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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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Breaking the brain barrier:cell competition in neural development and disease

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Neural Regeneration Research 2024年第9期19卷 1863-1864页

作者： Patrizia Morciano daniela Grifoni Department of“Life Health and Environmental Sciences”University of L’AquilaItaly “INFN-Laboratori Nazionali del Gran Sasso” AssergiItaly

General information on cell competition:Social behaviors are the basis of biological *** species and populations,cell communities experience Darwinian ecological interactions,and in case space and nutrient availabilit... 详细信息

关键词： neural barrier throughout

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Climate change impacts on eutrophication in the Po River(Italy):Temperature-mediated reduction in nitrogen export but no effect on phosphorus

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Journal of Environmental Sciences 2024年第9期143卷 148-163页

作者： Elisa Soana Maria Pia Gervasio Tommaso Granata daniela Colombo Giuseppe Castaldelli Department of Environmental and Prevention Sciences University of FerraraVia Luigi Borsari 4644121 FerraraItaly CESI-Italian Electrical and Technical Experimental Center via Rubattino 5420134MilanoItaly

Rivers worldwide are under stress from eutrophication and nitrate pollution,but the ecological consequences overlap with climate change,and the resulting interactions may be unexpected and still *** Po River basin(northern Italy)is one of the most agriculturally productive and densely populated areas in *** remains unclear whether the climate change impacts on the thermal and hydrological regimes are already affecting nutrient dynamics and transport to coastal *** present work addresses the long-term trends(1992-2020)of nitrogen and phosphorus export by investigating both the annual magnitude and the seasonal patterns and their relationship with water temperature and discharge *** the constant diffuse and point sources in the basin,a marked decrease(-20%)in nitrogen export,mostly as nitrate,was recorded in the last decade compared to the 1990 s,while no significant downward trend was observed for *** water temperature of the Po River has warmed,with the most pronounced signals in summer(+0.13℃/year)and autumn(+0.16℃/year),together with the strongest increase in the number of warm days(+70%-80%).An extended seasonal window of warm temperatures and the persistence of low flow periods are likely to create favorable conditions for permanent nitrate removal via denitrification,resulting in a lower delivery of reactive nitrogen to the *** present results show that climate change-driven warming may enhance nitrogen processing by increasing respiratory river metabolism,thereby reducing export from spring to early autumn,when the risk of eutrophication in coastal zones is higher.

关键词： Nutrient export Eutrophication Climate change Water temperature Denitrification Po River

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Experimental Exclusion of Guanaco Grazing Increases Cover, Diversity, Land Function and Plant Recruitment in Patagonia

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1383-1401页

作者： Carla Cepeda Gabriel Oliva daniela Ferrante INTA Instituto Nacional de Tecnología Agropecuaria Santa Cruz9400Rio GallegosArgentina Universidad Nacional de la Patagonia Austral Santa Cruz9400Rio GallegosArgentina

Semiarid Patagonia represents 25%of the rangeland area in Argentina,and sheep overgrazing has degraded about a third of it in the *** this century,depleted domestic stocks have mostly stabilized,but Guanaco populations have *** native camelids share habitat and diets with sheep,but their effect on vegetation is poorly understood and has long been *** set up an exclusion experiment in Monte León and Cañadón Vaca,a semiarid shrubland grassland in southern Patagonia,currently grazed only by *** baselines were studied in 2016 in twelve plots,and half of them were protected from guanaco ***-six plots were cleared to study *** was reassessed in 2021,and changes were evaluated using a paired *** protected plots,vegetation cover increased,bare soil diminished,and vegetated patches grew in size,but the density of the patch-interpatch arrangement did not ***,measured by richness and the Shan-non-Wiener(SW)index,grew signiﬁ*** recycling increased,as did the Stability and Inﬁltration Land Function indexes,although these last differences were not signiﬁ*** cover under guanaco grazing also increased,mainly due to the growth of dwarf shrubs,a typical tendency in sheep grazing-induced transitions in the *** patches under grazing fragmented,resulting in smaller patches and denser patch struc-tures,while diversity and land function indexes remained *** plants established in cleared plots without guanacos showed higher cover density and individual *** effects are similar to those observed in numerous experimental sheep *** grazing may thus prevent restoration and contribute to the generalized land degradation processes that overgrazing has been causing in Patagonia for over a century.

关键词： Rangelands herbivory biodiversity overgrazing carrying capacity fauna

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High CO_(2)permeation using a new Ce_(0.85)Gd_(0.15)O_(2-δ)-LaNiO_(3)composite ceramic–carbonate dual-phase membrane

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Journal of Environmental Sciences 2024年第6期140卷 219-229页

作者： daniela González-Varela JFrancisco Gómez-García Gustavo Tavizon Heriberto Pfeiffer Instituto de Investigaciones en Materiales Universidad Nacional Autónoma de MéxicoCd.UniversitariaDel.CoyoacánCP 04510Ciudad de MéxicoMéxico Departamento de Física y Química Teórica Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoCd.UniversitariaDel.CoyoacánCP 04510Ciudad de MéxicoMéxico 不详

This work shows the synthesis,characterization and evaluation of dense-ceramic membranes made of Ce_(0.85)Gd_(0.15)O_(2-δ)-LaNiO_(3)(CG-LN)composites,where the fluorite-perovskite ratio(CG:LN)was varied as follows:75:25,80:20 and 85:15 wt.%.Supports were initially characterized by XRD,SEM and electrical conductivity(using vacuum and oxygen atmospheres),to determine the composition,microstructural and ionic-electronic conductivity ***,supports were infiltrated with an eutectic carbonates mixture,producing the corresponding dense dual-phase membranes,in which CO_(2)permeation tests were ***,CO_(2)permeation experiments were performed from 900 to 700℃,in the presence and absence of oxygen(flowed in the sweep membrane side).Results showed that these composites possess high CO_(2)permeation properties,where the O_(2)addition significantly improves the ionic conduction on the sweep membrane ***,the GC80-LN20 composition presented the best results due to the following physicochemical characteristics:high electronic and ionic conductivity,appropriate porosity,interconnected porous channels,as well as thermal and chemical stabilities between the composite support and carbonate phases.

关键词： CO_(2)permeation Doped CeO_(2) LaNiO_(3) Impedance Ceramic carbonate membrane

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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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Use of DREAM to assess relative risks of presence of pharmaceuticals and personal care products from a wastewater treatment plant

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Frontiers of Environmental Science & Engineering 2024年第9期18卷 91-104页

作者： daniela M.Pampanin Daniel Schlenk Matteo Vitale Pierre Liboureau Magne O Sydnes Department of Chemistry Bioscience and Environmental EngineeringUniversity of StavangerStavanger 224021Norway Department of Environmental Sciences University of California RiversideRiversideCA 92521USA

Concerns related to environmental risks associated with pharmaceuticals and personal care products(PPCPs)have led researchers to seek methods for assessing and monitoring these contaminants in the aquatic *** and validating risk assessment tools that can evaluate ecological concerns and risks associated with PPCPs is ***,the suitability of a dose-related risk and effect assessment model,which estimates predicted environmental concentrations and allowed comparisons with predicted no effect concentrations determined,in combination with in vitro analyses of the whole effluent toxicity,was verified for the characterization of a PPCP *** of the most utilized PPCPs in Norway were measured in influent and effluent samples and used to parameterize the fate *** than 90%removal was attained for 12 out of 22 detected *** was not dependent on the class or the concentration of the specific substance and varied between 12%and 100%.The PPCPs detected in the discharged wastewater were utilized to assess individual contributions to the risk of the effluent,and no risk was identified for the targeted 30 *** simulations provided valuable information regarding the discharge plume distribution over time,which can aid planning of future environmental monitoring ***(using fish liver cells,PLHC-1)were used for assessing overall effluent toxicity,through cell viability,production of reactive oxygen species,and ethoxyresorufin-O-deethylase(EROD)*** present study may allow regulators to use risk-based strategies over removal criteria for monitoring studies and confirms the importance to take PPCP contamination into consideration when establishing environmental regulations.

关键词： Pharmaceuticals Wastewater effluent Ciprofloxacin Metoprolol Amitriptyline Carbamazepine Modelling Risk assessment Monitoring

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Optimal therapy for HIV infection containment and virions inhibition

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Infectious Disease Modelling 2024年第1期9卷 10-26页

作者： Paolo Di Giamberardino daniela Iacoviello Muhammad Zubair Dept.of Computer Control and Management EngineeringSapienzaUniversity of RomeVia Ariosto 2500185RomeItaly

Prevention and early diagnosis are the best and most effective ways for defeating *** is still no vaccine,but treatments with antiretroviral drugs are now available which,in many cases,allow the infection to become ***,research has highlighted side effects of these drugs and the fact that a flare-up of the infection occurs if the therapy is *** recent years,the presence of virus reserves located in various parts of the body,including the brain,has been *** possibility of controlling the infection of healthy cells and of interrupting the proliferation of virions inside the brain has been studied,proposing optimal control strategies.

关键词： Epidemic modeling HIV-AIDS Optimal control

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Translating Pathological Brain Activity Primers in Parkinson’s Disease Research

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Research 2024年第1期2023卷 735-752页

作者： daniela Mirzac Svenja L.Kreis Heiko J.Luhmann Gabriel Gonzalez-Escamilla Sergiu Groppa Movement Disorders and Neurostimulation Department of NeurologyFocus Program Translational NeuroscienceRhine Main Neuroscience NetworkUniversity Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany Institute of Physiology University Medical Center of the Johannes Gutenberg University Mainz55131 MainzGermany

Translational experimental approaches that help us better trace Parkinson’s disease(PD)pathophysiological mechanisms leading to new therapeutic targets are urgently *** this article,we review recent experimental and clinical studies addressing abnormal neuronal activity and pathological network oscillations,as well as their underlying mechanisms and *** aim is to enhance our knowledge about the progression of Parkinson's disease pathology and the timing of its symptom’s ***,we present mechanistic insights relevant for the generation of aberrant oscillatory activity within the cortico-basal ganglia *** summarize recent achievements extrapolated from available PD animal models,discuss their advantages and limitations,debate on their differential applicability,and suggest approaches for transferring knowledge on disease pathology into future research and clinical applications.

关键词： clinical knowledge insight

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Beyond dentistry:could prevention and screening for neurodegenerative diseases start in the dental office?

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Neural Regeneration Research 2024年第1期19卷 156-157页

作者： Francesca R.Buccellato daniela Galimberti Gianluca M.Tartaglia Department of Biomedical Surgical and Dental SciencesUniversity of MilanMilanItalyFondazione IRCCS Ca’GrandaOspedale Maggiore PoliclinicoMilanItaly

The differential diagnosis of neurodegenerative diseases is complex and relies on clinical assessment,biomarker levels in cerebrospinal fluid,neuroimaging and neuropsychological *** efforts of the scientific community are focused on two aspects:a)the discovery of minimally invasive biomarkers;b)the discovery of early biomarkers that can predict the progression to clinical disease in the presymptomatic stage of a *** the impact of the number of patients affected by chronic neurodegenerative diseases on public health expenditures,early diagnosis seems to be a primary need of our society.

关键词： diagnosis diseases prevention

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