4（CA-4） to the tumor site based on a chemiexcitation mechanism. Such a poly-prodrug successfully achieved the co-activation of CO and CA-4 in response to H2O2at the tumor site both in vitro and in vivo. Importantly, a synergist effect between CO and CA-4 was observed in suppressing tumor growth in a mouse tumor model. It is anticipated that such a poly-prodrug system could be potentially adapted for the co-delivery of CO and another drug payload for combinational therapy for other indications.

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EZH2-dependent myelination following sciatic nerve injury

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Neural Regeneration research 2025年第8期20卷 2382-2394页

作者： Hui Zhu Li Mu Xi Xu Tianyi Huang Ying Wang Siyuan Xu Yiting Wang Wencong Wang Zhiping Wang Hongkui Wang Chengbin Xue research center of Clinical Medicine Affiliated Hospital of Nantong UniversityKey Laboratory of Neuroregeneration of Jiangsu and Ministry of EducationCo-innovation Center of NeuroregenerationNMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology ProductsNantong UniversityNantongJiangsu ProvinceChina Medical School of Nantong University NantongJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Rehabilitation Medicine Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Department of Critical Care Medicine Nantong Fourth People’s HospitalNantongJiangsu ProvinceChina

Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve ***,the gene regulatory network of regenerated myelin differs from that of native *** of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in *** further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were *** results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain *** highlights the crucial role of Ezh2 in initiating Schwann cell ***,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type *** suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and *** conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve *** EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.

关键词： demyelination EZH2 myelination peripheral nerve injury PRC2 remyelination Schwann cells sciatic nerve crush sciatic nerve transection

Mechanistic insight into the synergy between nickel single atoms and nanoparticles on N-doped carbon for electroreduction of CO2

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Journal of Energy Chemistry 2025年第1期100卷 327-336页

作者： Mingdong Sun Wenwen Guan Cailing Chen Chao Wu Xiaoling Liu Biao Meng Tao Chen Yu Han Jun Wang Shibo Xi Yu Zhou State Key Laboratory of Materials-Oriented Chemical engineering College of Chemical Engineering Nanjing Tech University Advanced Membranes and Porous Materials center Physical Sciences and Engineering Division King Abdullah University of Science and Technology Institute of Sustainability for Chemicals Energy and Environment A*STAR (Agency for Science Technology and Research) College of Materials Science and engineering Sichuan University

The synergy of single atoms （SAs） and nanoparticles （NPs） has demonstrated great potential in promoting the electrocatalytic carbon dioxide reduction reaction （CO2RR）;however,the rationalization of the SAs/NPs proportion remains one challenge for the catalyst ***,a Ni2+-loaded porous poly（ionic liquids）(PIL) precursor synthesized through the free radical self-polymerization of the ionic liquid monomer,1-allyl-3-vinylimidazolium chloride,was pyrolyzed to prepare the Ni,N co-doped carbon materials,in which the proportion of Ni SAs and NPs could be facilely modulated by controlling the annealing *** catalyst Ni-NC-1000 with a moderate proportion of Ni SAs and NPs exhibited high efficiency in the electrocatalytic conversion of CO2into *** Ni K-edge X-ray absorption near-edge structure （XANES） spectra and theoretical calculations were conducted to gain insight into the synergy of Ni SAs and *** charge transfer from Ni NPs to the surrounding carbon layer and then to the Ni SAs resulted in the electron-enriched Ni SAs active *** the electroreduction of CO2,the coexistence of Ni SAs and NPs strengthened the CO2activation and the affinity towards the key intermediate of*COOH,lowering the free energy for the potential-determining*CO2→*COOH step,and therefore promoted the catalysis efficiency.

关键词： Activation energy

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine center of Tissue engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

engineering N3C vacancies in hierarchical porous carbon nitride nanosheets for room temperature ultradeep photocatalytic aerobic oxidative desulfurization

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Science China Chemistry 2025年

作者： Yina Nie Weijie Yang Xin Wang Xiang Li Lele Wei Xiaolin Bai Lin Liu Feng Fu Jun Wan College of Chemistry & Chemical engineering Research Institute of Comprehensive Energy Industrial Technology Shaanxi Key Laboratory of Chemical Reaction Engineering Yan'an University Anhui engineering research center of Carbon Neutrality College of Chemistry and Materials Science Anhui Normal University

The production of ultra-low sulfur clean fuels holds global significance for improving energy efficiency and reducing environmental pollution. Photocatalytic aerobic oxidative desulfurization（PODS） offers an attractive approach to efficiently remove refractory heterocyclic aromatic sulfur compounds under mild conditions. However, the sluggish charge dynamics,insufficient molecule activation, and slow mass transfer within photocatalysts restrict the overall desulfurization efficiency,hindering the widespread application of this technology. Herein, we developed a defective g-C3N4（M1U3CN） photocatalyst with bridged N3Cvacancies and hierarchical porous structures to address these limitations. This catalyst not only demonstrates outstanding dibenzothiophene（DBT） removal efficiency of 99.6% for model oil with high conversion and selectivity but also achieves complete sulfur removal from gasoline as well as 96.7% sulfur removal for distilled diesel at room temperature,successfully achieving ultradeep aerobic oxidative desulfurization. The introduction of rich N3Cvacancies and abundant micromeso-macroporous distribution in M1U3CN enhances kinetic efficiencies by promoting charge carrier separation, mass transfer,and molecular activation simultaneously; resulting in exceptional PODS performance. This work provides a collaborative strategy to overcome kinetic challenges in aerobic oxidative desulfurization via defect and structural engineering of the catalyst.

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PD-YOLO:Colon Polyp Detection Model Based on Enhanced Small-Target Feature Extraction

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Computers, Materials & Continua 2025年第1期82卷 913-928页

作者： Yicong Yu Kaixin Lin Jiajun Hong Rong-Guei Tsai Yuanzhi Huang New engineering Industry College Putian UniversityPutian351100China engineering research center of Big Data Application in Private Health Medicine(Putian University) Fujian Province UniversityPutian351100China Computer College Guangdong University of Science&TechnologyDongguan523668China

In recent years,the number of patientswith colon disease has increased *** polyps are the precursor lesions of colon *** not diagnosed in time,they can easily develop into colon cancer,posing a serious threat to patients’lives and health.A colonoscopy is an important means of detecting colon ***,in polyp imaging,due to the large differences and diverse types of polyps in size,shape,color,etc.,traditional detection methods face the problem of high false positive rates,which creates problems for doctors during the diagnosis *** order to improve the accuracy and efficiency of colon polyp detection,this question proposes a network model suitable for colon polyp detection(PD-YOLO).This method introduces the self-attention mechanism CBAM(Convolutional Block Attention Module)in the backbone layer based on YOLOv7,allowing themodel to adaptively focus on key information and ignore the unimportant *** help themodel do a better job of polyp localization and bounding box regression,add the SPD-Conv(Symmetric Positive Definite Convolution)module to the neck layer and use deconvolution instead of *** results indicate that the PD-YOLO algorithm demonstrates strong robustness in colon polyp *** to the original YOLOv7,on the Kvasir-SEG dataset,PD-YOLO has shown an increase of 5.44 percentage points in AP@0.5,showcasing significant advantages over other mainstream methods.

关键词： Polyp detection YOLOv7 SPD-Conv CBAM deconvolution

Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina Henan Medical Key Laboratory for research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical center of Tissue engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells