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Further understanding of mechanisms involved in liver cancer chemoresistance

Hepatoma Research 2017年第1期3卷 22-26页

作者： Oscar Briz maria j.perez jose j.G.Marin Department of Physiology and Pharmacology University of Salamanca37007 SalamancaSpain

An important limitation for the success of chemotherapy in the treatment of primary liver cancer (hepatocellular carcinoma,hepatoblastoma and cholangiocarcinoma) is the marked efficacy of mechanisms of chemoresistance (MOC).These have been previously classified into five groups depending on whether they result in:a reduced drug uptake or enhanced drug export (MOC-1);poor intracellular activation of prodrugs or higher inactivation of active drugs (MOC-2);changes in the molecular targets that impairs the action of the drug by increasing the activity of the metabolic route to be inhibited or stimulating alternative routes (MOC-3);ability of tumor cells to repair drug-induced modifications in the target molecule,usually DNA (MOC-4);and the activation or inhibition of intracellular signaling pathways that lead to a change in the balance between proand anti-apoptotic factors favoring tumor cell survival (MOC-5).Nevertheless,novel information appeared over the last few years has recommended to consider two additional groups,MOC-6 and MOC-7,based on changes in tumor microenvironment,mainly hypoxia and acidity,and epithelial-mesenchymal transition,*** contribute to the defensive armamentaria developed or enhanced in liver cancer cells to resist the pharmacological attack,which accounts for a negligible beneficial effect of commonly used antitumor drugs and only a modest response to novel targeted therapies based on tyrosine kinase inhibitors,such as ***,further advances are urgently needed to better understand the molecular and cellular bases of the chemoresistant barrier and help scientists in this field to develop new tools able to overcome cancer cell defenses.

关键词： Chemotherapy cholangiocarcinoma hepatoblastoma hepatocellular carcinoma tumor environment epithelial-mesenchymal transition

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Experimental test of a building thermal system for preventive maintenance based on thermoeconomic analysis

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Energy Storage and Saving 2024年第1期3卷 42-51页

作者： I.Prol-Godoy A.Picallo-perez j.M.Sala-Lizarraga j.Rey-Martínez Research group ENEDI Department of Thermal EngineeringUniversity of the Basque Country(UPV/EHU)Bilbao48013Spain Research Group Termotecnia University of ValladolidValladolid47002Spain

An analysis of the sectorial structure of energy consumption shows that residential and tertiary sector buildings are the third-highest consumers,responsible for 29.5%of a city’s final energy *** Building Quality Control Laboratory of the Basque Government aims to promote quality,innovation,and sustainability in *** accomplish this goal,it has constructed an experimental facility with different energy generation technologies and a very versatile control system for testing different energy systems and operation *** this study,we tested a facility for supplying domestic hot water and heating for a multi-family house by means of a condensing boiler and an aerothermal heat pump(together with the corresponding control).This installation could reproduce the thermal demands required to be satisfied by the generation equipment through a programmed operation of the installation based on real ***,this installation was analyzed using thermoeconomics(TE)to solve problems unable to be solved using traditional energy analyses based on the First Law of *** problems include:(1)Determining the costs of the products of the installation based on physical criteria,(2)detecting the places where losses actually occur,evaluating their costs,and proposing cost-effective improvements,and(3)diagnosing issues in the *** a result,this paper suggests a solution to the preventive maintenance problems confronting the technical maintenance personnel for thermal installations in buildings by applying TE knowledge and using real data collected from sensors.

关键词： Experimental essay Energy savings in thermal systems Thermoeconomics Thermoeconomic costs Diagnosis

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Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-perez jose j.Gil-Cosano Esther Ubago-Guisado Francisco j.Llorente-Cantarero juan Francisco Pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino jonatan R.Ruiz Luis Gracia-Marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary Research Institute ibs.GranadaGranada 18012Spain Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain Pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this ***,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar *** This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,***‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression *** regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass *** More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference *** strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all *** 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral *** Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all *** results suggest that interventions designed to improve muscle strength in t

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

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On-Chip Micro Temperature Controllers Based on Freestanding Thermoelectric Nano Films for Low-Power Electronics

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Nano-Micro Letters 2024年第7期16卷 98-108页

作者： Qun jin Tianxiao Guo Nicolas perez Nianjun Yang Xin jiang Kornelius Nielsch Heiko Reith Institute for Metallic Materials Leibniz Institute for Solid State and Materials Research01069 DresdenGermany Institute of Materials Engineering University of Siegen57076 SiegenGermany Institute of Applied Physics Technical University of Dresden01069 DresdenGermany Institute of Materials Science Technical University of Dresden01069 DresdenGermany

Multidimensional integration and multifunctional com-ponent assembly have been greatly explored in recent years to extend Moore’s Law of modern ***,this inevitably exac-erbates the inhomogeneity of temperature distribution in microsystems,making precise temperature control for electronic components extremely ***,we report an on-chip micro temperature controller including a pair of thermoelectric legs with a total area of 50×50μm^(2),which are fabricated from dense and flat freestanding Bi2Te3-based ther-moelectric nano films deposited on a newly developed nano graphene oxide membrane *** tunable equivalent thermal resistance is controlled by electrical currents to achieve energy-efficient temperature control for low-power electronics.A large cooling temperature difference of 44.5 K at 380 K is achieved with a power consumption of only 445μW,resulting in an ultrahigh temperature control capability over 100 K mW^(-1).Moreover,an ultra-fast cooling rate exceeding 2000 K s^(-1) and excellent reliability of up to 1 million cycles are *** proposed on-chip temperature controller is expected to enable further miniaturization and multifunctional integration on a single chip for microelectronics.

关键词： Temperature control Low-power electronics On-chip micro temperature controller Freestanding thermoelectric nano films Temperature-sensitive components

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Bile-acid-induced cell injury and protection

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World journal of Gastroenterology 2009年第14期15卷 1677-1689页

作者： maria j.perez Oscar Briz Research Unit University Hospital of Salamanca Laboratory of Experimental Hepatology and Drug Targeting CIBERehd University of Salamanca E.D. 129 37007 Salamanca Spain

Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids （BAs） in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyI-N- methylglycine or pharmacological properties. cholylsarcosine, interest owing have also aroused to their protective

关键词： Apoptosis Cholestasis Liver Necrosis Oxidative stress Ursodeoxycholic acid

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Overcoming thermo-optical dynamics in broadband nanophotonic sensing

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Microsystems & Nanoengineering 2021年第4期7卷 47-57页

作者： Mingkang Wang Diego j.perez-Morelo Vladimir Aksyuk Microsystems and Nanotechnology Division National Institute of Standards and TechnologyGaithersburgMD 20899USA Institute for Research in Electronics and Applied Physics University of MarylandCollege ParkMD 20742USA

Advances in integrated photonics open up exciting opportunities for batch-fabricated optical sensors using high-quality-factor nanophotonic cavities to achieve ultrahigh sensitivities and *** sensitivity improves with increasing optical power;however,localized absorption and heating within a micrometer-scale mode volume prominently distorts the cavity resonances and strongly couples the sensor response to thermal dynamics,limiting the sensitivity and hindering the measurement of broadband time-dependent ***,we derive a frequency-dependent photonic sensor transfer function that accounts for thermo-optical dynamics and quantitatively describes the measured broadband optomechanical signal from an integrated photonic atomic force microscopy nanomechanical *** this transfer function,the probe can be operated in the high optical power,strongly thermo-optically nonlinear regime,accurately measuring low-and intermediate-frequency components of a dynamic signal while reaching a sensitivity of 0.7fm/Hz^(1/2) at high frequencies,an improvement of=10x relative to the best performance in the linear ***,we discover that a higher transduction gain and sensitivity are achieved with lower quality-factor optical modes for low signal *** limited to optomechanical transducers,the derived transfer function is generally valid for describing the small-signal dynamic responses of a broad range of technologically important photonic sensors subject to the thermo-optical effect.

关键词： dynamics regime hinder

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一种带混合进化机制的膜聚类算法

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软件学报 2015年第5期26卷 1001-1012页

作者：彭宏蒋洋王军 Mario j.perez-jIMENEZ 西华大学无线电管理技术研究中心四川成都610039 西华大学电气信息学院四川成都610039 Research Group of Natural Computing University of Seville Sevilla Spain

膜计算(也称为P系统或膜系统)是一种新颖的分布式、并行计算模型.为了处理数据聚类问题,提出了一种采用混合进化机制的膜聚类算法.它使用了一个由3个细胞组成的组织P系统,为一个待聚类的数据集发现最优的簇中心.其对象表示候选的簇中心... 详细信息

膜计算(也称为P系统或膜系统)是一种新颖的分布式、并行计算模型.为了处理数据聚类问题,提出了一种采用混合进化机制的膜聚类算法.它使用了一个由3个细胞组成的组织P系统,为一个待聚类的数据集发现最优的簇中心.其对象表示候选的簇中心,并且这3个细胞分别使用了3种不同的进化机制:遗传算子、速度-位移模型和差分进化机制.然而,所使用的速度-位移模型和差分进化机制是结合了这个特殊膜结构和转运机制所提出的改进版本.这种混合进化机制能够增强系统中对象的多样性和改善收敛性能.在混合进化机制和转运机制控制下,这种膜聚类算法能够确定一个数据集的良好划分.所提出的膜聚类算法在3个人工数据集和5个真实数据集上被评估,并与k-means和几种进化聚类算法进行比较.统计显著性测试建立了所提出的膜聚类算法的优势.

关键词：膜计算 P系统组织P系统数据聚类膜聚类算法混合进化机制

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The Deep Thioredoxome in Chlamydomonas reinhardtii： New Insights into Redox Regulation

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Molecular Plant 2017年第8期10卷 1107-1125页

作者： maria Esther perez-perez Adeline Mauries Alexandre Maes Nicolas j. Tourasse Marion Hamon Stephane D. Lemaire Christophe H. Marchand Institut de Biologie Physico-Chimique UMR8226 CNRS Sorbonne Universit6s UPMC Univ Paris 06 13 rue Pierre et Marie Curie 75005 Paris France Institut de Biologie Physico-Chimique Plateforme de Proteomique FRC550 CNRS 13 rue Pierre et Marie Curie 75005 Paris France Instituto de Bioquimica Vegetal y Fotosintesis Consejo Superior de Investigaciones Cientificas (CSIC)-Universidad de Sevilla Seville Spain ARNA Laboratory INSERM U1212 CNRS UMR5320 Universite Bordeaux 2 Bordeaux France

Thiol-based redox post-translational modifications have emerged as important mechanisms of signaling and regulation in all organisms, and thioredoxin plays a key role by controlling the thiol-disulfide status of target proteins. Recent redox proteomic studies revealed hundreds of proteins regulated by glutathio- nylation and nitrosylation in the unicellular green alga Chlamydomonas reinhardtii, while much less is known about the thioredoxin interactome in this organism. By combining qualitative and quantitative proteomic analyses, we have comprehensively investigated the Chlamydomonas thioredoxome and 1188 targets have been identified. They participate in a wide range of metabolic pathways and cellular pro- cesses. This study broadens not only the redox regulation to new enzymes involved in well-known thiore- doxin-regulated metabolic pathways but also sheds light on cellular processes for which data supporting redox regulation are scarce （aromatic amino acid biosynthesis, nuclear transport, etc）. Moreover, we char- acterized 1052 thioredoxin-dependent regulatory sites and showed that these data constitute a valuable resource for future functional studies in Chlamydomonas. By comparing this thioredoxome with proteomic data for glutathionylation and nitrosylation at the protein and cysteine levels, this work confirms the existence of a complex redox regulation network in Chlamydomonas and provides evidence of a tremendous selectivity of redox post-translational modifications for specific cysteine residues.

关键词： Chlamydomonas reinhardtii disulfide bond isotope-coded affinity tag redox proteomics redox regulation thioredoxin targets

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Photosynthetic Regulation of the Cyanobacterium Synechocystis sp. PCC 6803 Thioredoxin System and Functional Analysis of TrxB （Trx x） and TrxQ （Trx y） Thioredoxins

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Molecular Plant 2009年第2期2卷 270-283页

作者： M. Esther perez-perez Eugenio Martin-Figueroa Francisco j. Florencio Instituto de Bioquimica Vegetal y Fotosintesis Universidad de Sevilla-CSIC Avda Americo Vespucio 49 41092-Sevilla Spain

The expression of the genes encoding the ferredoxin-thioredoxin system including the ferredoxin-thioredoxin reductase （FTR） genes ftrC and ftrV and the four different thioredoxin genes trxA （m-type; sir0623）, trxB （x-type; sir1139）, trxC （sll1057） and trxQ （y-type; sir0233） of the cyanobacterium Synechocystis sp. PCC 6803 has been studied according to changes in the photosynthetic conditions. Experiments of light-dark transition indicate that the expression of all these genes except trxQ decreases in the dark in the absence of glucose in the growth medium. The use of two electron transport inhibitors, 3-（3,4-dichlorophenyl）-1,1-dimethylurea （DCMU） and 2,5-dibromo-3-methyl-6-isopropyl-p- benzoquinone （DBMIB）, reveals a differential effect on thioredoxin genes expression being trxC and trxQ almost unaffected, whereas trxA, trxB, and the ftr genes are down-regulated. In the presence of glucose, DCMU does not affect gene expression but DBMIB still does. Analysis of the single TrxB or TrxQ and the double TrxB TrxQ Synechocystis mutant strains reveal different functions for each of these thioredoxins under different growth conditions. Finally, a Synechocystis strain was generated containing a mutated version of TrxB （TrxBC34S）, which was used to identify the potential in-vivo targets of this thioredoxin by a proteomic analysis.

关键词： Cyanobacteria photosynthetic electron transport Synechocystis oxidative stress thioredoxin.

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High-performance polymer electrolyte membranes incorporated with 2D silica nanosheets in high-temperature proton exchange membrane fuel cells

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journal of Energy Chemistry 2022年第1期31卷 323-334,I0009页

作者： Zunmin Guo jianuo Chen jae jong Byun Rongsheng Cai maria perez-Page Madhumita Sahoo Zhaoqi ji Sarah j.Haigh Stuart M.Holmes Department of Chemical Engineering and Analytical Science The University of ManchesterM139PLUnited Kingdom Department of Materials The University of ManchesterM139PLUnited Kingdom

Silica nanosheets(SN)derived from natural vermiculite(Verm)were successfully incorporated into polyethersulfone-polyvinylpyrrolidone(PES-PVP)polymer to fabricate high-temperature proton exchange membranes(HT-PEMs).The content of SN filler was varied(0.1-0.75 wt%)to study its influence on proton conductivity,power density and *** from the hydroxyl groups of SN that enable the formation of additional proton-transferring pathways,the inorganic-organic membrane displayed enhanced proton conductivity of 48.2 mS/cm and power density of 495 mW/cm^(2) at 150℃ without humidification when the content of SN is 0.25 wt%.Furthermore,exfoliated SN(E-SN)and sulfonated SN(S-SN),which were fabricated by a liquid-phase exfoliation method and silane condensation,respectively,were embedded in PES-PVP polymer matrix by a simple blending *** to the significant contribution from sulfonic groups in S-SN,the membrane with 0.25 wt%S-SN reached the highest proton conductivity of51.5 mS/cm and peak power density of 546 mW/cm^(2) at150℃,48%higher than the pristine PES-PVP *** to unaltered PES-PVP membrane,SN added hybrid composite membrane demonstrated excellent durability for the fuel cell at 150℃.Using a facile method to prepare 2D SN from natural clay minerals,the strategy of exfoliation and functionalization of SN can be potentially used in the production of HT-PEMs.

关键词： Silica nanosheets Vermiculite High-temperature proton exchange membrane Proton conductivity

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