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The Effect of a Novel Complex, Composed of Ceramide, Energizing Peptide and Camu Camu Extract, on Epidermal Barrier Function and Dermal Antiaging Properties in Ex Vivo Human Skin Small Live Cohort

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Journal of Cosmetics, Dermatological Sciences and Applications 2024年第1期14卷 1-11页

作者： Landau marina Landau-Blum Shir Samuel Kassirer Audrey Le Mestr Armelle Perrin Julien Verdon Laurine Bergeron Corinne Morel Isabelle Imbert Arena Dermatology Herzliya Israel American Medical Program Tel Aviv University Tel Aviv-Yafo Israel Ashland Ashland Specialty Ingredients Sophia Antipolis France

The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary structures and components responsible for the skin’s barrier function are susceptible to environmental variables, dermatological conditions, and the aging process. The ensuing alterations to structure, composition, and organizational attributes of the epidermal barrier can impact its integrity and functionality. The aim of this study was to assess the effect of a novel complex composed of a ceramide, energizing peptide, and Camu Camu extract (SUPCERATTM complex) on specific markers of epidermal barrier integrity, as well as epidermal and dermal function. All the experiments were conducted on fresh human abdominal skin explants. Intradermal production of hyaluronic acid, epidermal claudin-1, and ceramide synthase 3 expressions, as well as epidermal lipids content were assessed using specific fluorescent stainings on ex vivo skin after the application of the complex or placebo. Additionally, dermal elastase and collagenase activities were assessed using in tubo enzymatic assays. Lastly, the effect of a cosmetic cream containing SUPCERATTM complex was assessed using subjective Global Aesthetic Improvement Scale (GAIS) in a small cohort of patients after 60 days of use. The application of the SUPCERATTM complex on ex vivo skin led to significant increase in dermal hyaluronic acid content and epidermal activity of claudin-1, ceramide synthase 3 and epidermal ceramide content. Furthermore, in tubo enzymatic assays demonstrated inhibition of both dermal elastase and collagenase activities. In addition, the patient-reported results indicated significant improvements in skin quality and appearance. .

关键词： SUPCERATTM Complex Epidermal Skin Barrier Moisturization Antiaging Ceramide Camu Camu Extract

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Soil organic carbon stocks in native forest of Argentina:a useful surrogate for mitigation and conservation planning under climate variability

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Ecological Processes 2024年第1期13卷 3-24页

作者： Pablo L.Peri Juan Gaitán Matías Mastrangelo Marcelo Nosetto Pablo E.Villagra Ezequiel Balducci Martín Pinazo Roxana P.Eclesia Alejandra Von Wallis Sebastián Villarino Francisco Alaggia marina González Polo Silvina Manrique Pablo A.Meglioli Julián Rodríguez-Souilla Martín Mónaco Jimena E.Chaves Ariel Medina Ignacio Gasparri Eugenio Alvarez Arnesi María Paula Barral Axel von Müller Norberto M.Pahr Josefina Uribe Echevarria Pedro Fernández marina Morsucci Dardo López Juan Manuel Cellini Leandro Alvarez Ignacio Barberis Hernán Colomb Ludmila La Manna Sebastián Barbaro Cecilia Blundo Ximena Sirimarco Laura Cavallero Gualberto Zalazar Guillermo Martínez Pastur Instituto Nacional de Tecnología Agropecuaria (INTA) Universidad Nacional de la Patagonia Austral (UNPA) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Universidad Nacional de Luján Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Grupo de Estudio de Agroecosistemas y Paisajes Rurales (GEAP) Universidad Nacional de Mar del Plata Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET ) CCT San Luis Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Instituto Argentino de Nivología Glaciología y Ciencias Ambientales (IANIGLA) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Universidad Nacional de Cuyo Instituto de Investigaciones en Biodiversidad y Medioambiente (INIBIOMA) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Instituto de Investigaciones en Energía No Convencional CCT Salta-JujuyConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Laboratorio de Recursos Agroforestales Centro Austral de Investigaciones Científicas (CADIC) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Dirección Nacional de Bosques Ministerio de Ambiente y Desarrollo Sostenible de la Nación Instituto de Ecología Regional Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET )Universidad Nacional de Tucumán Universidad Nacional de Rosario Instituto de Investigaciones en Ciencias Agrarias de Rosario Centro Científico Tecnológico CONICET Grupo de Estudio de Agroecosistemas y Paisajes Rurales (GEAP) Universidad Nacional de Mar del Plata Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET ) Laboratorio de Investigaciones en Maderas (LIMAD) Universidad Nacional de La Plata (UNLP) Administración de Parques Nacionales (APN) Parque Nacional Los Alerces Centro de Estudios Ambientales Integrados (CEAI) Universidad Nacional de la Patagonia San Juan Bosco (UNPASJB) Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET )

Background The nationally determined contribution（NDC） presented by Argentina within the framework of the Paris Agreement is aligned with the decisions made in the context of the United Nations Framework Conven-tion on Climate Change（UNFCCC） on the reduction of emissions derived from deforestation and forest degradation, as well as forest carbon conservation（REDD+）. In addition, climate change constitutes one of the greatest threats to forest biodiversity and ecosystem services. However, the soil organic carbon（SOC） stocks of native forests have not been incorporated into the Forest Reference Emission Levels calculations and for conservation planning under cli-mate variability due to a lack of information. The objectives of this study were:（i） to model SOC stocks to 30 cm of native forests at a national scale using climatic, topographic and vegetation as predictor variables, and（ii） to relate SOC stocks with spatial–temporal remotely sensed indices to determine biodiversity conservation concerns due to threats from high inter-annual climate *** We used 1040 forest soil samples（0–30 cm） to generate spatially explicit estimates of SOC native forests in Argentina at a spatial resolution of approximately 200 m. We selected 52 potential predictive environmental covari-ates, which represent key factors for the spatial distribution of SOC. All covariate maps were uploaded to the Google Earth Engine cloud-based computing platform for subsequent modelling. To determine the biodiversity threats from high inter-annual climate variability, we employed the spatial–temporal satellite-derived indices based on Enhanced Vegetation Index（EVI） and land surface temperature（LST） images from Landsat *** SOC model（0–30 cm depth） prediction accounted for 69% of the variation of this soil property across the whole native forest coverage in Argentina. Total mean SOC stock reached 2.81 Pg C（2.71–2.84 Pg C with a probability of 90%） for a total area of 460,790 km2,

关键词： Soil organic carbon Biodiversity Native forest Climate change mitigation Modelling Resilience

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The challenging management of malignant ureteral obstruction:Analysis of a series of 188 cases

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Current Urology 2024年第1期18卷 34-42页

作者： Alberto Artiles Medina Inés Laso García Fernando González Tello Sara Álvarez Rodríguez Manuel Hevia Palacios marina Mata Alcaraz César Mínguez Ojeda Fernando Arias Funez Victoria Gómez Dos Santos Francisco Javier Burgos Revilla Department of Urology Hospital Universitario Ramón y CajalMadridSpain Department of Radiology Hospital Universitario Ramón y CajalMadridSpain

Background:Malignant ureteral obstruction(MUO)is a common condition that complicates the course of advanced *** aims of this study are to analyze the causes,management,and survival of patients with obstructive nephropathy due to malignant ureteric obstruction and to determine prognostic ***,we studied the complications and outcomes in patients who underwent urinary *** and methods:A retrospective study was conducted on patients with computed tomography-confirmed MUO between January 2016 and November ***,clinical,radiological,laboratory,and management data were *** curves were estimated using the Kaplan-Meier method,and univariate and multivariate Cox proportional hazards models were used to test the association between parameters and ***:A total of 188 patients were *** mean age was 69.01 years(SD,14.95 years),and the majority(54.8%)were *** most common mechanism leading to MUO was compression by a pelvic mass(36.9%),and the 3 most frequent tumors causing MUO were prostate(17.6%),bladder(16.5%),and rectal cancer(11.7%).Forty-seven patients(25%)underwent urinary diversion:23(48.9%)underwent double-J stenting and 21(44.7%)underwent percutaneous *** most common reason for urinary diversion was acute kidney injury(53.3%).Recovery of renal function was observed in 55.8%of the patients after urinary *** most frequently identified complications after urinary diversion were urinary tract infection(24.4%),hematuria(17.0%),and urinary sepsis(14.9%).The median survival after hydronephrosis diagnosis was 6.43 months(interquartile range,1.91-14.81 months).In patients who underwent urinary decompression,the median survival after urinary diversion was 8.67 months(interquartile range,2.99-17.28 months).In the multivariate analysis,a lower grade of hydronephrosis and cancer cachexia negatively impacted ***:Cancer patients with MUO have a poor pro

关键词： Hydronephrosis Ureteral obstruction Neoplasms Urinary diversion Survival Prognosis

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Deregulation of interferon-gamma receptor 1 expression and its implications for lung adenocarcinoma progression

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World Journal of Clinical Oncology 2024年第2期15卷 195-207页

作者： Angeles C Tecalco-Cruz Karen H Medina-Abreu Enrique Oropeza-Martínez Jesus Zepeda-Cervantes AleidaVázquez-Macías marina Macías-Silva Posgrado en Ciencias Genómicas Universidad Autónoma de la Ciudad de MéxicoCDMX 03100Mexico Facultad de Medicina Veterinaria y Zootecnia Universidad Nacional Autónoma de MéxicoCDMX 04510Mexico Colegio de Ciencias y Humanidades Universidad Autónoma de la Ciudad de MéxicoCDMX 03100Mexico Instituo de Fisiología Celular Universidad Nacional Autónoma de MéxicoCDMX 04510Mexico

Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of *** deregulation of the IFN-γcanonic pathway is associated with several disorders,including vulner-ability to viral infections,inflammation,and cancer *** particular,the interplay between lung adenocarcinoma(LUAD)and viral infections appears to exist in association with the deregulation of IFN-γ*** this mini-review,we investigated the status of the IFN-γsignaling pathway and the expression level of its components in ***,a reduction in IFNGR1 expression seems to be associated with LUAD progression,affecting defenses against viruses such as severe acute respiratory syndrome coronavirus *** addition,alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-γsignaling in LUAD.

关键词： Interferon-gamma IFNGR1 JAK1 Antiviral Anti-tumor Lung adenocarcinoma

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在当前猪圆环病毒2型流行病学背景下重新审视猪圆环病毒病诊断标准

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国外畜牧学（猪与禽） 2024年第3期44卷 1-9页

作者：孟霞(译) 王祎汀(校) 夏俊花(复校) Joaquim Segalés marina Sibila 不详

目前,人们对猪圆环病毒2型(porcine circovirus 2,PCV2)引起的猪圆环病毒病(porcine circovirus diseases,PCVDs)的认识是,该病包括PCV2的亚临床感染(porcine circovirus 2 subclinical infection,PCV2-SI)、全身性疾病(PCV2 systemic diseases,PCV2-SD)和繁殖障碍(PCV2 reproductive diseases,PCV2-RD)以及猪皮炎肾病综合征(porcine dermatitis and nephropathy syndrome,PDNS)。多年来,确诊这些疾病的诊断标准没有变,因此,由临床症状、病变和病变组织中病毒的检测组成的三要素仍然是PCV2-SD和PCV2-RD确诊的标志。相比之下,正常情况下不对PCV2-SI进行诊断,因为这种疾病被默认通过接种疫苗就能得到控制。PDNS可以通过大体病变和组织病理学检查进行诊断,检测PCV2被认为不是该病的诊断标准。在过去十年中,分子生物学方法作为PCVDs诊断的替代方法已得到广泛使用,不过这些技术被视为监测工具,而不是诊断工具。多年来,PCV2的流行病学发生了很大的变化,由于大规模接种疫苗,猪群的感染压下降,猪群的整体免疫力降低。因此,近来来对PCVDs诊断的需求有所增加,尤其是接种疫苗后仍出现PCV2-SD症状的病例。本综述的目的是更新有关PCVDs诊断标准,并在PCV2感染的不同流行病学情况下,将分子生物学方法应用于这些疾病的整体诊断中。

关键词：猪圆环病毒2型猪圆环病毒病临床症状病理学诊断流行病学

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Landscape of global urban environmental resistome and its association with local socioeconomic and medical status

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Science China(Life Sciences) 2024年第6期67卷 1292-1301页

作者： Jun Wu Yige Hu Michael H Perlin David Danko Jun Lu Manuela Oliveira Johannes Werner Maria M Zambrano Maria A Sierra Olayinka O Osuolale Paweł Łabaj Nicolás Rascovan Nur Hazlin Hazrin-Chong Soojin Jang Haruo Suzuki marina Nieto-Caballero Bharath Prithiviraj Patrick K H Lee Agnieszka Chmielarczyk Anna Różańska Yongxiang Zhao Lan Wang Christopher E Mason Tieliu Shi Center for Bioinformatics and Computational Biology and the Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Biology Program on Disease EvolutionUniversity of LouisvilleLouisville 40292USA Weill Cornell Medicine New York 10065USA The Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine New York 10065USA Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200025China i3S-Instituto de Investiga玢o e Inova玢o em Saúde Universidade do PortoPorto 4050-290Portugal Ipatimup-Instituto de Patologia e Imunologia Molecular da Universidade do Porto Porto 4200-465Portugal Departamento de Biologia Faculdade de CiênciasUniversidade do PortoPorto 4050-290Portugal High Performance and Cloud Computing Group Zentrum für Datenverarbeitung(ZDV)Eberhard Karls University of TübingenW鋍hterstra遝7672074TübingenGermany Corporación Corpogen Research Center Bogotá110311Colombia Applied Environmental Metagenomics and Infectious Diseases Research(AEMIDR) Department of Biological SciencesElizade UniversityIlara-Mokin 340271Nigeria Maopolska Centre of Biotechnology Jagiellonian UniversityKraków 30-005Poland Aix-Marseille Université Mediterranean Institute of OceanologyUniversitéde ToulonCNRSIRDUM 110Marseille 83041France Department of Biological Sciences and Biotechnology Faculty of Science and TechnologyUniversiti Kebangsaan Malaysia43600 UKM BangiSelangor Institut Pasteur Korea Seoul 13488Republic of Korea Faculty of Environment and Information Studies Keio UniversityFujisawaKanagawa 252-0882Japan University of Colorado at Boulder CivilEnvironmental and Architectural DepartmentBoulder 80303USA Brooklyn College of the City University of New York Brooklyn 11210USA School of Energy and Environment City University of Hong KongHong Kong 999077China Department of Microbiology Faculty of MedicineJagiellonian UniversityKraków 30-005Poland Biological Targeting Diagnosis and The

Antimicrobial resistance(AMR)poses a critical threat to global health and development,with environmental factors—particularly in urban areas—contributing significantly to the spread of antibiotic resistance genes(ARGs).However,most research to date has been conducted at a local level,leaving significant gaps in our understanding of the global status of antibiotic resistance in urban *** address this issue,we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples,which were collected by the Meta SUB International Consortium involving diverse urban environments in 60 cities of 27 countries,utilizing a deep-learning based *** findings demonstrated the strong geographical specificity of urban environmental resistome,and their correlation with various local socioeconomic and medical *** also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters(BGCs)across different countries,and discovered that the urban environment represents a rich source of novel *** study provides a comprehensive overview of the global urban environmental resistome,and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

关键词： urban environment metagenome antibiotic resistance resistance diversity biosynthetic gene clusters

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Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer

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Chinese Journal of Cancer Research 2022年第6期34卷 612-622页

作者： marina Alessandra Pereira Marcus Fernando Kodama Pertille Ramos André Roncon Dias Leonardo Cardili Rafael Dyer Rodrigues de Moraes Renan ribeiro E ribeiro Venancio Avancini Ferreira Alves Bruno Zilberstein Evandro Sobroza de Mello Ulysses ribeiro Jr Department of Gastroenterology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil Department of Pathology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil

Objective:Remnant gastric cancer(RGC)is usually associated with a worse *** they are less common and very heterogeneous tumors,new prognostic and reliable determinants are required to predict patients’clinical course for *** study aimed to investigate the tumor-infiltrating lymphocytes(TILs)and programmed cell death ligand 1(PD-L1)status as prognostic biomarkers in a cohort of patients with RGC to develop an immunerelated ***:Patients with gastric cancer(GC)who underwent curative intent gastrectomy were retrospectively *** resections with histological diagnosis of gastric adenocarcinoma were enrolled in the *** risk score based on immune parameters was developed using binary logistic regression *** were divided into high-risk(HR),intermediate-risk(IR),and low-risk(LR)groups based on their immune *** markers(CD3+,CD4+/CD8+T cells and PD-L1)were selected for their potential prognostic,therapeutic value,and evaluated by immunohistochemistry(IHC).Results:A total of 42 patients with RGC were enrolled in the *** score based on immune parameters exhibited an accuracy of 79%[the area under the receiver operating characteristic curve(AUC)=0.79,95%confidence interval(95%CI),0.63-0.94,P=0.002],and the population was divided into 3 prognostic groups:10(23.8%)patients were classified as LR,15(35.7%)as IR,and 17(40.5%)as HR *** were no differences in clinicopathological and surgical characteristics between the three *** survival analysis,HR and IR groups had worse disease-free survival and overall survival rates compared to the LR *** the multivariate analysis,lymph node metastasis and the immune score risk groups were independent factors related to worse ***:A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with ***,tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic bi

关键词： Stomach neoplasms gastric remnant tumor-infiltrating lymphocytes immune microenvironment

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Targeting the motor cortex to restore walking after incomplete spinal cord injury

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Neural Regeneration Research 2022年第7期17卷 1489-1490页

作者： marina Martinez Département de Neurosciences Groupe de recherche sur la Signalisation Neurale et la Circuiterie and Centre Interdisciplinaire de Recherche sur le Cerveau au service de l’ApprentissageUniversitéde MontréalCIUSSS du Nord-de-l’Île-de-MontréalMontréalQCCanada

Spinal cord injury(SCI),second only to stroke,is the leading cause of *** ability to walk is often lost after SCI,reducing independence and quality of *** of walking is cited as a priority among persons with SCI of all degrees of severity,chronicity,or age at *** 70%of SCIs are anatomically incomplete,some neural connections relaying information to and from the brain are spared.

关键词： incomplete paralysis injury

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Study of tree shrew biology and models: A booming and prosperous field for biomedical research

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Zoological Research 2024年第4期45卷 877-909页

作者： Yong-Gang Yao Li Lu Rong-Jun Ni Rui Bi Ceshi Chen Jia-Qi Chen Eberhard Fuchs marina Gorbatyuk Hao Lei Hongli Li Chunyu Liu Long-Bao Lv Kyoko Tsukiyama-Kohara Michinori Kohara Claudia Perez-Cruz Gregor Rainer Bao-Ci Shan Fang Shen An-Zhou Tang Jing Wang Wei Xia Xueshan Xia Ling Xu Dandan Yu Feng Zhang Ping Zheng Yong-Tang Zheng Jumin Zhou Jiang-Ning Zhou Key Laboratory of Genetic Evolution and Animal Models Yunnan Key Laboratory of Animal Models and Human Disease MechanismsKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility) and National Resource Center for Non-Human PrimatesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650204China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China Mental Health Center and Psychiatric Laboratory West China HospitalSichuan UniversityChengduSichuan 610041China Sichuan Clinical Medical Research Center for Mental Disorders ChengduSichuan 610044China German Primate Center Leibniz Institute of Primate ResearchGöttingen 37077Germany Department of Optometry and Vision Science School of OptometryUniversity of Alabama at BirminghamBirminghamAL 35294USA State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Soong Ching Ling Institute of Maternity and Child Health International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Transboundary Animal Diseases Center Joint Faculty of Veterinary MedicineKagoshima UniversityKagoshima-cityKagoshima 890-8580Japan Department of Microbiology and Cell Biology Tokyo Metropolitan Institute of Medical ScienceTokyo 156-8506Japan Pharmacology Department CinvestavMexico City 07360Mexico Department of Medicine University of FribourgFribourg CH-1700Switzerland Beijing Engineering Research Center of Radiog

The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with *** recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain ***,the limited availability of tree shrews globally remains a substantial challenge in the ***,determining the key questions best answered using tree shrews constitutes another *** shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative *** these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical *** review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this *** emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew *** use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.

关键词： Tree shrew Animal model Neurodegenerative diseases Infectious diseases Neuroscience Phenome

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Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

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