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Phase Ⅱ trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/CDKN2A

Signal Transduction and Targeted Therapy 2023年第11期8卷 5518-5527页

作者： javier martin-broto Jeronimo martinez-Garcia David SMoura Andres Redondo Antonio Gutierrez Antonio Lopez-Pousa javier martinez-Trufero Isabel Sevilla Roberto Diaz-Beveridge Maria Pilar Solis-Hernandez Amancio Carnero Marco Perez David Marcilla Jesus Garcia-Foncillas Pablo Romero javier Fernandez-Jara Daniel Lopez-Lopez Ivan Arribas Nadia Hindi Health Research Institute-Fundación Jiménez Díaz University Hospital Universidad Autónoma de Madrid(IIS-FJDUAM)28040MadridSpain Medical Oncology Department Fundación Jimenez Diaz University Hospital28040MadridSpain General de Villalba University Hospital 28400MadridSpain Medical Oncology Department University Hospital Virgen de la Arrixaca30120MurciaSpain Department of Medical Oncology Hospital Universitario La Paz-IdiPAZP.Castellana26128046MadridSpain Hematology Department University Hospital Son Espases07120MallorcaSpain Medical Oncology Department Sant Pau Hospital08025BarcelonaSpain Medical Oncology Department University Hospital Miguel Servet50009ZaragozaSpain Investigación Clínica y Traslacional en Cáncer/Instituto de Investigaciones Biomédicas de Malaga(IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Malaga MalagaSpain Medical Oncology Department Hospital Universitari i Politècnic La Fe46026ValenciaSpain Medical Oncology Department Central University Hospital of Asturias33011OviedoSpain Instituto de Biomedicina de Sevilla(IBiS HUVRCSICUS)41013SevillaSpain Pathology Department Virgen del Rocio University Hospital41013SevillaSpain Radiology Department Fundación Jimenez Diaz University Hospital28040MadridSpain Computational Medicine Platform Fundación progreso y salud(FPS)Hospital Virgen del Rocío41013SevilleSpain Bioinformatics in Rare Diseases(BiER).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER) FPSHospital Virgen del RocioSevillaSpain Universitat de València-ERI-CES 46010ValenciaSpain

Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 ***4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK *** investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in *** adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this *** was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at *** 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 *** median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,*** research showed a significant correlation between CDK4 mRNA and protein *** was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.

关键词： CDKN2A sarcoma CDK4

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Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

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Neural Regeneration Research 2025年第4期20卷 973-989页

作者： María Belén Cieri Alberto javier Ramos Laboratorio de Neuropatología Molecular IBCN UBA-CONICETFacultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

Traumatic brain injury is a global health crisis,causing significant death and disability *** that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this *** traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain *** astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are *** altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive *** addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional *** therapeutic strategies for traumatic brain injury are focused on preventing acute ***,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of *** this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

关键词： astrocyte glial scar innate immunity neuroinflammation stab injury Toll-like receptors

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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría javier García-Pardo Salvador Ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

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The Locust (Tropidacris spp) within the Ejido “El Cuayo”

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Advances in Entomology 2025年第1期13卷 200-224页

作者： Compeán-Guzmán Francisco javier Carlos Ricardo Menéndez Gámiz Institute of Social Sciences and Faculty of Forestry Sciences Jurez University of the State of Durango Durango Mexico Agricultural Development Planning UNAM FES Aragn Nezahualcyotl Mexico

Tropidacris spp. represent the largest known group among acridoids. Their presence ranges from southeastern Mexico and has so far been confirmed only in tropical habitats. This publication seeks to highlight the current and potential challenges associated with their presence. For decades, the use of chemical insecticides has been the primary method for controlling locust populations, though these substances pose significant risks to human health and the environment. Recent research efforts are directed toward developing control methods that are less detrimental to both ecological and human health, such as biopesticides derived from pathogenic fungi, plant extracts, and strategically prescribed burns. Satellite surveillance enables the monitoring of the origination and progression of outbreaks to inform control strategy selection.

关键词： Ejido “El Cuayo” Locust Infestation Tropidacris Collaris

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Sarcoma stratification by combined pH2AX and MAP17(PDZK1IP1)levels for a better outcome on doxorubicin plus olaparib treatment

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Signal Transduction and Targeted Therapy 2020年第1期5卷 697-709页

作者： Marco Perez JoséManuel García-Heredia Blanca Felipe-Abrio Sandra Muñoz-Galván javier Martín-broto Amancio Carnero Instituto de Biomedicina de Sevilla(IBIS) Hospital Universitario Virgen del RocíoUniversidad de SevillaConsejo Superior de Investigaciones CientíficasSevillaSpain Ciber de Cancer IS Carlos IIIMadridSpain Departamento de Bioquímica Vegetal y Biología Molecular Universidad de SevillaSevillaSpain Departamento de Anatomía Patológica Hospital Universitario Virgen del RocíoSevillaSpain

Sarcomas constitute a rare heterogeneous group of tumors,including a wide variety of histological *** advances in our understanding of the pathophysiology of the disease,first-line sarcoma treatment options are still limited and new treatment approaches are *** H2AX phosphorylation is a sensitive marker for double strand breaks and has recently emerged as biomarker of DNA damage for new drug *** this study,we explored the role of H2AX phosphorylation at Ser139 alone or in combination with MAP17 protein,an inducer of DNA damage through ROS increase,as prognostic biomarkers in sarcoma ***,we proposed doxorubicin and olaparib combination as potential therapeutic strategies against sarcomas displaying high level of both *** evaluate retrospectively the levels of pH2AX(Ser139)and MAP17 in a cohort of 69 patients with different sarcoma types and its relationship with clinical and pathological *** found that the levels of pH2AX and MAP17 were related to clinical features and poor ***,we pursued PARP1 inhibition with olaparib to potentiate the antitumor effect of DNA damaging effect of the DNA damaging agent doxorubicin to achieve an optimal synergy in *** demonstrated that the combination of olaparib and doxorubicin was synergistic in vitro,inhibiting cell proliferation and enhancing pH2AX intranuclear accumulation,as a result of DNA *** synergism was corroborated in patient-derived xenografts(PDX)where the combination was effective in tumors with high levels of pH2AX and MAP17,suggesting that both biomarkers might potentially identify patients who better benefit from this combined therapy.

关键词： H2AX doxorubicin treatment

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Transformation of leather waste into microwave-activated and N-doped carbon for Li-S batteries

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新型炭材料(中英文) 2025年

作者： Carolina Pano-Azucena Roberto Rosas-Rangel Miguel Olvera-Sosa David Salvador González-González Rene Rangel-Mendez Luis Felipe Chazaro-Ruiz Miguel Avalos-Borja javier Antonio Arcibar-Orozco CIATEC.Center for Applied Innovation in Competitive Technologies Tecnologico de Monterrey School of Engineering and Sciences Instituto Potosino de Investigación Científica y Tecnológica Universidad Autónoma de Coahuila Facultad de SistemasCiudad Universitaria

The use of carbon from waste biomass has the potential to buffer the drawbacks of Li-S batteries and improve their overall performance. Chrome-Tanned-LeatherShavings(CTLS) are undesirable wastes, highly available for transformation into porous carbon. Microwave activation is an efficient state-of-the-art procedure to obtain unique porous structures and nitrogen incorporation can improve the performance of porous carbons. This study proposes the transformation of CTLS into a microwave activated porous carbon, and then was modified to introduce nitrogen. A microporous activated carbon with a specific surface area of 556 m2g-1 with honeycomb-like structure was obtained. Both urea thermal decomposition and ethanolamine impregnation improves the nitrogen and amine presence of surface groups. However,the results indicated that only urea treatment was effective in improving the initial capacity of the cell(1363 mAhg-1), which is probably linked with the sorption of long-chain polysulfides. This investigation confirms that it is possible to obtain carbon materials from CTLS, for use as sulfur-host cathodes in Li-S batteries, and improve their performance with urea thermal decomposition. Furthermore, a Radial basis function neural network was fitted to provide statistical support to the experimental results. The trained model corroborated the importance of nitrogen content of the carbons in the discharge capacity of the cells.

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Arabidopsis photoperiodic regulator CONSTANS feeds back to control the circadian clock

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Molecular Plant 2024年第9期17卷 1338-1340页

作者： Abril San martin Marcelo javier Yanovsky Instituto de Investigaciones Bioquimicas de Buenos Aires(Fundacion Instituto Leloir-CONICET) Av.Patricias Argentinas 435Buenos Aires C1405BWEAraentina

Human beings live in a world defined by daily cycles of light and darkness caused by the Earth’s rotation around its ***,like most living organisms,have evolved internal circadian clocks that time biological processes in anticipation of these daily environmental changes(Young and Kay,2001).The plant clock relies on core genes encoding transcription factors(TFs),which regulate each other’s expression through intricate networks of interlocking transcriptional-translational feedback loops(Nohales and Kay,2016).These loops ultimately control the expression of thousands of genes,allowing plants to adapt to daily fluctuations in light,temperature,and humidity(Covington et al.,2008).In addition to daily rhythms,the Earth experiences yearly seasonal cycles marked by longer,warmer days in spring and summer,followed by shorter,cooler days in autumn and *** changes in day length and temperature intensify with distance from the ***,the ability of plants to adjust their growth and development in anticipation of seasonal changes determines their latitudinal distribution(McMillan,1960).

关键词： circadian seasonal Arabidopsis

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Heterogeneous catalysts with programmable topologies generated by reticulation of organocatalysts into metal-organic frameworks:The case of squaramide

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Nano Research 2021年第2期14卷 458-465页

作者： Anna broto-Ribas Claudia Vignatti Alicia Jimenez-Almarza javier Luis-Barrera Zahra Dolatkhah Felipe Gandara Inhar Imaz Ruben Mas-Balleste Jose Aleman Daniel Maspoch Catalan Institute of Nanoscience and Nanotechnology(ICN2) CSIC and The Barcelona Institute of Science and Technology08193 BarcelonaSpain Inorganic Chemistry Department Modulo 7Universidad Autonoma de Madrid28049 MadridSpain Organic Chemistry Department Modulo 1Universidad Autonoma de Madrid28049 MadridSpain Materials Science Factory Instituto de Ciencia de Materiales de Madrid(ICMM)Consejo Superior de Investigaciones Cientificas(CSIC)Calle Sor Juana Ines de la Cruz328049 MadridSpain Institute for Advanced Research in Chemical Sciences(IAdChem) Campus Universidad Autonoma de Madrid28049 MadridSpain Institucio Catalana de Recerca i Estudis Avangats(ICREA) 08100 BarcelonaSpain

A well-established strategy to synthesize heterogeneous,metal-organic framework(MOF)catalysts that exhibit nanoconfinement effects,and specific pores with highly-localized catalytic sites,is to use organic linkers containing organocatalytic ***,we report that by combining this linker approach with reticular chemistry,and exploiting three-dimensioanl(3D)MOF-structural data from the Cambridge Structural Database,we have designed four heterogeneous MOF-based catalysts for standard organic *** programmable MOFs are isoreticular versions of pcu IRMOF-16,feu UiO-68 and pillared-pcu SNU-8X,the three most common topologies of MOFs built from the organic linker p.p'-terphenyldicarboxylic acid(tpdc).To synthesize the four squaramide-based MOFs,we designed and synthesized a linker,4,4’-((3,4-dioxocyclobut-1-ene-1,2-diyl)bis(azanedyil))dibenzoic acid(Sq_tpdc),which is identical in directionality and length to tpdc but which contains organocatalytic squaramide *** were chosen because their immobilization into a framework enhances its reactivity and stability while avoiding any self-quenching ***,the four MOFs share the same organocatalytic squaramide moiety,but confine it within distinct pore *** then evaluated these MOFs as heterogeneous H-bonding catalysts in organic transformations:a Friedel-Crafts alkylation and an epoxide *** of them exhibited good performance in both reactions but all showed distinct catalytic profiles that reflect their structural differences.

关键词： reticular chemistry metal-organic frameworks H-bond catalysis squaramide Friedel-Cratts epoxide ring-opening

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Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

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Elutriation, attrition and segregation in a conical spouted bed with a fountain confiner

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Particuology 2020年第4期18卷 35-44页

作者： Aitor Pablos Roberto Aguado Jorge Vicente Mikel Tellabide javier Bilbao martin Olazar Department of Chemical Engineering University of the Basque Country UPV/EHUP.O.Box 644E48080 BilbaoSpain Novattia Desarrollos Ltd.Scientific and Technologic Park of BizkaiaAstondo BideaBuilding 612E48160 DerioSpain

This study examined elutriation,attrition,and segregation in a conical spouted bed with a fountain confiner and incorporating an open sided draft *** silica sand with a wide particle size distribution was employed as a model material,operating in both the batch and continuous *** use of a fountain confiner is crucial when operating with fine particles,because otherwise the bed rapidly exhibits significant *** extent of attrition was quantified using a tracing technique based on differently-coloured sand fractions as well as monitoring size distributions by *** breakage was found to be the primary attrition mechanism,and the fountain confiner was determined to limit the elutriation of fine particles resulting from ***,only a small fraction of the finest particles were entrained from the *** incorporation of a confiner increased operational stability while reducing segregation,especially in the upper half of the bed where the majority of segregation typically ***,the bed was perfectly mixed apart from very minimal segregation close to the wall and at the bottom of the *** results provide a basis for the design and operation of larger scale equipment for the continuous drying of materials.

关键词： Spouted bed Fine sand Elutriation Attrition Segregation Fountain confinement device

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