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Analysis of new bone,cartilage,and fibrosis tissue in healing murine allografts using whole slide imaging and a new automated histomorphometric algorithm

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Bone Research 2015年第4期3卷 226-234页

作者： Longze Zhang Martin Chang Christopher A Beck Edward M Schwarz brendan f boyce Center for Musculoskeletal Research School of Medicine and DentistryUniversity of Rochester Medical Center

Histomorphometric analysis of histologic sections of normal and diseased bone samples,such as healing allografts and fractures,is widely used in bone ***,the utility of traditional semi-automated methods is limited because they are labor-intensive and can have high interobserver variability depending upon the parameters being assessed,and primary data cannot be re-analyzed *** histomorphometry has long been recognized as a solution for these issues,and recently has become more feasible with the development of digital whole slide imaging and computerized image analysis systems that can interact with digital ***,we describe the development and validation of an automated application（algorithm）using Visiopharm＇s image analysis system to quantify newly formed bone,cartilage,and fibrous tissue in healing murine femoral allografts in high-quality digital images of H＆E/alcian blue-stained decalcified histologic *** validate this algorithm,we compared the results obtained independently using OsteoMeasureTM and Visiopharm image analysis *** intraclass correlation coefficient between Visiopharm and OsteoMeasure was very close to one for all tissue elements tested,indicating nearly perfect reproducibility across *** new algorithm represents an accurate and labor-efficient method to quantify bone,cartilage,and fibrous tissue in healing mouse allografts.

关键词： cartilage slide automated healing fibrous figure automatically sections segmentation quantify

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis f.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk brendan boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

fibrous dysplasia(fD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in fD tissue and its likely indirect effects on osteoprogenitors by evaluating human fD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in fD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal fD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces fD lesion activity by decreasing fD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of fD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

Asymmetric reversible structural switching of a diene coordination polymer promoted by UV-visible light

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Science China Chemistry 2024年第2期67卷 536-541页

作者： Yong Wang Qiaoqiao Zhang Yong-Yong Cao Qi Liu brendan f.Abrahams Jian-Ping Lang College of Chemistry Chemical Engineering and MaterialsSoochow UniversitySuzhou215123China State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai200032China College of Biological Chemical Science and EngineeringJiaxing UniversityJiaxing314001China School of Chemistry University of MelbourneVictoria3010Australia

In natural and artificial systems,reversible reactions are commonly asymmetric with respect to the time scale and nature of the stimuli which drive the forward and backward *** applications for which switching behavior is required,it is desirable that the reversible reaction goes as close to symmetric as possible;however,such systems are ***,we report an example of ultraviolet(UV)-visible light-regulated asymmetric reversible structural switching involving a diene-based coordination polymer,CP1 and its monocyclobutane product,*** is possible to cycle at least ten times through a forward [2+2] photocycloaddition reaction and the reverse,photocleavage reaction.A single cycle can be completed within a few *** transformation is accompanied by fast and distinct fluorescence changes,arising from optimisation of the reaction *** functional theory calculations allow rationalisation of the asymmetric reversible transformation between CP1 and CP1a rather than between CP1 and its dicyclobutane product *** work provides a clear illustration of reversible structural switching which approaches symmetric behaviour with respect to reaction rate and *** insights gained from this work also assist in the design of fast,reversible switching materials.

关键词： asymmetrical reversible structural switching coordination polymer photocycloaddition UV-visible light-controlled fluorescence switching

Classification of Soft Tissue Sarcoma Specimens with Raman Spectroscopy as Smart Sensing Technology

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Cyborg and Bionic Systems 2021年第1期2021卷 90-101页

作者： Liming Li Vamiq M.Mustahsan Guangyu He felix B.Tavernier Gurtej Singh brendan f.boyce fazel Khan Imin Kao Department of Mechanical Engineering Stony Brook UniversityNYUSA Department of Pathology and Laboratory Medicine Stony Brook University HospitalStony BrookNYUSA Division of Plastic Surgery Department of SurgeryStony Brook University HospitalStony BrookNYUSA Department of Orthopaedic Surgery Stony Brook University HospitalStony BrookNYUSA

Intraoperative confirmation of negative resection margins is an essential component of soft tissue sarcoma *** section examination of samples from the resection bed after excision of sarcomas is the gold standard for intraoperative assessment of margin ***,it takes time to complete histologic examination of these samples,and the technique does not provide real-time diagnosis in the operating room(OR),which delays completion of the *** paper presents a study and development of sensing technology using Raman spectroscopy that could be used for detection and classification of the tumor after resection with negative sarcoma margins in real *** acquired Raman spectra from samples of sarcoma and surrounding benign muscle,fat,and dermis during surgery and developed(i)a quantitative method(QM)and(ii)a machine learning method(MLM)to assess the spectral patterns and determine if they could accurately identify these tissue types when compared to findings in adjacent H&E-stained frozen *** classification accuracy(>85%)was achieved with both methods,indicating that these four types of tissue can be identified using the analytical methodology.A hand-held Raman probe could be employed to further develop the methodology to obtain spectra in the OR to provide real-time in vivo capability for the assessment of sarcoma resection margin status.

关键词： surgery diagnosis operative

Osteoclast fusion and regulation by RANKL-dependent and independent factors

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World Journal of Orthopedics 2012年第12期3卷 212-222页

作者： Lianping Xing Yan Xiu brendan f boyce Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY 14642 United States

Osteoclasts are the bone resorbing cells essential for bone *** are formed from hematopoietic progenitors in the monocyte/macrophage *** is composed of several steps including progenitor survival,differentiation to mononuclear pre-osteoclasts,fusion to multi-nuclear mature osteoclasts,and activation to bone resorbing *** regulation of osteoclastogenesis has been extensively studied,in which the receptor activator of Nf-κB ligand(RANKL)-mediated signaling pathway and downstream transcription factors play essential ***,less is known about osteoclast fusion,which is a property of mature osteoclasts and is required for osteoclasts to resorb *** proteins that affect cell fusion have been *** them,dritic cell-specific transmembrane protein(DC-STAMP)is directly associated to osteoclast fusion in *** and factors influence osteoclast fusion through regula-tion of *** we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP.A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone ***-cell fusion is essential for a variety of cellular biological *** mammals,there is a limited number of cell types that fuse to form multinucleated cells,such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant *** most cases,cellcell fusion is beneficial for cells by enhancing *** fusion increases myofiber size and diameter and thereby increases contractile *** osteoclasts have far more bone resorbing activity than their mono-nuclear *** giant cells are much more efficient in the removal of implanted materials

关键词： Osteoclasts fusion Dritic cell-specific transmembrane protein Receptor activator of Nf-κB ligand Bone resorption

Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

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Bone Research 2019年第3期7卷 225-242页

作者： Elysia A. Masters Ryan P. Trombetta Karen L. de Mesy Bentley brendan f boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani Masahiro Ishikawa Yugo Morita Hiromu Ito Sheila N. Bello-Irizarry Mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA Department of Biomedical Engineering University of Rochester Medical Center Rochester NY USA Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA Department of Orthopaedics University of Rochester Medical Center Rochester NY USA Department of Microbiology & Immunology University of Rochester Medical Center Rochester NY USA Department of Orthopaedic Surgery Kyoto University Kyoto Japan Department of Orthopaedic Surgery Virginia Commonwealth University Medical Center Richmond VA USA

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, *** intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

关键词： disease caused by soft tissue necrotic tissuel

One-pot pyrolysis synthesis of highly active Ru/RuOx nanoclusters for water splitting

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Nano Research 2022年第2期15卷 1020-1026页

作者： fengyuan Zhu Jiangyan Xue Lingjian Zeng Jingrui Shang Shuanglong Lu Xueqin Cao brendan f.Abrahams Hongwei Gu Jianping Lang College of Chemistry Chemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China School of Chemical and Material Engineering Jiangnan UniversityWuxi 214122China School of Chemistry University of MelbourneVictoria 3010Australia

Using simple methods to obtain efficient catalysts has been a long-standing goal for *** this work,the employment of a one-pot pyrolysis reaction to achieve molecular confinement,has led to the preparation of ruthenium(Ru)-based nanoclusters in a carbon matrix.A unique feature of the synthetic approach employed is that solvent and substrates were calcined *** solvent evaporates,during calcination,the substrates form a dense solid which has the effect of limiting the aggregation of Ru centers during the carbonization *** catalyst prepared in this simple manner showed an impressively high activity with respect to the hydrogen/oxygen evolution reaction(HER/OER).The Ru nanoclusters(Ru NCs),as the hydrogen evolution reaction(HER)catalysts,require ultralow overpotentials of 5 mV and 5.1 mV at-10 mA·cm^(-2) in 1.0 M KOH,and 0.5 M H_(2)SO_(4),***,the catalyst prepared by the one-pot method has higher crystallinity,a higher Ru content and an ultrafine cluster size,which contributes to its exceptional electrochemical ***,the RuO_(x) nanoclusters(RuO_(x) NCs),obtained by oxidizing the aforementioned Ru NCs,exhibited good oxygen evolution reaction(OER)performance with an overpotential of 266 mV at 10 mA·cm^(-2).When applied to overall water splitting,Ru/RuO_(x) nanoclusters as the cathode and anode catalysts can reach 10 mA·cm^(-2) at cell voltages of only 1.49 V in 1 M KOH.

关键词： pyrolysis ruthenium nanoclusters ruthenium dioxide nanoclusters hydrogen evolution reaction oxygen evolution reaction overall water splitting

A hybrid catalyst for efficient electrochemical N_(2)fixation formed by decorating amorphous MoS_(3)nanosheets with MIL-101(fe)nanodots

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Science China Chemistry 2022年第5期65卷 885-891页

作者： Wan-Ying Xu Cong Li fei-Long Li Jiang-Yan Xue Wei Zhang Hongwei Gu brendan f.Abrahams Jian-Ping Lang College of Chemistry Chemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China School of Materials Engineering Changshu Institute of TechnologyChangshu 215500China School of Chemistry University of MelbourneVictoria 3010Australia

Metal-organic frameworks possessing relatively large pores,high surface areas,and unsaturated metal sites are attractive materials for use as electrocatalysts in the reduction of N_(2)to NH_(3).In this work,a MIL-101(fe)/MoS_(3)hybrid catalyst,prepared by using a precursor-transformation strategy,is shown to be an effective electrocatalyst for the N_(2)reduction reaction(NRR).Under solvothermal conditions,micro-sized octahedral MIL-101(fe)precursors are converted into ultra-small nanodots,while amorphous MoS_(3)derived from(NH_(4))_(2)MoS_(4)provides a surface suitable for anchoring the MIL-101(fe)*** asprepared composite exhibits excellent electrocatalytic activity and durability for the NRR with a faraday efficiency of 36.71%and an NH_(3)yield of 25.7μg h^(-1)mg_(cat)^(-1)at-0.1 V *** in 0.1 M *** results show that the dispersion and adherence of MIL-101(fe)nanodots on amorphous MoS_(3)improves the exposure of active centers and aids mass transfer,resulting in greatly enhanced catalytic activity and stability.

关键词： nitrogen reduction reaction MIL-101(fe)nanodots amorphous MoS_(3) precursor-transformation hybrid electrocatalysts

Temperature-dependent chloride-mediated access to atom-precise silver thiolate nanoclusters

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Science China Chemistry 2022年第6期65卷 1094-1099页

作者： Ling Yang Xin-Yao Wang Xiao-Yan Tang Meng-Yi Wang Chun-Yan Ni Hong Yu Ying-Lin Song brendan f.Abrahams Jian-Ping Lang College of Chemistry Chemical Engineering and Materials ScienceSoochow UniversitySuzhou215123China School of Materials Engineering Changshu Institute of TechnologyChangshu215500China School of Physical Science and Technology Soochow UniversitySuzhou215006China School of Chemistry University of MelbourneParkvilleVictoria3010Australia

By using a unique temperature-dependent,chloride-mediated approach,two atom-precise silver nanoclusters[Cl@Ag_(14)(Tab)_(12)-(C_(5)H_(4)NCl)_(12)](Pf_(6))_(13)(Cl@Ag_(14))and[Cl_(3)@Ag_(24)(Tab)_(20)(C_(5)H_(4)NCl)_(11)]Cl(Pf_(6))_(20)(Cl_(3)@Ag_(24))(Tab=4-(trimethylammonio)benzenethiolate,C_(5)H_(4)NCl=3-chloropyridine)were obtained ***,the number of chloride ions encapsulated inside the Ag-S shell could be regulated by the slow dissolution of almost insoluble KCl at various *** inclusion of additional core chloride ions results in the expansion of the surrounding Ag-S *** article provides a promising synthetic approach for controlling the number of Ag atoms that form a shell around the anionic core,in addition to offering a potential pathway for the introduction of other inorganic anions into silver *** broadly,through the use of related ligands,the synthetic strategy offers scope for generating new families of silver thiolate clusters of varying size and composition.

关键词： temperature-dependent chloride-mediated core expansion silver thiolate nanocluster transformation