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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt Department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(DKTK) EssenGermany German Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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Learning to become addicted,one synapse at a time

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Neural Regeneration Research 2024年第2期19卷 401-402页

作者： Alessio Attardo Sidney B.Cambridge Leibniz Institute for Neurobiology MagdeburgGermany Institute for Anatomy II Dr.Senckenberg AnatomyGoethe-University Frankfurt am MainFrankfurtGermany

Addiction has been extensively studied on many levels:from the molecular level,with various“omics”approaches(Natividad et al.,2018;Grecco et al.,2021),to the clinical level,with psychotherapy and MRI imaging(Ceceli ... 详细信息

关键词： clinical therapy

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Three cases of uncommon medication-associated osteonecrosis of temporal bone

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世界耳鼻咽喉头颈外科杂志英文版 2024年第3期10卷 237-240页

作者： VanDolah Hunter Crossley Jason R. Jeffrey Kim H. Georgetown University School of Medicine Washington DC USA Department of Otolaryngology–Head and Neck Surgery MedStar Georgetown University Hospital Washington DC USA

Introduction: Medication-related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti-resorptive and biologic agents. Here, we present the first case of tyrosine-kinase inhibitor-related external auditory canal (EAC) osteonecrosis as well as two cases related to anti-resorptive ***: A retrospective case ***: Case one: an 84-year-old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally. She had a history of osteoporosis treated with denosumab and risedronic acid. She successfully underwent left EAC reconstruction using an inferiorly-based pedicle periosteal flap while the right ear canal was managed conservatively. Case two: a 69-year-old male presented with osteonecrosis of the right EAC. He had a history of osteoporosis treated with alendronic acid and zoledronic acid. His osteonecrosis is conservatively managed with local debridement and antibiotic application. Case three: a 60-year-old male presented with osteonecrosis of the right inferior EAC. He had a history of chronic myelogenous leukemia treated with a tyrosine-kinase inhibitor, imatinib. After failing conservative therapy, he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his ***: Anti-resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis. When a local debridement and antibiotic therapy fail, definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

关键词： bisphosphonates denosumab external auditory canal imatinib medication-related osteonecrosis osteonecrosis temporal bone tyrosine-kinase Inhibitors

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Litter production and leaf nutrient concentration and remobilization in response to climate seasonality in the central amazon

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Journal of Forestry Research 2024年第3期35卷 131-141页

作者： Ricardo Antonio Marenco Saul Alfredo Antezana-Vera Daniela Pereira Dias Luiz Antonio Candido Instituto Nacional de Pesquisas da amazonia Coordenagao de Uso da Terra e Mudanca ClimaticaAv.Andre Araujo 2936ManausAM69067-375Brazil Programa de pos-Graduagao em Agricultura no Tropico Umido Instituto Nacional de Pesquisas da Amazonia-INPAManausAMBrazil Unidade Academica de Ciencias Agrarias Universidade Federal de JataiBR 364km 195JataiGO 75801-615Brazil

Litterfall is the largest source of nutrients to for-est soils of tropical ***,variability in lit-terfall production,nutrient remobilization,and changes in leaf nutrient concentration with climate seasonality remain largely unknown for the central *** study meas-ured litterfall production,leaf nutrient remobilization,and leaf area index on a forest plateau in the central *** was measured at monthly intervals during 2014,while nitrogen,phosphorus,potassium,calcium and mag-nesium concentrations of leaf litter and canopy leaves were measured in the dry and rainy seasons,and remobilization rates *** area index was also recorded in the dry and rainy *** litterfall varied from 33.2(in the rainy season)to 87.6 g m^(-2) in the dry season,while leaf area index increased slightly in the rainy *** seasonality had no effect on concentrations of nitrogen,calcium,and magnesium,whereas phosphorous and potassium responded to rainfall seasonality *** phosphorous increased,potassium decreased during the dry *** seasons,nitrogen,potassium,and phosphorous decreased in leaf litter;calcium increased in leaf litter,while magnesium remained unaffected with leaf ***,the five nutrients had similar remobilization rates over the *** absence of climate seasonality on nutrient remobilization suggests that the current length of the dry season does not alter nutrient remobilization rates but this may change as dry periods become more prolonged in the future due to climate change.

关键词： Throughfall Nutrient cycling Climatic seasonality Leaf mass per area

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Optimal Model Average Prediction in Orthogonal Kriging Models

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Journal of Systems Science & Complexity 2024年第3期37卷 1080-1099页

作者： WANG Jun HE Jiabei LIANG Hua LI Xinmin School of Mathematics and Statistics Qingdao UniversityQingdao 266071China Department of Statistics George Washington UniversityWashington DC 20052USA

The main objective of this paper is to consider model averaging methods for kriging *** paper proposes a Mallows model averaging procedure for the orthogonal kriging model and demonstrate the asymptotic optimality of the model averaging estimators in terms of mean square *** studies are conducted to evaluate the performance of the proposed method and compare it with the competitors to demonstrate its *** authors also analyse a real dataset for an illustration.

关键词： Asymptotic optimality Mallows criterion optimal model averaging orthogonal kriging model

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Systematic pan-cancer analysis reveals OGT and OGA as potential biomarkers for tumor microenvironment and therapeutic responses

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Genes & Diseases 2024年第4期11卷 1-4页

作者： Chunyan Hou Ci Wu Wenge Zhu Huadong Pei Junfeng Ma Department of Oncology Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonDC 20007USA Department of Biochemistry and Molecular Medicine School of Medicine and Health ScienceGeorge Washington UniversityWashingtonDC20052USA

Protein O-linkedβ-N-acetylglucosamine(O-GlcNAc)modification(O-GlcNAcylation)is a unique monosaccharide modification of essential importance in physiology and pathology.1,2 As a highly dynamic process,O-GlcNAcylation is mediated by two paired enzymes:O-GlcNAc transferase(OGT)and O-GlcNAcase(OGA),which add or remove the modification from proteins,*** evidence demonstrates that the aberrant O-GlcNAcylation underlies the initiation,progression,and metastasis of cancer.

关键词： metastasis pathology therapeutic

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Temperature and structure measurements of heavy-ion-heated diamond using in situ X-ray diagnostics

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Matter and Radiation at Extremes 2024年第4期9卷 80-89页

作者： J.Lutgert P.Hesselbach M.Schorner V.Bagnoud R.Belikov P.Drechsel B.Heuser O.SHumphries P.Katrik B.Lindqvist C.Qu R.Redmer D.Riley G.Schaumann S.Schumacher A.Tauschwitz D.Varentsov K.Weyrich X.Yu B.Zielbauer Zs.Major P.Neumayer D.Kraus Institut fur Physik Universitat RostockAlbert-Einstein-Str.2318059 RostockGermany GSI Helmholtzzentrum fur Schwerionenforschung Planckstr.164291 DarmstadtGermany Institut für Angewandte Physik Goethe-Universität Frankfurt am MainMax-von-Laue-Str.160438 Frankfurt am MainGermany Institut fur Geowissenschaften Goethe-Universitat Frankfurt am MainAltenhoferallee 160438 Frankfurt am MainGermany Helmholtz-Zentrum Dresden-Rossendorf Bautzner Landstr.40001328 DresdenGermany European XFEL GmbH Holzkoppel 422869 SchenefeldGermany Centre for Plasma Physics School of Mathematics and PhysicsQueen’s University BelfastUniversity RoadBelfast BT71NNUnited Kingdom Institut für Kernphysik Technische Universität DarmstadtSchlossgartenstr.964289 DarmstadtGermany State Key Laboratory of Nuclear Physics and Technology Institute of Heavy Ion PhysicsPeking UniversityBeijing 100871China Helmholtz Institut Jena Frobelstieg 307743 JenaGermany

We present in situ measurements of spectrally resolved X-ray scattering and X-ray diffraction from monocrystalline diamond samples heatedwith an intense pulse of heavy *** this way,we determine the samples’heating dynamics and their microscopic and macroscopic structuralintegrity over a timespan of several *** the ratio of elastic to inelastic scattering with state-of-the-art density functionaltheory molecular dynamics simulations allows the inference of average temperatures around 1300 K,in agreement with predictions fromstopping power *** simultaneous diffraction measurements show no hints of any volumetric graphitization of the material,butdo indicate the onset of fracture in the diamond *** experiments pave the way for future studies at the Facility for Antiproton andIon Research,where a substantially increased intensity of the heavy ion beam will be available.

关键词： heated intense structure

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Snapshot imaging of ultrashort electron bunches

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Light(Science & Applications) 2024年第7期13卷 1226-1228页

作者： Andreas Döpp Ludwig-Maximilian-Universität München Am Coulombwall 185748GarchingGermany Max Planck Institut für Quantenoptik Hans-Kopfermann-Strasse 1Garching85748Germany

New measurements combine spatial and temporal information from optical transition radiation to estimate the three-dimensional structure of electron bunches from a laser wakefield accelerator.

关键词： ultrashort Snapshot electron

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Optimal Stochastic Scheduling Strategy of Multi-vector Energy Complex Integrated with Full-blown Power-to-biomethane Model

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Journal of Modern Power Systems and Clean Energy 2024年第3期12卷 863-873页

作者： Guanwei Zeng Chengxi Liu Minfang Liao Yongjian Luo Xuzhu Dong Hubei Engineering and Technology Research Center for AC/dc Intelligent Distribution Network WuhanChina the School of Electrical Engineering and Automation Wuhan UniversityWuhanChina

We propose an optimal stochastic scheduling strategy for a multi-vector energy complex(MEC),considering a fullblown model of the power-to-biomethane(Pt M)*** conventional optimization that uses a simple efficiency coefficient to coarsely model energy conversion between electricity and biomethane,a detailed Pt M model is introduced to emphasize the reactor kinetics and chemical equilibria of *** model crystallizes the interactions between the Pt M process and MEC flexibility,allowing to adjust the operating condition of the methanation reactor for optimal MEC operation in stochastic *** optimization and flowsheet design of the Pt M process increase the average selectivity of methane(i.e.,ratio between net biomethane production and hydrogen consumption)up to 83.7%in the proposed synthesis *** results can provide information and predictions to operators about the optimal operating conditions of a Pt M unit while improving the MEC flexibility.

关键词： Multi-vector energy complex optimal stochastic scheduling power-to-biomethane unit process synthesis natural gas

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Experimental and numerical investigation on alternatives to sandy gravel

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Defence Technology（防务技术） 2024年第1期31卷 130-141页

作者： V.Denefeld H.Aurich Fraunhofer Institute for High-Speed Dynamics Ernst-Mach-Institut(EMI)Ernst-Zermelo-Str.479104FreiburgGermany Fraunhofer Institute for High-Speed Dynamics Ernst-Mach-Institut(EMI)Am Christianswuhr 279400KandernGermany

The NATO agreement STANAG 4569 defines the protection levels for the occupants of logistic and light armored *** Allied Engineering Publication,AEP-55,Volume 2 document outlines the test conditions for underbelly improvised explosive device(IEDs),which must be buried in water-saturated sandy *** use of sandy gravel has some drawbacks,for instance reproducibility,time consumption,and *** paper focuses on the investigation of four alternatives to sandy gravel,which could produce similar specific and cumulative impulses:a concrete pot filled with water,a concrete pot filled with quartz sand,a steel pot without filling and a concrete pot filled with glass spheres(diameter 200μm—300μm)and different water *** impulses are measured with a ring technology developed at the Fraunhofer EMI.A numerical soil model based on the work of Marrs,2014 and Fi serov a,2006 and considering the soil moisture was used to simulate the experiments with glass spheres at different water contents,showing much better agreement with the experiments than the classical Laine&Sandvik model,even for high saturation *** results can be used to create new test conditions at original scale that are more cost-effective,more reproducible and simpler to manage in comparison to the current tests carried out with STANAG sandy gravel.

关键词： Improvised explosive device(IED) Specific impulse Momentum transfer Sandy gravel Glass spheres Numerical model Soil moisture

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