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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

Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical Medical College Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second Clinical Medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

Mesospheric tide comparisons at low latitudes observed by two collocated meteor radars

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Earth and planetary physics 2025年第1期9卷 54-68页

作者： Jian Li Wen Yi XiangHui Xue Jie Zeng HaiLun ye JianYuan Wang JinSong Chen Na Li TingDi Chen Chinese Academy of Sciences(CAS)Key Laboratory of Geospace Environment Department of Geophysics and Planetary SciencesUniversity of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Comparative planetology Anhui Mengcheng Geophysics National Observation and Research StationUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230026China Collaborative Innovation Center of Astronautical Science and Technology Harbin 150001China National Key Laboratory of Electromagnetic Environment China Research Institute of Radiowave PropagationQingdao 266107China Yunnan Kunming Electromagnetic Environment National Observation and Research Station Qujing Kunming 655000China

Accurate knowledge of mesospheric winds and waves is essential for studying the dynamics and climate in the mesosphere and lower thermosphere(MLT)*** this study,we conduct a comparative analysis of the mesosphere tidal results obtained from two adjacent meteor radars at low latitudes in Kunming,China,from November 2013 to December *** two radars operate at different frequencies of 37.5 MHz and 53.1 MHz,***,overall good agreement is observed between the two radars in terms of horizontal winds and tide *** results show that the dominant tidal waves of the zonal and meridional winds are diurnal and semidiurnal ***,we conduct an exhaustive statistical analysis to compare the tidal amplitudes and vertical wavelengths recorded by the dual radar systems,which reveals a high degree of alignment in tidal *** investigation includes variances and covariances of tidal amplitudes,which demonstrate remarkable consistency across measurements from both *** finding highlights clear uniformity in the mesospheric tidal patterns observed at low latitudes by the two neighboring meteor *** of the comparative analysis specifically underscore the significant correlation in vertical wavelength measurements,validating the robustness of radar observations for tidal research.

关键词： mesosphere and lower thermosphere region meteor radar mesospheric winds tides

Nanograting-Based Dynamic Structural Colors Using Heterogeneous Materials

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NANO-MICRO LETTERS 2025年第1期17卷 1-14页

作者： Wang, Jingang Yu, Haibo Zheng, Jianchen Zhang, Yuzhao Guo, Hongji Qiu, ye Wang, Xiaoduo Yang, Yongliang Liu, Lianqing Chinese Acad Sci Shenyang Inst Automat State Key Lab Robot Shenyang 110016 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China

A 2.5-dimensional dynamic structural color based on nanogratings of heterogeneous materials was proposed by interweaving a pH-responsive hydrogel with Ip-L *** nanogrid structures exhibit brilliant tuneable structural color, high sensitivity, and ultrafast recovery speeds in response to *** 4D printing-based grayscale design approach was proposed for the patterned encoding and array printing of dynamic structural colors, promoting their application in patterned printing, information encryption, and microfluidic chip sensing. Dynamic structural colors can change in response to different environmental stimuli. This ability remains effective even when the size of the species responsible for the structural color is reduced to a few micrometers, providing a promising sensing mechanism for solving microenvironmental sensing problems in micro-robotics and microfluidics. However, the lack of dynamic structural colors that can encode rapidly, easily integrate, and accurately reflect changes in physical quantities hinders their use in microscale sensing applications. Herein, we present a 2.5-dimensional dynamic structural color based on nanogratings of heterogeneous materials, which were obtained by interweaving a pH-responsive hydrogel with an Ip-L photoresist. Transverse gratings printed with pH-responsive hydrogels elongated the period of longitudinal grating in the swollen state, resulting in pH-tuned structural colors at a 45 degrees incidence. Moreover, the patterned encoding and array printing of dynamic structural colors were achieved using grayscale stripe images to accurately encode the periods and heights of the nanogrid structures. Overall, dynamic structural color networks exhibit promising potential for applications in information encryption and in situ sensing for microfluidic chips.

关键词： Dynamic structural colors Four-dimensional printing pH-responsive Nanogrid Heterogeneous materials

Comparative analysis of empirical and deep learning models for ionospheric sporadic E layer prediction

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Earth and planetary physics 2025年第1期9卷 10-19页

作者： BingKun Yu pengHao Tian XiangHui Xue Christopher JScott HaiLun ye JianFei Wu Wen Yi TingDi Chen XianKang Dou Institute of Deep Space Sciences Deep Space Exploration LaboratoryHefei 230088China CAS Key Laboratory of Geospace Environment School of Earth and Space SciencesUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China Department of Meteorology University of ReadingReading RG66BBUK

Sporadic E(Es)layers in the ionosphere are characterized by intense plasma irregularities in the E region at altitudes of 90-130 *** they can significantly influence radio communications and navigation systems,accurate forecasting of Es layers is crucial for ensuring the precision and dependability of navigation satellite *** this study,we present Es predictions made by an empirical model and by a deep learning model,and analyze their differences comprehensively by comparing the model predictions to satellite RO measurements and ground-based ionosonde *** deep learning model exhibited significantly better performance,as indicated by its high coefficient of correlation(r=0.87)with RO observations and predictions,than did the empirical model(r=0.53).This study highlights the importance of integrating artificial intelligence technology into ionosphere modelling generally,and into predicting Es layer occurrences and characteristics,in particular.

关键词： ionospheric sporadic E layer radio occultation ionosondes numerical model deep learning model artificial intelligence

On Resilience Against Cyber-physical Uncertainties in Distributed Nash Equilibrium Seeking Strategies for Heterogeneous Games

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IEEE/CAA Journal of Automatica Sinica 2025年第1期 138-147页

作者： Maojiao ye IEEE the School of Automation Nanjing University of Science and Technology

This paper designs distributed Nash equilibrium seeking strategies for heterogeneous dynamic cyber-physical *** particular, we are concerned with parametric uncertainties in the control channel of the players. Moreover, the weights on communication links can be compromised by time-varying uncertainties, which can result from possibly malicious attacks,faults and disturbances. To deal with the unavailability of measurement of optimization errors, an output observer is constructed,based on which adaptive laws are designed to compensate for physical uncertainties. With adaptive laws, a new distributed Nash equilibrium seeking strategy is designed by further integrating consensus protocols and gradient search ***, to further accommodate compromised communication weights resulting from cyber-uncertainties, the coupling strengths of the consensus module are designed to be adaptive. As a byproduct, the coupling strengths are independent of any global information. With theoretical investigations, it is proven that the proposed strategies are resilient to these uncertainties and players' actions are convergent to the Nash equilibrium. Simulation examples are given to numerically validate the effectiveness of the proposed strategies.

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An Unprecedented Efficiency with Approaching 21%Enabled by Additive‑Assisted Layer‑by‑Layer processing in Organic Solar Cells

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Nano-Micro Letters 2025年第2期17卷 372-375页

作者： Shuai Xu Youdi Zhang Yanna Sun pei Cheng Zhaoyang Yao Ning Li Long ye Lijian Zuo Ke Gao Key Laboratory of Advanced Green Functional Materials College of ChemistryChangchun Normal UniversityChangchun 130032People’s Republic of China Shandong provincial Key Laboratory for Science of Material Creation and Energy Conversion School of Chemistry and Chemical EngineeringShandong UniversityQingdao 266237People’s Republic of China College of polymer Science and Engineering Sichuan UniversityChengdu 610065People’s Republic of China State Key Laboratory and Institute of Elemento‑Organic Chemistry Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer MaterialsRenewable Energy Conversion and Storage Center(RECAST)College of ChemistryNankai UniversityTianjin 300071People’s Republic of China Institute of polymer Optoelectronic Materials and Devices State Key Laboratory of Luminescent Materials and Devices South China University of TechnologyGuangzhou 510640People’s Republic of China Tianjin Key Laboratory of Molecular Optoelectronic Sciences School of Materials Science and EngineeringTianjin UniversityTianjin 300350People’s Republic of China State Key Laboratory of Silicon Materials MOE Key Laboratory of Macromolecular Synthesis and FunctionalizationDepartment of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China

Recently published in Joule,Feng Liu and colleagues from Shanghai Jiaotong University reported a record-breaking 20.8%power conversion efficiency in organic solar cells(OSCs)with an interpenetrating fibril network active layer morphology,featuring a bulk p-in structure and proper vertical segregation achieved through additive-assisted layer-by-layer *** optimized hierarchical gradient fibrillar morphology and optical management synergistically facilitates exciton diffusion,reduces recombination losses,and enhances light capture *** approach not only offers a solution to achieving high-efficiency devices but also demonstrates the potential for commercial applications of OSCs.

关键词： Organic solar cells Additive-assisted layer-by-layer processing Three-dimensional fibril morphology Bulk p-i-n structure Optical management

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

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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