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Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice

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Protein & Cell 2024年第4期15卷 261-284页

作者： He-Zhou Huang Wen-Qing Ai Na Wei Ling-Shuang Zhu Zhi-Qiang liu Chao-Wen Zhou Man-Fei Deng Wen-Tao Zhang Jia-Chen Zhang Chun-Qing Yang Ya-Zhuo Hu Zhi-Tao Han Hong-Hong Zhang Jian-Jun Jia Jing Wang fang-fang liu Ke Li Qi Xu Mei Yuan Hengye Man Ziyuan Guo Youming Lu Kai Shu Ling-Qiang Zhu Dan liu Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Medical Genetics School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China Department of Pathology School of Basic MedicineZhengzhou UniversityZhengzhou 450002China The Second Affiliated Hospital Department of NeurologyHengyang Medical SchoolUniversity of South ChinaHengyang 421001China Beijing Key Laboratory of Aging and Geriatrics National Clinical Research Center for Geriatric DiseaseInstitute of GeriatricsChinese PLA General Hospital and Chinese PLA Medical AcademyBeijing 100853China Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of Biology Boston UniversityBostonMA 02215USA Center for Stem Cell and Organoid Medicine(CuSTOM) Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA

Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family *** genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of ***,the underlying mechanisms of social isolation in AD progression remain *** the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD *** also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related ***,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious ***,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its ***,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD *** together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

关键词： Alzheimer’s disease memory impairment synaptic disorder tau pathology

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Construction,Expression and Purification of SUMO1-GST Fusion Protein

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Chemical Research in Chinese Universities 2011年第2期27卷 245-248页

作者： QIAO Xiao-fang fang Xue-dong liu Jun The Second Hospital of Jilin University Changchun 130041 P. R.China

Sumoylation is an important protein modification discovered recently. SUMO（small ubiquitin-related modifier） pathway regulates the protein stability and transcriptional activity with a 12-kDa small molecular protein, SUMO, ligated to the target protein. The purification of SUMO proteins is a key step to reveal their function. The purpose of this study was to construct the recombinant SUMO1 gene cloned to a pGEX-4T-1 vector to express and purify the SUMO1-GST fusion protein in Escherichia coli. First, the full length DNA sequence of SUMO1 gene was amplified by PCR and was ligated to pMD18-T vector. Then the SUMO1 gene was subcloned to pGEX-4T-1 prokaryotic expression vector between BamHI and XhoI sites, and transformed in Escherichia coli DH5α cells. The right colonies were identified by restrictive enzyme digestion and sequencing. The correct rebombinant plasmid of pGEX-4T-1-SUMO1 was transformed in Escherichia coli BL21 cells and then induced by IPTG（isopropyl- β-D-1- thiogalacto-pyranoside） to express the SUMO1-GST fusion protein. The highly purified SUMO1-GST（glutathione S-transferase） fusion protein was obtained by affinity chromatography. Finally, the properties of SUMO1-GST fusion protein were confirmed by Coomassie brilliant blue strain and Western blot analysis. The recombinant plasmid of pGEX-4T-1-SUMO1 was successfully constructed, and SUMO1-GST fusion proteins were successfully expressed.

关键词： Small ubiquitin-related modifier 1 (SUMO1) Gutathione S-transferase(GST) fusion protein Affinity chromatography

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Alkenyl-type ligands functionalized tin-lanthanide oxo nanoclusters as molecular lithography resists

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Science China Chemistry 2023年第6期66卷 1731-1736页

作者： fang-fang liu Di Wang Guang-Hui Chen Yang Qiao Feng Luo Jian Zhang Lei Zhang State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China Institute of Modern Optics College of Electronic Information and Optical EngineeringNankai UniversityTianjin 300350China School of Materials Science and Engineering&Smart Sensing Interdisciplinary Science Center Nankai UniversityTianjin 300350China College of Chemistry and Materials Science Fujian Normal UniversityFuzhouFujian 350007China

Both the cluster chemistry of tin and lanthanides have attracted extensive research interest,showing wide applications in catalysis,magnetism,luminescence,and ***,their fusion into heterometallic Sn-Ln oxo clusters is still to be *** this study,through the stabilization of alkenyl-type cis-5-norbornene-endo-2,3-dicarboxylic acid(H_(2)NE)ligands,a series of atomically precise Sn-Ln oxo nanoclusters have been successfully constructed from the assembly of heterometallic tetranuclear Sn_(x)Ln((4-x))building ***,Sn_(12)Eu_(8) and Sn_(13)Er_(6) with the highest nuclearities are built from multiple assembly of 8{Sn_(2)Eu_(2)}units and 6{Sn_(3)Er}and{Sn_(2)Er_(2)}units,***-MS analysis indicates that Sn_(13)Er_(6) has high solution stability,allowing their packing into thin films for lithography *** a result of electron beam lithography(EBL)studies,the condensation of Sn_(13)Er_(6) can be triggered by low energy radiation of 10μC/cm^(2),and 50 nm lines have been fabricated at expose energy of 50μC/cm^(2),confirming the satisfying sensitivity and resolution of Sn_(13)Er_(6).Hence,the success of this study develops the chemistry of heterometallic tin-lanthanide clusters that can be applied as novel negative photoresist materials.

关键词： cluster compounds tin lanthanides nanolithography photoresists

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Synthesis and Properties of Novel Polyimide Fibers Containing Phosphorus Groups in the Side Chain (DATPPO)

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Chinese Journal of Polymer Science 2017年第3期35卷 372-385页

作者： Yong Zhao Guo-min Li fang-fang liu Xue-min Dai 董志鑫邱雪鹏 Polymer Composites Engineering Laboratory Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 China University of Chinese Academy of Sciences Beijing 100049 China

A series of polyamic acid copolymers(co-PAAs) containing phosphorous groups in the side chains were synthesized from [2,5-bis(4-aminophenoxy) phenyl] diphenylphosphine oxide(DATPPO) and 4,4′-oxydianiline(ODA) with 3,3′,4,4′-biphenyltetracarboxylic dianhydride(s-BPDA) through the polycondensation in N,N′-dimethyacetamide(DMAc). The co-PAA solutions were spun into fibers by a dry-jet wet spinning process followed by thermal imidization to obtain co-polyimide(co-PI) fibers. FTIR spectra and elemental analysis confirmed the chemical structure of PI fibers. SEM results indicated that the resulting PI fibers had a smooth and dense surface, a uniform and circle-shape diameter. The thermogravimetric measurements showed that with the increase of DATPPO content, the resulting PI fibers possessed high decomposition temperature and residual char yield, indicating that the PI fibers had good thermal stability. The corresponding limiting oxygen index(LOI) values from the experiment results showed that the co-PI fibers possessed good flame-retardant property. Furthermore, the mechanical properties of the co-PI fibers were investigated systematically. When the DATPPO content increased, the tensile strength and initial modulus of the co-PI fibers decreased. However, the mechanical properties were improved by increasing the draw ratio of the fibers. When the draw ratio was up to 2.5, the tensile strength and initial modulus of the co-PI fibers reached up to 0.64 and 10.02 GPa, respectively. The WAXD results showed that the order degree of amorphous matter increased with increased stretching. In addition, the SAXS results displayed that valuably drawing the fibers could eliminate the voids inside and lead to better mechanical property. WAXD revealed that the orientation of the amorphous polymer influenced the mechanical properties of the fibers.

关键词： [2,5-Bis(4-aminophenoxy) phenyl] diphenylphosphine oxide Dry-jet wet spinning process Phosphorous Polyimide fibers

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Mechanical Properties of Polyimide/Multi-walled Carbon Nanotube Composite Fibers

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Chinese Journal of Polymer Science 2016年第11期34卷 1386-1395页

作者： Zhi-xin Dong Tao Feng Chao Zheng Guo-min Li fang-fang liu 邱雪鹏 Polymer Composites Engineering Laboratory Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Academy of Space Electronic Information Technology Xi'an 710100China

A series of polyimide（PI）/multi-walled carbon nanotube（MWCNT） composite fibers were prepared by copolymerizing a mixture of monomers and carboxylic-functionalized MWCNTs, followed by dry-jet wet spinning, thermal imidization, and hot-drawing process. The content of the carboxylic groups of MWCNTs significantly increased when treated with mixed acid, whereas their length decreased with treatment time. Both the carboxylic content and length of MWCNTs influenced the mechanical properties of the composite fibers. Fiber added with 0.1 wt% MWCNTs treated for 4 h exhibited the best mechanical properties, i.e., 1.4 GPa tensile strength and 14.30% elongation at break, which were 51% and 32% higher than those of pure PI fibers, respectively. These results indicated that a suitable MWCNT content strengthened and toughened the resultant PI composite fibers, simultaneously. Moreover, raising draw ratio resulted in the increase of tensile strength and tensile modulus of the composite fibers.

关键词： walled nanotube tensile modulus resultant carboxylic length spinning elongation dispersed

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AO-resistant Properties of Polyimide Fibers Containing Phosphorous Groups in Main Chains

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Chinese Journal of Polymer Science 2016年第12期34卷 1469-1478页

作者： Yong Zhao Guo-min Li Xue-min Dai fang-fang liu 董志鑫邱雪鹏 Polymer Composites Engineering Laboratory Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Chinese Academy of Sciences Beijing 100049China

A series of polyimide fibers containing phosphorus element derived from （3-aminophenyl） methyl phosphine oxide （DAMPO） diamine was exposed to an artificial atomic oxygen environment which simulated the space environment in low earth orbit （LEO）. The mass loss, surface morphology, chemical composition, and mechanical properties of the fibers before and after atomic oxygen （AO） exposure were compared in detail with a blank sample. Results showed that the phosphor-containing fibers demonstrated lower mass change and less tensile strength reduction. SEM results showed that the fibers with phosphorous element had relatively dense surface after AO exposure. Meanwhile, XPS results indicated that a passivated phosphate layer, which could protect the following under-layer from attacking by AO, was formed on the surface of the fibers. These results indicated that the incorporation of diamine （DAMPO） into the main chains could protect the fibers for avoiding further erosion from AO exposure. Hence, the phosphor-containing PI fibers exhibits potential application in space fields.

关键词： Atomic oxygen Phosphorous Polyimide Fibers LEO environment.

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Synthesis and AO Resistant Properties of Novel Polyimide Fibers Containing Phenylphosphine Oxide Groups in Main Chain

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Chinese Journal of Polymer Science 2019年第1期37卷 59-67,1-3页

作者： Yong Zhao Hong Gao Guo-Min Li fang-fang liu Xue-Min Dai Zhi-Xin Dong Xue-Peng Qiu Polymer Composites Engineering Laboratory Changchun Institute of Applied Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences China Academy of Space Technology

A series of co-polyimide(PI)fibers containing phenylphosphine oxide(PPO)group were synthesized by incorporating the bis(4-aminophenoxy)phenyl phosphine oxide(DAPOPPO)monomer into the PI molecular chain followed by dry-jet wet *** effects of DAPOPPO molar content on the atomic oxygen(AO)resistance of the fibers were investigated *** the AO fluence increased from 0to 3.2×1020the mass loss of the fibers showed the dependence on DAPOPPO molar content in co-PI *** PI fiber containing 40%DAPOPPO showed lower mass loss compared to those containing 0%and 20%*** higher AO fluence,the higher DAPOPPO content gave rise to dense carpet-like surface of *** results indicated that the passivated phosphate layer was deposited on the fiber surface when exposed to AO,which effectively prevented fiber from AO *** the DAPOPPO content increasing from 0%to 40%,the retentions of tensile strength and initial modulus for the fibers exhibited obvious growth from 44%to 68%,and 59%to 70%,after AO exposure with the fluence of 3.2×1020The excellent AO resistance benefits the fibers for application in low Earth orbit as flexible construction components.

关键词： Polyimide fibers Bis(4-aminophenoxy)phenyl phosphine oxide(DAPOPPO) Dry-jet wet spinning AO resistance

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Cortactin Overexpression Correlates with Poor Prognosis in Hepatocellular Carcinoma

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Chinese Journal of Cancer Research 2010年第2期22卷 112-118页

作者： Ke-min Jin Min Lu fang-fang liu Jin Gu Xiao-juan Du Bao-cai Xing Key laboratory of Carcinogenesis and Translational Research （Ministry of Education） Department of Hepatic Biliary ＆ Pancreatic Surgery Unit I Department of Genetics Department of Gastrointestinal Surgery Unit II Peking University School of Oncology Beijing Cancer Hospital ＆ Institute Beijing 100142 China Department of Pathology Department of Cell Biology Cancer Research Center Peking University Health Science Center Beijing 100191 China

Objective： To investigate cortactin expression in hepatocellular carcinoma （HCC） and explore its significance in the prognosis of HCC patients. Methods： Immunohistochemistry was performed for paraffin samples of 119 pairs of HCC tissues （HCCs） and paratumorous liver tissues （PTLTs） to evaluate cortactin expression. The cortactin expression difference in HCCs and PTLTs were analyzed by the McNemar＇s test. The relationship of cortactin expressions in HCCs and clinicopathologic factors was analyzed with Mann-Whitney U test. The Kaplan-Meier method and log-rank test were employed to compare the overall survival between Cortactin negative expression group, weak expression group and strong expression group. Expression of cortactin was further determined in 19 pairs of fresh HCCs and PTLTs specimens with Western blotting. Results： Cortactin expression rate was significantly higher in HCCs （53/119, 44.5%） than that in PTLTs （2/119, 1.7%）（P〈0.001）. The upregulated cortactin expression in HCCs was significantly correlated to absence of capsule formation （P=0.012）, vascular invasion （P=0.037） and high Edmondson-Steiner grade （P=0.020）, and predicted shorter overall survival. Western blotting demonstrated that cortactin expression was upregulated in 9 out of 19 HCCs （47.4%） compared to corresponding PTLTs. Conclusion： Cortactin expression is upregulated in HCC and is related to shorter overall survival of patients, suggesting that cortactin might play roles in the metastasis of HCC and predict a poor prognosis of HCC patients.

关键词： Hepatoeellular carcinoma (HCC) Carcinogenesis Prognosis Cortactin

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Comparison of Different Methods for Determining the Imidization Degree of Polyimide Fibers

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Chinese Journal of Polymer Science 2016年第2期34卷 209-220页

作者： Wen-ke Yang fang-fang liu Guo-min Li En-song Zhang Yan-hu Xue Zhi-xin Dong 邱雪鹏姬相玲 State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences Laboratory of Polymer Composites and Engineering Changchun Institute of Applied Chemistry Chinese Academy of Sciences

In this study, polyimide fibers at different stages of imidization were characterized by TGA, DSC, and FTIR. The imidization degree （ID） calculated by TGA was based on the weight loss of each sample, which was caused by the imidization of residual amic acid groups. The results of TGA showed good regularity with the thermal treatment temperature of the PI fibers. For DSC, the ID was calculated based on the area of endothermal peak of each sample. Compared with TGA, DSC showed a relatively higher value because the endothermal peak was reduced by the exothermic re-formation of polyamic acid which may be partially degraded during thermal treatment. The IDs obtained by the FTIR spectra generally showed poorer regularities than those obtained by both TGA and DSC, especially for the results calculated using the 730 cm^-1 band. Based on the 1350 cm^-1 band, the obtained IDs showed better agreement with the TGA or DSC results. The results obtained by these three methods were compared and analyzed. The ID obtained by TGA showed much more reliability among these three methods.

关键词： Imidization degree Polyimide fibers Polyamic acid Polyimide Characterization.

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Removal of Cr(Ⅵ)by glutaraldehyde-crosslinked chitosan encapsulating microscale zero-valent iron:Synthesis,mechanism,and longevity

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Journal of Environmental Sciences 2024年第8期142卷 115-128页

作者： Yijun Duan fang liu Xiang liu Miao Li School of Environment Tsinghua UniversityBeijing 100084China Transportation Institute of Inner Mongolia University Hohhot 010070China

Microscale zero-valent iron(mZVI)has shown great potential for groundwater Cr(Ⅵ)***,low Cr(Ⅵ)removal capacity caused by passivation restricted the wide use of *** prepared mZVI/GCS by encapsulating mZVI in a porous glutaraldehydecrosslinked chitosan matrix,and the formation of the passivation layer was alleviated by reducing the contact between zero-valent iron *** average pore diameter of mZVI/GCS was 8.775 nm,which confirmed the mesoporous characteristic of this *** of batch experiments demonstrated that mZVI/GCS exhibited high Cr(Ⅵ)removal efficiency in a wide range of pH(2-10)and temperature(5-35℃).Common groundwater coexisting ions slightly affected m ZVI/*** material showed great reusability,and the average Cr(Ⅵ)removal efficiency was 90.41%during eight *** this study,we also conducted kinetics and isotherms ***-second-order model was the most matched kinetics *** Cr(Ⅵ)adsorption process was fitted by both Langmuir and Freundlich isotherms models,and the maximum Langmuir adsorption capacity of m ZVI/GCS reached243.63 mg/g,which is higher than the adsorption capacities of materials reported in most of the previous ***,the column capacity for Cr(Ⅵ)removal of a mZVI/GCS-packed column was 6.4 times higher than that of a mZVI-packed column in a 50-day ***,mZVI/GCS with a porous structure effectively relieved passivation problems of mZVI and showed practical application prospects as groundwater Cr(Ⅵ)remediation material with practical application prospects.

关键词： Chitosan Glutaraldehyde mZVI Cr(Ⅵ) Groundwater

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