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Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling

Signal Transduction and Targeted Therapy 2023年第11期8卷 5404-5416页

作者： Catarina Macedo-Silva vera Miranda-Gonçalves Nuno Tiago Tavares Daniela Barros-Silva Joana Lencart João Lobo Ângelo Oliveira Margareta PCorreia Lucia Altucci Carmen Jerónimo Cancer Biology&Epigenetics Group Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Precision Medicine University of Campania“Luigi Vanvitelli”80138NaplesItaly Department of Pathology and Molecular Immunology ICBAS-School of Medicine&Biomedical SciencesUniversity of PortoR.Jorge de Viterbo Ferreira 2284050-313PortoPortugal Medical Physics Radiobiology and Radiation Protection Group-Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Medical Physics Portuguese Oncology Institute of Porto4200-072PortoPortugal Department of Pathology Portuguese Oncology Institute of PortoPortoPortugal Department of Radiation Oncology Portuguese Oncology Institute of PortoPortoPortugal BIOGEM Molecular Biology and Genetics Research Institute83100AvellinoItaly IEOS Institute of Endocrinology and Oncology80100NaplesItaly

External beam radiotherapy(RT)is a leading first-line therapy for prostate cancer(PCa),and,in recent years,significant advances have been ***,RT resistance can arise and result in long-term recurrence or disease progression in the worst-case ***,making crucial the discovery of new targets for PCa ***,we generated a radioresistant PCa cell line,and found p53 to be highly expressed in radioresistant PCa cells,as well as in PCa patients with recurrent/disease progression submitted to *** dissection revealed that RT could promote p53 expression via epigenetic ***,a decrease of H3K27me3 occupancy at TP53 gene promoter,due to increased KDM6B activity,was observed in radioresistant PCa ***,p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated ***,KDM6B inhibition by GSK-J4 significantly decreased p53 expression,consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor ***,this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair,as well as the impact of epigenetic targeting for PCa radiosensitization.

关键词： TP53 damage cancer

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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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A Local Differential Privacy Trajectory Protection Method Based on Temporal and Spatial Restrictions for Staying Detection

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Tsinghua Science and Technology 2024年第2期29卷 617-633页

作者： Weiqi Zhang Zhenzhen Xie Akshita Maradapu vera Venkata Sai Qasim Zia Zaobo He Guisheng Yin College of Computer Science and Technology Harbin Engineering UniversityHarbin 150001China School of Computer Science and Technology Shandong UniversityQingdao 266237China Department of Computer Science Georgia State UniversityAtlantaGA 30303USA College of Information Science and Technology Jinan UniversityGuangzhou 510632China

The widespread availability of GPS has opened up a whole new market that provides a plethora of location-based ***-based social networks have become very popular as they provide end users like us with several such services utilizing GPS through our ***,when users utilize these services,they inevitably expose personal information such as their ID and sensitive location to the *** to untrustworthy servers and malicious attackers with colossal background knowledge,users'personal information is at risk on these ***,many privacy-preserving solutions for protecting trajectories have significantly decreased utility after *** have come up with a new trajectory privacy protection solution that contraposes the area of interest for ***,Staying Points Detection Method based on Temporal-Spatial Restrictions(SPDM-TSR)is an interest area mining method based on temporal-spatial restrictions,which can clearly distinguish between staying and moving ***,our privacy protection mechanism focuses on the user's areas of interest rather than the entire ***,our proposed mechanism does not rely on third-party service providers and the attackers'background knowledge *** test our models on real datasets,and the results indicate that our proposed algorithm can provide a high standard privacy guarantee as well as data availability.

关键词： local-differential privacy stay points detection trajectory data areas of interest temporal-spatial clustering

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Deep optics preconditioner for modulation-free pyramid wavefront sensing

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Photonics Research 2024年第2期12卷 301-312页

作者： FELIPE GUZMÁN JORGE TAPIA CAMILO WEINBERGER NICOLÁS HERNÁNDEZ JORGE BACCA BENOIT NEICHEL ESTEBAN vera School of Electrical Engineering Pontificia Universidad Católica de Valparaı´soValparaı´soChile Department of Systems Engineering Universidad Industrial de SantanderBucaramangaColombia Laboratoire d’Astrophysique de Marseille MarseilleFrance

The pyramid wavefront sensor(PWFS)can provide the sensitivity needed for demanding adaptive optics applications,such as imaging exoplanets using the future extremely large telescopes of over 30 m of diameter(D).However,its exquisite sensitivity has a limited linear range of operation,or dynamic range,although it can be extended through the use of beam modulation—despite sacrificing sensitivity and requiring additional optical *** by artificial intelligence techniques,this work proposes to train an optical layer—comprising a passive diffractive element placed at a conjugated Fourier plane of the pyramid prism—to boost the linear response of the pyramid sensor without the need for cumbersome *** develop an end-2-end simulation to train the diffractive element,which acts as an optical preconditioner to the traditional least-square modal phase estimation *** results with a large range of turbulence conditions show a noticeable improvement in the aberration estimation performance equivalent to over 3λ∕D of modulation when using the optically preconditioned deep PWFS(DPWFS).Experimental results validate the advantages of using the designed optical layer,where the DPWFS can pair the performance of a traditional PWFS with 2λ∕D of *** and adding an optical preconditioner to the PWFS is just the tip of the iceberg,since the proposed deep optics methodology can be used for the design of a completely new generation of wavefront sensors that can better fit the demands of sophisticated adaptive optics applications such as ground-to-space and underwater optical communications and imaging through scattering media.

关键词： process optics pyramid

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Polycyclic Aromatic Hydrocarbons May Contribute for Prostate Cancer Progression

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Journal of Cancer Therapy 2013年第4期4卷 37-46页

作者： Mariana Freitas vera alves Ana Sarmento-Ribeiro Anabela Mota-Pinto CIMAGO—Centre of Investigation in Environment Genetics and Oncobiology Faculty of Medicine University of Coimbra Coimbra Portugal General Pathology Laboratory Faculty of Medicine University of Coimbra Coimbra Portugal Immunology Laboratory Faculty of Medicine University of Coimbra Coimbra Portugal

Prostate cancer is the most common form of cancer affecting men in the Western world. Risk factors include ageing, genetics, recurrent inflammation, lifestyle and diet intake, related to an increase of oxidative stress. Prostate cancer risk is also associated with exposure to carcinogen such as polycyclic aromatic hydrocarbons (PAHs), originated from the incomplete combustion of carbon-containing fuels like tobacco, wood, diesel, or charbroiled meat. Although numerous studies have associated the effect of PAHs to tumour development, few investigations have associated its effects to cancer progression. Considering that prostate cancer patients don’t die from localized prostate cancer but from advanced disease, we are interested in investigating whether PAHs may potentially influence prostate cancer progression and how this could be related to an increase in oxidative stress. Likewise we evaluated the effect of PAHs (pyrene, benzo(a) pyrene, chrysene and benzo(k)fluoranthene) on cell growth and in the expression of molecules involved in cancer metastization such as the vascular endothelial growth factor (VEGF) and hypoxia inducible factor (HIF) using prostatederived cell lines from localized adenocarcinoma (HPV10), bone metastasis (PC3) and in non-neoplastic prostate epithelium cells. Moreover, we evaluated oxidative stress parameters, assessing reactive oxygen species (ROS) production and reduced glutathione content. Our data clearly demonstrates that PAHs can stimulate cell growth, particularly in localized cancer cells and induce an increase of VEGF and HIF expression. These results are concomitant with an increase of ROS production, suggesting that PAHs exposure may participate in prostate cancer progression, in part, due to an increase of ROS. Therefore this study suggests that PAHs exposure should be avoided to prevent prostate cancer progression.

关键词： Prostate Cancer Progression Polycyclic Aromatic Hydrocarbons (PAHs) Vascular Endothelial Growth Factor (VEGF) Hypoxia Inducible Factor (HIF) Oxidative Stress

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The ILux^(®) compared to the mechanical meibomian gland expression for the treatment of moderate and severe meibomian gland dysfunction

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1042-1048页

作者： María Ximena Núñez Andrea Acosta-Ortega Guillermo Raul vera-Duarte Catalina Gómez-Duarte Unit of Cornea Cataract and Refractive SurgeryVision Sana Research GroupClínica de Oftalmología de CaliFaculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Faculty of Medicine Pontificia Universidad Javeriana CaliCali 760031Colombia Department of Ophthalmology Hospital de ClínicasNational University of AsunciónAsunción 111421Paraguay

AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)of<15 in the lower eyelid of each eye,and non-invasive tear break-up time(NI-TBUT)<10s,who were randomized 1:1 to ILux®or ***:The mean age was 58±*** total MGS scores in both treatment groups were *** follow-up,there were significant differences in total MGS and per sector with P<*** analysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,NIBUT,and *** was a significant difference between ILux®and MMGE(P<0.001)at follow-up from the first to the twelfth month in MGS,NI-BUT,and OSDI *** adverse events were ***:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.

关键词： meibomian gland dysfunction ILux® ocular surface dry eye

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Plant triterpenoid saponins function as susceptibility factors to promote the pathogenicity of Botrytis cinerea

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Molecular Plant 2024年第7期17卷 1073-1089页

作者： Francisco J.Escaray Amelia Felipo-Benavent Cristian J.Antonelli Begona Balaguer Maria Pilar Lopez-Gresa Pablo vera Instituto de Biologia Molecular y Celular de Plantas Universidad Politecnica de Valencia-C.S.l.CCiudad Politecnica de la InnovacionEdificio 8Eacceso GIngeniero Fausto Elios/n46022ValenciaSpain

The gray mold fungus Botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species,including high-value *** polyxenous nature and pathogenic success are due to its ability to perceive host signals in its *** this study,we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by *** to cause ***,poor-in-latex(pil)mutants,which lack laticifer cells,show full resistance to this pathogen,whereas lot-of-latex mutants,which produce more laticifer cells,are *** S factors are triterpenoid saponins,which are widely distributed natural products of vast structural *** downregulation of laticifer-specific oxydosqualene cyclase genes,which encode the first committed step enzymes for triterpene and,therefore,saponin biosynthesis,conferred disease resistance to ***,the Medicago truncatula Iha-1 mutant,compromised in triterpenoid saponin biosynthesis,showed enhanced ***,the application of different purified triterpenoid saponins pharmacologically complemented the diseaseresistant phenotype ofpil and hla-1 mutants and enhanced disease susceptibility in different plant *** found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in ***,leading to a change in its growth habit and infection strategy,culminating in the abundant formation of infection cushions,the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in *** together,these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote *** pathogenicity.

关键词： Euphorbia lathyris laticifer cell latex appressorium infection cushion necrotrophic fungi

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Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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Neural Regeneration Research 2024年第2期19卷 289-295页

作者： Dina Medina-vera Antonio Jesús López-Gambero Juan Antonio Navarro Carlos Sanjuan Elena Baixeras Juan Decara Fernando Rodríguez de Fonseca Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND UGC Salud MentalMálagaSpain Facultad de Ciencias Universidad de MálagaMálagaSpain CIBER Enfermedades Cardiovasculares(CIBERCV) Hospital Universitario Virgen de la VictoriaUGC del CorazónMálagaSpain University of Bordeaux INSERMNeurocentre MagendieBordeauxFrance Euronutra S.L.Calle Johannes Kepler MálagaSpain Departamento de Bioquímica y Biología Molecular Facultad de MedicinaUniversidad de MálagaMálagaSpain

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s *** pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau *** the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug *** present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

关键词： Alzheimer’s disease cyclin-dependent kinase 5 diabetes D-Pinitol inositols insulin resistance kinases phosphorylation PI3K/Akt tau

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Pylephlebitis-induced acute liver failure: A case report and review of literature

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World Journal of Hepatology 2024年第1期16卷 103-108页

作者： vera Hapshy Steven Imburgio Harshavardhan Sanekommu Brandon Nightingale Sobaan Taj Mohammad A Hossain Swapnil Patel Department of Internal Medicine Jersey Shore University Medical CenterNeptuneNJ 07753United States

BACKGROUND Pylephlebitis is an extremely rare form of septic thrombophlebitis involving the portal vein,carrying high rates of morbidity and *** SUMMARY We present a case of a 42-year-old male with no past medical history who presented with acute onset of abdominal pain and altered mental status with laboratory tests demonstrating new-onset acute liver *** was determined to be the underlying etiology due to subsequent workup revealing polymicrobial gram-negative anaerobic bacteremia and complete thrombosis of the main and left portal *** our knowledge,this is the first documented case of acute liver failure as a potential life-threatening complication of *** Our case highlights the importance of considering pylephlebitis in the broad differential for abdominal pain,especially if there are co-existing risk factors for *** also demonstrate that fulminant hepatic failure in these patients can potentially be reversible with the immediate initiation of antibiotics and anticoagulation.

关键词： Portal vein thrombosis Septic thrombophlebitis Gram negative anaerobic bacteremia Pylephlebitis Acute liver failure Case report

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MicroRNA-630:A promising avenue for alleviating inflammation in diabetic kidney disease

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World Journal of Diabetes 2024年第7期15卷 1398-1403页

作者： Javier Donate-Correa Ainhoa González-Luis Jésica Díaz-vera Juan Ramón Hernandez-Fernaud Research Unit University Hospital Nuestra Señora de Candelaria(UHNSC)Santa Cruz de Tenerife 38010Spain Department of Biochemistry MicrobiologyCell Biology and GeneticsInstituto de Tecnologías BiomédicasUniversidad de La LagunaSanta Cruz de Tenerife 38000Spain

Diabetic kidney disease(DKD)is one of the complications of diabetes,affecting millions of people *** relentless progression of this condition can lead to kidney failure,requiring life-altering interventions such as dialysis or *** evidence suggests that immunologic and inflammatory elements play an important role in initiating and perpetuating the damage inflicted on renal tissues,exacerbating the decline in organ ***-like receptors(TLRs)are a family of receptors that play a role in the activation of the innate immune system by the recognition of pathogen-associated molecular *** data from in vitro and in vivo studies have highlighted the critical role of TLRs,mainly TLR2 and TLR4,in the pathogenesis of *** the diabetic milieu,these TLRs recognize diabetic-associated molecular signals,triggering a proinflammatory cascade that initiates and perpetuates inflammation and fibrogenesis in the diabetic *** non-traditional strategies targeting TLR signaling with potential therapeutic implications in DKD have been *** of these approaches is the use of microRNAs,small non-coding RNAs that can regulate gene *** editorial comments on the results of this approach carried out in a rat model of diabetes by Wu et al,published in this issue of the World Journal of *** results of the experimental study by Wu et al shows that microRNA-630 decreased levels compared to non-diabetic ***,microRNA-630 exerted anti-inflammatory effects in the kidneys of diabetic rats through the modulation of *** findings indicate that the microRNA-630/TLR4 axis might represent a pathological mechanism of DKD and a potential therapeutic target capable of curbing the destructive inflammation characteristic of DKD.

关键词： Diabetes Diabetic kidney disease Inflammation Toll-like receptor 4 microRNA-630

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