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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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Evaluation of Clinical Characteristics and Plasma Cortisol Concentrations in Individuals with COVID-19 and Post-COVID Syndrome

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Case Reports in Clinical Medicine 2024年第1期13卷 12-24页

作者： david Alejandro García lópez Stephania Ramos Hernández Yamile lópez-Hernández María Argelia lópez luna Elena Donaji Ramírez Alvarado Rosa María Ramírez Santoyo Sergio Hugo Sánchez Rodríguez laboratorio de Biología Celular y Neurobiología Universidad Autónoma de Zacatecas México Zacatecas Unidad Académica de Ciencias Químicas Universidad Autónoma de Zacatecas México Zacatecas laboratorio de Metabolómica y Proteómica Universidad Autónoma de Zacatecas México Zacatecas laboratorio de Bacterias y Hongos filamentosos Universidad Autónoma de Zacatecas México Zacatecas

COVID-19 generates systematic alterations in humans both in active stages of infection and over time, called post-COVID syndrome. Cortisol is a hormone that is overexpressed in inflammation and cellular stress processes. Its main function is to return to physiological homeostasis, so its evaluation together with other clinical parameters can allow us to determine the degree of systemic affectation by COVID-19. Objective: To evaluate changes in clinical parameters and plasma cortisol concentrations in patients with active COVID-19 and post-COVID syndrome. Material and Methods: Healthy patients, in stages of mild infection, critical and with post-COVID syndrome, were recruited, obtaining, through clinical diagnoses and interviews, their main clinical characteristics, in addition to plasma, in which cortisol concentrations were determined using competitive ElISA. Results: The critical stage group had higher frequencies of comorbidities, clinical symptoms, as well as more altered laboratory parameters compared to the other subgroups. In the post-COVID syndrome group after the initial infection, most laboratory parameters recovered, however, several clinical symptoms remained latent over time. The determination of cortisol showed an increase in its concentration, being higher in patients in critical stage and with post-COVID syndrome. Conclusion: COVID-19 disease generates clinical alterations that trigger an increase in plasma cortisol. These alterations increase as the stages of infection become more severe and some of them remain altered in patients with post-COVID syndrome.

关键词： COVID-19 Cortisol Post-COVID Syndrome

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Rumen microbial degradation of bromoform from red seaweed(Asparagopsis taxiformis)and the impact on rumen fermentation and methanogenic archaea

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Journal of Animal Science and Biotechnology 2024年第1期15卷 412-426页

作者： Pedro Romero Alejandro Belanche Elisabeth Jiménez Rafael Hueso Eva Ramos-Morales Joan King Salwen Ermias Kebreab david R.Yáñez-Ruiz Estacion Experimental del Zaidin Consejo Superior de Investigaciones Cientificas(CSIC)Profesor Albareda 1Granada 18008Spain Department of Animal Production and Food Sciences University of ZaragozaMiguel Servet 177Saragossa 50013Spain Blue Ocean Barns Inc. Redwood CityCAUSA Department of Animal Science University of CaliforniaDavisCA 95618USA

Background The red macroalgae Asparagopsis is an effective methanogenesis inhibitor due to the presence of halogenated methane(CH_(4))analogues,primarily bromoform(CHBr_(3)).This study aimed to investigate the degradation process of CHBr3 from A taxiformis in the rumen and whether this process is *** in vitro batch culture system was used according to a 2×2 factorial design,assessing two A taxiformis inclusion rates[0(CTl)and 2%DM diet(AT)]and two diets[high-concentrate(HC)and high-forage diet(HF)].Incubations lasted for 72 h and samples of headspace and fermentation liquid were taken at 0,0.5,1,3,6,8,12,16,24,48 and 72 h to assess the pattern of degradation of CHBr_(3) into dibromomethane(CH_(2)Br_(2))and fermentation ***,an in vitro experiment with pure cultures of seven methanogens strains(Methanobrevibacter smithii,Methanobrevibacter ruminantium,Methanosphaera stadtmanae,Methanosarcina barkeri,Methanobrevibacter millerae,Methanorhermobacter wolfei and Methanobacterium mobile)was conducted to test the effects of increasing concentrations of CHBr3(0.4,2,10and 50μmol/l).Results The addition of AT significantly decreased CH_(4) production(P=0.002)and the acetate:propionate ratio(P=0.003)during a 72-h *** concentrations of CHBr_(3) showed a rapid decrease with nearly 90%degraded within the first 3 h of *** the contrary,CH_(2)Br_(2) concentration quickly increased during the first 6 h and then gradually decreased towards the end of the *** CHBr_(3) degradation nor CH_(2)Br_(2) synthesis were affected by the type of diet used as substrate,suggesting that the fermentation rate is not a driving factor involved in CHBr_(3)*** in vitro culture of methanogens showed a dose-response effect of CHBr3 by inhibiting the growth of ***,***,***,***,***,***,and *** The present work demonstrated that CHBr_(3) from *** is quickly degrad

关键词： Bromoform metabolism Dibromomethane metabolism Methane mitigation Methanogens Rumen microbiota Seaweed

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Data-driven systematic analysis of waterborne viruses and health risks during the wastewater reclamation process

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Environmental Science and Ecotechnology 2024年第3期19卷 80-90页

作者： Jia-Xin Ma Xu Wang Yi-Rong Pan Zhao-Yue Wang Xuesong Guo Junxin liu Nan-Qi Ren david Butler Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing100085China State Key laboratory of UrbanWater Resource and Environment School of Civil and Environmental EngineeringHarbin Institute of TechnologyShenzhenShenzhen518055China University of Chinese Academy of Sciences Beijing100049China Centre for Water Systems College of EngineeringMathematics and Physical SciencesUniversity of ExeterExeterEX44QFUnited Kingdom

Waterborne viral epidemics are a major threat to public *** interest in wastewater reclamation highlights the importance of understanding the health risks associated with potential microbial hazards,particularly for reused water in direct contact with *** study focused on identifying viral epidemic patterns in municipal wastewater reused for recreational applications based on long-term,spatially explicit global literature data during 2000e2021,and modelled human health risks from multiple exposure pathways using a well-established quantitative microbial risk assessment *** median viral loads in municipal wastewater ranged from 7.92×10^(4)to 1.4×10^(6)GC l^(-1)in the following ascending order:human adenovirus(HAdV),norovirus(NoV)GII,enterovirus(EV),NoV GI,rotavirus(RV),and severe acute respiratory syndrome coronavirus 2(SARSCoV-2).Following secondary or tertiary wastewater treatment,NoV GI,NoV GII,EV,and RV showed a relatively higher and more stable log reduction value with medians all above 0.8(84%),whereas SARSCoV-2 and HAdV showed a relatively lower reduction,with medians ranging from 0.33(53%)to 0.55(72%).A subsequent disinfection process effectively enhanced viral removal to over 0.89-log(87%).The predicted event probability of virus-related gastrointestinal illness and acute febrile respiratory illnesses in reclaimed recreational water exceeded the World Health Organization recommended recreational risk benchmark(5%and 1.9%,respectively).Overall,our results provided insights on health risks associated with reusing wastewater for recreational purposes and highlighted the need for establishing a regulatory framework ensuring the safety management of reclaimed waters.

关键词： Reclaimed water Waterborne virus Recreational Human health Data-driven analysis

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Elite,transformable haploid inducers in maize

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The Crop Journal 2024年第1期12卷 314-319页

作者： Brent Delzer Dawei liang david Szwerdszarf Isadora Rodriguez Gonzalo Mardones Sivamani Elumalai Francine Johnson Samson Nalapalli Rachel Egger Erin Burch Kerry Meier Juan Wei Xiujuan Zhang Huaping Gui Huaibing Jin Huan Guo Kun Yu Yubo liu Becky Breitinger Ana Poets Jason Nichols Wan Shi david Skibbe Qiudeng Que Timothy Kelliher Seeds Development Syngenta SeedsJanesvilleWI 53546USA Seeds Research Syngenta Biotechnology China Co.Ltd.Beijing 102206China Centro de Investigación de Cultivos Arica Syngenta R&DArica 1000000Chile Syngenta S.A. Proyecto la SoledadGraneros 2880000Chile Seeds Research Syngenta Crop Protection LLCRTPNC 27709USA Seeds Development Syngenta SeedsSlaterIA 50244USA

The introduction of alleles into commercial crop breeding pipelines is both time consuming and *** technologies that are disrupting traditional breeding processes are doubled haploid(DH)breeding and genome editing(GE).Recently,these techniques were combined into a GE trait delivery system called HI-Edit(Haploid Inducer-Edit).In HI-Edit,the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety,obviating recurrent *** HI-Edit to operate at scale,an efficient transformable HI line is needed,but most maize varieties are recalcitrant to transformation,and haploid inducers are especially difficult to transform given their aberrant reproductive *** marker assisted selection and a three-tiered testing scheme,we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable,have high haploid induction rates,and exhibit a robust,genetically-dominant anthocyanin native trait that may be used for rapid haploid *** show that transformation of these elite‘‘HI-Edit”lines is enhanced using the BABYBOOM and WUSCHEl morphogenetic ***,we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk *** strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.

关键词： Zea mays l Doubled haploids Transformation Genome editing QTl

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TRAIl and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua lI Yu-lin REN Chun-guang david P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIl)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/l)and TRAIl(0-500 ng/ml)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIl(TRAIl 100 ng/ml),Cel(celastrol 0.5µmol/l)and TCCT(TRAIl 100 ng/ml+celastrol 0.5µmol/l).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(liCl,20 mol/l)and the mechanism for action of TCCT was *** Celastrol and TRAIl synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(Plated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(Pluding c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,liCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(Plusions Celastrol and TRAIl can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph david Gimbel Jonathan Grossberg Daniel l.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico

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World Journal of Transplantation 2024年第2期14卷 76-87页

作者： Andrés Gómez-De león Yesica A lópez-Mora Valeria García-Zárate Ana Varela-Constantino Sergio U Villegas-De leon Xitlaly J González-leal Raúl del Toro-Mijares Anna C Rodríguez-Zúñiga Juan F Barrios-Ruiz Victor Mingura-ledezma Perla R Colunga-Pedraza Olga G Cantú-Rodríguez César H Gutiérrez-Aguirre luz Tarín-Arzaga Elías E González-lópez david Gómez-Almaguer Hematology Service Universidad Autónoma de Nuevo LeónFacultad de Medicina y Hospital Universitario Dr.JoséEleuterio GonzálezMonterrey 64460Nuevo LeónMexico Hemato-logy Service Clínica Gómez AlmaguerMonterrey 64710Nuevo LeónMexico Hematology Service Instituto Tecnológico de Estudios Superiores de MonterreyTec SaludEscuela de Medicina Ignacio SantosMonterrey 64710Nuevo LeónMexico

BACKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly *** observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-pocket vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHSCT)in two of Mexico's largest public and private *** To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in *** In this retrospective cohort study,we included adolescents and adults≥16 years who received a matched sibling or haploidentical transplant from *** were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in *** payment groups were compared:Out-of-pocket(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo leon and *** outcomes included overall survival(OS),categorized by residence,referral,and payment *** outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRM).Statistical analyses employed appropriate tests,kaplan-Meier method,and Cox proportional hazard regression *** software included SPSS and R with tidycmprsk *** Our primary outcome was overall *** included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRM,or graft-versus-host-relapse-free survival were observed for patients dia

关键词： Hematopoietic cell transplant Social determinants of health Geography Haploidentical Out-of-pocket Financial toxicity Survival Health services and outcomes Hematopoietic malignancy Aplastic anemia

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Storylines of family medicine Ⅵ:ways of being—in the office with patients

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Family Medicine and Community Health 2024年第S3期12卷 52-60页

作者： William B Ventres leslie A Stone lisa A laVallee david loxterkamp Jonisha R Brown Dael M Waxman Peter S Dorward Jeanne Cawse-lucas larry B Mauksch Autumn M Kieber-Emmons Benjamin F Crabtree William l Miller Veronica M Brohm Timothy P Daaleman Kelly Bossenbroek Fedoriw Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA MAHEC Family Medicine Residency Mountain Area Health Education CenterAshevilleNorth CarolinaUSA Bucksport Regional Health Center BucksportMaineUSA Family Medicine Atrium HealthCharlotteNorth CarolinaUSA Southfield Medical Practice EdinburghUK Family Medicine University of Washington School of MedicineSeattleWashingtonUSA Family Medicine Lehigh Valley Health NetworkAllentownPennsylvaniaUSA Morsani College of Medicine University of South FloridaTampaFloridaUSA Family Medicine and Community Health Rutgers Robert Wood Johnson Medical SchoolPiscatawayNew JerseyUSA Cancer Institute of New Jersey New BrunswickNew JerseyUSA Family Medicine UNC School of MedicineChapel HillNorth CarolinaUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅵ:ways of being—in the office with patients’,authors address the following themes:‘Patient-centred care—cultivating deep listening skills’,‘Doctor as witness’,‘Words matter’,‘Understanding others—metaphor and its use in medicine’,‘Communicating with patients—making good use of time’,‘The patient-centred medical home—aspirations for the future’,‘Routine,ceremony or drama?’and‘The life course’.May readers better appreciate the nuances of patient care through these essays.

关键词： centre illustration dimensions

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Correction:Efficiency improvement by using metal–insulator‑semiconductor structure in InGaN/GaN micro‑light‑emitting diodes

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Frontiers of Optoelectronics 2024年第1期17卷 95-99页

作者： Jian Yin david Hwang Hossein Zamani Siboni Ehsanollah Fathi Reza Chaji Dayan Ban Department of Electrical and Computer Engineering Waterloo Institute NanotechnologyUniversity of WaterlooWaterlooON N2L 3G1Canada Vuereal InC 440 Philip StreetUnit 100WaterlooON N2L 5R9Canada

Open Access This article is licensed under a Creative Commons Attribution 4.0 International license,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were *** images or other third party material in this article are included in the article’s Creative Commons licence.

关键词： Efficiency diodes Creative

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