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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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A proctolin-like peptide is regulated after baculovirus infection and mediates in caterpillar locomotion and digestion

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Insect Science 2022年第1期29卷 230-244页

作者： a.gel llopis-giménez Stefano Parenti Yue Han Vera I.D.Ros Salvador Herrero Department of Genetics and Institut Universitari en Biotecnologia i Biomedicina(BIOTECMED) Universitat de ValenciaValenciaSpain Laboratory of Virology Wageningen University and ResearchWageningenthe Netherlands Current address.Department of Pathology University of CambridgeCambridgeUK

Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues, included the central nervous system (CNS). As a main component of the CNS, neuropeptides are small protein-like molecules functioning as neurohormones, neurotransmitters, or neuromodulators. These peptides are involved in regulating animal physiology and behavior and could be altered after baculovirus infection. In this study, we have investigated the effect of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) infection on expression of Spodoptera exigua neuropeptides and neuropeptide-like genes. Expression of the gene encoding a polypeptide that resembles the well-known insect neuropeptide proctolin and named as proctolin-like peptide (PLP), was downregulated in the larval brain following infection and was chosen for further analysis. A recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV) overexpressing the C-terminal part of the PLP was generated and used in bioassays using S. exigua larvae to study its influence on the viral infection and insect behavior. AcMNPV-PLP-infected larvae showed less locomotion activity and a reduction in growth compared to larvae infected with wild type AcMNPV or mock-infected larvae. These results are indicative of this new peptide as a neuromodulator that regulates visceral and skeletal muscle contractions and offers a novel effector involved in the behavioral changes during baculovirus infection.

关键词： beet armyworm behavior neuromodulator neuropeptide physiology SeM-NPV

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A new perspective on immune evasion:escaping immune surveillance by inactivating tumor suppressors

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Signal Transduction and Targeted Therapy 2022年第2期7卷 337-338页

作者： Svenja Mergener Samuel Peña-llopis Translational Genomics in Solid Tumors German Cancer Consortium(DKTK)and German Cancer Research Center(DKFZ)at University Hospital EssenHufelandstrasse 55D-45147 EssenGermany Division of Solid Tumor Translational Oncology German Cancer Consortium(DKTK)and German Cancer Research Center(DKFZ)D-69120 HeidelbergGermany

Inactivating mutations in tumor suppressor genes(TSGs)are known to drive tumorigenesis by decoupling proliferation and survival from tight regulatory *** a recent study published in Science,Martin et al.1 shed light on an unappreciated role of TSGs in preventing immune evasion by demonstrating enrichment of TSG inactivation in tumor cell transplants in mice when facing an intact adaptive immune system.

关键词： suppressor immune

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Color pref ere nee cool versus warm in nursing homes depends on the expected activity for interior spaces

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Frontiers of Architectural Research 2020年第4期9卷 739-750页

作者： Ana Torres Juan Serra Jorge llopis Anna Delcampo Instituto de Restauracion Del Patrimonio Universitat Politecnica de ValenciaValencia 46022Spain

This study explores the color preferences of elderly residents of nursing homes based on the expected activities for different rooms,activity rooms,and bedrooms and compares the results with the arousal level induced by each *** experime nts were con ducted,one with elderly people living in nursing homes in the Valen cian Comm unity,and the other in a laboratory with virtual reality and physiological markers(i.e.,heart rate variability).I dlviduals assessed six colors in two groups of warm and *** demonstrate that preferences for warm and cool colors depend on the room *** the activity room,warm colors were preferred over the cool colors by both genders,fitting the higher arousal levels induced by warm versus cool *** the bedrooms,cool colors were preferred by both genders,fitting the lower arousal levels induced by cool colors in females and the other models that suggest a U-shaped relation between the arousal level and the visible spectra of ***,the color preferences for interior spaces in nursing homes depend on the room type and are related to the arousal level for the expected activity in them.

关键词： Color Elderly Preference Arousal Architecture

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Mating Disruption of Striped Rice Stem Borer: Importance of Early Deployment of Dispensers and Impact on Airborne Pheromone Concentration

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Rice science 2021年第6期28卷 525-528,I0027-I0029页

作者： Aitor GAVARA Sandra VACAS Jaime PRIMO Vicente NAVARRO-llopis Centre for Agricultural Chemical Ecology Mediterranean Agroforestry InstitutePolytechnic University of ValenciaBuilding 6CCamino de Vera s/n46022 ValenciaSpain

Mating disruption(MD)is an effective environmentally-friendly control method against the striped rice stem borer(RSB),Chilo suppressalis(Lepidoptera:Crambidae).In this study,the current MD dispensers release the pheromone exponentially,with higher initial release rates that decrease throughout the *** adjust the timing of dispensers'deployment and evaluate the importance of controlling the early first or the second male flight,field trials were carried out to test the efficacy of two strategies:the early dispenser deployment prior to the first male flight(May)and the late deployment prior to the second flight(June).The early dispenser deployment was more effective in reducing plant damage inflicted by RSB when assessed at ***,neither of these strategies was able to inhibit the male catches of the third flight due to the dispensers5 *** to the airborne pheromone concentrations obtained,around 1.60 ng/m3 were capable to inhib社*** male flight effectively.

关键词： release Impact adjust

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Correlation between the Degree of Liver Fibrosis and Driving Test Alterations as an Indicator of Minimal Hepatic Encephalopathy

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Open Journal of Gastroenterology 2015年第4期5卷 28-30页

作者： Carlos Tornero Simona Cioaia Marina llopis Ana Ventura Internal Medicine Hospital Francesc de Borja Gandia Spain

Minimal hepatic encephalopathy is a subclinical disorder in patients with liver cirrhosis that may have an impact upon driving capacity. This study in highly selected patients without other confounding factors examines whether there is a relationship between the degree of liver fibrosis as determined by Fibroscan exploration and the driving test scores. Using the ASDE DRIVER-TEST N-845 system, validated for obtaining the driving license in Spain, we assessed the calculation of distances and time, bimanual visual-motor coordination, reaction time to different stimuli, concentrated attention, and resistance to monotony. The data were processed using the SPSS statistical package, with an analysis of the correlation between the degree of fibrosis and the test scores based on the Spearman statistic and the comparison of means (Mann-Whitney U-test). We found no alterations in driving capacity in patients diagnosed of hepatitis C with different degrees of early stage fibrosis or cirrhosis.

关键词： Minimal Hepatic Encephalopathy Driving

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C++游戏编程

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丛书名：游戏开发经典丛书

2004年

作者：（美）Noel llopis 李鹏贾传俊译

本书从游戏开发的角度出发，把C++应用到游戏软件领域，介绍了一些C++实战经验，从常规的C++技术解决游戏开发中常遇到的问题，重点讲述在实际项目中应用的技术。

ISBN: (数字)7302090483

ISBN: (纸本)7302090483

关键词：游戏 C语言程序设计

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World Federation of Acupuncture-Moxibustion Societies(WFAS)Clinical Practice Guideline on Acupuncture and Moxibustion:Migraine recommendation summaries

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World Journal of Acupuncture-Moxibustion 2024年第3期34卷 204-212页

作者： Wen-qian MA Shuo CUI Jing HU Zhong-jie CHEN Jin HUO Ya-ping LIU Xiao-yu WANG Zi-wei SONG Qi GAO Shu-hua MA Yi ZHANG Zhong-chao WU Ji-ping ZHAO Xiang-hong JING Xiao-dong WU Yu-tong FEI Bin XU Shao-zong CHEN Cheng QIAN Chun-gui YANG Dong-qing ZHANG Ling ZHAO Bin LI Filomena Petti Aldo Liguori Carlos llopis Claudia Skopalik Zhao DONG Jian YIN Zhen HUA Dong-sheng WANG Gerd Lutterjohann Yue JIAO Jing-jing WANG Institute of Acupuncture and moxibustion China Academy of Chinese Medical SciencesBeijing 100700China Experimental Research Center China Academy of Chinese Medical SciencesBejing100700China Dongzhimen Hospital Beijing University of Chinese MedicineBeijing 100007China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100105China Key Laboratory of the Ministry of Education for the Integration of Needle and Medicine Nanjing University of Chinese MedicineNanjing 210023China School of Acupuncture-moxibustion and Tuina Mossage Shandong University of Traditional Chinese MedicineJinan 250355China Shenzhou Open University of Traditional Chinese medicine Noord-Holland 671011 EKNetherlands Chinese Medicine Society Sweden Stockholm 10653Sweden School of Acupuncture-moxibustion and Tuina Mossage Chengdu University of Traditional Chinese MedicineChengdu 610075China Acupuncture-moxibustion Department of Beijing Hospital of Traditional Chinese Mediane Bejing 100010China Istituto Paracelso Rome 00153Italy European Foundation of Traditional Chinese Medicine Madrid 28000Spain Department of Neurology First Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Neurology of Beijing Hospital Beijing 100853China Anesthesiology Department and pain diagnosis and treatment center Beijing HospitalBejing 100853China Division of Psychology of Beijing Normal University Beijing 100091China German Medical Association for Acupuncture(DAGfA) Munich 80801Germany Tsinghua University Hospital Bejing 100084China

Clinical Practice Guideline on Acupuncture and Moxibustion:Migraine(WFAS 007.9-2023)is a clinical practice guideline officially released by the World Federation of Acupuncture-Moxibustion Societies(WFAS)on October 9,2023,and is the first international guideline on the treatment of migraine with *** international standard was developed under the guidance of rigorous evidence-based methodology,and it contains guideline purpose,scope,applicable population,applicable settings,overview of acupuncture for migraine,guideline development process and *** promoting the understanding and application of this guideline,this article summarizes a total of 18 recommendations in order to assist clinical decisions for migraine with acupuncture.

关键词： Acupuncture acupuncture Moxibustion

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Production of Volatile Moth Sex Pheromones in Transgenic Nicotiana benthamiana Plants

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BioDesign Research 2021年第1期2021卷 79-95页

作者： Rubén Mateos-Fernández Elena Moreno-giménez Silvia Gianoglio Alfredo Quijano-Rubio Jose Gavaldá-García Lucía Estellés Alba Rubert JoséLuis Rambla Marta Vazquez-Vilar Estefanía Huet Asunción Fernández-del-Carmen Ana Espinosa-Ruiz Mojca Juteršek Sandra Vacas Ismael Navarro Vicente Navarro-llopis Jaime Primo Diego Orzáez Institute for Plant Molecular and Cell Biology(IBMCP) Consejo Superior de Investigaciones Científicas(CSIC)-Universidad Politécnica de Valencia(UPV)ValenciaSpain Jaume I University Castellon de la PlanaSpain Department of Biotechnology and Systems Biology National Institute of BiologyLjubljanaSlovenia Jožef Stefan International Postgraduate School LjubljanaSlovenia Centro de Ecología Química Agrícola Instituto Agroforestal del MediterráneoUniversitat Politècnica de ValènciaValenciaSpain Ecología Y Protección Agrícola SL ValenciaSpain

Plant-based bioproduction of insect sex pheromones has been proposed as an innovative strategy to increase the sustainability of pest control in ***,we describe the engineering of transgenic plants producing(Z)-11-hexadecenol(Z11-16OH)and(Z)-11-hexadecenyl acetate(Z11-16OAc),two main volatile components in many Lepidoptera sex pheromone *** assembled multigene DNA constructs encoding the pheromone biosynthetic pathway and stably transformed them into Nicotiana benthamiana *** constructs contained the Amyelois transitella AtrΔ11 desaturase gene,the Helicoverpa armigera fatty acyl reductase HarFAR gene,and the Euonymus alatus diacylglycerol acetyltransferase EaDAct gene in different *** the pheromone-producing plants showed dwarf phenotypes,the severity of which correlated with pheromone *** but one of the recovered lines produced high levels of Z11-16OH,but very low levels of Z11-16OAc,probably as a result of recurrent truncations at the level of the EaDAct *** one plant line(SxPv1.2)was recovered that harboured an intact pheromone pathway and which produced moderate levels of Z11-16OAc(11.8μg g^(-1) FW)and high levels of Z11-16OH(111.4μg g^(-1)).Z11-16OAc production was accompanied in SxPv1.2 by a partial recovery of the dwarf ***1.2 was used to estimate the rates of volatile pheromone release,which resulted in 8.48 ng g-1 FW per day for Z11-16OH and 9.44 ng g^(-1 )FW per day for *** results suggest that pheromone release acts as a limiting factor in pheromone biodispenser strategies and establish a roadmap for biotechnological improvements.

关键词： release dwarf transformed

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“拆除”领导力的挑战

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科学新闻 2022年第4期24卷 62-63页

作者： Samuel Pe?a-llopis 倪伟波埃森大学医院德国癌症联盟（DKTK）肿瘤学院

“砰！”炸弹爆炸了。但别担心，这是一个虚拟炸弹，是我在大流行病早期通过电话会议和研究小组玩的一个游戏的一部分。游戏名为“保持通话，爆炸不炸”（KTANE），是由一名“拆弹者”——我（拥有炸弹但不知道如何拆除它），和一组“...

“砰！”炸弹爆炸了。但别担心，这是一个虚拟炸弹，是我在大流行病早期通过电话会议和研究小组玩的一个游戏的一部分。游戏名为“保持通话，爆炸不炸”（KTANE），是由一名“拆弹者”——我（拥有炸弹但不知道如何拆除它），和一组“专家”——我的团队成员（拥有操作说明书但看不到炸弹）组成。

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