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Microglia lactylation in relation to central nervous system diseases

Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang school of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(spine surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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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

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Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu Department of spinal surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijingChina Department of Orthopedic surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin Dong Dan Zou Zhijun Yang Lili Guo Ruxiang Xu Department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurosurgery Chinese PLA General HospitalBeijingChina Department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and *** previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological ***,the mechanism of CXCR4 upregulation in induced neural stem cells remains *** this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 ***,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial *** agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury ***,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head *** conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neura

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

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Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3

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Oncology research 2025年第1期33卷 103-121页

作者： Yan Lu Kang Wang Yuanhong Peng Meng Chen Lin Zhong Luji Huang F U Cheng Xindan sheng Xin Yang Manzhao Ouyang George A Calin Zhiwei He China-America Cancer Research Institute Guangdong Medical University Dongguan 523808 China. GCP Center Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China. Department of Gastrointestinal surgery Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China. The second school of Clinical Medicine Southern Medical University Guangzhou 510080 China. Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA. Department of Oncology Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China.

Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays, which identified the specific action sites of interaction. The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR (qPCR). experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis. Additionally, the regulatory impact of hsa-miR-214-3p on B7H3 was examined. Enzyme-linked immunosorbent assays (ELIsA) and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells (PBMCs) on immune cells and associated cytokines.Results:In breast cancer tissues, the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p, as well as with the regulatory effects on breast cancercell behavior. Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3. Importantly, our research identified, for the first time, two binding sites for hsa-miR-214-3p on the 3' UTR of B7H3, both of which exert similar effects independently. Co-culture experime

关键词： B7H3 Breast cancer Hsa-miR-214-3p Immunotherapy

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Primary parenchymal squamous cell carcinoma of the kidney:A case report

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World Journal of Clinical Cases 2025年第4期13卷 34-40页

作者： Zhi-Hui Zheng Bo shao Chao-Min Xu Ke Wang Jia-Zhu Wen Li-Kang Luo Jia-Cheng Guan Department of Ultrasound The Second People’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina Department of Radiology Shulan(Quzhou)HospitalQuzhou 324000Zhejiang ProvinceChina Department of Radiology The Second People’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina Department of Pathology The Second people’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina

BACKGROUND Primary squamous cell carcinoma(sCC)of the renal parenchyma is extremely rare,with only nine cases *** sUMMARY This study reports a 51-year-old man with primary sCC of the renal *** patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross *** antigen(sCCA)levels were elevated,and imaging revealed a renal mass with associated *** patient underwent laparoscopic unilateral nephrectomy and lymph node *** pathology confirmed highly differentiated sCC with necrosis in the right renal parenchyma,with negative renal pelvis and *** pathological stage was *** months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena *** patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease *** We report a case of primary sCC of the renal parenchyma,a rare renal *** clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis *** to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum sCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

关键词： Renal tumor Renal parenchyma squamous cell carcinoma Renal calculi Computed tomography Case report

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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang Li Pengjun Wang Xiaoxu Zhang song Mao Yini Li Dongzhen Yu Xiaoyan Li Yazhi Xing Haibo shi shankai Yin Department of Otolaryngology Head and Neck surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

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Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang Department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China Cancer Research Center Beijing Chest HospitalBeijing 101149China Department of Thoracic surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation *** average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation *** The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

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The complex effects of miR-146a in the pathogenesis of Alzheimer's disease

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Neural Regeneration Research 2025年第5期20卷 1309-1323页

作者： Yunfan Long Jiajia Liu Yu Wang Haidong Guo Guohong Cui Department of Neurology Shanghai No.9 People’s HospitalShanghai Jiaotong University School of MedicineShanghaiChina Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina school of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Neurology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral *** plaques formed through the extracellular deposition of amyloid-βproteins,as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins,comprise two typical pathological features of Alzheimer's *** symptomatic treatment,there are no effective therapies for delaying Alzheimer's disease ***(miR)are small,non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological ***,miR-146a,a NF-κB-regulated gene,has been extensively implicated in the development of Alzheimer's disease through several *** has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this *** R-146a is believed to reduce amyloid-βdeposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway;however,there is also evidence supporting that it can promote these processes through many other pathways,thus exacerbating the pathological manifestations of Alzheimer's *** has been widely reported that miR-146a mediates synaptic dysfunction,mitochondrial dysfunction,and neuronal death by targeting m RNAs encoding synapticrelated proteins,mitochondrial-related proteins,and membrane proteins,as well as other *** the impact on glial cells,miR-146a also exhibits differential *** one hand,it causes widespread and sustained inflammation through certain pathways,while on the other hand,it can reverse the polarization of astrocytes and microglia,alleviate neuroinflammation,and promote oligodendrocyte progenitor cell differentiation,thus maintaining the normal function of the myelin sheath and exerting a protective effect on *** this review,we provide a

关键词： Alzheimer's disease amyloid-β glial cells microRNAs miR-146a neuroinflammatory

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Pharmacological targeting cGAs/sTING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(spine surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina school of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAs/sTING/NF-κB ***,we found that targeting the cGAs/sTING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAs/sTING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAs/sTING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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