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An update on the molecular biology of glioblastoma,with clinical implications and progress in its treatment

Cancer Communications 2022年第11期42卷 1083-1111页

作者： Elena Verdugo Iker Puerto miguelÁngel Medina Department of Molecular Biology and Biochemistry University of MálagaMálagaMálaga E-29071Spain Biomedical Research Institute of Málaga(IBIMA-Plataforma Bionand) MálagaMálaga E-29071Spain Spanish Biomedical Research Network Center for Rare Diseases(CIBERER) Spanish Health Institute Carlos III(ISCIII)MálagaMálaga E-29071Spain

Glioblastoma multiforme(GBM)is the most aggressive and common malig-nant primary brain *** with GBM often have poor prognoses,with a median survival of∼15 *** understanding of the molecular biology of central nervous system tumors has led to modifications in their classifications,the most recent of which classified these tumors into new categories and made some changes in their nomenclature and grading *** review aims to give a panoramic view of the last 3 years’findings in glioblastoma characterization,its heterogeneity,and current advances in its *** molecular parameters have been used to achieve an accurate and personalized characterization of glioblastoma in patients,including epigenetic,genetic,transcriptomic and metabolic features,as well as age-and sex-related patterns and the involvement of several noncoding RNAs in glioblastoma ***-like neural stem cells and outer radial glial-like cells from the subven-tricular zone have been proposed as agents involved in GBM of IDH-wildtype origin,but this remains *** metabolism is characterized by upregulation of the PI3K/Akt/mTOR signaling pathway,promotion of the gly-colytic flux,maintenance of lipid storage,and other *** metabolism also contributes to glioblastoma’s resistance to conventional *** heterogeneity,a hallmark of GBM,has been shown to affect the genetic expresion,modulation of metabolic pathways,and immune system ***’s aggressive invasion potential is modulated by cell-to-cell crosstalk within the tumor microenvironment and altered expressions of specific genes,such as ANXA2,GBP2,FN1,PHIP,and ***,the rising number of active clinical trials illustrates the efforts to identify new targets and drugs to treat this *** is still relevant for research purposes,given the amount of ongoing clinical trials based on this strategy to treat GBM,and neoantigen and nuclei

关键词： cancer molecular biology diagnosis glioblastoma multiforme ongoing clinical trials targeted therapy tumor heterogeneity tumor metabolism

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Prefoldins Negatively Regulate Cold Acclimation in Arabidopsis thaliana by Promoting Nuclear Proteasome-Mediated HY5 Degradation

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Molecular Plant 2017年第6期10卷 791-804页

作者： Carlos Perea-Resa miguel A. rodriguez-Milla Elisa Iniesto Vicente Rubio Julio Salinas Departamento de Biologia Medioambiental Centro de Investigaciones Biologicas CSIC 28040 Madrid Spain Departamento de Genetica Molecular de Plantas Centro Nacional de Biotecnologia CSIC 28049 Madrid Spain present address: Department of Molecular Biology Massachusetts General Hospital Boston MA 02214 USA Present address: Unidad de Biotecnologia Celular Instituto de Salud Garlos Ⅲ 28222 Madrid Spain

The process of cold acclimation is an important adaptive response whereby many plants from temperate regions increase their freezing tolerance after being exposed to low non-freezing temperatures. The correct development of this response relies on proper accumulation of a number of transcription factors that regulate expression patterns of cold-responsive genes. Multiple studies have revealed a variety of molecular mechanisms involved in promoting the accumulation of these transcription factors. Interestingly, however, the mechanisms implicated in controlling such accumulation to ensure their adequate levels remain largely unknown. In this work, we demonstrate that prefoldins （PFDs） control the levels of HY5, an Arabidopsis transcription factor with a key role in cold acclimation by activating anthocyanin biosynthesis, in response to low temperature. Our results show that, under cold conditions, PFDs accumulate into the nucleus through a DELLA-dependent mechanism, where they interact with HY5, triggering its ubiquitination and subsequent degradation. The degradation of HY5 would result, in turn, in anthocyanin biosynthesis attenuation, ensuring the accurate development of cold acclimation. These findings uncover an unanticipated nuclear function for PFDs in plant responses to abiotic stresses.

关键词： prefoldins cold acclimation Arabidopsis HY5 anthocyanin DELLAs

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Machine learning guided high-throughput search of non-oxide garnets

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npj Computational Materials 2023年第1期9卷 1717-1725页

作者： Jonathan Schmidt Hai-Chen Wang Georg Schmidt miguel A.L.Marques Institut für Physik Martin-Luther-Universität Halle-WittenbergD-06099 HalleGermany

Garnets have found important applications in modern technologies including magnetorestriction,spintronics,lithium batteries,*** overwhelming majority of experimentally known garnets are oxides,while explorations(experimental or theoretical)for the rest of the chemical space have been limited in scope.A key issue is that the garnet structure has a large primitive unit cell,requiring a substantial amount of computational *** perform a comprehensive search of the complete chemical space for new garnets,we combine recent progress in graph neural networks with high-throughput *** apply the machine learning model to identify the potentially(meta-)stable garnet systems before performing systematic density-functional calculations to validate the *** discover more than 600 ternary garnets with distances to the convex hull below 100 meV⋅atom−*** includes sulfide,nitride,and halide *** analyze their electronic structure and discuss the connection between the value of the electronic band gap and charge balance.

关键词： structure sulfide oxides

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Hybrid magnetorheological elastomers enable versatile soft actuators

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npj Computational Materials 2022年第1期8卷 1546-1559页

作者： miguel Angel Moreno-Mateos Mokarram Hossain Paul Steinmann Daniel Garcia-Gonzalez Department of Continuum Mechanics and Structural Analysis Universidad Carlos III de MadridAvda.de la Universidad 3028911LeganésMadridSpain Zienkiewicz Centre for Computational Engineering Faculty of Science and EngineeringSwansea UniversitySA18ENSwanseaUK Institute of Applied Mechanics University of Erlangen-NurembergEgerland Str.5ErlangenGermany Glasgow Computational Engineering Centre School of EngineeringUniversity of GlasgowG128QQGlasgowUK

Recent advances in magnetorheological elastomers(MREs)have posed the question on whether the combination of both soft-and hard-magnetic particles may open new routes to design versatile multifunctional ***,we conceptualise ultra-soft hybrid MREs(≈1–10 kPa stiffness)combining experimental and computational ***,a comprehensive experimental characterisation is *** results unravel that the magneto-mechanical performance of hybrid MREs can be optimised by selecting an adequate mixing ratio between ***,a multi-physics computational framework provides insights into the synergistic magneto-mechanical interactions at the *** particles amplify the magnetisation and hard particles contribute to torsional *** numerical results suggest that the effective response of hybrid MREs emerges from these intricate ***,we uncover exciting possibilities to push the frontiers of MRE *** are demonstrated by simulating a bimorph beam that provides actuation flexibility either enhancing mechanical bending or material stiffening,depending on the magnetic stimulation.

关键词： versatile magneto enable

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MEC-based architecture for interoperable and trustworthy internet of moving things

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Digital Communications and Networks 2023年第1期9卷 270-279页

作者： Jesus Sanchez-Gomez Rafael Marin-Perez Ramon Sanchez-Iborra miguel Angel Zamora Department of Information and Communications Engineering University of MurciaMurciaSpain Odin Solutions S.L. MurciaSpain University Center of Defense San Javier Air Force BaseMurciaSpain

The expansion of the Internet of Moving Things(IoMT)leads to limitless and continuous working playgrounds exploited by highly dynamic end *** requires the adoption of multi-Radio Access Technologies(RATs)-based strategies to provide IoMT units with ubiquitous *** this end,the development of secure bootstrapping and authentication mechanisms is necessary to permit the secure operation of end *** the transmission and power limitations of these elements,current cryptographic solutions do not address these stringent *** that reason,in the study we present a Multi-Access Edge Computing(MEC)-based endto-end architecture that enables an efficient and secure authentication and key agreement between end devices and network servers over heterogeneous resource-limited networks such as the Low Power Wide Area Networks(LPWANs).Our proposal is based on the Authentication,Authorization,and Accounting(AAA)architecture and the recent Internet Engineering Task Force initiatives Static Context Header Compression and Low-Overhead *** results obtained from experimental tests reveal the validity of the proposal as it enables constrained IoMT devices to gain IPv6 connectivity as well as performs end-to-end secure authentication with notable reliability and controlled latency.

关键词： Internet of moving things LPWAN Authentication LO-CoAP-EAP SCHC

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Back to pluripotency:fully chemically induced reboot of human somatic cells

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2658-2659页

作者： Lucas Lange miguel A.Esteban Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannover 30625Germany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannover 30625Germany Laboratory of Integrative Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMA 02115USA

In a recent study published in Nature,Guan et al.1 showed an exciting strategy to reprogram human somatic cells into human chemically induced pluripotent stem cells(hCiPSCs).Thereby,they identified crucial steps and p... 详细信息

关键词： al. chemically steps

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Cannabinoid receptor antagonist SR141716A decreases operant ethanol self administration in rats exposed to ethanol-vapor chambers

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中国药理学报 1999年第12期20卷 1109-1114页

作者： Feinando rodriguez DE FONSECA Amanda J ROBERTS Ainhoa BILBAO George F KOOB miguel NAVARRO Instituto Complutense de Drogodependencias Departamenta de PsicobiologiaFacultad de PsicologiaUniversidad Complutense de Madrid28223-MadridSpain Department of Neuropharmacology The Scripps Research InstituteLa Jolla CA 92037USA

AIM:To study the potential role of dependence statuson CB_(1)-mediated blockade of ethanol ***:We examined the effects of thecannabinoid antagonist SR141716A(0,0.03,0.3,and 3 mg/kg)on pperant ethanol(10%v/v)self-administration in male Wistar rats that were madeethanol-dependent by chronic(14 d)exposure toethanol vapor-chambers or exposed to air in identicalvapor ***:Dependent animalsresponded more for ethanol than did air controlnondependent *** acute administration of a 3mg/kg dose of SR141716A almost suppressed ethanolself-administration ouly in ethanol dependent ***,operant responses for food were not afected by the administration of ***:These results further support that cannabinoid CB_(1) receptor blockade may have a potential utility for the treatment of alcobolism.

关键词： ethanol self administration cannabinoid rcceptors SR141716A

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Fe-doped olivine and char for in-bed elimination of gasification tars in an air-blown fluidised bed reactor coupled with oxidative hot gas filtration

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Carbon Resources Conversion 2022年第4期5卷 271-288页

作者： miguel Ruiz Adam Schnitzer Claire Courson Guillain Mauviel LRGP CNRSUniversity of LorraineENSIC1 Rue GrandvilleNancyFrance University of Lorraine LERMaBENSTIB27 Rue Philippe S´eguinPO Box 1041F-88051 EpinalFrance Institut of Chemistry and Processes for Energy Environment and HealthICPEES–UMR 7515University of Strasbourg25 Rue Becquerel67087 StrasbourgFrance

Gasification experiments were carried out in a pilot scale fluid bed reactor operated under allothermal mode and low fluidisation regime with iron-doped olivine and char as catalyst for in-situ tar *** catalyst combination resulted in a reduction of 50%in the overall tar yield with respect to the reference ***,the integration of an oxidative Hot Gas Filtration unit downstream the gasification reactor led to a further reduction in overall tar yield and relatively clean gas was obtained(approx.1 g/Nm3,benzene-free).The tar dew point of the resulting producer gas was estimated to 80℃,only 40℃ above the threshold value recommended for its valorisation in standard internal combustion ***,catalyst elutriation and char hold-up took place to a large extent inside the *** analysis of catalyst samples at different Time-On-Stream(TOS)revealed:(i)a considerable loss of iron oxides during the first hour of test because of the interparticle mechanical attrition(mostly surface abrasion)and partial reduction of hematite to magnetite and wustite but,stable composition at higher TOS,(ii)the loss of the iron oxide coverage of Fe/olivine particles and the formation of agglomerates with increasing TOS and,(iii)the amount of carbon deposited in the surface of the Fe/olivine particles increased with TOS,but in any case,these carbon deposits can be completely oxidized above 650℃.

关键词： Gasification Tar Oxidative hot gas filtration Char Iron-doped olivine

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Soil organic carbon storage in forest restoration models and environmental conditions

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Journal of Forestry Research 2022年第4期33卷 1123-1134页

作者： Ranieri Ribeiro Paula miguel Calmon Maria Leonor Lopes-Assad Eduardo de SáMendonça Departamento de Agronomia Programa de Pós-Graduação em Produção VegetalUniversidade Federal do Espírito SantoAlto UniversitárioGuararemaAlegreEspírito Santo CEP 29500-000Brazil World Resources Institute SalvadorBahia CEP 40290-040Brazil Departamento de Recursos Naturais e Proteção Ambiental Universidade Federal de São CarlosArarasSão Paulo CEP 13600-970Brazil

The scale of forest and landscape restoration is expected to increase during the UN Decade on Ecosystem Restoration and its contribution to the provision of critical ecosystem services to *** models of forest restoration may improve ecosystem services,including soil organic carbon(SOC)storage.A review was carried out to access:(1)the variability of SOC storage between worldwide forest restoration models and,(2)the effects of climate,soil class,soil texture,and vegetation type on SOC *** reviewed 119 primary studies with information on SOC and soil texture for different forest restoration *** restoration models were grouped into four categories:natural regeneration,monocultures,agroforestry,and mixed *** data was extracted from these four restoration models,other land uses(cropland,bare land,grassland,and natural forest),climate regimes,and soil *** SOC storage in the forest restoration models and other land uses at a global scale ranged between 0.1 to 514 Mg ha^(-1).The overall mean value for SOC storage was higher for natural regeneration(112 Mg ha^(-1)),followed by agroforestry(74 Mg ha^(-1)),mixed forest(73 Mg ha^(-1)),and monocultures(68 Mg ha^(-1)).However,the average SOC storage was similar among the four restoration models in the moist warm climate *** SOC storage mean value in the moist cool zone was 23%higher than the dry cool zone(81 and 62 Mg ha^(-1),respectively),and 50%higher for the moist warm zone when compared to the dry warm climatic zone(74 and 38 Mg ha^(-1),respectively).The SOC storage of the restoration models was positively related to soil depth(0.59;p<0.01),clay content(0.29;p<0.01),and stand age(0.17;p<0.01).Globally,the mean values of SOC storage were 26,66,and 139 Mg ha^(-1) at zero-10,zero-30,and zero-100 cm depths,*** addition,sandy soils showed smaller mean values of SOC storage than medium to clay soils,especially in deeper soil ***,SOC storage was positively re

关键词： Forest restoration Land uses Soil type Soil texture Climate

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Topological protection of partially coherent light

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Photonics Research 2022年第5期10卷 1223-1231页

作者： KONRAD TSCHERNIG GABRIEL MARTINEZ-NICONOFF KURT BUSCH miguel A.BANDRES ARMANDO PEREZ-LEIJA Max-Born-lnstitut 12489 BerlinGermany Humboldt-Universität zu Berlin Institut fur PhysikAG Theoretische Optik&Photonik12489 BerlinGermany Coordinacidn deÓptica Instituto Nacional de AstrofisicaÓpticay Electronica72840 TonantzintlaPueblaMexico CREOL The College of Optics and PhotonicsUniversity of Central FloridaOrlandoFlorida 32816USA

Topological physics exploits concepts from geometry and topology to implement systems capable of guiding waves in an unprecedented *** ideas have led to the development of photonic topological insulators,which are optical systems whose eigenspectral topology allows the creation of light states that propagate along the edge of the system without any coupling into the bulk or backscattering even in the presence of ***,topological protection is a fully coherent effect,and it is not clear to what extent topological effects endure when the wavefronts become partially ***,we study the interplay of topological protection and the degree of spatial coherence of classical light propagating in disordered photonic topological *** results reveal the existence of a well-defined spectral window in which partially coherent light is topologically *** opens up the design space to a wider selection of light sources,possibly yielding smaller,cheaper,and more robust devices based on the topological transport of light.

关键词： topological coherent topology

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