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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan he Maoju Wang Lei Xia Guiqiong he Weihong song Yehong Du Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing Medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

COMBINED LEGENDRE SPECTRAL-FINITE ELEMENTMETHOD FOR The TWO-DIMENSIONAL UNSTEADYNAVIER-STOKES EQUATION

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Journal of Computational Mathematics 1999年第5期17卷 495-508页

作者： song-man he Cai-ping Yang(Department of Basic Courses, Civil Aviation University of China, Tianjin 300300, China) 中国民用航空学院天津

A combined Legendre spectral-finite element approximation is proposed for solving two-dimensional unsteady Navier-Stokes equation. The artificial compressibility is used. The generalized stability and convergence are ... 详细信息

关键词： Navier-Stokes equation combined Legendre spectral-finite element approximation

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

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Journal of Molecular Cell Biology 2024年第1期16卷 43-53页

作者： Xiaozhen song Ruixing Hu Yi Chen man Xiao Hong Zhang Shengnan Wu Qing Lu Molecular Diagnostic Laboratory Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200040China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China Laboratory of Development and Diseases and State Key Laboratory for Medical Genomics Shanghai Institute of HematologyRuĳin HospitalShanghai JiaoTong University School of MedicineShanghai 200025China

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic *** mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental ***,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains *** this study,we employed zebrafish as an in vivo model ***7 knock down caused defects in zebrafish embryonic *** determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic ***,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of ***,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

关键词： TRAF7 coiled-coil domain crystal structure trimerization embryonic development

A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

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Neuroscience Bulletin 2024年第3期40卷 310-324页

作者： man Yuan Sen Jin Gao Tan Siyuan song Yizong Liu Huadong Wang Yin Shen Eye Center Renmin Hospital of Wuhan UniversityWuhan UniversityWuhan430060China The Brain Cognition and Brain Disease Institute Shenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of Sciences(CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsNational Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Quality Control Technology for Virus-Based TherapeuticsGuangdong Provincial Medical Products AdministrationShenzhen518055China Jan and Dan Duncan Neurological Research Institute Baylor College of MedicineHouston77030USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Key Laboratory of Magnetic Resonance in Biological SystemsWuhan Center for Magnetic ResonanceInnovation Academy for Precision Measurement Science and TechnologyCASWuhan430071China Frontier Science Center of Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan430071China

Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various ***,their role in transmitting visual information remains ***,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual *** applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole ***,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual ***,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic ***,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual *** results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.

关键词： Parvalbumin-positive retinal ganglion cell Innate fear Superior colliculus Excitatory-excitatory neuronal connection Looming-evoked defensive response Subcortical pathway

Flame-retardant ammonium polyphosphate/MXene decorated carbon foam materials as polysulfide traps for fire-safe and stable lithium-sulfur batteries

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Journal of Energy Chemistry 2024年第2期89卷 313-323,I0008页

作者： Yang Li Yong-Cheng Zhu Sowjanya Vallem man Li Seunghyun song Tao Chen Long-Cheng Tang Joonho Bae Department of Physics Gachon UniversitySeongnam-siGyeonggi-do 13120South Korea Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education College of MaterialChemistry and Chemical EngineeringHangzhou Normal UniversityHangzhou 311121ZhejiangChina Key laboratory of Advanced Energy Materials Chemistry(Ministry of Education) College of ChemistryNankai UniversityTianjin 300071China School of Materials Engineering Changzhou Vocational Institute of Industry TechnologyChangzhou 213164JiangsuChina

Lithium-sulfur(Li-S)batteries are one of the most promising modern-day energy supply systems because of their high theoretical energy density and low ***,the development of high-energy density Li-S batteries with high loading of flammable sulfur faces the challenges of electrochemical performance degradation owing to the shuttle effect and safety issues related to fire or explosion *** this work,we report a three-dimensional(3D)conductive nitrogen-doped carbon foam supported electrostatic self-assembled MXene-ammonium polyphosphate(NCF-MXene-APP)layer as a heat-resistant,thermally-insulated,flame-retardant,and freestanding host for Li-S batteries with a facile and costeffective synthesis ***,through the use of NCF-MXene-APP hosts that strongly anchor polysulfides,the Li-S batteries demonstrate outstanding electrochemical properties,including a high initial discharge capacity of 1191.6 mA h g^(-1),excellent rate capacity of 755.0 mA h g^(-1)at 1 C,and long-term cycling stability with an extremely low-capacity decay rate of 0.12%per cycle at 2 *** importantly,these batteries can continue to operate reliably under high temperature or flame attack ***,this study provides valuable insights into the design of safe high-performance Li-S batteries.

关键词： Flame-retardant MXene Ammonium polyphosphate Safety Lithium-sulfur battery

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

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Chinese Journal of Integrative Medicine 2024年第1期30卷 25-33页

作者： GAO Quan LI Lin ZHANG Qi-man SheNG Qin-song ZHANG Ji-liang JIN Li-jun SHANG Rui-yan School of Pharmacy and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China Department of Colorectal Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Beijing Tong Ren Tang Chinese Medicine Co. Ltd.Beijing(100000)China Department of Traditional Chinese Medicine Hangzhou Shangcheng District People's HospitalHangzhou(310006)China Department of Gynecology Hangzhou Women's HospitalHangzhou(310008)China

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(Phermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G_1–S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9(P<0.05), and might play an anticancer role through Akt signaling pathway. Conclusions: Monotropein exerts its antitumor

关键词： monotropein Chinese medicine anticancer activity colorectal cancer cells network pharmacology

An effective strategy for dendrite free Li metal anodes:Nickel foam decorated with high lattice-matching CoN and CoF_(2) nanosheets for dense deposition

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Nano Research 2024年第5期17卷 4069-4078页

作者： Wenlong Liu Jianzong man Xiaodong Sun Ning Zhang Yehong Du Kun Liu Zhongsheng Wen song Li Juncai Sun Institute of Materials and Technology Dalian Maritime UniversityDalian 116026China Shandong Provinvial Key Laboratory of Chemical Energy Storage and Novel Cell Technology and School of Chemistry and Chemical enginneringLiaocheng UniversityLiaocheng 252000China Department of Public Security management Liaoning Police CollegeDalian 116036China

The notorious dendrite and infinite volume change seriously restrict the advancement of lithium metal anodes(LMAs),during the long-term process of stripping/***,the nanosheets of metal fluoride(CoF_(2))and metal nitride(CoN)with magnificent lithiophilicity on the nickel(Ni)foam are designed as the“regulator”to uniform the Li plating and build stronger solid electrolyte interface(SEI)layer for dendrite free *** Ni foam offers abundant space to receive deposited Li *** CoN nanosheets can guarantee the fast transfer of electrons,which provides a stable interface of Li^(+)***,the nanosheet structure with lithiophilicity would accelerate the move of Li+and decrease the nucleation barrier,due to the high lattice-matching of Li and ***,the CoF_(2) could increase the content of F(LiF)in the SEI layer,which enhances the strength and avoids the destruction of SEI *** the cooperation of CoN and CoF_(2),the composited anode(Li/NF@CNCF)exhibits ultra-long cycle performance(more than 1200 h)and fantastic structure stability at 1 mA·cm^(-2) with 1 mAh·cm^(-2).Based on the LiFePO_(4) and Li/NF@CNCF,the full cells deliver excellent specifical capacity and steady coulombic *** strategy contributes an effective approach to alleviate the issues of lithium metal anodes in the field of LMAs.

关键词： CoN and CoF_(2) lattice-matching nanosheet lithiophilicity lithium metal anodes

Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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Cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan man song Gao Jihui Hao Department of Pancreatic Cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China Department of Gastrointestinal Pancreatic Surgery Shanxi Provincial People’s HospitalTaiyuan 030012China

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell ***-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine ***,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains ***:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were *** of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was ***:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and *** GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic *** tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and ***:Ki-67 is a valuable prognostic indicator for *** of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： Pancreatic ductal adenocarcinoma prognosis Ki-67 differentiation TNM stage

Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung song Suah Yang Jinseong Kim Yujeong Moon Nayeon Shim Hong Yeol Yoon Sehoon Kim man Kyu Shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation