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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

Three-dimensional fracture of UO2 ceramic pellets by phase field modeling

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 169-180页

作者： Wei Xiong Xuan ye Hongzhang Cheng Xiaoming Liu Institute of Nuclear and New Energy Technology Collaborative Innovation Center of Advanced Nuclear Energy Technology Key Laboratory of Advanced Reactor Engineering and Safety of Ministry of Education Tsinghua University State Key Laboratory of Nonlinear Mechanics Institute of Mechanics Chinese Academy of Sciences School of Engineering Science University of Chinese Academy of Sciences

Fracture is the primary failure type for the UO2ceramic pellets,which are operated under irradiation and thermal processes,and physically confined by the *** this work,by combining closely coupled physical processes of heat conduction,heat transfer,and mechanical deformation with the cohesive phase field framework,we proposed a high-precision modeling of quasistatic cracking of three-dimensional （3D） UO2ceramic fuel pellets under high temperature and *** simulation results agree well with the experimental results,indicating that the proposed method has the potential to capture 3D crack modes in the interested time ***,we studied the relation of the 3D fracture patterns of fuel pellets with the peak power *** was found that the power level plays a critical role in determining the competition between radial and circumferential cracks,as well as transverse penetrating cracks.

关键词： phase field method nuclear fuel pellet coupled thermo-mechanical model thermal fracture

Prussian Blue Analogue‑Templated Nanocomposites for Alkali‑Ion Batteries:Progress and Perspective

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Nano-Micro Letters 2025年第1期17卷 216-261页

作者： Jian‑En Zhou Yilin Li Xiaoming Lin Jiaye ye Key Laboratory of Theoretical Chemistry of Environment Ministry of EducationSchool of ChemistrySouth China Normal UniversityGuangzhou 510006People’s Republic of China School of Chemistry and Physics Faculty of ScienceQueensland University of Technology2 George StreetBrisbaneQLD 4000Australia Centre for Materials Science Queensland University of Technology2 George StreetBrisbaneQLD 4000Australia

Lithium-ion batteries(LIBs)have dominated the portable electronic and electrochemical energy markets since their commercialisation,whose high cost and lithium scarcity have prompted the development of other alkali-ion batteries(AIBs)including sodium-ion batteries(SIBs)and potassium-ion batteries(PIBs).Owing to larger ion sizes of Na^(+)and K^(+)compared with Li^(+),nanocomposites with excellent crystallinity orientation and well-developed porosity show unprecedented potential for advanced lithium/sodium/potassium *** enticing open rigid framework structures,Prussian blue analogues(PBAs)remain promising self-sacrificial templates for the preparation of various nanocomposites,whose appeal originates from the well-retained porous structures and exceptional electrochemical activities after thermal *** review focuses on the recent progress of PBA-derived nanocomposites from their fabrication,lithium/sodium/potassium storage mechanism,and applications in AIBs(LIBs,SIBs,and PIBs).To distinguish various PBA derivatives,the working mechanism and applications of PBA-templated metal oxides,metal chalcogenides,metal phosphides,and other nanocomposites are systematically evaluated,facilitating the establishment of a structure–activity correlation for these *** on the fruitful achievements of PBA-derived nanocomposites,perspectives for their future development are envisioned,aiming to narrow down the gap between laboratory study and industrial reality.

关键词： Prussian blue analogues Self-sacrificial template Lithium-ion batteries Sodium-ion batteries Potassium-ion batteries

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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Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

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Neural Regeneration Research 2025年第4期20卷 960-972页

作者： Kedong Zhu Hualong Wang Keqiang ye Guiqin Chen Zhaohui Zhang Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Neurology The First Hospital of Hebei Medical UniversityBrain Aging and Cognitive Neuroscience Laboratory of Heibei ProvinceShijiazhuangHebei ProvinceChina Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal *** profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic *** amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of *** findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative *** a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

关键词： Alzheimer’s disease axon guidance colorectal cancer Netrin-1 receptors Netrin-1 signaling pathways Netrin-1 neurodegenerative diseases neuron survival Parkinson’s disease UNC5C

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang Ji yezhong Wang Yingjia Li Yongyi ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

[Determination of 12 halogenated organic pollutants in edible fish by ultra performance liquid chromatography-high resolution mass spectrometry combined with ultrasound-assisted extraction and gel permeation chromatography purification]

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Se pu = Chinese journal of chromatography 2025年第1期43卷 68-77页

作者： Yi-Zhe Zhu rui-Fen Zheng Zi-Hao Fan Ling Liu Jing-Yao ye Kai Wang Cai-Ming Tang Research Center for Eco-Environmental Engineering Dongguan University of Technology Dongguan 523808 China. Guangdong Key Laboratory of Environmental Resources Utilization and Protection Guangzhou Institute of Geochemistry Chinese Academy of Sciences Guangzhou 510640 China.

Halogenated organic pollutants (HOPs) have attracted considerable attention owing to their persistence, bioaccumulation, and toxicity. The development of methods to detect HOPs in fish is challenging owing to the compositional complexity of fish matrices, which contain high levels of lipids and relatively low concentrations of HOPs. In addition, the lipophilicity of most HOPs renders their extraction difficult. Moreover, the simultaneous determination of multiple HOPs to achieve the high-throughput screening of these analytes is complex. In this study, a reliable and efficient pretreatment method based on ultrasound-assisted extraction, gel permeation chromatography purification, and ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was developed for the determination of 12 HOPs in edible fish. The procedures of sample extraction and purification and LC-HRMS detection parameters were optimized to improve the performance of the method. Fresh fish samples were thoroughly rinsed with water, and non-edible parts, including the skin, bones, and phosphorus, were removed. The fish were weighed, cut into small pieces, and vacuum freeze-dried for 48 h. Subsequently, a freeze grinder was used to grind the dried fish into a fine powder. Exactly 2 g of the fish powder was weighed, fortified with isotope-labeled internal standards of the HOPs, and allowed to stand for 5 min. Methanol-acetonitrile (1∶1, v/v) was then added, followed by vortex mixing and ultrasonication. After centrifugation, the supernatant was transferred to a fresh tube. The extraction process was repeated twice and all extracts were combined. The extract was evaporated under a gentle nitrogen flow and redissolved in a mixture of ethyl acetate-cyclohexane (1∶1, v/v). The sample mixture was cleaned using gel permeation chromatography, and the eluate was collected and concentrated under a nitrogen flow. Sample residuals were reconstituted with water-methanol (1∶1, v/v) prior to

关键词： edible fish gel permeation chromatography (GPC) halogenated organic pollutants (HOPs) ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS)

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor