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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

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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Tectonic Framework and Evolution of the Dabie Mountains in anhui, Eastern China

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Acta Geologica Sinica(English Edition) 1992年第3期66卷 221-238,326页

作者： Xu Shutong Jiang Laili Liu Yican Zhang Yong institute of geological sciences of anhui province, Hefei, anhui Sun Sheping institute of geological sciences of anhui province Hefei Anhui

The Dabie Mountains are believed to be a collisional orogenic belt between the Yangtze amd Sino-Koreancontinental plates. It is composed of the foreland fold-thrust zone, the subducting cover and basement of theYangtze continental plate, the coesite- and diamond-bearing ultra-high pressure metamorphic zone and themeta-ophiolitic melange zone in the subducting basement, the fore-arc flysch nappe and the back thrust zoneoccurring respectively on the southern and northern margins of the Sino-Korean continental plate and the in-herited basin with molassic deposits on the northern margin. When the palaeo-Dabie oceanic plate subductednorthward in the Early Palaeozoic, volcanic arc and back arc basin probably formed on the southern margin ofthe Sino-Korean continental plate. The Sm / Nd isotopic dating of the strata and eclogite which were drawn in-to the foreland fold-thrust zone indicates that the intense collision of the two continental plates took place inthe Early Mesozoic.

关键词： collisional orogenic belt ultra-high pressure metamorphic zone ophiolitic melange zone coesite diamond

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Petrochemistry, Age and Petrogenesis of the Shexian Pluton in Southern anhui

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Chinese Journal Of Geochemistry 1991年第3期10卷 244-256页

作者：邢凤鸣徐祥任思明李应运 institute of geological sciences of anhui province Hefei 230001

The Shexian gneissic granodiorite in southern anhui trends NE55°from Shexian in the west to Guitoujian in the east with a length of 22km and an outcrop area of 32km .It was considered formerly to be Caledonian on the basis of a biotite K-Ar age of 474Ma(1982).However,new evi-dence indicates that it may be Early Jinning in age as shown by:(1)it is found intruding into the Mid-Proterozoic Shangxi Group and is unconformably overlain by the Sinian Xiuning Formation,and (2) a zircon U-Th-Pb age of 928 Ma is obtained for the *** pluton is composed of plagioclase(An=27.37%),K-feldspar(14%),biotite(16%) and quartz(32%).Accessory minerals are ilmenite(150g/T),xenotime(15g/T),garnet(25g/T),monazite(10g/T),zircon(20g/T)and apatite(104g/T).Petrochemical characteristics of the intrusion are:(1)Al-enrichment(A/NKC=1.30);(2)H2O enrichment(H2O=1.74%);and (3)low oxidation index(?ˊ=0.10).It belongs to the continental crust transformation type as evidenced by :(1)MF and Mg/Y values of biotite are 0.41 and 0.31 respectively;(2)(^87Sr/^86Sr)=0.71119;(3)δEu=0.52;and (4)A/NKC=*** Shexian pluton is therefore considered as a product of melting of phyllite at depth in the light of similarities in trace element and REE contents with the phyllite of the Banxi *** of REE batch partial melting indicate that it may have re-sulted from 75% melting of the Banxi phyllite.

关键词：安徽岩石成因岩石化学深成岩体示踪元素硬绿泥石稀土元素地球化学

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Deep Mineralization Background and Metallogenic Regularity of the Tongling Ore District

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Acta Geologica Sinica(English Edition) 2020年第6期94卷 1893-1908页

作者： WAN Qiu DU Jianguo YANG Bo LAN Xueyi XIAO Xiao SHI Ke geological Survey of anhui province(anhui institute of geological sciences) Hefei 230001China Technology Innovation Center of Coverage Area Deep Resource Exploration Engineering MNRHefei 230001China institute of Mineral Resources Chinese Academy of Geological SciencesBeijing 100037China geological Exploration Technology institute of anhui province Hefei 230031China Central South University Changsha 410083China

Based on the geological conditions and characteristics of mineralization present,three-dimensional geological modelling is used in conjunction with previous deep research results,in order to discuss the process of deep mineralization in the Tongling ore *** structural analysis shows that surface deformation is strong,deep deformation is weak,the surface has mainly experienced brittle deformation,with the possibility of a large number of deep ductile *** is a thrust nappe between the Tongling uplift and the Nanling basin,that is the boundary of the Tongling block,which has resulted in the southwest uplift of the Tongling *** with the deep exploration data,the threedimensional shape of the main rock masses is interpreted,with three-layer structures in the deep magma *** spatial distribution of magmatic rocks is mainly controlled by the *** movement of magmatic hydrothermal fluid is dominated by mesoscale seepage in the deep part and'dike'type upwelling in the shallow *** is a certain coupling relationship between the ore-forming rock mass and the surrounding *** ore-forming age is dominated by the Yanshanian *** on the distribution,types and metallogenic characteristics of the deposits,the metallogenic model of'layer coupling'in the Tongling ore district is summarized,with the'one body,two belts and a multilayer metallogenic system'is established,which is significant for the future direction of deep prospecting in the Tongling area.

关键词： 3D model metallogenic model prospecting direction deep mineralization Tongling

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Genetic Types, Spatiotemporal Distribution of Ore Deposits and Sources of Ore-forming Materials in the Xuancheng Area, anhui province

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Acta Geologica Sinica(English Edition) 2020年第6期94卷 1874-1892页

作者： LU Sanming ZHANG Zanzan ZHAO Lili LI Jianshe ZHAO Zhuang QI Huasheng Public geological Survey Management Center of anhui province Hefei 230091China CAS Key Laboratory of Crust-Mantle Materials and Environments University of Science and Technology of ChinaHefei 230026China geological Survey of anhui province(anhui institute of geological sciences) Hefei 230001China

In recent years,several large and medium-sized ore deposits have been discovered in the shallow cover of Xuancheng,anhui province,indicating that this area has a productive metallogenic geological background and may be a potential prospecting *** on systematic investigation,the geological and mineralization characteristics of porphyry Cu-Au deposits and skarn Cu-Mo-W deposits in this region have been *** U-Pb dating(LA-ICPMS)of the Chating quartz-diorite porphyry and the Kunshan biotite pyroxene diorite yield concordia ages of 145.5±2.1 Ma and 131.8±2.1 Ma,***,the Re-Os dating analyses for molybdenite from the Shizishan and Magushan skarn Cu-Mo deposits yielded 133.81±0.86 Ma and 143.8±1.4 Ma ages,*** viewed in conjunction with previous studies,it is suggested that twostage(the early stage of 145-135 Ma and the late stage of 134-125 Ma)magmatism may have occurred during the Mesozoic in Xuancheng *** stage intrusive rocks are distributed along both sides of the Jiangnan deep fault(JDF).The intrusive rocks to the north of the JDF are mainly quartzdiorite porphyry and granodiorite(porphyry)rocks,related to porphyry Cu-Au deposits and skarn-type Cu-Mo-W *** deposits belong to the first stage of the porphyry-skarn copper gold metallogenic belt of the Middle-Lower Yangtze Metallogenic Belt(MLYB),associated with the high potassium calc-alkaline intermediate-acid *** magmatic and ore-forming materials are mainly derived from the enriched lithospheric *** of the JDF,the Magushan granodiorite is a representative intrusive rock of the first stage I-type granite,which hosts the Magushan Cu-Mo skarn deposit,similar to the W-Mo-Cu skarn deposits in the Eastern Segment of the Jiangnan Uplift Metallogenic Belt(ESJUB).The magmatic and metallogenic materials mainly came from the Neoproterozoic basement,with the possible participation of a small amount of mantle *** late stage ma

关键词： spatial and temporal distribution two stages of metallogenic events metallogenic materials Xuancheng area

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Two A-type Syenite-Granite Belts in anhui

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Chinese Journal Of Geochemistry 1994年第4期13卷 340-354页

作者：邢凤鸣徐祥 anhui institute of geological sciences Hefei

There ekist two parallel A-type syenitegranite belts on both banks of the Yangtze River inanhui province : one is the Dalongshan- Chengshan- Huangmeijian belt on the north bank and theother is the Huayuangong- Maotan- manshiling belt on the south bank. Both of them consist ofsyenite, quartz-syenite and alkali feldspar granite, which were formed at about 125 Ma ago and areenriched in alkalies and high-field-strength elements but depleted in water, with the total alkali ac-counting for 9- 12%, and H2O+ only for 0.50%’ The Ga x 10-4/Al raho is as high as 2.7 to 3.8for granite. They were formed in the extension stage of ancient riffing. So they are considered to bethe A-type Syenite-granite belts. Granites in the two belts resulted from a syedte magma by an AFCmechanism While the magma was derived from alkali basalt magma through thefractio nal-crystallization-dominated AFC mechanism.

关键词： A型花岗岩安徽稀土元素黑花岗石成因

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Zircon Dating and geological Implications of Granitic Gneiss in the Metamorphic Zone of Gaoligong Mountains in Western Yunnan, China

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Acta Geologica Sinica(English Edition) 2013年第2期87卷 440-453页

作者： TAN Xiaohong ZHAO Bo LI Xikang XU Zhangbao ZHANG Zhen institute of geological survey of Yunnan province institute of Mineral Resources Chinese Academy of Geological Sciences

The general classification of intermediate-acid intrusive rocks in the metamorphic zone of Gaoligong Mountains as one of the metamorphic terranes of Proterozoic Gaoligong Mountains is problematic regarding the intrusion stage and age, as well as the subsequent metamorphism and deformation. In this study, we investigated granitic gneiss in the metamorphic zone of Gaoligong Mountains based on the 1：50,000 regional geological survey of Qushi Street （2011-2013） and SHRIMP U-Pb zircon geochronology. Results showed that the SHRIMP U-Pb zircon dating of granitic gneiss ranged from 163.5±5.7 Ma to 74.0±2.0 Ma. Thus, the granitic gneiss was grouped into orthometamorphic rocks （metamorphic intrusions）. The dating data of granite rocks associated with intense metamorphism and deformation were divided into three groups, 163.5±5.7 to 162.3±3.1 Ma, 132.2-101.0 Ma and 99.4±3.5-74.0±2.0 Ma, which respectively represented three independent geologic events including an important magma intrusion with superimposed metamorphic effects in the late Middle Jurassic, regional dynamic metamorphism and superimposed reformation of fluid action in the early Cretaceous, and dynamic metamorphism dominated by ductile shear and metamorphism starting from the late Cretaceous.

关键词： Metamorphic zone granitic gneiss U-Pb zircon age Gaoligong Mountains Western Yunnan

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Calculating Hamiltonian parameters for Yb^(3+) in a low-symmetry lattice site,and fitting the structure and levels of Yb^(3+) :TaO_4 (= Gd,Y,and Sc)

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Chinese Physics B 2013年第6期22卷 522-529页

作者：张庆礼宁凯杰丁丽华刘文鹏孙敦陆江海河殷绍唐 The Key Laboratory of Photonic Devices and Materials of anhui province Anhui Institute of Optics and Fine MechanicsChinese Academy of Sciences

An iterative method is used to find the values of the Hamiltonian parameters for Yb^3＋ in a given low-symmetry crys- talline site. Samples of Yb^3＋：RETaO4 （RE = Gd, Y, and Sc） were prepared and their structures were determined. Based on the obtained structural data, their orbital-spin parameters and crystal field parameters were fitted by the superposition model （SM）. Using the crystal field parameters obtained by the SM fitting as the initial parameters, the Hamiltonian parameters were fitted iteratively. The calculated and experimental energy levels for Yb^3＋：RETaO4 are consistent, and the maximal mean-root-square deviation is only 2.84 cm^- 1, indicating that the method is effective to determine the Hamiltonian parameters of Yb^3＋ in low-symmetry crystalline sites.

关键词： crystal field parameter rare earth X-ray diffraction Yb^3+ :RETaO4

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REE Geochemistry of Skarns in the Tongshan Copper Deposit, Guichi, anhui province

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Acta Geologica Sinica(English Edition) 1987年第1期61卷 105-115页

作者： Qiu Ruilong anhui institute of geological sciences, He fei anhui institute of geological sciences Hefei

This paper presents REE abundance pattern and REE geochemistry of granodiorite porphyry, skarns, as well as late hydrothermal alterations in the Tongshan copper deposit, Guichi County and, in the light of their similarities and variations, deals with the genesis of the skarns and the transformation process of the post-skarn hydrothermal alterations. On such a basis, the inference is drawn that the skarn-forming solution was produced by further fractionation of residual magma, thus belonging to a transitional fluid between residual magma and hydrothermal solution which, with the continuous variation of its components during the metasomatism, tended to become a hydrothermal solution.

关键词： REE Geochemistry of Skarns in the Tongshan Copper Deposit Guichi anhui province

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