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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Orthopedic Surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

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中国组织工程研究 2025年第17期29卷 3537-3547页

作者： Yu Yangyi Song Zhuoyue Lian Qiang Ding Kang Li Guangheng shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration Division of Adult Joint Reconstruction and Sports MedicineDepartment of Orthopedic SurgeryShenzhen People’s Hospital(The Second Clinical Medical College Jinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020Guangdong ProvinceChina Department of Orthopedics Zhengzhou Orthopedics HospitalZhengzhou 450000Henan ProvinceChina Department of Orthopedics Shenzhen Pingle Orthopedics HospitalShenzhen 518000Guangdong ProvinceChina

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent ***,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory *** studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage ***:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis ***:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were *** efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into *** experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 *** were collected at 4,12,and 24 weeks *** staining,including safranin O and Alcian blue,was applied after collecting articular ***,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in *** AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis *** cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal *** either p65shRNA or BMP4

关键词： osteoarthritis adeno-associated virus bone morphogenetic protein 4 p65-short hairpin RNA gene therapy short hairpin RNA transforming growth factor-β1 extracellular matrix articular cartilage chondrocytes.

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

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Neural Regeneration Research 2025年第11期20卷 3302-3316页

作者： Yali Chen Yiyong Wei Jin Liu Tao Zhu Cheng Zhou Donghang Zhang Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Laboratory of Anesthesia and Critical Care Medicine National-Local Joint Engineering Research Center of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)ShenzhenGuangdong ProvinceChina Department of Anesthesiology Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative *** cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous *** the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal ***,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal *** explore the conservation and divergence across species,we compared these findings with those from *** the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic *** the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,*** comparative results revealed substantial heterogeneity in all glial cell types between humans and ***,we detected sex differences in gene expression in human spinal cord glial ***,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in *** all microglial subtypes,all differentially expressed genes were located on the sex *** addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in ***,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for explo

关键词： astrocyte glial cell human microglia oligodendrocyte sex differentiation single-nucleus RNA sequencing spatial transcriptomics species variation spinal cord

Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

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Science China Life Sciences 2025年第1期 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive Medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive Medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

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Deciphering the molecular mechanisms of Simiaowan in the treatment of hyperuricemia: in vivo and in silico approaches

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Traditional Medicine Research 2025年第2期10卷 37-54页

作者： Yong-Chang Zeng Jun-Hong Wu Dan-Dan Xu Kang He Chang-Qing Liu Li-Fei Song Zheng-Zhi Wu Qian-Qian Jiang Shao-Yu Liang Department of Neurology The First Affiliated Hospital of Shenzhen UniversityShenzhen 518020China Pharmaceutical Department The Affiliated TCM Hospital of Guangzhou Medical UniversityGuangzhou 510000China School of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang 550025China Guangzhou Zeli Medical Technology Co. Ltd.Guangzhou 510700China

Background:Simiaowan(SMW),a well-known traditional Chinese medicine,has been employed to treat hyperuricemia(HUA)and gout for ***,the bioactive components and underlying mechanisms have not been *** objective of this study was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation,serum pharmacochemistry,network pharmacology and molecular ***:HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were used to evaluate the pharmacodynamic effects of ***-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing *** pharmacology and molecular docking were utilized to elucidate the potential targets and underlying ***:SMW effectively ameliorated HUA rats via the inhibition of uric acid(UA)production,promotion of UA excretion,improvement of lipid and glucose metabolic abnormalities,antioxidant,anti-inflammatory and anti-insulin resistance effects.A total of 73 compounds detected in SMW-containing serum were identified as potential active components,with alkaloids,flavonoids,organic acids,and terpenoids emerging as the primary active *** 203 corresponding targets were obtained as SMW anti-HUA/gout targets,which mainly participated in apoptosis,insulin resistance,TNF,PI3K-Akt,HIF-1,NF-κB,MAPK,IL-17 and TLR signaling *** docking indicated that active compounds(***,phellodendrine,quercetin,formononetin,ferulic acid)had superior binding abilities to the key targets(*** carrier family 22 member 12(URAT1),solute carrier family 22 member 6(OAT1),ATP-binding cassette sub-family G member 2(ABCG2),solute carrier family 2,facilitated glucose transporter member 9(GLUT9),xanthine dehydrogenase/oxidase(XDH),transcription factor p65(RELA),toll-like receptor 4(TLR4),prostaglandin G/H synthase 2(PTGS2),caspase-3(CASP3),insulin(INS)).Conclusion:S

关键词： hyperuricemia network pharmacology serum pharmacochemistry Simiaowan UPLC-Q-Exactive-MS/MS

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

Assessing healthcare workers’knowledge and confidence in the diagnosis,management and prevention of Monkeypox

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World Journal of Clinical Cases 2025年第1期13卷 38-47页

作者： Epipode Ntawuyamara Thierry Ingabire Innocent Yandemye Polycarpe Ndayikeza Bina Bhandari Yan-Hua Liang Department of Dermatology Cosmetology and VenereologyShenzhen Hospital of Southern Medical UniversityShenzhen 518101Guangdong ProvinceChina Department of Dermatology and Venereology Kamenge Teaching HospitalUniversity of BurundiBujumbura 1020Burundi Department of Infectious Diseases Kamenge Teaching HospitalUniversity of BurundiBujumbura 1020Burundi General Directorate of Healthcare Supply Modern and Traditional MedicineNutrition and RegistrationMinistry of Public Health and Fight Against HIV/AIDSBujumbura 1055Burundi Department of Epidemiology National Institute of Public HealthBujumbura 350Burundi General Directorate of Planification Ministry of Public Health and Fight Against HIV/AIDSBujumbura 1055Burundi

BACKGROUND Monkeypox(Mpox),is a disease of global public health concern,as it does not affect only countries in western and central *** To assess Burundi healthcare workers(HCWs)s’level of knowledge and confidence in the diagnosis and management of *** We conducted a cross-sectional study via an online survey designed mainly from the World Health Organization course distributed among Burundi HCWs from June-July *** questionnaire comprises 8 socioprofessional-related questions,22 questions about Mpox disease knowledge,and 3 questions to assess confidence in Mpox diagnosis and *** data were analyzed via SPSS software version 25.0.A P value<0.05 was considered to indicate statistical *** The study sample comprised 471 HCWs who were mainly medical doctors(63.9%)and nurses(30.1%).None of the 22 questions concerning Mpox knowledge had at least 50%correct responses.A very low number of HCWs(17.4%)knew that Mpox has a *** confidence level to diagnose(21.20%),treat(18.00%)or prevent(23.30%)Mpox was low among *** confidence level in the diagnosis of Mpox was associated with the HCWs’age(P value=0.009),sex(P value<0.001),work experience(P value=0.002),and residence(P value<0.001).The confidence level to treat Mpox was significantly associated with the HCWs’age(P value=0.050),sex(P value<0.001),education(P value=0.033)and occupation(P value=0.005).The confidence level to prevent Mpox was associated with the HCWs’education(P value<0.001),work experience(P value=0.002),residence(P value<0.001)and type of work institution(P value=0.003).CONCLUSION This study revealed that HCWs have the lowest level of knowledge regarding Mpox and a lack of confidence in the ability to diagnose,treat or prevent *** is an urgent need to organize continuing medical education programs on Mpox epidemiology and preparedness for Burundi *** encourage future researchers to assess potential hesitancy toward Mpox vaccination and its asso

关键词： Monkeypox Public health emergency of international concern Healthcare workers Epidemic Preparedness Knowledge Confidence

Probes and nano-delivery systems targeting NAD(P)H:quinone oxidoreductase 1:a mini-review

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Frontiers of Chemical Science and Engineering 2023年第2期17卷 123-138页

作者： Xuewen Mu Yun Xu Zheng Wang Dunyun Shi School of Pharmaceutical Science&Technology Tianjin UniversityTianjin 300072China Central Lab Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen UniversityShenzhen 518035China Institute of Hematology Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen UniversityShenzhen 518035China

The two-electron cytoplasmic reductase NAD(P)H:quinone oxidoreductase 1 is expressed in many ***(P)H:quinone oxidoreductase 1 is well-known for being highly expressed in most ***,it could be a target for cancer *** it is a quinone reductase,many bioimaging probes based on quinone structures target NAD(P)H:quinone oxidoreductase 1 to diagnose *** expression is higher in tumours than in normal tissues,and using target drugs such asβ-lapachone to reduce side effects in normal tissues can ***,the physicochemical properties ofβlapachone limit its *** problem can be solved by using nanosystems to deliverβ-*** minireview summarizes quinone-based fluorescent,nearinfrared and two-photon fluorescent probes,as well as nanosystems for delivering the NAD(P)H:quinone oxidoreductase 1-activating drugβ-*** review provides valuable information for the future development of probes and nano-delivery systems that target NAD(P)H:quinone oxidoreductase 1.

关键词： NAD(P)H:quinone oxidoreductase 1 cancer therapy target probe nanosystem

Hydroxyl radical-involved cancer therapy via Fenton reactions

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Frontiers of Chemical Science and Engineering 2022年第3期16卷 345-363页

作者： Mengying Liu Yun Xu Yanjun Zhao Zheng Wang Dunyun Shi School of Pharmaceutical Science&Technology Tianjin UniversityTianjin300072China Central Lab Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen UniversityShenzhen518035China Institute of Hematology Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen UniversityShenzhen518035China

The tumor microenvironment features over-expressed hydrogen peroxide(H_(2)O_(2)).Thus,versatile therapeutic strategies based on H_(2)O_(2) as a reaction substrate to generate hydroxyl radical(•OH)have been used as a prospective therapeutic method to boost anticancer ***,the limited Fenton catalysts and insufficient endogenous H_(2)O_(2) content in tumor sites greatly hinder•OH production,failing to achieve the desired therapeutic ***,supplying Fenton catalysts and elevating H_(2)O_(2) levels into cancer cells are effective strategies to improve•OH *** therapeutic strategies are systematically discussed in this ***,the challenges and future developments of hydroxyl radical-involved cancer therapy are discussed to improve therapeutic efficacy.

关键词： hydroxyl radical Fenton catalyst hydrogen peroxide cancer therapy