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The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers

Cancer Drug Resistance 2023年第3期6卷 468-480页

作者： William J.E.Frye Lyn m.Huff josém.gonzález dalmasy Paula Salazar Rachel m.Carter Ryan T.Gensler Dominic Esposito Robert W.Robey Suresh V.Ambudkar michael m.Gottesman Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Protein Expression Laboratory Frederick National Laboratory for Cancer ResearchLeidos Biomedical ResearchIncFrederickMD 21704USA

Aim:Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid *** small molecule ferroptosis inducers(FINs)have been reported,yet little information is available regarding their interaction with the ATP-binding cassette(ABC)transporters P-glycoprotein(P-gp,ABCB1)and *** thus sought to characterize the interactions of FINs with P-gp and ABCG2,which may provide information regarding oral bioavailability and brain penetration and predict drug-drug ***:Cytotoxicity assays with ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2 were used to determine the ability of the transporters to confer resistance to FINs;confirmatory studies were performed in OVCAR8 and NCI/ADR-RES *** ability of FINs to inhibit P-gp or ABCG2 was determined using the fluorescent substrates rhodamine 123 or purpuin-18,***:P-gp overexpression conferred resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin.P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of *** FINs mL-162,GPX inhibitor 26a,and PACmA31 at 10µm were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing mDR-19 *** inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 ***:Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the *** ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions.

关键词： Ferroptosis drug resistance P-glycoprotein ABCG2

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mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

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Tracking the change in Spanish greenhouse gas emissions through an LmDI decomposition model:A global and sectoral approach

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Journal of Environmental Sciences 2024年第5期139卷 114-122页

作者： Paula Fernández gonzález maría josé Presno manuel Landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this *** this paper we pursue two ***,we analyze the evolution of GHG emissions in Spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining ***,we propose several actions specifically oriented to more tightly controlling the level of *** results showed a remarkable reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita *** detected somewhat different patterns among the various sectors *** the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of *** carbonization effect was revealed as crucial in the commerce *** above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in *** efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LmDI Decomposition Spain GHG emissions

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Estimation of Equivalent model of Photovoltaic Array Using Unscented Kalman Filters

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Journal of modern Power Systems and Clean Energy 2024年第3期12卷 819-827页

作者： m.A.gonzález-Cagigal joséA.Rosendo-macías A.Gómez-Expósito the Department of Electrical Engineering University of SevilleSpainand A.Gómez-Expósito is also with ENGREEN Laboratory of Engineering for Energy and Environmental SustainabilitySevilleSpain

This paper proposes the use of the unscented Kalman filter to estimate the equivalent model of a photovoltaic(PV)array,using external measurements of current and voltage at the inverter *** estimated model is of interest to predict the power output of PV plants,in both planning and operation scenarios,and thus improves the efficient operation of power systems with high penetration of renewable *** proposed technique has been assessed in several simulated scenarios under different operating *** results show that accurate estimates are provided for the model parameters,even in the presence of measurement noise and abrupt variations under the external conditions.

关键词： Equivalent model parameter estimation photovoltaic energy unscented Kalman filter

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Enhancement of the CO_(2)adsorption and hydrogenation to CH_(4)capacity of Ru–Na–Ca/γ–Al_(2)O_(3)dual function material by controlling the Ru calcination atmosphere

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Journal of Environmental Sciences 2024年第6期140卷 292-305页

作者： Alejandro Bermejo-López Beñat Pereda-Ayo Jon A.Onrubia-Calvo joséA.gonzález-marcos Juan R.gonzález-Velasco Department of Chemical Engineering Faculty of Science and TechnologyUniversidad del País Vasco UPV/EHUBarrio Sarrienas/n48940 LeioaBizkaiaSpain

Integrated CO_(2)capture and utilization(ICCU)technology requires dual functional materials(DFms)to carry out the process in a single reaction *** influence of the calcination atmosphere on efficiency of 4%Ru-8%Na_(2)CO_(3)-8%CaO/γ-Al_(2)O_(3)DFm is *** adsorbent precursors are first co-impregnated onto alumina and calcined in ***,Ru precursor is impregnated and four aliquotes are subjected to different calcination protocols:static air in muffle or under different mixtures(10%H_(2)/N_(2),50%H_(2)/N_(2)and N_(2))*** are characterized by XRD,N_(2)adsorption-desorption,H_(2)chemisorption,TEm,XPS,H_(2)-TPD,H_(2)-TPR,CO_(2)-TPD and *** catalytic behavior is evaluated,in cycles of CO_(2)adsorption and hydrogenation to CH_(4),and temporal evolution of reactants and products concentrations is *** calcination atmosphere influences the physicochemical properties and,ultimately,activity of *** data and catalytic performance discover the acccomodation of Ru nanoparticles disposition and basic sites is mostly influencing the catalytic *** calcined under N_(2)flow(RuNaCa-N_(2))shows the highest CH_(4)production(449μmol/g at 370℃),because a well-controlled decomposition of precursors which favors the better accomodation of adsorbent and Ru phases,maximizing the specific surface area,the Ru-basic sites interface and the participation of different basic sites in the CO_(2)methanation ***,the calcination in a N_(2)flow is revealed as the optimal calcination protocol to achieve highly efficient DFm for integrated CO_(2)adsorption and hydrogenation applications.

关键词： CO_(2)methanation Integrated CO_(2)capture and utilization(ICCU) Dual functional material(DFm) Ru calcination atmosphere

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Peripheral refraction of myopic eyes with spectacle lenses correction and lens free emmetropes during accommodation

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Eye and Vision 2021年第1期8卷 454-461页

作者： António Queirós Alejandro Cerviño josémanuel gonzález‑méijome Clinical&Experimental Optometry Research Lab(CEORLab) Center of Physics(Optometry)University of MinhoCampus de Gualtar4710‑057 BragaPortugal Optometry Research Group Department of Optics and Optometry and Vision SciencesUniversity of ValenciaValenciaSpain

Purpose:To measure axial and off-axis refraction patterns in myopic eyes with spectacle lenses correction and lens free emmetropes in young healthy subjects at different target distances from 2.00 m(0.50 D)to 0.20 m(5.00 D)in terms of sphere,astigmatism,and spherical equivalent ***:Refraction was measured at the center,20 and 40 degrees from the line of sight both nasally and temporally in 15 emmetropic and 25 myopic young healthy subjects with an open field,binocular,infrared autorefractor(Grand Seiko WAm-5500,Hiroshima,Japan).Fixation target was a maltese cross set at 2.00,0.50,0.33 and 0.20 m from the corneal *** in off-axis refraction with accommodation level were normalized with respect to distance axial values and compared between myopic eyes with spectacle lenses correction and lens free ***:Off-axis refraction in myopic eyes with spectacle lenses correction was significantly more myopic in the temporal retina compared to lens free emmetropes except for the closest target *** off-axis refractive error changed significantly with accommodation when compared to axial refraction particularly in the myopic *** change in the negative direction was due to changes in the spherical component of refraction that became more myopic relative to the center at the 0.20 m distance as the J0 component of astigmatism was significantly reduced in both emmetropes and myopes for the closest ***:Accommodation to very near targets(up to 0.20 m)makes the off-axis refraction of myopes wearing their spectacle correction similar to that of lens free emmetropes.A significant reduction in off-axis astigmatism was also observed for the 0.20 m distance.

关键词： Off-axis refraction Refractive error Accommodation myopia progression

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Simultaneous optimization of even flow and land and timber value in forest planning:a continuous approach

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Forest Ecosystems 2021年第4期8卷 645-658页

作者： jose m.gonzalez-gonzalez miguel E.Vazquez-mendez Ulises Dieguez-Aranda Departamento de Enxenaria Agroforestal Universidade de Santiago de Compostela.Escola Politecnica Superior de EnxenariaR/Benigno Ledo27002 LugoSpain Departamento de matematica Aplicada Instituto de MatematicasUniversidade de Santiago de Compostela.Escola Politecnica Superior de EnxenariaR/Benigno Ledo27002 LugoSpain

Background:Forest management planning involves deciding which silvicultural treatment should be applied to each stand and at what time to best meet the objectives established for the *** this,many mathematical formulations have been proposed,both within the linear and non-linear programming frameworks,in the latter case generally considering integer variables in a combinatorial *** present a novel approach for planning the management of forests comprising single-species,even-aged stands,using a continuous,multi-objective formulation(considering economic and even flow)which can be solved with gradient-type ***:The continuous formulation has proved robust in forest with different structures and different number of *** results obtained show a clear advantage of the gradient-type methods over heuristics to solve the problems,both in terms of computational time(efficiency)and in the solution obtained(effectiveness).Their improvement increases drastically with the dimension of the problem(number of stands).Conclusions:It is advisable to rigorously analyze the mathematical properties of the objective functions involved in forest management planning *** continuous bi-objective model proposed in this paper works with smooth enough functions and can be efficiently solved by using gradient-type *** advantages of the new methodology are summarized as:it does not require to set management prescriptions in advance,it avoids the division of the planning horizon into periods,and it provides better solutions than the traditional combinatorial ***,the graphical display of trade-off information allows an a posteriori articulation of preferences in an intuitive way,therefore being a very interesting tool for the decision-making process in forest planning.

关键词： Even-aged forest management Forest-level optimization Continuous optimization Gradient-type algorithms

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mushroom Production as an Alternative for Rural Development in a Forested mountainous Area

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Journal of mountain Science 2014年第2期11卷 535-543页

作者： josé *** josé R.gonzález-OLABARRIA Juan mARTíNEZ DE ARAGóN Departament de Producció Vegetal i Ciència Forestal Universitat de Lleida-Agrotecnio Center (UdL-Agrotecnio).Av. Rovira Roure 191 E-25198 Lleida Spain Centre Tecnològic Forestal de Catalunya (CTFC-CEmFOR). Ctra. de St. Lloren? de morunys km 2 E-25280 Solsona Spain

Wild mushrooms are recognized as important non-wood forest products in mountainous ecosystems, but their real potential for generating rural economies has not been fully evaluated due to the difficulties in obtaining reliable productivity data, minimizing their true potential as contributor to rural economies. mushroom yield models based on large data series from Pinus forest ecosystems in the region of Catalonia(Spain), combined with data from the Spanish National Forest Inventory allow us to estimate the potential mushroom productivity by forest ecosystems. The results of 24,500 tons/yr of mushrooms of which 16,300 tons are classified as edible and 7,900 tons are commonly marketed demonstrate the importance of mushroom productions in Catalonian pine forests, mostly located in mountainous areas where the development of agricultural activities is limited. Economic mushroom value is estimated at 48 million € for the edible mushroom and 32 million € for those corresponding to marketable yields, confirming the potential of this non-wood forest product. These production results and corresponding economic values provide a basis for the incorporation of wild mushrooms as significant non-wood forest products in the development of forest policies in mountainous areas.

关键词： Non-wood forest products mushroom models National Forest Inventory Economic value mushroom potential estimation

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Areas of research and clinical approaches to the study of liver abscess

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World Journal of Gastroenterology 2017年第2期23卷 357-365页

作者： Gregorio gonzález-Alcaide Jorge Peris josé manuel Ramos Department of History of Science and Documentation University of Valencia Deparment of Internal medicine Hospital Universitario Sant Joan d’Alacant Departament of Clinical medicine Universidad Miguel Hernández de Elche Department of Internal medicine Hospital General Universitario de Alicante

AImTo analyze the research activity on liver abscess (LA) and identify the main topic clusters in the *** identified all documents using the medical subject heading “LA” indexed in the mEDLINE database between 2001 and 2015. We performed a descriptive bibliometric analysis, characterizing the evolution of scientific activity, the publication types of the documents, the document categories of clinical interest (case reports, clinical trials, evaluation studies, meta-analysis, observational studies, practice guidelines and validation studies) and the geographic distribution of the research. We also carried out an analysis of networks and research clusters in order to identify the main topic areas of *** search yielded a total of 1278 documents, showing a stable scientific production over the study period and a marked multidisciplinary nature. The research was dominated by case reports (65.9% of the documents analyzed). In terms of geographic distribution, researchers from the United States led in the number of signatures (n = 229), followed by those from Taiwan (n = 185), India (n = 145), Japan (n = 144), South Korea (n = 100), and China (n = 84). With regard to amebic LA, the top-producing countries were India and mexico (n = 69 each), followed by the United States (n = 29). In the case of pyogenic LA, Taiwan Residents researchers led scientific production (n = 71), followed by the United States (n = 39) and China (n = 29). The most active areas of research in the field are diagnosis via computerized tomography scan, differential diagnosis with regard to liver cancer, treatment with antimicrobial agents, and Klebsiella infections (including bacteremia).CONCLUSIONClinical case reports associated with diagnosis and treatment are the main topic of study, highlighting the importance of this document type in advancing knowledge.

关键词： Liver abscess Cluster analysis Amebic abscess Pyogenic abscess Bibliometrics

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Immunomodulating effects of antibiotics used in the prophylaxis of bacterial infections in advanced cirrhosis

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World Journal of Gastroenterology 2015年第41期21卷 11493-11501页

作者： Pedro Zapater josé manuel gonzález-Navajas josé Such Rubén Francés CIBERehd Hospital General Universitario de Alicante Digestive Disease Institute Cleveland Clinic Abu Dhabi Departamento medicina Clínica Universidad Miguel Hernández

The use of norfloxacin either as primary or secondary prophylaxis of bacterial infections in advanced cirrhosis has improved patient's survival. This may be explained not only due to a significant decrease in the number of infections, but also because of a direct immunomodulatory effect. Selective intestinal decontamination with norfloxacin reduces translocation of either viable bacteria or bacteria-driven products from the intestinal lumen. In addition, norfloxacin directly modulates the systemic inflammatory response. The proinflammatory cytokine profile secreted by neutrophils from these patients shows a close, significant, and inverse correlation with serum norfloxacin levels. Similar effects have been described with other quinolones in different clinical conditions. Although the underlying mechanisms are not well defined for most of the antibiotics, the pathways triggered for norfloxacin to induce such immunomodulatory effects involve the down-regulation of pro-inflammatory inducible nitric oxide synthase, cyclooxygenase-2, and NF-κB and the up-regulation of heme-oxygenase 1 and IL-10 expression. The knowledge of these immunomodulatory effects, additional to their bactericidal role, improves our comprehension of the interaction between antibiotics and the cellular host response and offer new possibilities for the development of new therapeutic strategies to manage and prevent bacterial infections in cirrhosis.

关键词： Cirrhosis Prophylaxis Cytokines Bacterial DNA Norf

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