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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

Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan Zhou Hongdong zhao ye Hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

Dynamically self-adjustable liquid-liquid and self-adaptive softcontact solid-solid triboelectric nanogenerator for wave energy harvesting

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Nano Research 2025年第1期18卷 404-414页

作者： yong Long Bingqi zhao Jianan Niu Yuxiu Liu Wei Sha Jiangwen Wang Zhong Lin Wang Weiguo Hu Guangzhou Institute of Blue Energy Knowledge CityHuangpu DistrictGuangzhou 510555China Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China School of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China

Water wave energy exhibits great potential toalleviate the global energy crisis. However, harvesting andutilizing wave energy are challenging due to its irregularity,randomness, and low frequency. Triboelectric nanogenerators(TENGs) have gained significant attention for harvesting waveenergy with high efficiency. This study presents a novelellipsoidal, pendulum-like TENG integrating both liquid-liquid(L-L) and solid-solid (S-S) triboelectricity (LS-TENG). Thisinnovative design enables continuous wave energy harvestingand self-powered marine environment monitoring under variousconditions, including temperature, humidity, and light intensity. The binary immiscible liquids within the LS-TENG’s innersoft balloon create dynamic, and self-adjustable L-L contact interfaces, significantly increasing the L-L contact area andenhancing L-L contact electrification (CE). The unique self-adaptive, soft S-S contact increases the S-S contact areacompared to traditional hard point contact, better adapting to the irregular movements of waves and promoting efficient S-SCE. The LS-TENG achieves highly efficient wave energy harvesting by coupling L-L and S-S CE. Furthermore, the uniquesoft contact design protects the S-S interfaces from mechanical wear and damage during long-term work. The LS-TENG’snovel structure provides an innovative and effective way for water wave energy harvesting.

关键词： self-adaptive soft-contact solid-solid liquid-liquid self-adjustable triboelectric nanogenerator

Novel Multinuclear Cyclophosphazene Complexes as Potent Promoters of Plasmid DNA（pUC19）Cleavage

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Novel Multinuclear Cyclophosphazene Complexes as Potent Prom...

The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

第六届全国化学生物学学术会议

作者： Le Wang,Junliang Yang,Yanhong Liang,Ruyi Zou,Libo Ma,yong ye~*,Yufen zhao~* Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province,Department of Chemistry, Zhengzhou University,Zhengzhou 450052,China

＜正＞The stability of phosphate diesters toward solvolytic cleavage is vitally tied to the biological roles of DNA and RNA as guardians of genetic information in all living *** the absence of an enzyme,phosphodiester linkages of DNA are very stable to *** the last several years,many complexes have been developed as artificial *** these systems,multi-nuclear complexes are particular attractive due to their potential cooperative effects between the metal centers.

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma Ke ye Xue zhao Fangliang Ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of Basic Medical Sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Basic Medical Institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

Understanding the local structure and thermophysical behavior of Mg-La liquid alloys via machine learning potential

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 439-449页

作者： Jia zhao Taixi Feng Guimin Lu National Engineering Research Center for Integrated Utilization of Salt Lake Resource East China University of Science and TechnologyShanghai 200237China Joint International Laboratory for Potassium and Lithium Strategic Resources East China University of Science and TechnologyShanghai 200237China

The local structure and thermophysical behavior of Mg-La liquid alloys were in-depth understood using deep potential molecular dynamic(DPMD) simulation driven via machine learning to promote the development of Mg-La alloys. The robustness of the trained deep potential(DP) model was thoroughly evaluated through several aspects, including root-mean-square errors(RMSEs), energy and force data, and structural information comparison results;the results indicate the carefully trained DP model is reliable. The component and temperature dependence of the local structure in the Mg-La liquid alloy was analyzed. The effect of Mg content in the system on the first coordination shell of the atomic pairs is the same as that of temperature. The pre-peak demonstrated in the structure factor indicates the presence of a medium-range ordered structure in the Mg-La liquid alloy, which is particularly pronounced in the 80at% Mg system and disappears at elevated temperatures. The density, self-diffusion coefficient, and shear viscosity for the Mg-La liquid alloy were predicted via DPMD simulation, the evolution patterns with Mg content and temperature were subsequently discussed, and a database was established accordingly. Finally, the mixing enthalpy and elemental activity of the Mg-La liquid alloy at 1200 K were reliably evaluated,which provides new guidance for related studies.

关键词： magnesium-lanthanum liquid alloys local structure macroscopic properties thermodynamic behavior deep potential mo-lecular dynamic simulation

Extracting viewer interests for automated bookmarking in video-on-demand services

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Frontiers of Computer Science 2015年第3期9卷 415-430页

作者： Yang zhao ye TIAN yong LIU University of Science and Technology of China Hefei 230027 China Polytechnic Institute of New York University Brooklyn 11201 USA

Video-on-demand （VoD） services have become popular on the Internet in recent years. In VoD, it is challeng- ing to support the VCR functionality, especially the jumps, while maintaining a smooth streaming quality. Previous stud- ies propose to solve this problem by predicting the jump tar- get locations and prefetching the contents. However, through our analysis on traces from a real-world VoD service, we find that it would be fundamentally difficult to improve a viewer＇s VCR experience by simply predicting his future jumps, while ignoring the intentions behind these jumps. Instead of the prediction-based approach, in this paper, we seek to support the VCR functionality by bookmark- ing the videos. There are two key techniques in our pro- posed methodology. First, we infer and differentiate view- ers＇ intentions in VCR jumps by decomposing the inter- seek times, using an expectation-maximization （EM） algo- rithm, and combine the decomposed inter-seek times with the VCR jumps to compute a numerical interest score for each video segment. Second, based on the interest scores, we pro- pose an automated video bookrnarking algorithm. The algo- rithm employs the time-series change detection techniques of CUSUM and MB-GT, and bookmarks videos by detecting the abrupt changes on their interest score sequences. We evaluate our proposed techniques using real-world VoD traces from dozens of videos. Experimental results suggest that with our methods, viewers＇ interests within a video can be precisely extracted, and we can position bookmarks on the video＇shighlight events accurately. Our proposed video bookmark- ing methodology does not require any knowledge on video type, contents, and semantics, and can be applied on various types of videos.

关键词： video-on-demand (VoD) highlight bookmark-ing time-series change detection

Laser direct writing of flexible multifunctional airflow sensors on the Kevlar fabric

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Nano Research 2025年第1期18卷 443-454页

作者： Wei Wang Zi-Qing Chen yong-Qi Li Yu-Long Wang Mei-Chen Liu Yun-Bo Ruan Yang Zhang Shu-Juan Liu Qiang zhao College of Electronic and Optical Engineering and College of Flexible Electronics(Future Technology) Nanjing University of Posts and TelecommunicationsNanjing 210023China State Key Laboratory of Organic Electronics and Information Displays and Jiangsu Key Laboratory for Biosensors Institute of Advanced Materials(IAM)Nanjing University of Posts and TelecommunicationsNanjing 210023China Zhe Jiang Topsun Logistic Control CO. LTD.Yuhuan 317600China Department of Rehabilitation Medicine School of Acupuncture-Moxibustion and Tuina and School of Health Preservation and RehabilitationNanjing University of Chinese MedicineNanjing 210023China

The growing interest in flexible devices has emerged as a global trend due to their advantages in flexibility,lightweight structure,and wearability,addressing the limitations of traditional *** wearable airflow sensors have been previously reported,the development of flexible fabric-based airflow sensors capable of functioning in environments with open flames—critical for fire rescue operations—has yet to be explored,largely due to the poor fire resistance of conventional *** this work,we first present a flexible,wearable,and multifunctional airflow sensor with excellent fire-resistant properties,fabricated through a simple direct laser writing *** sensor maintains airflow detection capabilities even in the presence of open ***,the fabrication of fabric-based sensors involves complex procedures such as carbon materials doping or vapor-phase deposition,leading to lengthy preparation cycles and high ***,fabric-based devices are inherently prone to *** address these challenges,we introduce twice-vertical laser-induced graphene(TVLIG)as a sensitive and reliable component for fire-resistant airflow *** resulting TVLIG/Kevlar fabric can be integrated into various garments,particularly protective suits,to form sensitive and fire-resistant airflow sensors capable of detecting airflow velocity and direction in both two-dimensional(2D)and three-dimensional(3D)spaces during fire ***,the TVLIG patterns can be expanded to multifunctional platforms,such as glucose detection for injured individuals,offering further applications in rescue *** functional expansion reduces the burden on rescue personnel and streamlines device *** its outstanding sensing capabilities,fire resistance,and expandability,the developed flexible airflow sensor shows great potential for various real-world rescue scenarios,promising advancements in wearable sensing technology for rescue enginee

关键词： flexible airflow sensor direct laser writing twice-vertical laser-induced graphene fire accident rescue Kevlar fabric

Foam/fiber-structured catalysts: non-dip-coating fabrication strategy and applications in heterogeneous catalysis

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Science Bulletin 2016年第10期61卷 745-748页

作者： Guofeng zhao ye Liu yong Lu Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular Engineering East China Normal University

Development and use of the structured catalysts and reactors(SCRs)is a promising strategy to overcome the major drawbacks encountered in the traditional packed-bed reactor due to improved hydrodynamics in the combination with enhanced heat/mass transfer,thus being a hot topic in the heterogeneous *** of the most typical SCRs is the ceramic honeycomb catalyst extensively applied in the control of automotive emissions and the reduction of nitrogen oxides from power ***

关键词：催化剂包多相催化涂层制备应用纤维结构强化传热传质填充床反应器浸渍