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Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3063-3072页

作者： Yi Zhu Na Li Mingyang Huang Xi Chen Yu AAn Jianping Li Shangang Zhao Jan-Bernd Funck Jianhong Cao Zhenyan He Qingzhang Zhu Zhuzhen Zhang Zhao VWang Lin Xu kevin W.Williams Chien Li kevin Grove Philipp e.Scherer Touchstone Diabetes Center Department of Internal Medicinethe University of Texas Southwestern Medical Center at DallasDallasTX 75390USA Division of Cardiology Department of Internal Medicinethe University of Texas Southwestern Medical Center at DallasDallasTX 75390USA Division of Hypothalamic Research Department of Internal Medicinethe University of Texas Southwestern Medical Center at DallasDallasTX 75390USA Quantitative Biomedical Research Center Department of Population and Data Sciencesthe University of Texas Southwestern Medical Center at DallasDallasTX 75390USA Department of Pediatrics the University of Texas Southwestern Medical Center at DallasDallasTX 75390USA Novo Nordisk Research Center SeattleWA 98109USA Children’s Nutrition Research Center Department of PediatricsBaylor College of MedicineHoustonTX 77030USA Department of Cell Biology the University of Texas Southwestern Medical Center at DallasDallasTX 75390USA

Adipose tissue is a promising target for treating obesity and metabolic ***,pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization,especially in obese *** have previously shown that during cold exposure,connexin43(Cx43)gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple *** reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose *** an adipose tissue-specific Cx43 overexpression mouse model,we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of theβ_(3)-adrenergic receptor agonist Mirabegron and ***,combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced *** light of these findings,we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage ***,Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.

关键词： GJA1 Adipose tissue Gap junction Connexin43 FGF21 β3-Adrenergic receptor agonist Obesity Type 2 diabetes

Trichomeriaceae, a new sooty mould family of Chaetothyriales

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Fungal Diversity 2012年第5期56卷 63-76页

作者： Putarak Chomnunti D.J.Bhat e.B.Gareth Jones ekachai Chukeatirote Ali H.Bahkali kevin D.Hyde International Fungal Research and Development Centre The Research Institute of Resource InsectsChinese Academy of ForestryBailongsiKunmingYunnanPeople’s Republic of China 650224 Institute of excellence in Fungal Research School of ScienceMae Fah Luang UniversityChiang Rai 57100Thailand School of Science Mae Fah Luang UniversityChiang Rai 57100Thailand Institute of Ocean and earth Sciences(IOeS) C308Institute of Postgraduate Studies BuildingUniversity of Malaya50603Kuala LumpurMalaysia College of Science Botany and Microbiology DepartmentKing Saud UniversityRiyadh 1145Saudi Arabia

Trichomerium is a genus of foliar epiphytes with the appearance of sooty moulds,mostly occurring on the surface of living leaves and apparently gaining their nutrients from insect *** have ascostromata with setae and develop on a loosely interwoven mycelial mass of dark brown hyphae,while asci have a bitunicate appearance with hyaline *** this study,we made 16 collections of Trichomerium from *** were isolated,and the LSU and ITS rDNA gene regions *** analysis indicated that the Trichomerium species form a monophyletic clade within Chaetothyriales and warrant the introduction of a new family *** support for the Chaetothyriales is 100%and clearly separates Trichomeriaceae from Capnodiales which are morphologically very similar.A detailed account of Trichomerium is provided and we describe and illustrate three new species based on morphological and molecular *** propose that *** is adopted as the generic type of Trichomerium because it has been impossible to obtain the holotype specimen of *** and also no molecular data exists in worldwide databases for this species or genus.

关键词： Foliar epiphytes Phylogeny Sooty moulds Trichomerium

Creation and validation of a novel low-cost dry lab for early resident training and assessment of robotic prostatectomy technical proficiency

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Current Urology 2024年第2期18卷 133-138页

作者： kevin Kunitsky Abhishek Venkataramana Katherine e.Fero Jorge Ballon Jacob Komberg Robert Reiter Wayne Brisbane Institute of Urologic Oncology Department of UrologyDavid Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Charles e.Schmidt College of Medicine Florida Atlantic UniversityBoca RatonFLUSA

Purpose:To evaluate the preliminary validity and acceptability of a low-cost low-fidelity robotic surgery dry lab for training and assessing residents’technical proficiency with key robotic radical prostatectomy *** and methods:Three standardized inanimate tasks were created to simulate the radical prostatectomy steps of posterior dissection,neurovascular bundle release,and urethrovesical *** trainees and faculty at a single institution completed and evaluated each dry lab *** validity was evaluated by comparing task completion times and Global evaluative Assessment of Robotic Skills scores across four participant cohorts:medical students(n=5),junior residents(n=5),senior residents(n=5),and attending surgeons(n=7).Content validity,face validity,and acceptabilitywere evaluated through a posttask survey using a 5-point Likert ***:There was a significant difference in the individual and composite task completion times and Global evaluative Assessment of Robotic Skills scores across all participant cohorts(all pe model was rated favorably in terms of its content validity and acceptability for use in residency ***,model realism,compared with human tissue,was poorly *** dry lab production cost was less than US$***:This low-cost procedure-specific dry lab demonstrated evidence of content validity,construct validity,and acceptability for simulating key robotic prostatectomy technical steps and can be used to augment robot-assisted laparoscopic prostatectomy surgical training.

关键词： Robotic surgery education Radical prostatectomy Simulation Dry laboratory Validation

epidemiologic investigation of pediatric distal humerus fractures: An American insurance claims database study

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World Journal of Orthopedics 2024年第1期15卷 52-60页

作者： Kyle Jay Klahs Jake e Dertinger Grant T Mello kevin Thapa Alexis B Sandler e'Stephan J Jesus Garcia Nata Parnes Department of Orthopaedic Surgery Texas Tech University Health Sciences-El PasoEl PasoTX 79905United States Medical School California Health Sciences University College of Osteopathic MedicineClovisCA 93611United States Undergraduate School Binghampton UniversityVestalNY 13902United States Department of Orthopaedic Surgery William Beaumont Army Medical CenterFort BlissTX 79918United States Department of Orthopaedic Surgery Carthage Area HospitalCarthageNY 13619United States

BACKGROUND Distal humerus elbow fractures are one of the most common traumatic fractures seen in pediatric patients and present as three main types:Supracondylar(SC),lateral condyle(LC),and medial epicondyle(Me)*** To evaluate the epidemiology of pediatric distal humerus fractures(SC,LC,and Me)from an American insurance claims *** A retrospective review was performed on patients 17 years and younger with the ICD 9 and 10 codes for SC,LC and Me fractures based on the IBM Truven MarketScan®Commercial and IBM Truven MarketScan Medicare Supplemental *** from 2015 to 2020 were queried for treatments,patient age,sex,length of hospitalization,and *** A total of 1133 SC,154 LC,and 124 Me fractures were *** fractures had the highest percentage of operation at 83%,followed by LC(78%)and Me fractures(41%).Male patients were,on average,older than female patients for both SC and Me *** In the insurance claims databases used,SC fractures were the most reported,followed by LC fractures,and finally Me *** was identified to be a factor for how a pediatric distal humerus fractures,with patients with SC and LC fractures being younger than those with Me *** peak age per injury per sex was similar to reported historic central tendencies,despite reported trends for younger physiologic development.

关键词： Supracondylar humerus fracture Lateral condyle fracture Medial epicondyle fracture Pediatric elbow Truven epidemiology

Bone graft substitutes for spine fusion: A brief review

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World Journal of Orthopedics 2015年第6期6卷 449-456页

作者： Ashim Gupta Nitin Kukkar kevin Sharif Benjamin J Main Christine e Albers Saadiq F el-Amin Ⅲ Department of Medical Microbiology Immunology and Cell Biology Southern Illinois University School of Medicine Institute for Plastic Surgery Department of Surgery Southern Illinois University School of Medicine Division of Orthopaedics and Rehabilitation Department of Surgery Southern Illinois University School of Medicine Department of Surgery Kansas City University of Medicine and Biosciences

Bone graft substitutes are widely used in the field of orthopedics and are extensively used to promote vertebral fusion. Fusion is the most common technique in spine surgery and is used to treat morbidities and relieve discomfort. Allograft and autograft bone substitutes are currently the most commonly used bone grafts to promote fusion. These approaches pose limitations and present complications to the patient. Numerous alternative bone graft substitutes are on the market or have been developed and proposed for application. These options have attempted to promote spine fusion by enhancing osteogenic properties. In this review, we reviewed biology of spine fusion and the current advances in biomedical materials and biological strategies for application in surgical spine fusion. Our findings illustrate that, while many bone graft substitutes perform well as bone graft extenders, only osteoinductive proteins(recombinant bone morphogenetic proteins-2 and osteogenic protein-1) provide evidence for use as both bone enhancers and bone substitutes for specific types of spinal fusion. Tissue engineered hydrogels, synthetic polymer composites and viral based gene therapy also holds the potential to be used for spine fusion in future, though warrants further investigation to be used in clinical practice.

关键词： Bone enhancers Bone graft substitutes Spine fusion Autograft Allograft

Integrating the ISO 14034 standard as a platform for carbon capture and utilization technology performance evaluation

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Clean energy 2021年第4期5卷 600-610页

作者： Tim Hansen kevin McCabe Bill Chatterton Michael Leitch 350Solutions Inc.1053 E.Whitaker Mill RdSuite 115RaleighNC 27604USA XPRIZe Foundation 800 Corporate PointeSuite 350Culver CityCA 90230USA

Independent testing and verification of emerging technologies are vital parts of the technology-commercialization *** the rapid development of carbon capture and utilization(CCU)technologies,where existing standards and certifications do not exist,independent verification approaches and guidelines can provide a means to obtain credible information for an emerging *** ISO 14034:2016-environmental Management:environmental Technology Verification(eTV)standard can serve as a foundational platform to ensure the consistency,quality and credibility of data on CCU technology performance,enabling direct comparisons between technologies and reducing risk to decision-makers regarding potential investment,future deployment and ultimate impacts of CCU *** the fundamental principles of ISO 14034 to the evaluation of nine finalist CCU technologies competing in the NRG COSIA Carbon XPRIZe ensured that data used to evaluate competitors was of high quality,consistent across technologies and met the information needs of the XPRIZe and competition judges responsible for selecting *** approaches outlined here,including verification parameters and verification tasks for both XPRIZe-specific technology evaluations and full CCU technology evaluation by an accredited entity in conformance with the ISO 14034 standard,provide insight into the potential benefits-methodological consistency,high-quality data,independent oversight,methodological flexibility and broad applicability-and limitations-technology readiness and applicability,verification and instrumentation costs and lack of specificity-of the approach in an application for the evaluation of emerging *** application of the ISO 14034 standard and principles,developed through a consensus approach that incorporates other developing guidelines,can drive consistency and credibility for technology-performance evaluations across the CCU sector,ultimately leading to reduced risk and impr

关键词： carbon capture CCUS chemical engineering coal energy and environment fossil energy

Whole mount of adult ear skin as a model to study vascular malformations

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Animal Models and experimental Medicine 2023年第4期6卷 362-368页

作者： Brandee Decker-Rockefeller Qingfen Li kevin Pumiglia Biology Department Utica UniversityUticaNew YorkUSA Department of Regenerative and Cancer Cell Biology Albany Medical CollegeAlbanyNew YorkUSA

Background:Genetic analysis in human patients has linked mutations in PIK3CA,the catalytic subunit of PI-3′Kinase,to sporadic incidences of vascular ***:We have developed a mouse model with inducible and endothelial-specific expression of PIK3CA H1047R,resulting in the development of vascular *** induction of this mutation in adult mice results in rapid lethality,limiting our ability to track and study these lesions;therefore,we developed a topical and local induction protocol using the active metabolite of tamoxifen,4OH-T,on the ear skin of ***:This approach allows us to successfully model the human disease in a mature and established vascular bed and track the development of vascular *** validate the utility of this model,we applied a topical rapamycin ointment,as rapamycin is therapeutically beneficial to patients in clinical *** found that the induced ear lesions showed significant attenuation after treatment,which was easily ***:These data collectively provide evidence of a new model to study vascular malformations in adult tissues,which should be particularly useful in environments lacking specialized small-animal imaging facilities.

关键词： animal disease models pathological angiogenesis PIK3CA rapamycin vascular malformations

expanding beyond canonical metabolism:Interfacing alternative elements,synthetic biology,and metabolic engineering

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Synthetic and Systems Biotechnology 2018年第1期3卷 20-33页

作者： kevin B.Reed Hal S.Alper McKetta Department of Chemical engineering The University of Texas at Austin200E Dean Keeton St.Stop C0400AustinTX 78712USA Institute for Cellular and Molecular Biology The University of Texas at Austin2500 Speedway AvenueAustinTX 78712USA

Metabolic engineering offers an exquisite capacity to produce new molecules in a renewable ***,most industrial applications have focused on only a small subset of elements from the periodic table,centered around carbon *** review aims to illustrate the expanse of chemical elements that can currently(and potentially)be integrated into useful products using cellular ***,we describe recent advances in expanding the cellular scope to include the halogens,selenium and the metalloids,and a variety of metal *** examples range from small molecules,heteroatom-linked uncommon elements,and natural products to biomining and nanotechnology ***,this review covers the promise of an expanded range of elemental incorporations and the future impacts it may have on biotechnology.

关键词： Metabolic engineering Synthetic biology Unnatural metabolism Halogenation Cellular factories Non-canonical elements

Comparison of properties of traditional and accelerated carbonated solidified/stabilized contaminated soils

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Journal of environmental Sciences 2008年第5期20卷 593-598页

作者： LIU Jiangying XU Dimin XIONG Lan Colin HILLS Paula CAReY kevin GARDNeR State Key Laboratory of Pollution Control and Resource Reuse College of Environmental Science and Engineering Tongji University Shanghai 200092 China Department of Civil engineering University of Birmingham Edgbaston Birmingham B15 2TTUnited Kingdom Centre for Contaminated Land Remediation Department of Earth and Environmental Sciences University of Greenwich Chatham Maritime Kent ME4 4TB United Kingdom Department of Civil engineering University of New Hampshire Durham NH03824 USA

The investigation of the long-term performance of solidified/stabilized （S/S） contaminated soils was carried out in a trial site in southeast UK. The soils were exposed to the maximum natural weathering for four years and sampled at various depths in a controlled manner. The chemical properties （e.g., degree of carbonation （DOC）, pH, electrical conductivity （eC）） and physical properties （e.g., moisture content （MC）, liquid limit CLL）, plastic limit （PL）, plasticity index （PI）） of the samples untreated and treated with the traditional and accelerated carbonated S/S processes were analyzed. Their variations on the depths of the soils were also studied. The result showed that the broad geotechnical properties of the soils, manifested in their PIs, were related to the concentration of the water soluble ions and in particular the free calcium ions. The samples treated with the accelerated carbonation technology （ACT）, and the untreated samples contained limited number of free calcium ions in solutions and consequently interacted with waters in a similar way. Compared with the traditional cement-based S/S technology, e.g., treatment with ordinary portland cement （OPC） or envirOceM, ACT caused the increase of the PI of the treated soil and made it more stable during long-term weathering. The PI values for the four soils ascended according to the order： the envirOceM soil, the OPC soil, the ACT soil, and the untreated soil while their pH and eC values descended according to the same order.

关键词： solidified/stabilized accelerated carbonation contaminated soil electrical conductivity liquid limit plastic limit plasticity index