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The proteome of distal nerves: implication in delayed repair and poor functional recovery

Neural Regeneration Research 2022年第9期17卷 1998-2006页

作者： Song Guo Raymond M.Moore M.Cristine Charlesworth Kenneth L.johnson Robert j.Spinner anthony j.windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Biomedical Statistics and Informatics Mayo ClinicRochesterMNUSA Proteomics Core Mayo ClinicRochesterMNUSA Department of Neurology Mayo ClinicRochesterMNUSA

Chronic denervation is one of the key factors that affect nerve regeneration.Chronic axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for regeneration.Some of these factors/proteins have been individually studied.To better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair model.Four rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week delay.All the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting proteins.Twenty-five micrograms of protein from each sample were fractionated in SDS-PAGE gels.NanoLC-MS/MS analysis was applied to the gels.Protein expression levels of nerves on the surgery side were compared to those on the contralateral side.Any protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially expressed.All the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve regeneration.Ingenuity Pathway Analysis(IPA)software was used for pathway analysis.The results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were identified.The experimental group also had more beneficial proteins that were downregulated and more detrimental proteins that

关键词： chronic axotomy chronic denervation delayed repair distal nerve functional recovery nerve regeneration peripheral nerve prolonged denervation proteome sciatic nerve sciatic nerve transection

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Key changes in denervated muscles and their impact on regeneration and reinnervation

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Neural Regeneration Research 2014年第20期9卷 1796-1809页

作者： Peng Wu Aditya Chawla Robert j.Spinner Cong Yu Michael j.Yaszemski anthony j.windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Department of Hand Surgery Huashan HospitalFudan University Department of Orthopedic Surgery the Second Affiliated HospitalZhejiang University School of Medicine Department of Orthopedic Surgery Wake Forest School of MedicineWinston-SalemNCUSA Departments of Orthopedic Surgery and Biomedical Engineering Mayo ClinicRochesterMNUSA Department of Neurology Mayo ClinicRochesterMNUSA Shanghai Key Laboratory of Peripheral Nerve and Microsurgery

The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle＇s residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.

关键词： nerve regeneration denervation reinnervation fibrillation potential muscle fiberconduction velocity muscle fiber diameter maximal isometric force neuromuscular junction geneexpression neural regeneration

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A novel triple immunoenzyme staining enables simultaneous identification of all muscle fiber types on a single skeletal muscle cryosection from normal, denervated or reinnervated rats

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Neural Regeneration Research 2017年第8期12卷 1357-1364页

作者： Peng Wu Shuya Zhang Robert j.Spinner Michael Torres Lizardi Yudong Gu Cong Yu Michael j.Yaszemski anthony j.windebank Huan Wang Department of Neurological Surgery Mayo Clinic Rochester MN USA Department of Hand Surgery Huashan Hospital Fudan University Shanghai China Shanghai Tenth People's Hospital Tongji University Shanghai China Department of Neurology Mayo Clinic Rochesterl MN USA Department of Medicine New York Presbyterian Weill Cornell Medical Center New York NY USA Shanghai Key Laboratory of Peripheral Nerve and Microsurgery Shanghai China Departments of Orthopedic Surgery and Biomedical Engineering Mayo Clinic Rochester MN USA

Triple immunofluorescence staining has recently been developed to simultaneously identify all muscle fibers on a single cryosection which is helpful for clinical and basic research, but it has disadvantages such as fast photobleaching and unclear outlines of muscle fibers. Triple immunoenzyme staining（TIE） is likely to avoid these disadvantages. In this study, we aimed to establish a sensitive and specific TIE technique to identify fiber types in normal, denervated, and reinnervated rat muscles, and to develop a systematic sampling method for muscle fiber quantification. Tibialis anterior and soleus from normal, denervated, and reinnervated Lewis rat hind limbs were used. Five consecutive cryosections were cut from each muscle, including one for TIE and four for single immunoenzyme staining（SIE）. The TIE was performed using the polymerized reporter enzyme staining system for the first two antigens（A4.74 for My HC-IIA, BA-F8 for My HC-I） and alkaline phosphatase staining system for the third antigen（BF-F3 for My HC-IIB）, followed by corresponding detective systems and respective chromogens. The type of muscle fibers was quantified by systematic sampling at 12.5%, 25%, 33% and 50% of all muscle fibers, and was compared with that acquired from counting all the fibers（100%）. All muscle fiber phenotypes, including pure and hybrid, could be simultaneously identified on a single TIE cryosection with clear outlines. The fiber types on TIE slides matched well with their respective counterpart on the consecutive SIE slides with a 95% match rate. Systematic sampling of 12.5% fibers could represent the true fiber type distribution of the entire muscle section. Our results suggest that novel TIE can effectively visualize fiber types in normal, denervated or reinnervated rat muscles.

关键词： nerve regeneration muscle fiber phenotyping immunohistochemistry triple immunoenzymestaining myosin heavy chain rats neural regeneration

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Single-atom Pt on carbon nanotubes for selective electrocatalysis

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Carbon Energy 2024年第1期6卷 63-71页

作者： Samuel S.Hardisty Xiaoqian Lin anthony R.j.Kucernak David Zitoun Department of Chemistry Bar Ilan Institute of Nanotechnology and Advanced Materials(BINA)Bar Ilan UniversityRamat GanIsrael Department of Chemistry Molecular Science Research HubImperial College LondonLondonUK

Utilizing supported single atoms as catalysts presents an opportunity to reduce the usage of critical raw materials such as platinum,which are essential for electrochemical reactions such as hydrogen oxidation reaction(HOR).Herein,we describe the synthesis of a Pt single electrocatalyst inside single-walled carbon nanotubes(SWCNTs)via a redox reaction.Characterizations via electron microscopy,X-ray photoelectron microscopy,and X-ray absorption spectroscopy show the single-atom nature of the Pt.The electrochemical behavior of the sample to hydrogen and oxygen was investigated using the advanced floating electrode technique,which minimizes mass transport limitations and gives a thorough insight into the activity of the electrocatalyst.The single-atom samples showed higher HOR activity than state-of-the-art 30%Pt/C while almost no oxygen reduction reaction activity in the proton exchange membrane fuel cell operating range.The selective activity toward HOR arose as the main fingerprint of the catalyst confinement in the SWCNTs.

关键词： confinement electrocatalysis hydrogen platinum single atom catalysts

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Academic productivity correlates with industry earnings in foot and ankle fellowship programs in the United States:A retrospective analysis

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World journal of Orthopedics 2024年第2期15卷 129-138页

作者： Albert T Anastasio anthony N Baumann Kempland C Walley Kyle j Hitchman Conor O’Neill jonathan Kaplan Samuel B Adams Department of Orthopedic Surgery Duke University HospitalDurhamNC 27710United States College of Medicine Northeast Ohio Medical UniversityRootstownOH 44272United States Department of Orthopedic Surgery University of MichiganAnn ArborMI 48109United States School of Osteopathic Medicine Campbell UniversityLillingtonNC 27546United States

BACKGROUND The study investigates the connection between academic productivity and industry earnings in foot and ankle orthopedic surgery fellowships.Utilizing metrics like the H-index and Open Payments Database(OPD)data,it addresses a gap in understanding the relationship between scholarly achievements and financial outcomes,providing a basis for further exploration in this specialized medical field.AIM To elucidate the trends between academic productivity and industry earnings across foot and ankle orthopedic surgery fellowship programs in the United States.METHODS This study is a retrospective analysis of the relationship between academic productivity and industry earnings of foot and ankle orthopedic surgery fellowships at an individual faculty and fellowship level.Academic productivity was defined via H-index and recorded from the Scopus website.Industry earnings were recorded from the OPD.RESULTS Forty-eight foot and ankle orthopedic surgery fellowships(100%of fellowships)in the United States with a combined total of 165 physicians(95.9%of physicians)were included.Mean individual physician(n=165)total life-time earnings reported on the OPD website was United States Dollar(USD)451430.30±1851084.89(range:USD 25.16-21269249.85;median:USD 27839.80).Mean physician(n=165)H-index as reported on Scopus is 14.24±12.39(range:0-63;median:11).There was a significant but weak correlation between individual physician H-index and individual physician total life-time earnings(P<0.001;Spearman’s rho=0.334)and a significant and moderate positive correlation between combined fellowship H-index and total life-time earnings per fellowship(P=0.004,Spearman’s rho=0.409).CONCLUSION There is a significant and positive correlation between academic productivity and industry earnings at foot and ankle orthopedic surgery fellowships in the United States.This observation is true on an individual physician level as well as on a fellowship level.

关键词： Sunshine act Foot and ankle Orthopedic surgery Orthopedic fellowship Industry earnings

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Activation of cerebral Ras-related C3 botulinum toxin substrate(Rac) 1 promotes post-ischemic stroke functional recovery in aged mice

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Neural Regeneration Research 2024年第4期19卷 881-886页

作者： Fan Bu jia-Wei Min Md Abdur Razzaque Ahmad El Hamamy anthony Patrizz Li Qi Akihiko Urayama jun Li Department of Neurology University of Texas Health Science Center Department of Neurology&Psychology The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6j)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.

关键词： aging angiogenesis brain-derived neurotrophic factor(BDNF) cerebral ischemia cognitive recovery neurite Pak1 Rac1 sensorimotor recovery

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The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[^(18)F]fluoro-D-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology:A single centre retrospective study

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Asian journal of Urology 2024年第1期11卷 33-41页

作者： anthony Franklin Troy Gianduzzo Boon Kua David Wong Louise McEwan james Walters Rachel Esler Matthew j.Roberts Geoff Coughlina john W.Yaxley Department of Urology The Wesley HospitalBrisbaneQLDAustralia Wesley Medical Research BrisbaneQLDAustralia School of Medicine The University of QueenslandBrisbaneQLDAustralia Department of Radiology Wesley Medical ImagingBrisbaneQLDAustralia Department of Urology Royal Brisbane and Women's HospitalBrisbaneQLDAustralia

Objective:To review the risk of prostate cancer(PCa)in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography(18F-FDG PET/CT)ordered at Department of Urology,The Wesley Hospital,Brisbane,QLD,Australia for non-PCa related pathology.Methods:Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted.Men were classified as benign,indeterminate,or malignant depending of the results of prostate-specific antigen(PSA),PSA velocity,biopsy histopathology,and three-Tesla(3 T)multiparametric MRI(mpMRI)Prostate Imaging Reporting and Data System score,or gallium-68-prostate-specific membrane antigen(68Ga-PSMA)PET/CT results.Results:Three percent(273/9122)of men demonstrated 18F-FDG avidity within the prostate.Eighty-five percent(231/273)were further investigated,including with PSA tests(227/231,98.3%),3 T mpMRI(68/231,29.4%),68Ga-PSMA PET/CT(33/231,14.3%),and prostate biopsy(57/231,24.7%).Results were considered benign in 130/231(56.3%),indeterminate in 31/231(13.4%),and malignant in 70/231(30.3%).PCa was identified in 51/57(89.5%)of the men who proceeded to biopsy,including 26/27(96.3%)men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/CT.The most common Gleason score on biopsy was greater than or equal to 4+5(14/51,27.5%).68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33(78.8%).All 13 men with a positive concordant 18F-FDG,3 T mpMRI,and 68Ga-PSMA PET/CT had PCa on biopsy.There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups(5.7 vs.6.1;p=0.580).Conclusion:In this study,after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT,70 of the 231 cases(30.3%;0.8%of the entire cohort)had results consistent with PCa,most commonly as Gleason scor

关键词： Prostatecancer Positionemission tomography Multiparametric magneticresonance imaging Prostatebiopsy

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Two-stage corrective operation for the treatment of pes cavovarus in patients with spina bifida

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World journal of Orthopedics 2024年第7期15卷 618-626页

作者： anthony Mack Padgett Ezan Kothari Michael j Conklin Department of Orthopedics Indiana UniversityIndianapolisIN 46202United States Department of Orthopaedic Surgery University of Alabama at BirminghamBirminghamAL 35233United States Department of Orthopedic Surgery Children’s of AlabamaBirminghamAL 35233United States

BACKGROUND Pes cavovarus has an estimated incidence of 8%-17%in patients with spina bifida(SB).The majority of the current literature on surgical treatment of cavovarus feet in children and adolescents includes a variety of diagnoses.There are currently no case series describing a treatment algorithm for deformity correction in this specific patient population.The authors of this study present the results of a retrospective case series performed to assess the radiographic outcomes of two-stage corrective surgery in patients with SB.METHODS Retrospective chart review was performed on patients with SB with a diagnosis of pes cavovarus at a freestanding children’s hospital who underwent surgical correction of the deformity.Patients were excluded for lack of two-stage corrective operation,nonambulatory status,lack of at least six months follow-up,and age>18 years at the time of surgery.This resulted in a cohort of 19 patients.Radiographic analysis was performed on 11 feet that had a complete series of preoperative and postoperative weightbearing X-rays.Preoperative and postoperative radiographic outcome measurements were compared using a two-sample t-test.RESULTS Significant changes between the preoperative and postoperative measurements were seen in Meary’s angle,the anteroposterior talo-first metatarsal(AP TMT1)angle,and the talonavicular coverage.Mean values of Meary’s angle were 17.9±13.1 preoperatively and 4.7±10.3 postoperatively(P=0.016).Mean AP TMT1 angle was 20.6±15.1 preoperatively and 9.3±5.5 postoperatively(P=0.011).Mean talonavicular coverage values were-10.3±9.6 preoperatively and-3.8±10.1 postoperatively(P=0.025).CONCLUSION The two-stage corrective procedure demonstrated efficacy in correcting cavovarus deformity in patients with SB.Providers should strongly consider employing the staged surgical algorithm presented in this manuscript for management of these patients.

关键词： Cavovarus Spina bifida Osteotomy Plantar release Radiographs Pediatrics

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SCFD1 in amyotrophic lateral sclerosis: reconciling a genetic association with in vivo functional analysis

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Neural Regeneration Research 2024年第6期19卷 1201-1202页

作者： Ruben j.Cauchi Centre for Molecular Medicine and Biobanking Biomedical Sciences BuildingDepartment of Physiology and Biochemistry Faculty of Medicine and Surgery University of Malta

Amyotrophic lateral sclerosis(ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons,resulting in muscle weakness and spasticity,eventually leading to death due to respiratory failure.Analyses by our group of a casecontrol cohort from an isolated island population have found that genetics plays a significant role in disease etiology(Farrugia Wismayer et al.,2023).

关键词： PROTEIN SLY1

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Nanoengineering Metal–Organic Frameworks and Derivatives for Electrosynthesis of Ammonia

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纳微快报:英文版 2023年第11期15卷 205-240页

作者： Daming Feng Lixue Zhou Timothy j.White anthony K.Cheetham Tianyi Ma Fengxia Wei College of Chemistry Liaoning UniversityShenyang 110036People’s Republic of China School of Materials Science and Engineering Nanyang Technological University50 Nanyang AvenueSingapore 639798Singapore Materials Research Laboratory University of CaliforniaSanta BarbaraCA 93106USA School of Science RMIT UniversityMelbourneVIC 3000Australia Institute of Materials Research and Engineering(IMRE) Agency for ScienceTechnology and Research(A^(*)STAR)2 Fusionopolis WayInnovis 08‑03Singapore 138634Singapore

Electrocatalytic synthesis under mild conditions has become increasingly important as one of the practical alternatives for industrial applications,especially for the green ammonia(NH_(3))industry.A properly engineered electrocatalyst plays a vital role in the realization of superior catalytic performance.Among various types of promising nanomaterials,metal–organic frameworks(MOFs)are competitive candidates for developing efficient electrocatalytic NH_(3) synthesis from simple nitrogen-containing molecules or ions,such as N_(2) and NO_(3)^(−).In this review,recent advances in the development of electrocatalysts derived from MOFs for the electrosynthesis of NH_(3) are collected,categorized,and discussed,including their application in the N_(2) reduction reaction(NRR)and the NO_(3)^(−)reduction reaction(NO3RR).Firstly,the fundamental principles are illustrated,such as plausible mechanisms of NH_(3) generation from N_(2) and NO_(3)^(−),the apparatus of corresponding electrocatalysis,parameters for evaluation of reaction efficiency,and detection methods of yielding NH_(3).Then,the electrocatalysts for NRR processes are discussed in detail,including pristine MOFs,MOF-hybrids,MOF-derived N-doped porous carbons,single atomic catalysts from pyrolysis of MOFs,and other MOF-related materials.Subsequently,MOF-related NO3RR processes are also listed and discussed.Finally,the existing challenges and prospects for the rational design and fabrication of electrocatalysts from MOFs for electrochemical NH_(3) synthesis are presented,such as the evolution of investigation methods with artificial intelligence,innovation in synthetic methods of MOF-related catalysts,advancement of characterization techniques,and extended electrocatalytic reactions.

关键词： Metal–organic frameworks Electrosynthesis of ammonia Nitrogen reduction reactions Nitrate reduction reactions

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