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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing hai-Dong Qian Qiao gao Sheng-Lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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

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

Simulation of three-phase flow and lance height effect on the cavity shape

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International Journal of Minerals,Metallurgy and Materials 2014年第6期21卷 523-530页

作者： Kai Dong Rong Zhu Wei gao fu-hai Liu School of Mechanical Engineering University of Science and Technology Beijing School of Metallurgical and Ecological Engineering University of Science and Technology Beijing Beijing Shougang Design Institute

A three-dimensional computational fluid dynamics （CFD） model was developed to simulate a 150-t top-blown converter. The ef-fect of different lance heights on the cavity shape was investigated using the volume of fluid （VOF） method. Numerical simulation results can reflect the actual molten bath surface waves impinged by the supersonic oxygen jets. With increasing lance height, the cavity depth de-creases, and the cavity area, varying like a parabola, increases and then decreases. The cavity area maximizes at the lance height of 1.3 m. Under the three different lance heights simulated in this study, all of the largest impact velocities at the molten bath surface are between 50 m/s and 100 m/s.

关键词： metallurgical furnaces basic oxygen converters lance height cavity shape computational fluid dynamics computer simulation

A linear complementarity model for multibody systems with frictional unilateral and bilateral constraints

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Acta Mechanica Sinica 2011年第4期27卷 587-592页

作者： hai-Ping gao Qi Wang Shi-Min Wang Li fu Department of dynamics and control Beihang University 100191 Beijing China

The Lagrange-I equations and measure differential equations for multibody systems with unilateral and bilateral constraints are constructed. For bilateral constraints, frictional forces and their impulses contain the products of the filled-in relay function induced by Coulomb friction and the absolute values of normal constraint reactions. With the time-stepping impulse-velocity scheme, the measure differential equations are discretized. The equations of horizontal linear complementarity problems （HLCPs）, which are used to compute the impulses, are constructed by decomposing the absolute function and the filled-in relay function. These HLCP equations degenerate into equations of LCPs for frictional unilateral constraints, or HLCPs for frictional bilateral constraints. Finally, a numerical simulation for multibody systems with both unilateral and bilateral constraints is presented.

关键词： Coulomb friction Bilateral constraint Unilat-eral constraint - Horizontal linear complementarity problem(HLCP) Time-stepping impulse-velocity algorithm

Numerical Analysis and Verification of the Gas Jet from Aircraft Engines Impacting a Jet Blast Deflector

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Chinese Journal of Mechanical Engineering 2018年第5期31卷 127-137页

作者： fu-Dong gao De-Xin Wang hai-Dong Wang Ming-Ming Jia Department of Carrier Aviation Security and Station Management Naval Aeronautical University

The process of the gas jet from aircraft engines impacting a jet blast deflector is not only a complex fluid–solid coupling problem that is not easy to compute, but also a safety issue that seriously interferes with flight deck envi?ronment. The computational fluid dynamics(CFD) method is used to simulate numerically the impact e ect of gas jet from aircraft engines on a jet blast deflector by using the Reynolds?averaged Navier?Stokes(RANS) equations and turbulence models. First of all, during the pre?processing of numerical computation, a sub?domains hybrid meshing scheme is adopted to reduce mesh number and improve mesh quality. Then, four di erent turbulence models includ?ing shear?stress transport(SST) k-w, standard k-w, standard k-ε and Reynolds stress model(RSM) are used to compare and verify the correctness of numerical methods for gas jet from a single aircraft engine. The predicted values are in good agreement with the experimental data, and the distribution and regularity of shock wave, velocity, pressure and temperature of a single aircraft engine are got. The results show that SST k?w turbulence model is more suitable for the numerical simulation of compressible viscous gas jet with high prediction accuracy. Finally, the impact e ect of gas jet from two aircraft engines on a jet blast deflector is analyzed based on the above numerical method, not only the flow parameters of gas jet and the interaction regularity between gas jet and the jet blast deflector are got, but also the thermal shock properties and dynamic impact characteristics of gas jet impacting the jet blast deflector are got. So the dangerous activity area of crew and equipments on the flight deck can be predicted qualitatively and quantitatively. The proposed research explores out a correct numerical method for the fluid–solid interaction during the impact process of supersonic gas jet, which provides an e ective technical support for design, thermal ablation and structural damage analysis

关键词： Aircraft engine Gas jet Computational fluid dynamics Jet blast deflector Impact effect

Climate change projection over the Tibetan Plateau based on a set of RCM simulations

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Advances in Climate Change Research 2021年第3期12卷 313-321页

作者： fu Yuan-hai gao Xue-Jie ZHU Ying-Mo GUO Dong Climate Change Research Center Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing100029China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science&TechnologyNanjing210044China University of Chinese Academy of Sciences Beijing100049China Department of Atmospheric Sciences Yunnan UniversityKunming650504China

Tibetan Plateau(TP,with the height>3000 m)is a region with complex topographical features and a large diversity of climate both in space and *** use of higher resolution regional climate models(RCMs)to downscale global climate model simulations is of high *** the present study,future climate change over TP and the surrounding areas is investigated based on the ensemble of a set of the 21st century climate change projections using the RCM *** model is driven by five different GCMs at a grid spacing of 25 km under *** focus is on the December—January-February(DJF),June-July-August(JJA),and annual mean temperature and precipitation,with comparisons against the driving GCMs also ***,the RegCM4 greatly improves the simulation by providing finer scale spatial details of both temperature and precipitation distributions over the *** topographic effects are well reproduced by RegCM4 but not the *** the projected future changes,general wanning and increase in precipitation are found in both GCM and RegCM4 ***,substantial differences exist in both the spatial distribution and magnitude of the *** added value of RegCM4 for temperature,in addition to the finer spatial details,is characterized by a more pronounced warming in DJF over TP compared to its surrounding *** projected changes of precipitation show also differences between RegCM4 and the driving *** increase of precipitation is more pronounced and over the basins in DJF for RegCM4,and in general with a better agreement across the simulations compared to the driving GCMs.

关键词： Climate change Regional climate model Tibetan plateau

人参皂苷 Rg3激活线粒体功能改善慢性疼痛的机制

维普期刊数据库评论

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维普期刊数据库

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中国药理学通报 2025年第1期41卷 94-100页

作者：张培根朱海丽高卉湖北科技学院医学部药学院湖北咸宁437100

目的探究人参皂苷Rg3在慢性神经性疼痛中的作用及机制。方法筛选并分析慢性神经性疼痛数据中前额叶皮层内差异性表达基因;小鼠随机分为假手术组、模型组及给药组;采用坐骨神经慢性压迫损伤模型构建神经病理性疼痛动物模型,腹腔注射人参... 详细信息

目的探究人参皂苷Rg3在慢性神经性疼痛中的作用及机制。方法筛选并分析慢性神经性疼痛数据中前额叶皮层内差异性表达基因;小鼠随机分为假手术组、模型组及给药组;采用坐骨神经慢性压迫损伤模型构建神经病理性疼痛动物模型,腹腔注射人参皂苷Rg3给药;记录小鼠痛觉行为变化;HE染色、尼氏染色、免疫印迹及免疫组化检测各组PFC脑组织神经和线粒体损伤情况;分子对接探究人参皂苷Rg3的作用靶点;Mito-Tracker检测线粒体膜电位;ATP试剂盒分析ATP含量。结果与假手术组相比,模型组小鼠表现为痛觉过敏和运动能力受损;PFC内神经及线粒体损伤(P<0.05)。与模型组相比,人参皂苷Rg3给药可增加小鼠机械痛阈值、热缩足潜伏期和转棒停留时间;同时降低PFC内炎性细胞、尼氏小体及Dnm1l阳性细胞数,下调c-Fos、IL-1β和Dnm1l蛋白表达水平(P<0.05)。分子对接显示人参皂苷Rg3可结合Dnm1l。在细胞水平,人参皂苷Rg3给药可升高线粒体膜电位和ATP含量(P<0.05)。结论人参皂苷Rg3可通过调控降低PFC内炎症因子和线粒相关蛋白表达,改善线粒体功能,缓解CCI小鼠痛觉过敏。

关键词：人参皂苷Rg3 慢性神经性疼痛线粒体前额叶皮层 CCI PFC

Hot Deformation Behavior and Flow Stress Prediction of Ultra Purified 17% Cr Ferritic Stainless Steel Stabilized with Nb and Ti

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Journal of Iron and Steel Research International 2015年第9期22卷 827-836页

作者： Fei gao fu-xiao YU hai-tao LIU Zhen-yu LIU School of Materials & Metallurgy Northeastern Unversity State Key Laboratory of Rolling and Automation Northeastern University

The hot deformation behavior of ultra purified 17% Cr ferritic stainless steel stabilized with Nb and Ti was investigated using axisymmetric hot compression tests on a thermomechanical *** deformation was carried out at the temperatures ranging from 700 to 1 100℃ and strain rates from 1to *** microstructure was investigated using electron backscattering *** effects of temperature and strain rate on deformation behavior were represented by Zener-Hollomon parameter in an exponent type *** effect of strain was incorporated in the constitutive equation by establishing polynomial relationship between the material constants and strain.A sixth order polynomial was suitable to represent the effect of *** modified constitutive equation considering the effect of strain was developed and could predict the flow stress throughout the deformation conditions except at800℃in 1s-1 and at 700℃in 5and *** the reliability of the modified constitutive equation was possibly ascribed to the increase in average Taylor factor at 800℃in 1s-1 and the increase in temperature at 700℃in 5and10s-1 during hot *** optimum window for improving product quality of the ferritic stainless steels was identified as hot rolling at a low finisher entry temperature of 700℃,which can be achieved in practical production.

关键词： 17%Cr ferritic stainless steel hot deformation flow stress constitutive equation strain compensation