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The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

Bone Research 2023年第2期11卷 273-291页

作者： Hengwei Zhang Jane lliesveld laura MCalvi Brea Clipe lianping Xing Michael WBecker edward MSchwarz Shu-Chi A.Yeh Center for Musculoskeletal Research University of Rochester Medical Center601 Elmwood AveBox 665RochesterNY14642USA Department of Pathology and laboratory Medicine University of Rochester Medical CenterRochesterNYUSA Wilmot Cancer Center University of Rochester Medical CenterRochesterNYUSA Department of Medicine Division of Hematology/Oncology and Bone Marrow Transplantation ProgramUniversity of Rochester Medical CenterRochesterNYUSA Department of Medicine Division of Endocrinology/MetabolismUniversity of Rochester Medical CenterRochesterNYUSA Department of Orthopaedics University of Rochester Medical CenterRochesterNYUSA Department of Medicine Division of Allergy/Immunology/RheumatologyUniversity of Rochester Medical CenterRochesterNYUSA Department of Biomedical Engineering University of RochesterNYUSA Department of Physiology/Pharmacology University of Rochester Medical CenterRochesterNYUSA

Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell *** advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone *** findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel *** advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic ***,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting *** then discuss unresolved questions and ambiguities that remain in the field.

关键词： remodeling homeostasis likely

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Chromatographic finger print analysis of steroids in Aerva lanata l by HPTlC technique

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Asian Pacific Journal of Tropical Biomedicine 2011年第6期1卷 428-433页

作者： Yamunadevi Mariswamy Wesely edward Gnaraj Johnson M Research&Development Department Bharathiyar University Department of Botany Arignar Anna Government Arts College Department of Plant Biology and Plant Biotechnology St. Xavier's College(Autonomous)

Objective:To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata(***) ***:Preliminary phytochemicul screening was done by the method as Harborne *** studies were canied out as Harborne and Wagner et al *** Ethyl acetate-ethanol-water(8:2:1.2) was employed as mobile phase for ***:The desired aim was achieved using Chloroform-acetone(8:2) as the mobile *** methanolic extract of stem,leaves,root,flower and seeds of *** showed the presence of 30 different types of steroids with 30 different Rf values from 0.04 to 0.97. Maximum number(11) of steroids has been observed in leaves followed by root(10).Conclusions: HPTlC profile of steroids has been chosen here to reveal the diversity existing in *** finger printing is useful in differentiating the species from the adulterant and act as biochemical markers for this medicinally important plant in the pharma industry and plant systematic studies.

关键词： Steroids HPTlC profile Fingerprint Aerva lanata l.

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Regnase-1, a rapid response ribonuclease regulating nflammation and stress responses

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Cellular & Molecular Immunology 2017年第5期14卷 412-422页

作者： Renfang Mao Riyun Yang Xia Chen edward W Harhaj Xiaoying Wang Yihui Fan Basic Medical Research Center School of Medicine Nantong University Nantong Jiangsu 226001 People's Republic of China Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine Baltimore MD 21287 USA Department of Immunology School of Medicine Nantong University Nantong Jiangsu 226001 People's Republic of China

RNA-binding proteins （RBPs） are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 （MAlT1） mediated cleavage. The major function of Regnase-1 is promoting mRNA decay via its ribonuclease activity by specifically targeting a subset of genes in different cell types. In monocytes, Regnase-1 downregulates Il-6 and Il-12B mRNAs, thus mitigating inflammation, whereas in T cells, it restricts T-cell activation by targeting c-Rel, Ox40 and 11-2 transcripts. In cancer cells, Regnase-1 promotes apoptosis by inhibiting anti-apoptotic genes including Bcl2l1, Bcl2A1, RelB and Bcl3. Together with up-frameshift protein-1 （UPF1）, Regnase-1 specifically cleaves mRNAs that are active during translation by recognizing a stem-loop （Sl） structure within the 3＇UTRs of these genes in endoplasmic reticulum-bound ribosomes. Through this mechanism, Regnase-1 rapidly shapes mRNA profiles and associated protein expression, restricts inflammation and maintains immune homeostasis. Dysregulation of Regnase-1 has been described in a multitude of pathological states including autoimmune diseases, cancer and cardiovascular diseases. Here, we provide a comprehensive update on the function, regulation and molecular mechanisms of Regnase-1, and we propose that Regnase-1 may function as a master rapid response gene for cellular adaption triggered by microenvironmental changes.

关键词： Autoimmune diseases Regnase-1 ribonuclease RNA-binding proteins microenvironment

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Mechanosignaling activation of TGFβmaintains intervertebral disc homeostasis

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Bone Research 2017年第1期5卷 27-40页

作者： Qin Bian lei Ma Amit Jain Janet l Crane Khaled Kebaish Mei Wan Zhengdong Zhang X edward Guo Paul D Sponseller Cheryle A Seguin lee H Riley Yongjun Wang Xu Cao Department of Orthopaedic Surgery Institute for Cell EngineeringJohns Hopkins UniversityBaltimoreMDUSA Institute of Spine Longhua HospitalShanghai University of Traditional Chinese MedicineShanghaiPR China Department of Pediatrics Johns Hopkins UniversityBaltimoreMDUSA Department of Biomedical Engineering Columbia UniversityNYUSA Departments of Physiology and Pharmacology University of Western OntarioLondonCanada

Intervertebral disc （IVD） degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal （NC） cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta （TGFβ）, decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease （DDD）. Knockout of TGFβ type II receptor （TβRII） or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD.

关键词： Mechanosignaling activation of TGF maintains intervertebral disc homeostasis IVD

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Emerging roles of Aurora-A kinase in cancer therapy resistance

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药学学报:英文版 2023年第7期13卷 2826-2843页

作者： Dayong Zheng Jun li Han Yan Gang Zhang Wei li edward Chu Ning Wei School of Pharmacy North China University of Science and TechnologyTangshan 063210China Basic Medical Science College Liaoning University of Traditional Chinese MedicineShenyang 110032China Division of Biology and Biological Engineering California Institute of TechnologyPasadenaCA 91125USA Department of Oncology and Cancer Therapeutics Program Montefiore Einstein Cancer CenterAlbert Einstein College of MedicineBronxNY 10461USA

Aurora kinase A(Aurora-A),a serine/threonine kinase,plays a pivotal role in various cellular processes,including mitotic entry,centrosome maturation and spindle *** or gene-amplification/mutation of Aurora-A kinase occurs in different types of cancer,including lung cancer,colorectal cancer,and breast *** of Aurora-A impacts multiple cancer hallmarks,especially,immortalization,energy metabolism,immune escape and cell death resistance which are involved in cancer progression and *** review highlights the most recent advances in the oncogenic roles and related multiple cancer hallmarks of Aurora-A kinase-driving cancer therapy resistance,including chemoresistance(taxanes,cisplatin,cyclophosphamide),targeted therapy resistance(osimertinib,imatinib,sorafenib,etc.),endocrine therapy resistance(tamoxifen,fulvestrant) and ***,the mechanisms of Aurora-A kinase promote acquired resistance through modulating DNA damage repair,feedback activation bypass pathways,resistance to apoptosis,necroptosis and autophagy,metastasis,and ***,our review also summarizes the promising synthetic lethality strategy for Aurora-A inhibitors in RB1,ARID1A and MYC gene mutation tumors,and potential synergistic strategy for m TOR,PAK1,MDM2,MEK inhibitors or PD-l1 antibodies combined with targeting Aurora-A *** addition,we discuss the design and development of the novel class of Aurora-A inhibitors in precision medicine for cancer treatment.

关键词： Aurora-A Therapy resistance Chemoresistance Targeted therapy Radioresistance Synthetic lethality Alisertib PROTAC

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Treatment and disease management patterns for bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer in North America,Europe and Asia:A real-world data analysis

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Current Urology 2022年第3期16卷 147-153页

作者： edward I.Broughton Danielle S.Chun Kyna M.Gooden Katie l.Mycock Ivana Rajkovic Gavin Taylor-Stokes WW Health Economics and Outcomes Research Bristol Myers SquibbPrincetonNJUSA The University of North Carolina Chapel HillNCUSA Observational Research Department Adelphi Real WorldBollingtonUK

Background:This study examined real-world treatment and management of bacillus Calmette-Guérin(BCG)-unresponsive patients across 3 continents,including patients unable or unwilling to undergo *** and methods:Physicians actively involved in managing patients with nonmuscle invasive bladder cancer completed online case report forms for their 5 consecutive patients from the broad BCG-unresponsive population and a further 5 consecutive BCG-unresponsive patients who did not undergo cystectomy(in Japan,physicians provided a total of 5 patients across both cohorts).Results:Most patients had received 1(37%)or 2(24%)maintenance courses of *** or more maintenance BCG courses were received by patients in Japan(59%)and China(31%),while in Germany 76%of patients received only 1 *** patients became BCG-unresponsive during their first(44%)or second(22%)treatment course;in Germany,77%became BCG-unresponsive during their first treatment *** countries did not provide another course of BCG after a patient first became unresponsive,whereas unresponsive patients in Japan and China were most likely to be retreated with BCG."Untreated-on watch and wait"was the main treatment/management approach received post-BCG treatment for 42%or more of patients in most countries except China(39%)and the United States(36%)."Following treatment guidelines"was consistently the top reason for post-BCG treatment selection across all treatment ***:This study confirmed the global unmet need for patients with nonmuscle invasive bladder cancer,and found that many patients experienced periods of no treatment after not responding to BCG therapy.

关键词： Bacillus Calmette-Guérin Bladder cancer Cystectomy Treatment failure Urinary tract

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Ergatoid reproductives in the Neotropical termite Nasutitermes aquilinus (Holmgren) (Blattaria: Isoptera: Termitidae): developmental origin, fecundity, and genetics

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Insect Science 2020年第6期27卷 1322-1333页

作者： Iago Bueno da Silva Ives Haifig edward lVargo Fabiana Elaine Casarin Marcelo luiz da Mota Juliana Toledo lima Ana Maria Costa-leonardo laboratorio de Cupins Departamento de BiologiaInstituto de BiocienciasUniversidade Estadual Paulista-UN ESPRio ClaroSPBrazil Centro de Ciencias Naturais e Humanas Universidade Federal do ABCSao Bernardo do CampoSPBrazil Department of Entomology Texas A&M UniversityCollege StationTexasUSA Departamento de Ciencias Biologicas Universidade Federal de Sao Paulo-UNIFESPDiademaSPBrazil Instituto de Ciencias Agrarias Universidade Federal de Uberlandia—UFUMonte CarmeloMGBrazil Centro de Estudos em Recursos Naturais Universidade Estadual de Mato Grosso do SulDouradosMSBrazil

Termite colonies are usully headed by primary reproductives,which estab-listh nests during the swar ming ***,secondary reproductives may develop in some specics and become supplementary or replacement breeders,extending colony *** we investigate the developmental origin,fecundity and genetic characterizaion of ergatoid reproductives in the Neotropical termite Nasuitermes aquilinus(Holmgren),using morphometrical and histological techniques,five micosiallitle loci and the COI mitochondrial *** measurements performed on 208 apterous individuals of Nuauidius revealed 10 groups,including ergatoid females,which developed from major workers through two successive *** were characterized by the presence of imaginal features such as eyes andl wing *** difentiation of these features was correlated to physogastric development in these ergatoids,Histology revealed ooeytes in all matu-ration sages in worker-derived reproductives of N aquidinus,presence of nonflagellate spermatozoa inside the spermatheea,and royal fa ***,ergatoid reproduwetives were reproductively *** to the genotypes of 221 individuals from 11 nests,and mitochondrial haplotypes of 43 ergatoids,73%of the colomies were simple families,whereas 27%were extendbed *** the oecurenee of related reproductives,low inbreeding rates were detected within and among *** values could be explained given that sib mating itself cannot result in a higher inbreeding rate but depend on several factors discussed in *** is the first study to investigate the genetic structure of termite colonies influenced by the development of ergatoids and further investigations are encouraged 10 understand the inflwence of these reproductives on colony lifespan.

关键词： breeding syslem caste ifrentiation COI genotyping micosallites reproduction

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嵌入式实时操作系统的多线程计算基于ThreadX和ARM using threadX and ARM 4

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丛书名：嵌入式系统译丛

2005年

作者：（美）edward l. lamie 张炯等译

本书介绍和分析了嵌入式系统的重要概念和应用设计方法，并提供了多个基于ARM平台的多线程应用实例。重点从实时、多线程、ThreadX和ARM处理器结合的角度进行展开，并用实际案例分析将它们与应用结合。

ISBN: (数字)7810776290

ISBN: (纸本)7810776290

关键词：实时操作系统程序设计

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Meso-Scale VOC-Mixture Analyzer with Tunable Separation and Microsensor Array Detection

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稀有金属材料与工程 2006年第S3期 61-64页

作者： William H.Steinecker edward T.Zellers Department of Chemistry University of Michigan109 S.Observatory St.Ann ArborMI 48109-2029USA Department of Environmental Health Sciences University of Michigan109 S.Observatory St.Ann ArborMI 48109-2029USA.Department of ChemistryUniversity of Michigan109 S.Observatory St.Ann ArborMI 48109-2029USA

A novel portable instrument developed for field determinations of complex mixtures of volatile organic compounds (VOCs) is *** key features of the instrument are a miniature multi-stage adsorbent preconcentrator/focuser,two series-coupled separation columns with pressure and temperature tunable retention control,and an integrated array of four chemiresistor (CR) sensors coated with Au-thiolate monolayer-protected nanoparticles (MPN).MPN-CR array response patterns are used with retention times to identify eluting *** is used as the carrier *** of 20 common indoor air contaminants gave lODs in the range of 0.05 ng/g～0.53 ng/g for a 1 l sample *** of preliminary analyses of characteristic VOCs generated from *** as well as vapor-phase markers of environmental tobacco smoke (ETS) at low-or sub-ng/g levels are presented.

关键词： microsensor gas chromatography nanoparticle sensor array portable ETS

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FlUID AND CARBOHYDRATE REPlACEMENT DURING EXERCISE:HOW MUCH AND WHY?

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中国运动医学杂志 2001年第3期20卷 331-336页

作者： edward F. Coyle,Ph.D.

KEY *** prolonged exercise in the heat, peoplecan become dehydrated at a rate of 1-2l everyhour (about 2-4lbs of body weight loss per hour).The rate of dehydration can be monitored byrecording changes in nude body wei... 详细信息

关键词： FlUID AND CARBOHYDRATE REPlACEMENT DURING EXERCISE

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