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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl lászlóGál Sylvia Nürnberger Barbara Schaedl james Ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

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The HIF-1α/PlOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy l.Strong Yuxiao Sun lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon lee Sowmya Ramesh Aaron W.james David Hudson Kevin N.Dalby lin Xu Robert J.Tower Benjamin levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PlOD2/lOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-lOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PlOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PlOD2/lOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PlOD2/lOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

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Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

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Acta Pharmaceutica Sinica B 2024年第2期14卷 653-666页

作者： Shining loo Antony Kam Bamaprasad Dutta Xiaohong Zhang Nan Feng Siu Kwan Sze Chuan-Fa liu Xiaoliang Wang james P.Tam School of Biological Sciences Nanyang Technological UniversitySingapore 637551Singapore Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Department of Biological Sciences Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China Institute of Materia Medica Chinese Academy of Medical SciencesBeijing 100050China Department of Health Sciences Brock UniversityNiagara RegionON L2S 3A1Canada

Stress and illness connection is complex and involves multiple physiological *** ginsengs,reputed for their broad-spectrum“cure-all”effect,are widely prescribed to treat stress and related ***,the identity of ginseng’s“cure-all”medicinal compounds that relieve stress remains ***,we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to *** are disulfide-rich,cell-penetrating and proteolytic-stable *** affinity-enrichment mass spectrometry target identification together with in vitro,ex vivo and in vivo validations,we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway,alleviate a1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta,decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet *** administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation,to prevent collagen and adrenalineinduced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in ***,these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra-and intra-cellular proteins to reverse stress-induced damages.

关键词： Ginseng Cysteine-rich peptides Microproteins Cure-all Stress Homeostasis

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Gated container molecules

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Science China Chemistry 2011年第12期54卷 2038-2044页

作者： houk K.N. Department of Chemistry and Biochemistry University of California at Los AngelesLos Angeles

Donald J. Cram, the great UClA chemist, received the Nobel Prize for his discoveries about host-guest complexes . Both theoretical and experimental studies have been conducted about the nature and strength of interactions between the host and guest molecules. The concepts of constrictive binding （the activation energy of the binding process） and intrinsic binding （the free energy difference between the complex and the free host and guest molecules） were introduced to characterize different binding properties （Figure 1）

关键词：客体分子容器闸门主客体配合物加州大学诺贝尔奖相互作用结合特性

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Estimating geographic variation of infection fatality ratios during epidemics

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Infectious Disease Modelling 2024年第2期9卷 634-643页

作者： Joshua ladau Eoin l.Brodie Nicola Falco Ishan Bansal Elijah B.Hoffman Marcin P.Joachimiak Ana M.Mora Angelica M.Walker Haruko M.Wainwright Yulun Wu Mirko Pavicic Daniel Jacobson Matthias Hess james B.Brown Katrina Abuabara Departments of Computational Precision Health and Dermatology University of CaliforniaSan FranciscoCA94115USA Arva Intelligence Inc.Salt Lake CityUT84101USA Computational Biosciences Group Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Earth and Environmental Sciences Area Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Graduate Group in Biostatistics University of CaliforniaBerkeleyCA94720USA Biosystems Data Science Environmental Genomics and Systems BiologyLawrence Berkeley National LaboratoryBerkeleyCA94720USA Center for Environmental Research and Community Health(CERCH) School of Public HealthUniversity of CaliforniaBerkeleyCA94720USA Bredesen Center for Interdisciplinary Research and Graduate Education University of TennesseeKnoxvilleTN37996USA Department of Nuclear Science and Engineering Massachusetts Institute of TechnologyBostonMA02139USA Biosciences Oak Ridge National LaboratoryOak RidgeTN37830USA University of California DavisCA95616USA Statistics Department University of CaliforniaBerkeleyCA94720USA Division of Epidemiology and Biostatistics University of California Berkeley School of Public Health2121 Berkeley WayBerkeleyCA94720USA

Objectives We aim to estimate geographic variability in total numbers of infections and infection fatality ratios(IFR;the number of deaths caused by an infection per 1,000 infected people)when the availability and quality of data on disease burden are limited during an *** We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek *** demonstrate the robustness,accuracy,and precision of this framework,and apply it to the United States(U.S.)COVID-19 pandemic to estimate county-level SARS-CoV-2 *** The estimators for the numbers of infections and IFRs showed high accuracy and precision;for instance,when applied to simulated validation data sets,across counties,Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928,respectively,and they showed strong robustness to model *** the county-level estimators to the real,unsimulated COVID-19 data spanning April 1,2020 to September 30,2020 from across the U.S.,we found that IFRs varied from 0 to 44.69,with a standard deviation of 3.55 and a median of *** The proposed estimation framework can be used to identify geographic variation in IFRs across settings.

关键词： Infection fatality ratio Infection fatality rate Noncentral hypergeometric distribution COVID-19 SARS-CoV-2

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Decision-Making and Management of Self-Care in Persons with Traumatic Spinal Cord Injuries: A Preliminary Study

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Journal of Behavioral and Brain Science 2024年第2期14卷 47-63页

作者： Paul E. Plonski Jasmin Vassileva Ryan Shahidi Paul B. Perrin William Carter lance l. Goetz Amber Brochetti james M. Bjork Institute for Drug and Alcohol Studies Virginia Commonwealth University Richmond VA USA Richmond Veterans Affairs Medical Center Richmond VA USA Department of Psychiatry Virginia Commonwealth University Richmond VA USA Department of Psychology Virginia Commonwealth University Richmond VA USA Department of Physical Medicine and Rehabilitation Virginia Commonwealth University Richmond VA USA Department of Spinal Cord Injury Cleveland Veterans Affairs Medical Center Cleveland OH USA Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond VA USA

Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In lASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.

关键词： Spinal Cord Injury Self-Care Decision-Making Paraplegia Impulsive Behavior Health Care

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理解老年人的身体活动:基于时空行为视角的研究

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体育科学 2024年第1期44卷 78-87页

作者：成佳俐仇军 james F.Sallis 于洪军河北师范大学公共体育教学部河北石家庄050024 湖州师范学院体育与大健康研究院浙江湖州313000 美国加州大学圣地亚哥分校家庭医学与公共卫生系加利福尼亚圣地亚哥92093 清华大学体育部北京100084

目的:从时空行为视角对建成环境与老年人户外身体活动的时空行为特征进行研究,为促进我国老年人身体活动水平提升和应对老龄化趋势提供新思路。方法:采用全球定位系统(global position system,GPS)和三维加速度计对126名老年人时空行为... 详细信息

目的:从时空行为视角对建成环境与老年人户外身体活动的时空行为特征进行研究,为促进我国老年人身体活动水平提升和应对老龄化趋势提供新思路。方法:采用全球定位系统(global position system,GPS)和三维加速度计对126名老年人时空行为数据进行同步收集,通过空间算法将环境暴露数据与身体活动数据相关联,总结其出行方式、出行时间、出行频率、出行范围等特征。结果:1)老年人户外身体活动存在“点-线”型、“候鸟”型、“条链”型、“自由”型、“邻里”型、“综合”型6种时空模式;2)老年人主要户外身体活动范围为家附近500 m左右;3)老年人近45%的热量消耗和中高强度身体活动发生在户外空间,主要户外活动兴趣点为休闲娱乐、购物和运动健身;4)老年人户外身体活动特征以出行频率高和短时耗为主,出行次数对身体活动水平有显著影响,出行次数每增加1次,平均每周户外身体活动水平增加20.5 min。结论:我国老年人户外身体活动呈现出多样化的时空行为模式,未来可以将增加出行次数作为促进老年人身体活动水平的切入点。

关键词：时空行为建成环境老年人户外身体活动

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Allergic dermatitis after knee arthroscopy with repeated exposure to Dermabond Prineo^(TM) in pediatric patients:Two case reports

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World Journal of Orthopedics 2021年第11期12卷 931-937页

作者： james Robinson Kevin P Smidt Garrett houk Janay McKie R Shane Barton Patrick Massey Department of Orthopaedic Surgery Louisiana State UniversityShreveportLA 71103United States School of Medicine Louisiana State UniversityShreveportLA 71103United States Department of Orthopaedic Surgery Shriners Hospital for ChildrenShreveportLA 71103United States

BACKGROUND Allergic contact dermatitis(ACD)secondary to Dermabond Prineo^(TM) is rare,but *** our knowledge,there are no described reports of this ACD reaction within the pediatric population following arthroscopic *** SUMMARY We report two cases of pediatric ACD upon second exposure to Dermabond Prineo^(TM) after knee *** cases presented within two weeks of the inciting second *** cases resolved with differing described combinations of sterile cleaning,diphenhydramine,and antibiotic *** long-term sequelae were *** This case report elucidates the rare complication of allergic dermatitis secondary to Dermabond Prineo^(TM) repeat exposure use in pediatric arthroscopy.

关键词： Dermabond Prineo Arthroscopy Sports medicine Contact dermatitis Case report

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Watershed science:linking hydrological science with sustainable management of river basins

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Science China Earth Sciences 2021年第5期64卷 677-690页

作者： Chansheng HE l.Allan james Department of Geography Western Michigan UniversityKalamazooM149008USA Center for Dryland Water Resources Research and Watershed Science Key Laboratory of West China’s Environmental System(Ministry of Education)College of Earth and Environmental SciencesLanzhou UniversityLanzhou 730000China Department of Geography University of South CarolinaColumbiaSC 29208USA

Over the past decades,a number of water sciences and management programs have been developed to better understand and manage the water cycles at multiple temporal and spatial scales for various purposes,such as ecohydrology,global hydrology,sociohydrology,supply management,demand management,and integrated water resources management(IWRM).At the same time,rapid advancements have also been taking place in tracing,mapping,remote sensing,machine learning,and modelling technologies in hydrological *** those programs and advancements,a water crisis is intensifying *** missing link is effective interactions between the hydrological research and water resource management to support implementation of the UN Sustainable Development Goals(SDGs)at multiple spatial *** the watershed is the natural unit for water resources management,watershed science offers the potential to bridge this missing *** study first reviews the advances in hydrological research and water resources management,and then discusses issues and challenges facing the global water ***,it describes the core components of watershed science:(1)hydrological analysis;(2)water-operation policies;(3)governance;(4)management and *** framework takes into account water availability,water uses,and water quality;explicitly focuses on the storage,fluxes,and quality of the hydrological cycle;defines appropriate local water resource thresholds through incorporating the planetary boundary framework;and identifies specific actionable measures for water resources *** provides a complementary approach to the existing water management programs in addressing the current global water crisis and achieving the UN SDGs.

关键词： Water crisis Hydrology Watershed science Integrated water resources management(IWRM)

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Abiotic and biotic constituents of oil sands process-affected waters

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Journal of Environmental Sciences 2023年第5期127卷 169-186页

作者： Nora A.S.Hussain james l.Stafford Department of Biological Sciences University of AlbertaEdmontonAlberta T6G 2N8Canada

The oil sands in Northern Alberta are the largest oil sands in the world,providing an important economic resource for the Canadian energy *** extraction of petroleum in the oil sands begins with the addition of hot water to the bituminous sediment,generating oil sands process-affected water(OSPW),which is acutely toxic to *** of litres of OSPW are stored on oil sands mining leased sites in man-made reservoirs called tailings *** the volume of OSPW increases,concerns arise regarding the reclamation and eventual release of this water back into the *** is composed of a complex and heterogeneous mix of components that vary based on factors such as company extraction techniques,age of the water,location,and bitumen ore ***,the effective remediation of OSPW requires the consideration of abiotic and biotic constituents within it to understand short and long term effects of treatments *** review summarizes selected chemicals and organisms in these waters and their interactions to provide a holistic perspective on the physiochemical and microbial dynamics underpinning OSPW.

关键词： OSPW toxicants Reclamation Tailings ponds Remediation Microbial AOPs Bioremediation

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