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ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

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Bone Research 2024年第2期12卷 453-468页

作者： Lei Xiong Hao-Han Guo Jin-Xiu Pan Xiao Ren Daehoon Lee Li Chen Lin Mei Wen-Cheng Xiong Department of Neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Louis Stoke va medical center ClevelandOH 44106USA

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and *** how Wnt/β-catenin signaling is regulated in OBs remain ***6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling ***,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone *** we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone *** knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone *** and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not *** cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

关键词： LRP6 impaired organs

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Long non-coding RNA BANCR promotes pancreatic cancer lymphangiogenesis and lymphatic metastasis by regulating the HIF-1α/VEGF-C/VEGFR-3 pathway via miR-143-5p

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Genes & Diseases 2024年第4期11卷 57-60页

作者： Shaolong Hao Yu Ji Weixuan Pan Hao Sun Fang Nie Jonathan Ray Warren Yuchuan Ding Wei Han Department of General Surgery Beijing Luhe HospitalCapital Medical UniversityTongzhouBeijing 101149China Department of Central Laboratory Beijing Luhe HospitalCapital Medical UniversityTongzhouBeijing 101149China Department of Neurosurgery Wayne State University School of MedicineJohn D.Dingell VA Medical CenterDetroitMI 48201USA

Pancreatic cancer is one of the most aggressive malignant tumors of the digestive *** node metastasis(LNM),as the main way of invasion and metastasis,can occur in the early stage of pancreatic cancer and be considered... 详细信息

关键词： metastasis cancer invasion

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Pretreatment and analysis techniques development of TKIs in biological samples for pharmacokinetic studies and therapeutic drug monitoring

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Journal of Pharmaceutical Analysis 2024年第4期14卷 439-459页

作者： Lan Chen Yuan Zhang Yi-Xin Zhang Wei-Lai Wang De-Mei Sun Peng-Yun Li Xue-Song Feng Yue Tan school of Pharmacy China Medical UniversityShenyang110122China Institute of Pharmacology and Toxicology Institution National Engineering Research Center for Strategic DrugsBeijing100850China Department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyang110022China

Tyrosine kinase inhibitors(TKIs)have emerged as the first-line small molecule drugs in many cancer therapies,exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling ***,there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites,which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments,alongside other potential side effects or adverse ***,an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods,clinical pharmacokinetics,and therapeutic drug monitoring of different *** paper provides a comprehensive overview of the advancements in pretreatment methods,such as protein precipitation(PPT),liquid-liquid extraction(LLE),solid-phase extraction(SPE),micro-SPE(μ-SPE),magnetic SPE(MSPE),and vortex-assisted dispersive SPE(va-DSPE)achieved since *** also highlights the latest analysis techniques such as newly developed high performance liquid chromatography(HPLC)and high-resolution mass spectrometry(HRMS)methods,capillary electrophoresis(CE),gas chromatography(GC),supercritical fluid chromatography(SFC)procedures,surface plasmon resonance(SPR)assays as well as novel nanoprobes-based biosensing *** addition,a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

关键词： TKIs Microextraction technique HRMS methods Pharmacokinetic studies Therapeutic drug monitoring

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Beyond ribosomal function:RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3931-3948页

作者： Wenkang Fu Yanyan Lin Mingzhen Bai Jia Yao Chongfei Huang Long Gao Ningning Mi Haidong Ma Liang Tian Ping Yue Yong Zhang Jinduo zhang Yanxian Ren Liyun Ding Lunzhi Dai Joseph WLeung Jinqiu Yuan Wenhua Zhang Wenbo Meng The First school of Clinical Medicne Lanzhou UniversityLanzhou 730030China Department of General Surgery the First Hospital of Lanzhou UniversityLanzhou 730030China Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province the First Hospital of Lanzhou UniversityLanzhou 730000China school of Physical Science and Technology Lanzhou UniversityLanzhou 730000China National Clinical Research center for Geriatrics and Department of General Practice State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Division of Gastroenterology UC Davis Medical Center and Sacramento VA Medical CenterSacramentoCA 95817USA Clinical Research center Big Data Centerthe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China school of Life Sciences Lanzhou UniversityLanzhou 730000China

Cholangiocarcinoma(CCA)is a bile duct malignancy with a dismal *** study systematically investigated the role of the ribosomal protein S6(RPS6)gene,which is dependent in *** found that RPS6 upregulation in CCA tissues was correlated with a poor *** investigations have shown that alterations in RPS6 expression,both gain-and loss-of function could affect the proliferation of CCA *** xenograft tumor models,RPS6 overexpression enhances tumorigenicity,whereas RPS6 silencing reduces *** analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle,especially DNA *** followed by mass spectrometry has identified numerous spliceosome complex proteins associated with *** profiling revealed that RPS6 affects numerous alternative splicing(AS)events,and combined with RNA immunoprecipitation sequencing,revealed that minichromosome maintenance complex component 7(MCM7)binds to RPS6,which regulates its AS and increases oncogenic activity in *** RPS6 with vivo phosphorodiamidate morpholino oligomer(V-PMO)significantly inhibited the growth of CCA cells,patient-derived organoids,and subcutaneous xenograft *** together,the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

关键词： Cholangiocarcinoma Ribosomal protein S6 Alternative splicing p53 Minichromosome maintenance complex component 7 Vivo morpholino Patient-derived organoids

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Distribution of licensed acupuncturists and educational institutions in the United States at the start of 2023,during the late stage of the COVID-19 pandemic

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Journal of Integrative Medicine 2024年第4期22卷 379-384页

作者： Arthur Yin Fan De-guang He Anu Sangraula Sarah Faggert Alemi Amy Matecki American Traditional Chinese Medicine Association ViennaVA 22182USA McLean center for Complementary and Alternative Medicine ViennaVA 22182USA New England school of Acupuncture Massachusetts College of Pharmacy and Health SciencesBostonMA 02115USA Lombardi Comprehensive Cancer center Cancer Prevention and Control ProgramGeorgetown UniversityWashington DC 20057USA Eastern Roots Wellness PLCMcLeanVA 22101USA Sutter Health Alta Bates Summit Medical CenterOaklandCA 94609USA

This study was conducted to identify the number and density of active licensed acupuncturists(LAcs),as well as the number of accredited schools in acupuncture and Oriental medicine(AOM),as of January 1,2023,in the United States(U.S.).The number of active LAcs as of January 1,2023 was 34,524,potentially33,364 after removing license duplication in multiple states,among which the largest three states were California(with 7317 LAcs[21.19%of the total]),New York(5024[14.55%])and Florida(2644[7.66%]).The total number of LAcs decreased by 8.87%from 2018,and fell short of our projected number of LAcs in 2023 by 9037,or 20.75%.The overall LAc density in the *** as the number of LAcs per 100,000 populationDwas 10.36,less than in *** were 56 active,accredited AOM schools which offered a total of 147 programs(121 at the level necessary for licensing[entry-level],12 for an advanced practicing degree[advanced-level],and 14 for certifications).Broken down further,offerings included 50 master's degrees in acupuncture,40 master's degrees in Oriental medicine,31 entry-level doctorate degrees(10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine),and 12advanced-level doctorate degrees in *** certification programs included one in East-Asian medical Bodywork and 13 in *** these schools in 2023,institutions in the West and East Coast states comprised 67.86%(decreased from 77.42%in 2018)of the national ***,Florida and Illinois represented 39.29%.There were 48 jurisdictions with acupuncture practice laws in *** data suggests that the acupuncture profession in the *** been significantly impacted during the coronavirus disease 2019 pandemic.

关键词： Acupuncturist Acupuncture educational institution Distribution Density Oriental medicine United States

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CSPP1 stabilizes microtubules by capping both plus and minus ends

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Journal of Molecular Cell Biology 2024年第2期16卷 36-46页

作者： Zhikai Wang Wenwen Wang Shuaiyu Liu Fengrui Yang Xu Liu Shasha Hua Lĳuan Zhu Aoqing Xu Donald LHill Dongmei Wang Kai Jiang Jennifer Lippincott-Schwartz Xing Liu Xuebiao Yao MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics Center for Advanced Interdisciplinary Science and Biomedicine of IHMUniversity of Science and Technology of China School of Life SciencesHefei 230027China Anhui Key Laboratory for Cellular Dynamics and Chemical Biology Hefei National Research Center for Interdisciplinary Sciences at the MicroscaleHefei 230027China Frontier Science center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430071China Comprehensive Cancer center University of AlabamaBirminghamAL 35233USA Janelia Research Campus Howard Hughes Medical InstituteAshburnVA 20147USA

Although the dynamic instability of microtubules(MTs)is fundamental to many cellular functions,quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular ***,how these free MT tips are stabilized remains poorly ***,we report that centrosome and spindle pole protein 1(CSPP1)caps and stabilizes both plus and minus ends of static ***-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends,whose dynamic instability was concomitantly ***,MT ends in CSPP1-overexpressing cells were hyper-stabilized,while those in CSPP1-depleted cells were much more *** CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting ***,CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated *** findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.

关键词： CSPP1 microtubule plus end minus end capping

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Percutaneous decannulation of extracorporeal membrane oxygenation using MANTA device:A real-world single-center experience

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World Journal of Cardiology 2024年第10期16卷 574-579页

作者： Ioannis Milioglou Alice Qian Pedro Rafael Vieira de Oliveira Salerno Gabriel Tensol Rodrigues Pereira Luis Augusto Palma Dallan Kelsey E Gray Michael Morrison Yasir Abu-Omar Mohammad Eldiasty Cristian Baeza Department of Cardiology University Hospitals Cleveland Medical CenterClevelandOH 44106United States Department of Surgery University Hospitals Cleveland Medical Center and Case Western Reserve University School of MedicineClevelandOH 44106United States

BACKGROUND The MANTA vascular closure device(VCD)represents a novel approach to achieving hemostasis after large-bore femoral access *** clinical studies have evaluated the efficacy of the MANTA device across a range of patient populations undergoing different ***,there is still a paucity of data available concerning the use of MANTA devices in aiding the decannulation of venoarterial extracorporeal membrane oxygenation(vaECMO).AIM To present our single-center experience of utilizing the MANTA VCD in patients undergoing this *** This single-center study included all patients undergoing percutaneous decannulation of femoral va-ECMO using the MANTA plug-based VCD between January 2021 and October 2023 at university Hospitals Cleveland medical *** criteria were adult patients who required prolonged(>24 hours)hemodynamic support with *** included all-cause mortality,hemostasis,bleeding,limb ischemia,and site *** This is a retrospective cohort study of 19 patients with a mean age of 56.8 *** of them were males with a mean body mass index of *** most common extracorporeal membrane oxygenation indication was acute coronary syndrome complicated by cardiogenic shock at 36.8%.The mean length of intensive care unit stay for these patients was 18.8±8.42 *** out of 19 patients survived to *** MANTA device was successfully deployed in 19 patients,with 10 procedures conducted at the bedside and 9 in an operating room *** hemostasis was achieved within 5 minutes of MANTA deployment in 17 out of 19 *** 2 patients manual compression after Manta deployment was required to achieve adequate ***,acute lower extremity ischemia was noted in two patients,necessitating endovascular *** infections were reported at the site of MANTA *** Overall,based on our experience and that of other centers,the MANTA VCD

关键词： Extracorporeal membrane oxygenation MANTA Decannulation Hemostasis Ischemia

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MMP-9 deficiency accelerates the progress of periodontitis

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Genes & Diseases 2024年第5期11卷 117-121页

作者： Chun-Yan Wan Yixin Yin Xiaoyan Li Meng Meng Liu Graham Goldman Li-An Wu Feng Wang Dao-Shu Luo Zhuo Chen Wen-An Xu Stephen Chen Mary MacDougall Merry L.Lindsey Zhi Chen Shuo Chen Department of Endodontics The Affiliated Hospital of Qingdao UniversitySchool of StomatologyQingdao UniversityQingdaoShandong 266003China Department of Developmental Dentistry School of DentistryThe University of Texas Health Science Center at San AntonioSan AntonioTX 78229USA Oral Implantology center Jinan Stomatological HospitalJinanShandong 250001China Department of Endodontics School and Hospital of StomatologyCheeloo College of MedicineShandong Key Laboratory of Oral Tissue RegenerationShandong Engineering Laboratory for Dental Materials and Oral Tissue RegenerationShandong UniversityJinanShandong 250012China Department of Pediatric Dentistry School of StomatologyThe Fourth Military Medical UniversityXi’anShaanxi 710032China Laboratory of Clinical Applied Anatomy Department of Human AnatomySchool of Basic Medical SciencesFujian Medical UniversityFuzhouFujian 350108China Key Laboratory for Oral Biomedical Research of Zhejiang Province Affiliated Hospital of StomatologyMedical CollegeZhejiang UniversityHangzhouZhejiang 310027China Department of Stomatology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China UBC Faculty of Dentistry University of British ColumbiaVancouverBC V6T 1Z3Canada school of Graduate Studies and Research Meharry Medical College and Research BiologistResearch Service Nashville VA Medical CenterNashvilleTN 37208USA State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST) Key Laboratory for Oral Biomedicine of Ministry of Education(KLOBM)School and Hospital of StomatologyWuhan UniversityWuhanHubei 430079China

Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria that affects periodontal support tissues.1 If left untreated,it results in loss of periodontal attachment and alveolar bone *** one-half of adults in the United States older than 30 years have periodontal disease.2 Though the disease is initiated by bacterial infection,it activates host defense systems that eventually lead to the degradation of the *** periodontitis,the disease progress involves further production of pro-inflammatory mediators such as cytokines,proteolytic enzymes like matrix metalloproteinases(MMPs),and their inhibitors.

关键词： period eventually untreated

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Myosin va‑dependent Transport of NMDA Receptors in Hippocampal Neurons

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Neuroscience Bulletin 2024年第8期40卷 1053-1075页

作者： Ru Gong Linwei Qin Linlin Chen Ning Wang Yifei Bao Wei Lu Ministry of Education(MOE)Key Laboratory of Developmental Genes and Human Disease School of Life Science and TechnologySoutheast UniversityNanjing 210096China Department of Neurosurgery State Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai 200032China Department of Neurobiology Nanjing Medical UniversityNanjing 210096China Co‑innovation center of Neuroregeneration Nantong UniversityNantong 226001China

N-methyl-D-aspartate receptor(NMDAR)trafficking is a key process in the regulation of synaptic efficacy and brain ***,the molecular mechanism underlying the surface transport of NMDARs is largely *** we identified myosin va(Myova)as the specific motor protein that traffics NMDARs in hippocampal *** found that Myova associates with NMDARs through its cargo binding *** association was increased during NMDAR surface *** of Myova suppressed NMDAR *** further demonstrated that Ca^(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)regulates NMDAR transport through its direct interaction with ***,Myova employed Rab11 family-interacting protein 3(Rab11/FIP3)as the adaptor proteins to couple themselves with NMDARs during their ***,the knockdown of FIP3 impairs hippocampal ***,we conclude that in hippocampal neurons,Myova conducts active transport of NMDARs in a CaMKII-dependent manner.

关键词： Myosin va NMDA receptor CaMKⅡ Transport Memory

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu Emily Choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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