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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

Oncology Research 2025年第1期33卷 225-234页

作者： WEI ZHANG WEICHENG WANG RUI WANG XIAO HAN LIJUN ZHU WENJIE guO YANHONG gu Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Department of Oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

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Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第1期68卷 249-256页

作者： Qing-Yun Fang Chengyihan gu Yinghan Chen Wencheng Yan Yong Liang Weipeng Li Chengjian Zhu Jie Han Jin Xie State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State Key Laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

关键词： gold catalysis peptide alkylation C-C coupling radical

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Analgesic effects of receptin, a chemically modified cobratoxin from Thai-land cobra venom

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Neuroscience Bulletin 2006年第5期22卷 267-273页

作者：张慧灵韩蓉陈志欣顾振纶 Paul F.Reid Laurence N.Raymond 秦正红苏州大学医学院药理学教研室苏州215123 ReceptoPharm Inc.

Objective To investigate the analgesia induced by receptin （REC）, a chemically modified cobratoxin （CTX, a long-chain postsynaptic α-neurotoxin from Thailand cobra venom）, and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally （5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.） or intra-cerebral venticularly （62.5 μg/kg, i.c.v.）. The antinociceptive action was determined using the hotlate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine （Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.） or naloxone （Nal; 3 mg/kg, i.p.）. The effect of REC on motor activity was tested using the Animex test in mice. Results REC （5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.） exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 μg/kg （1/160 of systemic dose; i.c.v.）produced marked analgesic effects. Atropine at 0.5 mg/kg （i.m.）, 10 mg/kg （i.p.） or naloxone at 3 mg/kg （i.p.） failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC＇s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.

关键词： receptin analgesia central nervous system atropine naloxone

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Boosting hydrocarbon conversion via Cu-doping induced oxygen vacancies on CeO2 in CO2 electroreduction

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Journal of Energy Chemistry 2025年第1期100卷 66-76页

作者： Lei Xue Tong Shi Chenhui Han Heng Zhang Fenrong Liu Haorun Li Yan Wang Xiaojun gu Shanghong Zeng Inner Mongolia Key Laboratory of Chemistry and Physics of Rare Earth Materials School of Chemistry and Chemical Engineering Inner Mongolia University State Key Laboratory of Coal Conversion Institute of Coal Chemistry Chinese Academy of Sciences Institute of Catalysis Department of Chemistry Zhejiang University National Key Laboratory of Baiyunobo Rare Earth Resource Research and Comprehensive Utilization Baotou Research Institute of Rare Earths

Conversion of CO2back to hydrocarbons is the most direct way of closing the“carbon cycle”,and its significance is further enlarged if this process is driven by renewable energies such as ***,precisely controlling the product selectivity towards hydrocarbons against the competitive hydrogen evolution remains challenging,especially for Cu-based ***,we report a novel defect engineering strategy,by which Cu-doping-induced oxygen vacancies on CeO2nanorods were effectively created,with adjustable vacancy/Cu *** resulting optimum catalyst shows up to 79% catalytic current density to hydrocarbons （excluding CO）,with 49% faradaic efficiency to *** and density functional theory unveil that the ratio between oxygen vacancy and Cu affects significantly the formation of*CHO and activation of H2O,which leads to the following deep hydrogenation to *** findings may spur new insights for designing and developing more controllable chemical process relevant to CO2utilization.

关键词： Nanorods

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Dynamic modeling of a three-dimensional braided composite thin plate considering braiding directions

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 123-138页

作者： Chentong GAO Huiyu SUN Jianping gu W.M.HUANG College of Aerospace Engineering Nanjing University of Aeronautics and Astronautics School of Mechanical and Aerospace Engineering Nanyang Technological University Jiangsu Key Laboratory of Advanced Structural Materials and Application Technology School of Materials Science and EngineeringNanjing Institute of Technology

Currently, there are a limited number of dynamic models available for braided composite plates with large overall motions, despite the incorporation of three-dimensional(3D) braided composites into rotating blade components. In this paper, a dynamic model of 3D 4-directional braided composite thin plates considering braiding directions is established. Based on Kirchhoff's plate assumptions, the displacement variables of the plate are expressed. By incorporating the braiding directions into the constitutive equation of the braided composites, the dynamic model of the plate considering braiding directions is obtained. The effects of the speeds, braiding directions, and braided angles on the responses of the plate with fixed-axis rotation and translational motion, respectively, are investigated. This paper presents a dynamic theory for calculating the deformation of 3D braided composite structures undergoing both translational and rotational motions. It also provides a simulation method for investigating the dynamic behavior of non-isotropic material plates in various applications.

关键词： Constitutive equations

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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu zhengliang Ma Xiaoping gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Preparation of Modified Composite Nanofiltration Membrane Synergistically Using Carboxylic Multi- walled Carbon Nanotube and β-cyclodextrin

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 232-239页

作者： LIU Peng MAO Junpeng FANG Yanfeng YU Yunwu CHEN Changxiu TANG Ning WAN Ye gu Yaxin LIU Yunxue WANG Lihua School of Materials Science and Engineering Shenyang Jianzhu UniversityShenyang 110168China

A new modified blend ultrafiltration(UF)membrane with good hydrophilicity,high porosity and excellent anti-fouling performance was developed by using carboxylic multi-walled carbon nanotube(CMWCNT)as casting solution ***,a composite nanofiltration(NF)membrane with large water flux and good retention rate was fabricated by using the PVDF/CMWCNT blend UF membrane as the substrate,and polyvinyl alcohol(PVA),β-cyclodextrin(β-CD)and polyethylenimine(PEI)as the coating *** results show that with the appropriate addition of CMWCNT in the casting solution,the surface roughness,porosity and recovery rate of the PVDF/CMWCNT blend UF membrane is obviously *** water flux of blend UF membrane is significantly improved when the CMWCNT content increases from 0 wt%to 0.2 wt%.The water flux of blend UF membrane with 0.2 wt%CMWCNT is 162.7 L/(m^(2)·h),which is 44.3%higher than that of the pure PVDF ***β-CD content is 0.8 wt%,the retention rate of Congo red by PVDF/CMWCNT/β-CD composite NF membrane reaches 98.7%,which is 28.3%higher than that of single PVA/PEI modified *** research will provide a new idea and simple method for developing novel high-performance composite NF membranes.

关键词： CMWCNT cyclodextrin nanofiltration membrane

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Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

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Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning Li Yakun gu Wei Ma Yuying guan Mengyuan guo Qianqian Shao Xunming Ji Jia Liu Department of Clinical Laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

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Exploration of Gas‑Dependent Self‑Adaptive Reconstruction Behavior of Cu_(2)O for Electrochemical CO_(2)Conversion to Multi‑Carbon Products

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Nano-Micro Letters 2025年第3期17卷 280-296页

作者： Chaoran Zhang Yichuan gu Qu Jiang Ziyang Sheng Ruohan Feng Sihong Wang Haoyue Zhang Qianqing Xu Zijian Yuan Fang Song State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China

Structural reconstruction of electrocatalysts plays a pivotal role in catalytic performances for CO_(2)reduction reaction(CO_(2)RR),whereas the behavior is by far superficially ***,we report that CO_(2)accessibility results in a universal self-adaptive structural reconstruction from Cu_(2)O to Cu@CuxO composites,ending with feeding gas-dependent microstructures and catalytic *** CO_(2)-rich atmosphere favors reconstruction for CO_(2)RR,whereas the CO_(2)-deficient one prefers that for hydrogen evolution *** the assistance of spectroscopic analysis and theoretical calculations,we uncover a CO_(2)-induced passivation behavior by identifying a reductionresistant but catalytic active Cu(I)-rich amorphous layer stabilized by*CO ***,we find extra CO production is indispensable for the robust production of *** inverse correlation between durability and FECO/FEC2H4 is disclosed,suggesting that the selfstabilization process involving the absorption of*CO intermediates on Cu(I)sites is essential for durable *** by this insight,we design hollow Cu_(2)O nanospheres for durable and selective CO_(2)RR electrolysis in producing *** work recognizes the previously overlooked passivation reconstruction and self-stabilizing behavior and highlights the critical role of the local atmosphere in modulating reconstruction and catalytic processes.

关键词： CO_(2)reduction reaction Electrocatalysts Cu_(2)O Reconstruction Self-adaptive electrocatalysis

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Impacts of household living consumption on energy use and carbon emissions in China based on the input–output model

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Advances in Climate Change Research 2020年第2期11卷 118-130页

作者： ZHOU Xiao-Yu gu A-lun Institute of Energy Environment and EconomyTsinghua UniversityBeijing100084China

China must urgently accelerate its decrease of energy use,optimize its energy structure,reduce CO2 emissions,and promote the early realization of an ecological ***,meeting the growing consumer demand is one of the reasons for the increase in energy *** study investigates the impacts of household consumption on energy use and CO2 emissions from the perspective of the lifestyle of Chinese *** the basis of the input–output model of 30 provinces,we analyze the current situation of energy use and CO2 emissions in different regions(spatial scale)with economic development and income improvement(time scale),investigate the pulling effect of household consumption in different provinces on industrial sectors,examine the influencing factors of indirect CO2 emissions from food,clothing,housing,and transportation in key regions,and explore the policy implications of the transition to a low-carbon lifestyle in different *** show that the fuel structure of Chinese residents should be optimized *** household energy consumption and total CO2 emissions considerably *** 2012,total household energy consumption accounted for nearly 30%of total energy consumption,while indirect CO2 emissions accounted for 66.3%of total household *** regard to the structures of indirect household energy consumption,the housing sector accounted for the largest proportion,reaching 23.4%in indirect energy consumption in *** pulling effect of the housing sector on industrial sectors was also *** decomposition analysis showed that the rapid increase in indirect household CO2 emissions was primarily due to the increase in per capita living *** consumption structures in different provinces produced various impacts,and the energy intensity effect was identified as an important factor for reducing indirect household CO2 emissions.

关键词： Household living consumption CO2 emissions Input–output model Logarithmic mean divisia index(LMDI)decomposition Regional differences

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