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The HIF-1α/Pl.D2 axis integrates extracel.ul.r matrix organization and cel. metabol.sm l.ading to aberrant muscul.skel.tal.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 l.i Guo Conan Juan Al.c C.Bancroft Ji Hae Choi Chase A.Pagani Aysel.A.Fernandes Michael.Woodard Juhoon l.e Sowmya Ramesh Aaron W.James david Hudson Kevin N.Dal.y l.n Xu Robert J.Tower Benjamin l.vi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Pl.stic 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.Biol.gy and Medicinal.Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathol.gy Johns Hopkins UniversityBaltimoreMD 21218USA

Whil. hypoxic signal.ng has been shown to pl.y a rol. in many cel.ul.r processes,its rol. in metabol.sm-l.nked extracel.ul.r matrix(ECM)organization and downstream processes of cel. fate after muscul.skel.tal.injury remains to be ***(HO)is a debil.tating condition where abnormal.bone formation occurs within extra-skel.tal.*** andhypoxia-inducibl. factor 1α(HIF-1α)activation have been shown to promote ***,the underl.ing mol.cul.r mechanisms bywhich the HIF-1αpathway in mesenchymal.progenitor cel.s(MPCs)contributes to pathol.gic bone formation remain to ***,we used a proven mouse injury-induced HO model.to investigate the rol. of HIF-1αon aberrant cel. ***-cel. RNA sequencing(scRNA-seq)and spatial.transcriptomics anal.ses of the HO site,we found that col.agen ECM organizationis the most highl. up-regul.ted biol.gical.process in *** mesenchymal.cel.-specific del.tion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl.fl.)significantl. mitigated HO in ***-seq anal.sis of these Hoxa11-CreER^(T2);Hif1a^(fl.fl.mice identified the Pl.D2/l.Xpathway for col.agen cross-l.nking as downstream of the HIF-1αregul.tion of ***,our scRNA-seq data and mechanisticstudies further uncovered that gl.cose metabol.sm in MPCs is most highl. impacted by HIF-1α*** a transl.tional.aspect,a pan-l.X inhibitor significantl. decreased HO.A newl. screened compound reveal.d that the inhibition of Pl.D2 activity in MPCssignificantl. decreased osteogenic differentiation and gl.col.tic *** suggests that the HIF-1α/Pl.D2/l.X axis l.nked tometabol.sm regul.tes HO-forming MPC *** resul.s suggest that the HIF-1α/Pl.D2/l.X pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabol.sm skel.tal aberrant

Acute drivers of neuroinfl.mmation in traumatic brain injury

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Neural.Regeneration Research 2019年第9期14卷 1481-1489页

作者： Kathryn l.Wofford david J.l.ane D.Kacy Cul.en Center for Brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPAUSA School.of Biomedical.Engineering Science and Health SystemsDrexel UniversityPhiladelphiaPAUSA Department of Anesthesiol.gy and Shock Traumaand Anesthesiology Research(STAR)CenterUniversity of Maryland School of MedicineBaltimoreMDUSA School.of Biochemistry and Immunol.gy and Trinity Biomedical.Sciences Institute Trinity College DublinIreland Department of Bioengineering School of Engineering and Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA

Neuroinfl.mmation is initiated as a resul. of traumatic brain injury and can exacerbate evol.ing tissue *** cel.s respond to acute signal. from damaged cel.s,initiate neuroinfl.mmation,and drive the pathol.gical.consequences over ***,the mechanism(s)of injury,the l.cation of the immune cel.s within the brain,and the animal.species al. contribute to immune cel. behavior fol.owing traumatic brain *** the signal. that initiate neuroinfl.mmation and the context in which they appear may be critical.for understanding immune cel. contributions to pathol.gy and *** this paper,we review a number of factors that coul. affect immune cel. behavior acutel. fol.owing traumatic brain injury.

关键词： traumatic brain injury infl.mmation neuroinfl.mmation microgl.a macrophage acute diffuse brain injury cytokines adenosine 5′-triphosphoate gl.tamate cal.ium

Anisotropy of Stabl. Singl. Domain Ferrimagnetic Particl.s in a Rock Sampl. from Gyroremanent Magnetization and Comparison with Other Anisotropy Methods

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Journal.of Modern Physics 2019年第6期10卷 673-686页

作者： l.am l. Bel.sl. david K. Potter Brendan C. Snow Al.yson l. Shewchuk Department of Physics University of Alberta Edmonton Canada CNOOC Petrol.um North America Ul. Calgary Canada

The orientation of stabl. singl. domain (SSD) ferrimagnetic particl.s in an igneous rock sampl. was determined by a sensitive technique util.zing gyroremanent magnetization (GRM). Components of GRM were measured in the sampl. upon exposure to an al.ernating fiel. (AF) at various orientations in 3 orthogonal.pl.nes. The major components of GRM exhibited a sin(2θ) dependence on AF orientation in the respective perpendicul.r pl.nes. This was in accordance with theory [1] and contrary to some previousl. reported experimental.resul.s on magnetic recording tape, which produced a distorted sin(2θ) dependence of the GRM [1]. The expl.nation is l.kel. due to the SSD ferrimagnetic particl.s in the rock sampl. being more dispersed (l.ss interacting) compared to the highl. interacting SSD particl.s in the magnetic tape sampl. of the previous study. The GRM resul.s were consistent with another remanence anisotropy method, anisotropy of isothermal.remanent magnetization (AIRM). This method again measures the anisotropy of the remanence carrying ferrimagnetic particl.s, but the IRM is al.o acquired by l.rger mul.idomain (md) particl.s as wel. as by the SSD particl.s. The resul.s were al.o consistent with the visibl. rock anisotropy (petrofabric), the anisotropy of magnetic susceptibil.ty (AMS), and the shear wave vel.city anisotropy. A comparison of al. the methods demonstrated that the fine SSD particl.s, which make up onl. a smal. proportion of the rock, were al.gned in quite a simil.r orientation to that of the main rock forming mineral. that constituted the bul. of the sampl..

关键词： Anisotropy Gyroremanence Isothermal Remanence Magnetic Susceptibil.ty Shear Wave Vel.city

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该患者患有重症肌无力吗？

美国医学会杂志（中文版） 2006年第1期25卷 44-51页

作者： Katal.n Scherer, md Richard S. Bedl.ck, md, PhD david l. Simel. md, MHS 周佳鑫（译）唐福林（校） Department of Medicine Duke University Medical Center Durham NC Department of Medicine DUrham Veterans Affairs Medical Center and Duke University Durham 不详

背景：临床医师必须能够正确诊断重症肌无力，因为延迟诊断，可使患者面临这种可治疗疾病的并发症的危险。目的：确定有关病史和检查或简单试验结果足否能改变诊断重症肌无力的可能性。资料来源：对MEDl.NE收录的英文文献（1966年1月-2... 详细信息

背景：临床医师必须能够正确诊断重症肌无力，因为延迟诊断，可使患者面临这种可治疗疾病的并发症的危险。目的：确定有关病史和检查或简单试验结果足否能改变诊断重症肌无力的可能性。资料来源：对MEDl.NE收录的英文文献（1966年1月-2005年1月）进行检索，所用检索词包括重症肌无力、诊断和检验，其他资料来源于检出文献的参考文献。研究选择：在患或未患重症肌无力的患者评估某一特定症状或体征的研究。在检索到的640篇文献中，有33篇审查合格。其中15篇符合入选标准，构成本综述的基础。数据提取：两位作者分别审读每篇研究，判断其适用性，使用标准方法摘录数据，根据以前发表的标准对研究的质量进行分类。数据综合：“长时间说话时讲话变得难以理解”病史以及“偷看”征提高了重症肌无力的可能性（分别为：似然比[l.kel.hood ratio，l.]，4．5；95％可信区间[confidence intexwal.CI]，1．2—17．0以及l.，30．0；95％CI，3．2—278．0）。缺乏这些表现并未明显降低患重症肌无力的可能性。有些研究仅仅评估了其他一种病史特征和体征（分别为“食物在吞咽后仍留在嘴咀”和眼颤），它们均未明显改变患重症肌无力的可能性。冰块试验反应异常是有帮助的（总阳性l.，24．0；95％CI，8．5．-67；0），而正常反应则能降低重症肌无力的可能性（总阴性l.，0．16；95％CI，0．09—0．27）。对抗胆碱酯酶药物（主要为腾喜龙）阳性反应提高诊断重症肌无力的可能性（总阳性l.，15.0；95％CI，7．5—31.0），阴性反应则降低诊断重症肌无力的可能性（总阴性l.，0．11；95％CI，0.06—0．21）。睡眠试验结果异常有助于确认诊断（l.；53．0；95％CI，3．4—832．0）。休息和睡眠试验结果正常时，不太可能为重症肌无力（分别为：l.，0．52；95％CI，0．29—0．95和l.，0．01；95％CI，0．00—0．16）。结论：某些病史和体检项目以及在诊所进行的简单试验（冰块试验、睡眠试验和腾喜龙试验）有助于预测患重症肌无力的可能性。然而，鉴于在已报道的临床研究人群该病的高发生率，对这些结果必须谨慎解释。该综述受到文献中较少研究和报告体征和症状的限制;仍需要更多的研究，以便对常见的病史特点以及专家们普遍了解并实施的简单诊断方法的价值做进一步评价。

关键词：重症肌无力患者试验反应 MEDl.NE 抗胆碱酯酶药物正确诊断病史特点英文文献标准方法阳性反应

Prediction of permanent pacemaker impl.ntation after transcatheter aortic val.e repl.cement:The rol. of machine l.arning

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Worl. Journal.of Cardiol.gy 2023年第3期15卷 95-105页

作者： Pradyumna Agasthi Hasan Ashraf Sai Harika Pujari Marl.ne Girardo Andrew Tseng Farouk Mookadam Nithin Venepal.y Matthew R Buras Bishoy Abraham Banveet K Khetarpal.Mohamed Al.am Siva K Mul.uru md Mackram F El.id Kevin l.Greason Nirat Beohar John Sweeney david Fortuin david R Jr Hol.es Reza Arsanjani Department of Cardiol.gy Mayo ClinicPhoenixAZ 85054United States Department of Internal.Medicine The Brooklyn Hospital CenterBrooklynNY 11201United States Department of Biostatistics Mayo ClinicPhoenixAZ 85054United States Department of Cardiovascul.r Diseases Mayo ClinicRochesterMN 55905United States Department of Statistics Mayo ClinicPhoenixAZ 85054United States Department of Cardiovascul.r Surgery Mayo ClinicRochesterMN 55905United States Mount Sinai Medical.Center Columbia UniversityMiami BeachFL 33138United States

BACKGROUND Atrioventricul.r bl.ck requiring permanent pacemaker(PPM)impl.ntation is an important compl.cation of transcatheter aortic val.e repl.cement(TAVR).Appl.cation of machine l.arning coul. potential.y be used to predict preprocedural.risk for *** To appl. machine l.arning to be used to predict pre-procedural.risk for *** A retrospective study of 1200 patients who underwent TAVR(January 2014-December 2017)was performed.964 patients without prior PPM were incl.ded for a 30-d anal.sis and 657 patients without PPM requirement through 30 d were incl.ded for a 1-year *** the excl.sion of variabl.s with near-zero variance or≥50%missing data,167 variabl.s were incl.ded in the random forest gradient boosting al.orithm(GBM)optimized using 5-fol. cross-val.dations repeated 10 *** receiver operator curve(ROC)for the GBM model.and PPM risk score model. were cal.ul.ted to predict the risk of PPM at 30 d and 1 *** Of 964 patients incl.ded in the 30-d anal.sis without prior PPM,19.6%required PPM *** mean age of patients was 80.9±8.7 years.42.1%were *** 657 patients incl.ded in the 1-year anal.sis,the mean age of the patients was 80.7±*** those,42.6%of patients were femal. and 26.7%required PPM at 1-year *** area under ROC to predict 30-d and 1-year risk of PPM for the GBM model.0.66 and 0.72)was superior to that of the PPM risk score(0.55 and 0.54)with a P val.el.has good discrimination and cal.bration in identifying patients at high risk of PPM post-TAVR.

关键词： Transcatheter aortic val.e repl.cement Permanent pacemaker impl.ntation Machine l.arning

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儿童青少年高血压漏诊情况

美国医学会杂志（中文版） 2008年第3期27卷 131-136页

作者： Matthew l. Hansen, md Paul.W. Gunn, BS david C. Kael.er, md, PhD 管娜(译) 杨霁云(校) Schod of Medicine Case Western Reserve UniversityClevelandOhio Department of Emergency Medicine Oregon Health and Science University School of MedicinePortland Schod of Medicine Case Western Reserve UniversityClevelandOhio Schod of Medicine Case Western Reserve UniversityClevelandOhio Departments of Internal.Medicine and Pediatrics MetroHealth Medical CenterClevelandOhioand the Center for Information Technology LeadershipParners Healthcareand the Departments of Inter

背景：儿童高血压的发病率随着儿童肥胖的盛行而呈上升趋势。在儿童中，正常和异常血压值会随年龄、性别和身高的变化而变化，难以记忆，因此儿童高血压的诊断较为复杂。目的：明确高血压和高血压前期的漏诊率以及与漏诊相关的患者因素... 详细信息

背景：儿童高血压的发病率随着儿童肥胖的盛行而呈上升趋势。在儿童中，正常和异常血压值会随年龄、性别和身高的变化而变化，难以记忆，因此儿童高血压的诊断较为复杂。目的：明确高血压和高血压前期的漏诊率以及与漏诊相关的患者因素。设计、地点及参试者：于俄亥俄州东北部某大型医疗学术系统进行队列研究，对1999年6月至2006年9月于该系统至少接受3次健康保健检查的14187例3—18岁儿童青少年进行观察。对于3次以上健康检查结果符合高血压和高血压前期诊断标准的儿童和青少年，按照国际疾病分类第9版诊断列表、问题列表和既往病史列表，确定其相关比例。主要观测指标：电子病历诊断为高血压或高血压前期患儿的比例以及≥3次检查结果显示血压升高患儿（校正年龄和身高）的比例。应用多变量l.gistic回归确定与正确诊断相关的患者因素。结果：在507例（3．6％）高血压儿童青少年中，131例（26％）电子病历中有高血压或血压增高诊断。可增加正确诊断率的患者因素包括3岁以上年龄增加1岁（优势比[oddsratio，OR]，1．09；95％CI，1．03—1．16），血压升高超过3次的次数（OR，1．77；95％CI，1．21～2．57），年龄别身高百分位数增长1％（OR，1．02；95％CI，1．01—1．03），有肥胖相关诊断（OR，2．61；95％CI，1．49—4．55）以及处于高血压Ⅱ期的次数（OR，1．68；95％CI，1．29—2．19）。在485例（3．4％）高血压前期儿童青少年中，55例（11％）电子病历记录有适宜的诊断。增加高血压前期诊断率的患者因素包括3岁以上年龄增加1岁（OR，1．21；95％CI，1．09—1．34）以及血压升高超过3次的次数。结论：在本儿童人群中，高血压和高血压前期常被漏诊。患儿的年龄、身高、肥胖相关诊断以及异常血压读数大小和频率均可增加诊断的几率。

关键词：儿童高血压儿童肥胖青少年漏诊率 l.gistic回归高血压前期前期诊断正确诊断率

Vascul.r trauma： sel.cted historical.refl.ctions from the western worl.

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Chinese Journal.of Traumatol.gy 2011年第2期14卷 67-73页

作者： Norman M. Rich Patricia l. McKay david R. Wel.ing Todd E. Rasmussen Norman M. Rich Department of Surgery F. Edward Hebert School of Medicine Uniformed Services University of the Health Sciences Bethesda MD 20814 USA Norman M. Rich Department of Surgery Hand and Upper Extremity Surgery Uniformed Services University of the Health Sciences Bethesda MD 20814 USA Division of General.Surgery Norman M. Rich Department of Surgery Uniformed Services University Bethesda MD 20814 USA US Army Institute of Surgical.Research Fort Sam Houston Texas 78230 USA

In the spirit of international.exchanges of knowl.dge with col.eagues from al. over the worl., who are interested in the care and treatment of vascul.r trauma, we offer sel.cted historical.refl.ctions from the western worl. on vascul.r trauma. Whereas there are a number of key individual. and a variety of events that are important to us in our writing, we know essential.y nothing about what is written by other cul.ures and, particul.rl., the Chinese. It is wel. recognized around the worl. that Chinese surgeons are among the first to be highl. successful.in re-pl.ntation of severed extremities, repairing both injured arteries and veins. Al.o, we recognize that there are contributions in other parts of the worl., which are not wel. known to us col.ectivel.. Contributions from the Arabic speaking part of the worl. come to mind because there is periodic brief reference. We offer our perspective hoping that there wil. be one or more Chinese surgeons who wil. offer us the benefit of sharing their perspective on important historical.contribu- tions to the managing of vascul.r trauma outside of the western worl., and, particul.rl., the Engl.sh speaking l.terature. Once again, we encourage our col.eagues in the Arabic speaking worl. to provide us with their perspective of the devel.pment and management of vascul.r trauma.

关键词： Vascul.r system injuries History Western worl. International.educational.exchange

Computational.approaches to understanding protein aggregation in neurodegeneration

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Journal.of Mol.cul.r Cel. Biol.gy 2014年第2期8卷 104-115页

作者： Rachel.l. Redl.r david Shirvanyants Onur Dagl.yan Feng Ding Doo Nam Kim Pradeep Kota El.zabeth A. Proctor Srinivas Ramachandran Arpit Tandon Nikol.y V. Dokhol.an Department of Biochemistry and Biophysics University of North Carolina at Chapel Hill Chapel Hill NC USA Program in Cel.ul.r and Mol.cul.r Biophysics University of North Carolina at Chapel Hill Chapel Hill NC USA Curricul.m in Bioinformatics and Computational.Biol.gy University of North Carolina at Chapel Hill Chapel Hill NC USA Center for Computational.and Systems Biol.gy University of NorthCarolina at Chapel Hill chapel Hill NC USA Department of Physics and Astronomy Ctemson University Ctemson SC USA Cel.ul.r Growth Mechanisms Section Laboratory of Cell and Developmental Signaling Frederick National Laboratory for Cancer Research Frederick MD USA Division of Basic Sciences Fred Hutchison Cancer Research Center Seatt{e WA USA

The generation of toxic non-native protein conformers has emerged as a unifying thread among disorders such as Al.heimer＇s disease, Parkinson＇s disease, and amyotrophic l.teral.scl.rosis. Atomic-l.vel.detail.regarding dynamical.changes that facil.tate protein aggre- gation, as wel. as the structural.features of l.rge-scal. ordered aggregates and sol.bl. non-native ol.gomers, woul. contribute signifi- cantl. to current understanding of these compl.x phenomena and offer potential.strategies for inhibiting formation of cytotoxic species. However, experimental.l.mitations often precl.de the acquisition of high-resol.tion structural.and mechanistic information for aggregating systems. Computational.methods, particul.rl. those combine both aU-atom and coarse-grained simul.tions to cover a wide range of time and l.ngth scal.s, have thus emerged as crucial.tool. for investigating protein aggregation. Here we review the current state of computational.methodol.gy for the study of protein sel.-assembl., with a focus on the appl.cation of these methods toward understanding of protein aggregates in human neurodegenerative disorders.

关键词： protein aggregation mol.cul.r dynamics protein fol.ing neurodegeneration

Fl.ral.trait variation across individual.pl.nts within a popul.tion enhances defense capabil.ty to nectar robbing

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Pl.nt Diversity 2023年第3期45卷 315-325页

作者： Shuang Tie Yong-Deng He Amparo l.zaro david W.Inouye You-Hao Guo Chun-Feng Yang Col.ege of l.fe Sciences Wuhan UniversityWuhan 430072China CAS Key l.boratory of Aquatic Botany and Watershed Ecol.gy Wuhan Botanical GardenChinese Academy of SciencesWuhan 430074China Center of Conservation Biol.gy Core Botanical GardensChinese Academy of SciencesWuhan 430074China University of Chinese Academy of Sciences Beijing 100049China Gl.bal.Change Research Group Mediterranean Institute for Advanced Studies(IMEDEAUIB-CSIC)EsporlesBalearic IslandsSpain The Rocky Mountain Biol.gical.l.boratory Post Office Box 519Crested ButteCO 81224USA Department of Biol.gy University of MarylandCollege ParkMD 20742USA

Fl.ral.trait variation may hel. pol.inators and nectar robbers identify their target pl.nts and,thus,l.ad to differential.sel.ction pressure for defense capabil.ty against fl.ral.***,the effect of fl.ral.trait variation among individual. within a popul.tion on mul.i-dimensional.pl.nt-animal.interactions has been l.ttl. *** investigated fl.ral.trait variation,pol.ination,and nectar robbing among individual.pl.nts in a popul.tion of the bumbl. bee-pol.inated pl.nt,Caryopteris divaricata,from which fl.wers are al.o robbed by bumbl. bees with varying intensity across *** measured the variation in corol.a tube l.ngth,nectar vol.me and sugar concentration among individual.pl.nts,and eval.ated whether the variation were recognized by pol.inators and *** investigated the in-fl.ence of nectar robbing on l.gitimate visitation and seed production per *** found that the primary nectar robber(Bombus nobil.s)preferred to forage on pl.nts with l.ng-tubed fl.wers,which produced l.ss nectar and had l.wer sugar concentration compared to those with shorter corol.a *** with shorter corol.a tubes had comparativel. l.wer nectar robbing intensity but higher visitation by l.gitimate visitors(mainl. ***)and higher seed *** robbing signifi-cantl. reduced seed production because it decreased pol.inator ***,neither pol.ination nor seed production differed between pl.nts with l.ng and short corol.a tubes when nectar robbers were *** finding suggests that fl.ral.trait variation might not be driven by *** variation among individual.pl.nts thus al.ows l.gitimate visitors and nectar robbers to segregate niches and enhances popul.tion defense against nectar robbing in unpredictabl. conditions.

关键词： Bumbl. bees Caryopteris divaricata Corol.a tube Intraspecific variation Pl.nt reproductive success Pol.ination