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PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

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Neural Regeneration Research 2025年第10期20卷 2758-2775页

作者： Tianlong Liu Xiaolin Li Xiaowei Zhou wei chen Aidong Wen Minna Liu Yi Ding Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Pharmacy The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina Department of Pharmacy The 944 Hospital of Joint Logistics Support Forces of Chinese PLAJiuquanGansu ProvinceChina Department of Nephrology The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic *** a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from *** article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling *** key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic *** investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

关键词： apoptosis autophagy inflammation ischemic stroke neuroprotection oxidative stress pathogenesis phosphatidylinositol 3-kinase protein kinase B therapeutics

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan qi wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic Diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for Disease Control and Prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

A six-variable quasi-3D isogeometric approach for free vibration of functionally graded graphene origami-enabled auxetic metamaterial plates submerged in a fluid medium

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 157-176页

作者： wei chen Zhihong TANG Yufen LIAO Linxin PENG College of Civil Engineering University of South China College of Civil Engineering and Architecture Guangxi University Key Laboratory of Disaster Prevention and Structural Safety of Ministry of Education Guangxi University

This paper presents, for the first time, an effective numerical approach based on the isogeometric analysis(IGA) and the six-variable quasi-three dimensional(3D)higher-order shear deformation theory(HSDT) to study the free vibration characteristics of functionally-graded(FG) graphene origami(GOri)-enabled auxetic metamaterial(GOEAM) plates submerged in a fluid medium. The plate theory incorporates the thickness stretching and the effects of transverse shear deformation without using any shear correction factors. The velocity potential function and Bernoulli's equation are used to derive the hydrodynamic pressure acting on the plate surface. Both horizontally and vertically immersed plate configurations are considered here in the form of inertia *** plates are composed of multilayer GOEAMs, with the GOri content varying through the plate's thickness in a layer-wise manner. This design results in graded auxetic *** material properties are evaluated by mixing rules and a genetic programming(GP)-assisted micromechanical model. The governing equations of motion for the FG-GOEAM plates immersed in a fluid medium are derived by Hamilton's principle. After validating the convergence and accuracy of the present model, a comprehensive parametric study is carried out to examine the effects of the GOri content, GOri distribution pattern, GOri folding degree, fluid level, immersed depth, and geometric parameter on the natural frequencies of the FG-GOEAM plates. The results show that the natural frequencies for the four GOri distribution patterns increase with the increase in the layer number when the lay number is fewer than 10, and then stabilize after the layer number reaches ***, in general, the natural frequency of the FG-GOEAM plate in a vacuum or fluid increases when the GOri content increases, while decreases when the GOri folding degree increases. Some additional findings related to the numerical results are presented in the conclusions. It is belie

关键词： Equations of motion

Achieving ultralow leakage current in Schottky-MIS cascode anode lateral field-effect diode based on AlGaN/GaN HEMT

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Science China(Information Sciences) 2025年第1期68卷 379-385页

作者： Fangzhou WANG Changhong GAO Guojian DING cheng YU Zhuocheng WANG Xiaohui WANG qi FENG Ping YU Peng ZUO Wanjun chen Yang WANG Haiqiang JIA Hong chen Bo ZHANG Zeheng WANG Songshan Lake Materials Laboratory School of Microelectronics Southern University of Science and Technology State Key Laboratory of Electronic Thin Films and Integrated Devices University of Electronic Science and Technology of China Manufacturing Commonwealth Scientific and Industrial Research Organisation

In this paper,we design and fabricate a Schottky-metal-insulator-semiconductor（MIS） cascode anode GaN lateral field-effect diode（CA-LFED） to achieve ultralow reverse leakage current(ILEAK).The device based on AlGaN/GaN highelectron-mobility-transistor（HEMT） includes a normally-off MIS-controlled channel that is cascoded with a high barrier height Schottky *** reverse bias,the high electric-field is effectively prevented by the normally-off MIS-controlled channel *** with the high barrier height Schottky contact,this feature significantly suppresses the *** by the device fabrication,the CA-LFED with high breakdown voltage（BV）>600 V shows an ultralow ILEAKof 3.6×10-9A/mm as well as a low forward voltage drop（VF） of 2.2 *** performance suggests that the CA-LFED can be a promising candidate for ultralow ILEAKand better VF-ILEAKtrade-off GaN power diode applications.

关键词： Schottky-MIS cascode anode lateral field-effect diode (LFED) ultralow reverse leakage current ($I_{\rm{LEAK}}$) forward drop and reverse leakage trade-off AlGaN/GaN HEMTs

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From waste to wealth:Coal tar residue derived carbon materials as low-cost anodes for potassium-ion batteries

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 464-475页

作者： Zhonghua Lu Jun Shen Xin Zhang Lingcong Chao Liang chen Ding Zhang Tao wei Shoudong Xu College of Chemical Engineering and Technology Taiyuan University of TechnologyTaiyuan 030024China College of Chemistry Taiyuan University of TechnologyTaiyuan 030024China School of Chemical Engineering and Pharmacy Wuhan Institute of TechnologyWuhan 430205China School of Energy and Power Jiangsu University of Science and TechnologyZhenjiang 212003China

Carbon materials are widely recognized as highly promising electrode materials for various energy storage system *** tar residues(CTR),as a type of carbon-rich solid waste with high value-added utilization,are crucially important for the development of a more sustainable *** this study,we employed a straightforward direct carbonization method within the temperature range of 700-1000℃to convert the worthless solid waste CTR into economically valuable carbon materials as anodes for potassium-ion batteries(PIBs).The effect of carbonization temperature on the microstructure and the potassium ions storage properties of CTR-derived carbons(CTRCs)were systematically explored by structural and morphological characterization,alongside electrochemical performances *** on the co-regulation between the turbine layers,crystal structure,pore structure,functional groups,and electrical conductivity of CTR-derived carbon carbonized at 900℃(CTRC-900H),the electrode material with high reversible capacity of 265.6m Ah·g^(-1)at 50 m A·g^(-1),a desirable cycling stability with 93.8%capacity retention even after 100 cycles,and the remarkable rate performance for PIBs were ***,cyclic voltammetry(CV)at different scan rates and galvanostatic intermittent titration technique(GITT)have been employed to explore the potassium ions storage mechanism and electrochemical kinetics of *** indicate that the electrode behavior is predominantly governed by surface-induced capacitive processes,particularly under high current densities,with the potassium storage mechanism characterized by an“adsorption-weak intercalation”*** work highlights the potential of CTR-based carbon as a promising electrode material category suitable for high-performance PIBs electrodes,while also provides valuable insights into the new avenues for the high value-added utilization of CTR.

关键词： coal tar residue carbon materials anode potassium-ion batteries high value-added

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li weiwei Lin Zhihua Han Beijie qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

Depression mechanism of sulfite ions on sphalerite and Pb^(2+)activated sphalerite in the flotation separation of galena from sphalerite

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 335-345页

作者： Feng Zhang chenyang Zhang Linlin Wu wei Sun Hongliang Zhang Jianhua chen Yong Pei Songjiang Li Engineering Research Center of Ministry of Education for Carbon Emission Reduction in Metal Resource Exploitation and Utilization Hunan International Joint Research Center for Efficient and Clean Utilization of Critical Metal Mineral ResourcesSchool of Minerals Processing and BioengineeringCentral South UniversityChangsha 410083China State Key Laboratory of Mineral Processing Beijing General Research Institute of Mining&MetallurgyBeijing 100160China Hunan Provincial Key Laboratory of Micro&Nano Materials Interfaces Science College of Chemistry and Chemical EngineeringCentral South UniversityChangsha 410083China School of Resources Environment and MaterialsGuangxi UniversityNanning 530004China Department of Chemistry Xiangtan UniversityXiangtan 411105China China Railway Resource Group Co.Ltd Beijing 102300China

The depression mechanism of sulfite ions on sphalerite and Pb^(2+)activated sphalerite in the flotation separation of galena from sphalerite still lacked in-depth ***,the depression mechanism of sulfite ions on sphalerite and Pb^(2+)activated sphalerite in the flotation separation of galena from sphalerite was further systematically investigated with experiments and density functional theory(DFT)*** X-ray photoelectric spectroscopy(XPS)results,DFT calculation results,and frontier molecular orbital analysis indicated that sulfite ions were difficult to be adsorbed on sphalerite surface,suggesting that sulfite ions achieved depression effects on sphalerite through other non-adsorption ***,the oxygen content in the surface of sphalerite treated with sulfite ions in creased,which enhanced the hydrophilicity of the sphalerite and further increased the difference in hydrophilicity between sphalerite and ***,sulfite ions were chelated with lead ions to form PbSO_(3)in *** hydrophilic PbSO_(3)was more easily adsorbed on sphalerite than *** interaction between sulfite ions and lead ions could effectively inhibit the activation of *** addition the UV spectrum showed that after adding sulfite ions,the peak of perxanthate in the sphalerite treated xanthate solution was significantly stronger than that in the galena with xanthate solution,indicating that xanthate interacted more readily with sulfite ions and oxygen mo lecules within the sphalerite system,leading to the formation of ***,sulfite ions hardly depressed the flotation of ga lena and could promote the flotation of galena to some *** study deepened the understanding of the depression mechanism o sulfite ions on sphalerite and Pb^(2+)activated sphalerite.

关键词： sphalerite galena sulfite ion density functional theory depression mechanism

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge wei Xilei Liu Dai Li Xiaoqi Pang Fanglian chen Hailong Cao Ping Lei Haihe Laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

温度调控对人参皂苷积累及其关键酶基因表达的影响

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中草药 2020年第19期51卷 5035-5040页

作者：张涛王冠张维维陈湘张庆贺刘芳馨李卓然齐伟辰长春中医药大学药学院吉林长春130117

目的探究温度调控对人参皂苷积累及其合成途径关键酶基因表达量的影响。方法以培养23 d人参愈伤组织为实验材料,置于5、10、15、20、25、30℃6个培养箱中恒温培养,每天取样1次连续取样8 d,测定干、鲜质量和皂苷含量,确定响应敏感温度,以... 详细信息

目的探究温度调控对人参皂苷积累及其合成途径关键酶基因表达量的影响。方法以培养23 d人参愈伤组织为实验材料,置于5、10、15、20、25、30℃6个培养箱中恒温培养,每天取样1次连续取样8 d,测定干、鲜质量和皂苷含量,确定响应敏感温度,以GAPDH为内参基因,real-timePCR检测皂苷合成途径中9个关键酶3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR2)、法尼基焦磷酸合成酶(FPS)、角鲨烯合成酶(SS1)、角鲨烯环氧酶(SE1)、达玛烷二醇合成酶(DS-Ⅱ)、β-香树素合成酶(PNY1)、β-香树素C-28位羟基化酶(CYP716A52v2)、原人参三醇合成酶(CYP716A53v2)、原人参二醇合成酶(CYP716A47)基因表达量。结果 20℃为人参愈伤组织干、鲜质量积累最佳温度,5、10、15℃皂苷含量2~3 d达到最大值,5℃为人参皂苷积累响应敏感温度,与对照组差异显著,人参皂苷Re、Rg1和总皂苷分别为对照组1.93、11.93和1.54倍。HMGR2、SS1、DS-Ⅱ、SE1和CYP716A52v2基因表达量在低温2~4d均达最大值,为对照组2.8、1.6、3.5、3.7和3.8倍。相关性分析发现SE1与人参皂苷Re、Rg1和总皂苷呈显著正相关关系。结论适度的低温有利于人参皂苷的快速积累,SS1、DS-Ⅱ、SE1、HMGR2、CYP716A52v2为响应低温的关键基因,在人参皂苷生物合成抵御低温的过程中发挥重要作用。

关键词：温度人参皂苷Re 人参皂苷Rg1 基因表达量相关性