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Oral transforming growth factor-beta recep.or 1 inhibitor vactosertib p.omotes osteosarcoma regression by targeting tumor p.oliferation and enhancing anti-tumor immunity

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Cancer Communications 2024年第8期44卷 884-888页

作者： Sung Hee Choi Jay thomas Myers Suzanne Louise Tomchuck Melissa Bonner Saada Eid Daniel Tyler Kingsley Kristen Ashley Van Heyst Seong-Jin Kim Byung-Gyu Kim Alex Yee-Chen Huang Dep.rtment of p.diatrics CaseWestern Reserve University School of MedicineClevelandOhioUSA Case Comp.ehensive Cancer Center CaseWestern Reserve University School of MedicineClevelandOhioUSA Dep.rtment of p.thology CaseWestern Reserve University School of MedicineClevelandOhioUSA Medp.cto Inc. SeoulRepublic of Korea Center for p.diatric Immunotherap. Angie Fowler AYA Cancer InstituteUH Rainbow Babies and Children’s HospitalClevelandOhioUSA

Osteosarcoma is an aggressive malignant bone sarcoma common among children,adolescents,and young *** 20%of p.tients p.esent with p.lmonary metastasis,and an additional 40%develop.p.lmonary osteosarcoma *** survival ou... 详细信息

关键词： osteosarcoma immunity p.tients

Outcomes of critically ill children with p.e-existing mental health conditions

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p.diatric Investigation 2024年第2期8卷 108-116页

作者： Conrad Krawiec Morgan Cash Gary Ceneviva Zizhong Tian Shouhao Zhou Neal J.thomas Dep.rtment of p.diatrics Pediatric Critical Care MedicinePenn State Hershey Children's HospitalPennsylvaniaUSA Dep.rtment of p.blic Health Sciences Division of Biostatistics and BioinformaticsPennsylvania State University College of MedicinePennsylvaniaUSA Dep.rtment of p.blic Health_Sciences Pennsylvania State University College of MedicinePennsylvaniaUSA

Imp.rtance:Critically ill children with p.e-existing mental health conditions may have an increased risk of p.or health ***:We aimed to evaluate if p.e-existing mental health conditions in critically ill p.diatric p.tients would be associated with worse clinical outcomes,comp.red to children with no documented mental health ***:This retrosp.ctive observational cohort study utilized the TriNetX electronic health record database of critically ill subjects aged 12-18 *** were analyzed for demograp.ics,p.e-existing conditions,diagnostic,medication,p.ocedural codes,and ***:From a dataset of 102027 critically ill children,we analyzed 1999 subjects(284[14.2%]with a p.e-existing mental health condition and 1715[85.8%]with no p.e-existing mental health condition).Multivariable analysis demonstrated that death within one year was associated with the p.esence of p.e-existing mental health conditions(odds ratio 8.97[3.48-23.15],p.0.001),even after controlling for the p.esence of a comp.ex chronic ***:The p.esent study demonstrates that the p.esence of p.e-existing mental health conditions was associated with higher odds of death within 1 year after receiving critical ***,the confidence interval was wide and hence,the findings are *** studies with a larger samp.e size may be necessary to evaluate the true long-term imp.ct of children with p.e-existing mental health conditions who require critical care services.

关键词： Critical care p.ychiatry p.ychology p.blic health

Nanoscale inhibition of p.lymorp.ic and ambidextrous lAp. amyloid aggregation with small molecules

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Nano Research 2018年第7期11卷 3636-3647页

作者： Aleksandr Kakinen Jozef Adamcik Bo Wang Xinwei Ge Raffaele Mezzenga thomas p. Davis Feng Ding p. Chun Ke ARC Centre of Excellence in Convergent Bio-Nano Science and Technology Monash Institute of Pharmaceutical Sciences Monash University 381 Royal Parade Parkville VIC 3052 Australia Food & Soft Materials Department of Health Sciences & Technology ETH Zurich Schmelzbergstrasse 9 LFO E23 8092 Zurich Switzerland Dep.rtment of p.ysics andAstronomy Clemson University Clemson SC29634 USA Dep.rtment of Chemistry Warwick University Gibbet Hill Coventry CV4 7AL UK

Understanding how small molecules interface with amyloid fibrils at the nanoscale is of imp.rtance for develop.ng therap.utic treatments against amyloid-based diseases. Here, we show for the first time that human islet amyloid p.lyp.p.ides （LAp.） in the fibrillar form are p.lymorp.ic, ambidextrous, and p.ssess multip.e p.riodicities. Up.n interfacing with the small molecule ep.gallocatechin gallate （EGCG）, IAp. aggregation was rendered off-p.thway and assumed a form with soft and disordered clusters, while mature IAp. fibrils disp.ayed kinks and branching but conserved the twisted fibril morp.ology. These nanoscale p.enomena resulted from comp.titive interactions between EGCG and the IAp. amyloidogenic region, as well as end cap.ing of the fibrils by the small molecule. This information is crucial in delineating IAp. toxicity imp.icated in typ. 2 diabetes and for develop.ng new inhibitors against amyloidogenesis.

关键词： islet amyloid p.lyp.p.ides(LAp.) fibriUization p.rsistence length small molecule discrete moleculardynamics (DMD)simulations inhibition

p.en Tze Huang Inhibits p.oliferation of Colorectal Cancer Cells through Sup.ressing p.O1 Exp.ession and Activating p.3/p.1 Signaling p.thway

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Chinese Journal of Integrative Medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying thomas J.Sferra LIU Hui-xin LI Li p.NG Jun SHEN A-ling Clinical Research Institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of Integrative Medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Dep.rtment of p.diatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China Dep.rtment of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo exp.ore the regulatory effect of p.en Tze Huang (p.H) on targeting p.rtner of NOB1 (p.O1) and it’s down-stream mediators in colorectal cancer (CRC) *** p.lymerase chain reaction was p.rformed to determine mRNA levels of p.O1, Tp.3, and CDKN1A. Western blotting was p.rformed to determine p.otein levels of p.O1, p.3, and p.1. HCT-8 cells were transduced with a lentivirus over-exp.essing p.O1. Colony formation assay was used to detect cell survival in p.O1 overexp.ession of HCT-8 cells after p.H treatment. Cell-cycle distribution, cell viability and cell ap.p.osis were p.rformed to identify the effect of p.O1 overexp.ession on cell p.oliferation and ap.p.osis of HCT-8 cells after p.H treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-p.O1 or sh-Ctrl lentivirus were evaluated. Western blot assay was p.rformed to detect p.O1, p.3, p.1 and p.NA exp.ession in tumor sections. Terminal deoxynucleotidyl transferase dUTp.nick end labling (TUNEL) assay was used to determine the ap.p.otic cells in *** treatment decreased cell viability, down-regulated p.O1 exp.ession, and up.regulated p.3 and p.1 exp.essions in HCT-8 cells (p.0.05). p.O1 overexp.ession attenuated the effects of p.H treatment, including the exp.ession of p.3 and p.1, cell growth, cell viability, cell cycle arrest and cell ap.p.osis in vitro (p.0.05). p.O1 knockdown eliminated the effects of p.H treatment on tumor growth, inhibiting cell p.oliferation inhibition and ap.p.osis induction in vivo (p.0.05). Similarly, p.O1 knockdown attenuated the effects of p.H treatment on the down-regulation of p.O1 and up.regulation of p.3 and p.1 in vivo (p.0.05).ConclusionThe mechanism by which p.H induces its CRC anti-p.oliferative effect is at least in p.rt by regulating the exp.ession of p.O1 and its downstream targets p.3 and p.1.

关键词： colorectal cancer p.en Tze Huang Chinese medicine p.rtner of NOB1 p.oliferation p.3/p.1 p.thway

Defective maintenance of intracellular Ca2+ homeostasis is linked to increased muscle fatigability in the MG29 null mice

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Cell Research 2004年第5期14卷 373-378页

作者： Marco A. p. BROTTO,Ramakrishnan Y. NAGARAJ,Leticia S. BROTTO,thomas M. NOSEK Dep.rtment of p.ysiology and Biop.ysics UMDNJ-Robert Wood Johnson Medical School p.scataway NJ 08854 USA Dep.rtment of p.ysiology and Biop.ysics UMDNJ-Robert Wood Johnson Medical School p.scataway NJ 08854 USA Dep.rtment of p.ysiology and Biop.ysics UMDNJ-Robert Wood Johnson Medical School p.scataway NJ 08854 USA Dep.rtment of p.ysiology and Biop.ysics School of Medicine Case Western Reserve University Cleveland OH 44106 USA

Mitsugumin 29 (MG29) is a transmembrane p.otein that is normally found in the triad junction of skeletal muscle. Our p.evious studies have shown that targeted deletion of mg29 from the skeletal muscle resulted in abnormality of the triad junction structure, and also increased suscep.ibility to muscle fatigue. To elucidate the basis of these effects, we investigated the p.op.rties of Ca2+-up.ake and -release in toxin-skinned Extensor Digitorium Longus (EDL) muscle fibers from control and mg29 knockout mice. Comp.red with the control muscle, submaximal Ca2+-up.ake into the sarcop.asmic reticulum (SR) was slower and the storage of Ca2+ inside the SR was less in the mutant muscle, due to increased leakage p.ocess of Ca2+ movement across the SR. The leakage p.thway is associated with the increased sensitivity of Ca2+/caffeine -induced Ca2+ release to myop.asmic Ca2+. Therefore, the increased fatigability of mutant EDL muscles can result from a combination of a slowing of Ca2+ up.ake, modification of Ca2+-induced Ca2+ release (CICR), and a reduction in total SR Ca2+ content.

关键词： MG29 mutant skeletal muscle skinned fibers ECC Ca2+ up.ake CICR.

Functional lumen imaging p.obe use in a high-volume p.actice:p.actical and technical imp.ications

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World Journal of Gastrointestinal Endoscop. 2024年第7期16卷 396-405页

作者： Yan Jiang Raul Vazquez-Reyes Afrin Kamal thomas Zikos George Triadafilop.ulos John O Clarke Division of Gastroenterology and Hep.tology Stanford University School of MedicineRedwoodCA 94063United States

BACKGROUND The functional lumen imaging p.obe(FLIp.is a Food and Drug Administration ap.roved tool to aid the diagnosis and management of esop.ageal ***,widesp.ead adop.ion of FLIp.remains limited and its utility in highvolume p.actices remains *** To analyze large samp.e data on clinical use of FLIp.and p.ovide insight on several technical asp.cts when p.rforming *** We conducted a retrosp.ctive comp.rative and descrip.ive analysis of FLIp.p.ocedures p.rformed by a single p.ovider at an academic medical *** was a total of 398 FLIp.p.ocedures *** medical records were reviewed and data regarding demograp.ics and p.ocedural details were *** tests,including chi-squared,t-test,and multivariable logistic and linear regression,were *** There was an increase in FLIp.cases with each successive time p.riod of 13 months(n=68,146,184,resp.ctively)with notable rises sp.cifically for indications of dysp.agia and gastroesop.ageal reflux *** was a shift toward use of the longer FLIp.balloon catheter for diagnostic p.rp.ses(overall 70.4%vs 29.6%,p.0.01).Many cases(42.8%)were p.rformed in conjunction with other diagnostics/interventions,such as dilation and wireless p. p.obe *** were nearly equally p.rformed with anesthesia vs moderate sedation(51.4%anesthesia),with no major *** who had anesthesia were less likely to have recurrent antegrade contractions[odds ratio(OR)=0.4,95%CI:0.3-0.8]and were also more likely to have absent contractility(OR=2.4,95%CI:1.3-CONCLUSION FLIp.cases have increased in our p.actice with exp.nding indications for its *** limited normative data,p.oviders should be aware of several p.tential technical issues,including the p.ssible imp.ct of sedation choice when assessing esop.ageal motility p.tterns.

关键词： Gastroenterology Endoscop. Functional lumen imaging p.obe Esop.agus Motility

p.otometric investigation of eight ultra-short p.riod eclip.ing binaries from OGLE

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Research in Astronomy and Astrop.ysics 2020年第8期20卷 113-120页

作者： Shanti p.iya D. Ravi Raja p. Rukmini J. Raghu p.asad M. Vineet S.thomas Dep.rtment of Astronomy Osmania UniversityHyderabad-500007TelanganaIndia The University of Akron AkronOH44325USA

We p.rformed a detailed p.otometric analysis of eight ultra-short p.riod eclip.ing binaries(USp.Bs) using the Wilson-Devinney method. We p.esent the modeled light curves and derived p.otometric solutions. The USp.Bs with p.riod(p.≤0.21 d considered in our study belong to W-subtyp. having shallow contact factor(f)~0.7 and later sp.ctral typ.s. The absolute p.rameters for these short-p.riod binaries were derived ap.lying emp.rical relations. We discuss the evolutionary stage of these USp.Bs using the mass-radius, color-density and p.riod-color diagrams. The objects showed p.or metallicities, and some objects were even found to be existing around fully convective limits. The p.riod distribution of USp.Bs exhibited a sharp.cut-off at 0.22 d;however, we observed significant deficits for our objects in the literature. We examined the statistics of USp.Bs studied to date(in terms of the distribution of p.riod, mass ratio and comp.nent temp.ratures of USp.Bs) and observed that a dominant distribution of comp.nent temp.ratures for these USp.Bs was towards lower temp.ratures.

关键词： stars:low-mass stars:evolution stars:low-mass binaries:eclip.ing binaries:close

Investigations of ZnO thin films dep.sited by a reactive p.lsed laser ablation

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Science China(Technological Sciences) 2009年第1期52卷 99-103页

作者： Y. C. SOO H. KANDEL M. A. thomas C. p. DAGHLIAN Dep.rtment of p.ysics and Astronomy University of Arkansas at Little Rock Little Rock E. M. Facilities Dartmouth College Hanover

Highly transp.rent ZnO thin films were dep.sited at different substrate temp.ratures by p.lsed laser dep.sition in an oxygen atmosp.ere. The thin films were characterized by various techniques including X-ray diffraction, scanning electron microscop., op.ical absorp.ion, and p.otoluminescence. We demonstrated that oriented wurtzite ZnO thin films could be dep.sited at room temp.rature using a high p.rity zinc target. Variable temp.rature p.otoluminescence revealed new characteristics in the band edge emission. The underlying mechanism for the observed p.enomena was also discussed.

关键词： thin films p.lsed laser dep.sition op.ical p.op.rty zinc oxide

p.atelet-rich p.asma for de Quervain’s tenosynovitis: A systematic review and meta-analysis

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World Journal of Orthop.dics 2024年第9期15卷 858-869页

作者： Nucki Nursjamsi Hidajat Raden Moechammad Satrio Nugroho Magetsari Gregorius Steven Jethro Budiman Gregorius thomas p.asetiyo Dep.rtment of Orthop.edics and Traumatology Padjadjaran UniversityBandung 45363Jawa BaratIndonesia General p.actitioner Panti Wilasa Citarum HospitalSemarang 50121Indonesia

BACKGROUND p.atelet-rich p.asma(p.p.injection is used as an alternative non-op.rative management for de Quervain’s tenosynovitis(DQT)to regenerate tendon *** To assess and conclude the research-based study systematically to analyse the efficacy of p.p.on *** This systematic review used the Cochrane Handbook for Systematic Reviews and the guideline of p.eferred rep.rting items for systematic review and metaanalysis.A systematic literature search was ap.lied to 11 *** authors assessed the study quality and risk of bias of each included *** of the meta-analysis were p.esented using mean difference(MD)/standardized mean difference(SMD)and 95%condence interval(CI).RESULTS The authors evaluated 275 studies found in the literature search;12 studies met the criteria for this review,and then the study quality and risk of bias were *** analysis of data from two studies involving 194 subjects with DQT showed that,comp.red with conservative treatment,p.p.injection was associated with a greater reduction in visual analog scale p.in in one month and six months after treatment(MD:-0.67,p.valuep.valuep.valuep.valuep.p.can be used as an alternative non-op.rative treatment for DQT due to the tissue regenerative effect of p.p.

关键词： De Quervain’S disease De Quervain’S tenosynovitis p.atelet-rich p.asma Stenosing tenosynovitis