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Cancer immunotherapy with envelopedself-amplifying mRNA CARG-2020 thatmodulates IL-12,IL-17 and PD-L1 pathways toprevent tumor recurrence

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Acta Pharmaceutica Sinica B 2024年第1期14卷 335-349页

作者： Ju Chen Bhaskara Reddy Madina Elham Ahmadi Timur Olegovich Yarovinsky Marie Marthe Krady Eileen Victoria meehan Isabella China Wang Xiaoyang Ye Elise Pitmon Xian-Yong Ma Bijan Almassian Valerian Nakaar Kepeng Wang Department of Immunology School of MedicineUniversity of Connecticut Health CenterFarmingtonCT 06030USA CaroGen Corporation FarmingtonCT 06030USA The Eighth Clinical Medical College of Guangzhou University of Chinese Medicine Foshan Hospital of Traditional Chinese MedicineFoshan 528000China The Loomis Chaffee School WindsorCT 06095USA

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for ***,we describe the application of virus-like vesicles(VLV)for delivery of three immunomodulators alone and in combination,as a promising approach for cancer *** vectors were designed to deliver single chain interleukin(IL)-12,shorthairpin RNA(shRNA)targeting programmed death ligand 1(PD-L1),and a dominant-negative form of IL-17 receptor A(dn-IL17RA)as a single payload or as a combination *** delivery of the VLV vector expressing IL-12 alone,as well as the trivalent vector(designated CARG-2020)eradicated large established ***,only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice,indicating a benefit of the combined *** abscopal effects of CARG-2020 on the non-injected contralateral tumors,as well as protection from the tumor cell re-challenge,suggest immune-mediated mechanism of protection and establishment of immunological ***,CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting *** ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

关键词： Virus-like vesicles Oncolytic virus IL-12 IL-17 PD-L1 T cell exhaustion Combination therapy Cancer immunotherapy

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Axon regeneration:membrane expansion and lipidomics

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Neural Regeneration Research 2022年第5期17卷 989-990页

作者： Sean meehan Sanjoy K.Bhattacharya Graduate Program in Molecular and Cellular Pharmacology Miami Integrative Metabolomics Research CenterBascom Palmer Eye InstituteUniversity of MiamiMiamiFLUSA

Axon regeneration requires protein synthesis and membrane *** presence of granular material was discovered in the perikaryon of neurons but not axons using Nissl staining(Gomes,2019).This is one of the characteristic ... 详细信息

关键词： expansion. expansion regeneration

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Utility of D-dimer in total joint arthroplasty

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World Journal of Orthopedics 2023年第3期14卷 90-102页

作者： Brenden Cutter Zachary C Lum Mauro Giordani John P meehan Department of Orthopedic Surgery Valley Orthopedic Surgery Residency/Valley Consortium for Medical EducationModestoCA 95351United States Department of Orthopaedics Adult Reconstruction DivisionUniversity of CaliforniaDavis Medical CenterSacramentoCA 95817United States

As the number of patients receiving total joint replacements continues to rise,considerable attention has been directed towards the early detection and prevention of postoperative *** D-dimer has long been studied as a diagnostic tool in venous thromboembolism(VTE),this assay has recently received considerable attention in the diagnosis of periprosthetic joint infection(PJI).D-dimer values are substantially elevated in the acute postoperative period after total joint arthroplasty,with levels often exceeding the standard institutional cutoff for VTE(500µg/L).The utility of D-dimer in detecting VTE after total joint replacement is currently limited,and more research to assess its value in the setting of contemporary prophylaxis protocols is *** literature supports D-dimer as a good to excellent biomarker for the diagnosis of chronic PJI,especially when using serum sample *** should exercise caution when interpreting D-dimer levels in patients with inflammatory and hypercoagulability disorders,as the diagnostic value is *** updated 2018 Musculoskeletal Infection Society criteria,which includes D-dimer levels>860µg/L as a minor criterion,may be the most accurate for diagnosing chronic PJI to *** prospective trials with transparent lab testing protocols are needed to establish best assay practices and optimal cutoff values for D-dimer in the diagnosis of *** review summarizes the most current literature on the value of D-dimer in total joint arthroplasty and elucidates areas for future progress.

关键词： D-dimer Diagnosis Periprosthetic joint infection Venous thromboembolism Deep vein thrombosis Arthroplasty

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Effects of contact/collision sport history on gait in early-to mid-adulthood

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Journal of Sport and Health Science 2023年第3期12卷 398-405页

作者： Katherine J.Hunzinger Jaclyn B.Caccese Rebekah Mannix William P.meehanⅢ Jocelyn F.Hafer C.Buz Swanik Thomas A.Buckley Department of Biostatistics Epidemiologyand InformaticsUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPA 19104USA Penn Injury Science Center University of PennsylvaniaPhiladelphiaPA 19104USA School of Health and Rehabilitation Sciences The Ohio State University College of MedicineColumbusOH 43210USA Division of Emergency Medicine Boston Children's HospitalBostonMA 02115USA Departments of Pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA The Micheli Center for Sports Injury Prevention WalthamMA 02453USA Division of Sports Medicine Department of OrthopedicsBoston Children's HospitalBostonMA 02453USA Department of Pediatrics and Orthopedics Harvard Medical SchoolBostonMA 02453USA Department of Kinesiology and Applied Physiology University of DelawareNewarkDE 02453USA Interdisciplinary Program in Biomechanics and Movement Science University of DelawareNewarkDE 02453USA

Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged ***:The study recruited 113 adults(34.88±11.80 years,(mean±SD);53.0%female)representing 4 *** included(a)former non-contact/collision athletes and non-athletes who are not physically active(n=28);(b)former non-contact/collision athletes who are physically active(n=29);(c)former contact/collision sport athletes who participated in high-risk sports and are physically active(n=29);and(d)former rugby players with prolonged repetitive head impact exposure history who are physically active(n=27).Gait parameters were collected using inertial measurement units during ST and DT *** cost was calculated for all gait parameters(double support,gait speed,and stride length).Groups were compared first using one-way analysis of *** a multiple regression was performed for participants in the highrisk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career ***:There were no significant differences between groups on any ST,DT,or DT cost outcomes(p>0.05).Contact/collision sport duration did not predict any ST,DT,or DT cost gait ***:Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early-to mid-adulthood among physically active individuals.

关键词： Exercise Neurodegenerative disease Postural control Rugby Subconcussive impacts

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Crystallization and Preliminary Crystallographic Analysis of β-Trichosanthin,an Isoform of Trichosanthin from the Root Tuber of Trichosanthe kirilowii

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Chinese Journal of Structural Chemistry 2007年第11期26卷 1303-1307页

作者：侯晓敏陈明晃彭奇陈荔清 meehan Edward J 黄明东 State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterThe Chinese Academy of Sciences Laboratory for Structural Biology Department of ChemistryGraduate Programs of BiotechnologyChemistry and Materials ScienceUniversity of Alabama in Huntsville

β-Trichosanthin, a type 1 ribosome-inactivating protein （RIP） isolated from the root tuber of Trichosanthe kirilowii Maxim, is an isoform of trichosanthin. Here we report its crystallization in two crystal forms using the hanging-drop vapor-diffusion method. The form A and form B crystals belong to the orthorhombic space group P212121 and monoclinic space group P21, respectively. X-ray data have been collected to 1.6 and 1.2 A resolution for form A and form B crystals, respectively, using a synchrotron source.

关键词： ribosome-inactivating protein isoform trichosanthin crystallization

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Impaired eye tracking is associated with symptom severity but not dynamic postural control in adolescents following concussion

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Journal of Sport and Health Science 2021年第2期10卷 138-144页

作者： Jessie R.Oldham William P.meehan III David R.Howell The Micheli Center for Sports Injury Prevention WalthamMA 02453USA Division of Sports Medicine Department of OrthopedicsBoston Children’s HospitalBostonMA 02115USA Department of Pediatrics and Orthopedics Harvard Medical SchoolBostonMA 02115USA Sports Medicine Center Children’s Hospital ColoradoAuroraCO 80045USA Department of Orthopedics University of Colorado School of MedicineAuroraCO 80045USA

Purpose:The purpose of the study was to(1)examine the relationship between self-reported symptoms and concussion-related eye tracking impairments,and(2)compare gait performance between(a)adolescents with a concussion who have normal eye tracking,(b)adolescents with a concussion who have abnormal eye tracking,and(c)healthy ***:A total of 30 concussed participants(age:14.4±2.2 years,mean±SD,50%female)and 30 controls(age:14.2±2.2 years,47%female)completed eye tracking and gait *** BOX score is a metric of pupillary disconjugacy,with scores<10 classified as normal and≥10 *** were collected using the Post-Concussion Symptom Scale(PCSS),and gait speed was measured with triaxial inertial measurement *** conducted a linear regression to examine the relationship between PCSS and BOX scores and a two-way mixed effects analysis of variance to examine the effect of group(abnormal BOX,normal BOX,and healthy control)on single-and dual-task gait ***:There was a significant association between total PCSS score and BOX score in the concussion group(β=0.16,p=0.004,95%confidence interval(95%CI):0.06‒0.27),but not in the control group(β=0.21,p=0.08,95%CI:0.03 to 0.45).There were no significant associations between PCSS symptom profiles and BOX scores in the concussion or control *** were also no significant differences in singletask(Abnormal:1.00±0.14 m/s;Normal:1.11§0.21 m/s;Healthy:1.14±0.18 m/s;p=0.08)or dual-task(Abnormal:0.77±0.15 m/s;Normal:0.84±0.21 m/s;Healthy:0.90±0.18 m/s;p=0.16)gait ***:The concussed group with impaired eye tracking reported higher total symptom severity,as well as worse symptom severity across the 5 PCSS symptom domain ***,eye tracking deficits did not appear to be driven by any particular symptom *** not statistically significant,the slower gait speeds in those with abnormal BOX scores may still be clinically relevant since gait-related impairments may persis

关键词： Gait Mild traumatic brain injury Vision

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Systematic review of single stage revision for prosthetic joint infection

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World Journal of Orthopedics 2020年第12期11卷 559-572页

作者： Zachary C Lum Christopher Thomas Holland John P meehan Department of Orthopaedic Surgery Davis Medical CenterUniversity of CaliforniaSacramentoCA 95817United States Department of Orthopaedics University of CaliforniaDavis Medical CenterSacramentoCA 95817United States

While advanced technology,increased medical knowledge and improved surgical technique has improved patient outcomes in total joint arthroplasty,prosthetic joint infection still remains one of the leading causes of increased healthcare costs,medical resources and societal burdens in orthopaedic *** stage arthroplasty revision remains the gold standard for treatment of prosthetic joint *** of single stage revision arthroplasty for infection argue that it results in lower healthcare costs while improving patient reported functional outcomes and with equivalent success *** we review the history of single stage revision arthroplasty,discuss the key principles,highlight the indications and contraindications,and review the reported outcomes with a focus on future developments of single stage revision arthroplasty for hip and knee periprosthetic joint infections.

关键词： Prosthetic joint infection Single stage Revision total joint arthroplasty Total knee arthroplasty Infection

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Expression, Purification, Crystallization and Molecular Replacement Studies of TorI, an Inhibition Protein of Tor System

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Chinese Journal of Structural Chemistry 2007年第5期26卷 594-598页

作者： HUANG Wei YUAN Cai Ansaldi Mireille Morelli Xavier Edward J. meehan CHEN Li-Qing HUANG Ming-Dong State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter The Chinese Academy of Sciences Fuzhou Fujian 350002 China Graduate School of the Chinese Academy of Sciences Beo＇ing 100039 China Laboratoire de Chimie Bacte＇rienne Institut de Biologie Structurale et Microbiologie CentreNational de la Recherche Scientifique 31 Chemin Joseph Aiguier 13402 Marseille Cedex 20 France Laboratoire de Chimie Bactoéienne CNRS/IBSM BIP Laboratory 31 Chemin Joseph Aiguier 13402 Marseille Cedex 20 France Laboratory for Structural Biology Department of Chemistry Graduate Programs of Biotechnology Chemistry and Materials Science University of Alabama in Huntsville Huntsville AL 35899 USA

TorI, a Tor system inhibitor acting through protein-protein interaction with the TorR response regulator, is an excisionase that interacts with the integrase and DNA during prophage excision. It has been crystallized by the vapor-diffusion method using polyethylene glycol 3350 as a precipitant at pH 8.5. The X-ray diffraction data sets from the TorI crystal was collected at a resolution of 2.1 , using a synchrotron source. The crystal belongs to primitive monoclinic lattice with cell parameters of 46.210 × 53.992 × 73.561A

关键词： Torl inhibitor crystallization X-ray diffraction

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A New Drug Binding Subsite on Human Serum Albumin and Drug-Drug Interaction Studied by X-Ray Crystallography

A New Drug Binding Subsite on Human Serum Albumin and Drug-D...

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中国化学会第五届全国结构化学学术会议

作者： Edward J.meehan Laboratory for Structural Biology Department of ChemistryGraduate Programs of BiotechnologyChemistry and Materials ScienceUniversity of Alabama in HuntsvilleHuntsvilleAL 35899USA

＜正＞3′-azido-3′-deoxythymidine[1]（AZT）is the first clinically effective drug for the treatment of human immunodeficiency virus *** drug interaction with human serum albumin （HSA）[2]has been an important compon...

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Sequencing method comparison and crystal structure of luffaculin 1,a novel type 1 ribosome-inactivating protein

Sequencing method comparison and crystal structure of luffac...

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中国化学会第五届全国结构化学学术会议

＜正＞A novel type 1 ribosome-inactivating protein designated luffaculin 1 was isolated from the seeds of Luffa *** rRNA N-glycosidase activity,luffaculin 1 also demonstrates activities including inhibiting tumor cell...

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