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The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2243-2264页

作者： Edgar Pérez-Herrero alberto fernández-Medarde Departamento de Ingeniería Química y Tecnología Farmacéutica Universidad de La LagunaLa Laguna 38206TenerifeSpain Instituto Universitario de Bio-Orgánica Antonio González Universidad de La LagunaLa Laguna 38206TenerifeSpain Instituto Universitario de Tecnologías Biomédicas Universidad de La LagunaLa Laguna 38200TenerifeSpain Instituto de Biología Molecular y Celular Del Cáncer Centro de Investigación Del Cáncer(USAL-CSIC)Salamanca 37007Spain

Solid tumors are complex entities,comprising a wide variety of malignancies with very different molecular *** this,they share a set of characteristics known as"hallmarks of cancer"that can be used as common therapeutic ***,every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates,and these adaptations lead to alterations in extra-and intracellular *** changes in p H are common to all solid tumors,and can be used either as therapeutic targets,blocking the cell proton transporters and reversing the pH changes,or as means to specifically deliver anticancer *** this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic *** will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light ***,we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery,describing how nanocarriers are being used to increase drug stability and specificity.

关键词： pH-Gradient inversion Metabolism of glucose Proton transport inhibitors Proton-caged carriers Chemotherapy Targeted drug delivery pH-Sensitive nanocarriers Warburg effect Cancer

Rock mass structural recognition from drill monitoring technology in underground mining using discontinuity index and machine learning techniques

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International Journal of Mining Science and Technology 2023年第5期33卷 555-571页

作者： alberto fernández JoséA.Sanchidrián Pablo Segarra Santiago Gómez Enming Li Rafael Navarro Universidad Politécnica de Madrid–ETSI Minas y Energía Spain Universidad de Salamanca–GIR Charrock Spain

A procedure to recognize individual discontinuities in rock mass from measurement while drilling(MWD)technology is developed,using the binary pattern of structural rock characteristics obtained from in-hole images for *** from two underground operations with different drilling technology and different rock mass characteristics are considered,which generalizes the application of the methodology to different sites and ensures the full operational integration of MWD data *** approaches are followed for site-specific structural model building:a discontinuity index(DI)built from variations in MWD parameters,and a machine learning(ML)classifier as function of the drilling parameters and their *** prediction ability of the models is quantitatively assessed as the rate of recognition of discontinuities observed in borehole *** between the parameters involved in the models for each site,and differences in their weights,highlight the site-dependence of the resulting *** ML approach offers better performance than the classical DI,with recognition rates in the range 89%to 96%.However,the simpler DI still yields fairly accurate results,with recognition rates 70%to 90%.These results validate the adaptive MWD-based methodology as an engineering solution to predict rock structural condition in underground mining operations.

关键词： Drill monitoring technology Rock mass characterization Underground mining Similarity metrics of binary vectors Structural rock factor Machine learning

Extracting body surface dimensions from top-view images of pigs

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International Journal of Agricultural and Biological Engineering 2018年第5期11卷 182-191页

作者： Mingzhou Lu Tomas Norton Ali Youssef Nemanja Radojkovic alberto Peña fernández Daniel Berckmans College of Engineering/Jiangsu Province Engineering Lab for Modern Facility Agriculture Technology&Equipment Nanjing Agricultural UniversityNanjing 210031China M3-BIORES-Measure Model&Manage BioresponsesKU LeuvenKasteelpark Arenberg 30B-3001 LeuvenBelgium

Continuous live weight and carcass traits estimation are important for the pig production and breeding *** is widely known that top-view images of a pig’s body(excluding its head and neck)reveal surface dimension parameters,which are correlated with live weight and carcass ***,because a pig is not constrained when an image is captured,the body does not always have a straight *** creates a big challenge when extracting the body surface dimension parameters,and consequently the live weight and carcass traits estimation has a high level of *** primary goal of this study is to propose an algorithm to automatically extract pig body surface dimension parameters,with a better accuracy,from top-view pig ***,the backbone line of a pig was ***,lengths of line segments perpendicular to the backbone line were calculated,and then feature points on the pig’s contour line were extracted based on the lengths variation of the perpendicular line ***,the head and neck of the pig were removed from the pig’s contour by an ***,four length and one area parameters were *** proposed algorithm was implemented in Matlab®(R2012b)and applied to 126 depth images of *** the results of the manual labeling tool as the gold standard,the length and area parameters could be obtained by the proposed algorithm with an accuracy of 97.71%(SE=1.64%)and 97.06%(SE=1.82%),*** parameters can be used to improve pig live weight and carcass traits estimation accuracy in the future work.

关键词： body surface dimension image analysis skeleton triangulated network ellipse fitting

Bismuth-based halide double perovskite Cs_(2)KBiCl_(6): Disorder and luminescence

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Chinese Chemical Letters 2024年第5期35卷 504-508页

作者： Pan Liu Yanming Sun alberto J.fernández-Carrión Bowen Zhang Hui Fu Lunhua He Xing Ming Congling Yin Xiaojun Kuang MOE Key Laboratory of New Processing Technology for Nonferrous Metal and Materials Guangxi Key Laboratory of Optic and Electronic Materials and DevicesCollege of Materials Science and EngineeringGuilin University of TechnologyGuilin 541004China Analytical Instrumentation Center College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Spallation Neutron Source Science Center Dongguan 523803China Chinese Academic of Science Institute of PhysicsBeijing National Laboratory for Condensed Matter PhysicsBeijing 100190China Songshan Lake Materials Laboratory Dongguan 523808China College of Science Guilin University of TechnologyGuilin 541004China College of Chemistry and Bioengineering Guilin University of TechnologyGuilin 541004China

A new bismuth-based halide double perovskite Cs_(2)KBiCl_(6) was isolated successfully through solid-state reactions and investigated using X-ray and neutron *** than an ordered structure,the crystal structure consists of shifted Cs,K,Bi,and Cl sites from the ideal positions with fractional occupancy in compensation,leading to variable local coordination of Cs^(+)ions,as revealed by^(133)Cs solid-state nuclear magnetic resonance ***_(2)KBiCl_(6) displays volume hysteresis at 5-298 K range upon heating and *** Cs_(2)KBiCl_(6) has a direct bandgap of 3.35(2)eV and red-shift luminescence of around 600 nm upon Mn doping compared with the Na *** stabilization of disordered structure in Cs_(2)KBiCl_(6) is related to two factors including the large-sized K^(+)cation which prefers to coordinate with more than six Cl^(-),and the Bi^(3+)with 6s^(2) lone pair which has a preference for a local asymmetric *** findings could have general application and help to understand the structure and property of halide perovskites.

关键词： Halide perovskite Double perovskite Luminescence Disordered structure Direct bandgap

Characteristics and in-hospital mortality of elderly patients with heart failure in Spanish hospitals

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Journal of Geriatric Cardiology 2023年第4期20卷 247-255页

作者： alberto Esteban-fernández Manuel Anguita-Sánchez Juan Luis Bonilla-Palomas María Anguita-Gámez María García JoséLuis Bernal Náyade Del Prado Cristina fernández-Pérez Julián Pérez-Villacastin Juan JoséGómez-Doblas Francisco Javier Elola Cardiology Department Hospital Universitario Severo OchoaMadridSpain Cardiology Department Hospital Universitario Reina SofíaCórdobaSpain Cardiology Department Hospital San Juan de la CruzÚbedaSpain Cardiology Department Hospital Clínico San CarlosMadridSpain Fundación Instituto para la Mejora de la Asistencia Sanitaria MadridSpain Management Control Department Hospital Universitario 12 de OctubreMadridSpain Department of Preventive Medicine Área Sanitaria de Santiago de Compostela y BarbanzaInstituto de Investigación de SantiagoSantiago de CompostelaSpain Cardiology Department Hospital Universitario Virgen de la VictoriaMálagaSpain

BACKGROUND The prevalence of heart failure(HF)increases with age,and it is one of the leading causes of hospitalization and death in older ***,there are little data on in-hospital mortality in patients with HF≥75 years in *** A retrospective analysis of the Spanish Minimum Basic Data Set was performed,including all HF episodes discharged from public hospitals in Spain between 2016 and *** was performed using the International Classification of Diseases,10th ***≥75 years with HF as the principal diagnosis were *** calculated:(1)the crude in-hospital mortality rate and its distribution according to age and sex;(2)the risk-standardized in-hospital mortality ratio;and(3)the association between in-hospital mortality and the availability of an intensive cardiac care unit(ICCU)in the *** We included 354,792 HF episodes of patients over 75 *** mean age was 85.2±5.5 years,and 59.2%of patients were *** most frequent comorbidities were renal failure(46.1%),diabetes mellitus(35.5%),valvular disease(33.9%),cardiorespiratory failure(29.8%),and hypertension(26.9%).In-hospital mortality was 12.7%,and increased with age[odds ratio(OR)=1.07,95%CI:1.07–1.07,P<0.001]and was lower in women(OR=0.96,95%CI:0.92–0.97,P<0.001).The main predictors of mortality were the presence of cardiogenic shock(OR=19.5,95%CI:16.8–22.7,P<0.001),stroke(OR=3.5,95%CI:3.0–4.0,P<0.001)and advanced cancer(OR=2.6,95%CI:2.5–2.8,P<0.001).In hospitals with ICCU,the in-hospital risk-adjusted mortality tended to be lower(OR=0.85,95%CI:0.72–1.00,P=0.053).CONCLUSIONS In-hospital mortality in patients with HF≥75 years between 2016 and 2019 was 12.7%,higher in males and elderly *** main predictors of mortality were cardiogenic shock,stroke,and advanced *** was a trend toward lower mortality in centers with an ICCU.

关键词： patients mortality diagnosis

Genetic Rat Models of Schizophrenia-Relevant Symptoms

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World Journal of Neuroscience 2014年第3期4卷 261-278页

作者： Cristobal del Rio Ignasi Oliveras Toni Canete Gloria Blázquez Adolf Tobena alberto fernández-Teruel Medical Psychology Unit Department of Psychiatry and Forensic MedicineInstitute of NeurosciencesSchool of MedicineAutonomous University of BarcelonaBarcelonaSpain

It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and

关键词： Schizophrenia Genetic Rat Models Selective Breeding Prepulse Inhibition Dopamine Serotonin Glutamate

Radioisotopes and Analytical Chemistry

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World Journal of Nuclear Science and Technology 2013年第1期3卷 6-13页

作者： Manuel Navarrete Trinidad Martínez alberto fernández Miguelángel Zúniga Michelle Camacho Mónica Flores Department of Inorganic and Nuclear Chemistry Faculty of ChemistryNational University of MexicoMexico CityMexico

When Periodic Chart of elements is consulted to find natural radioisotopes, one firstly finds tritium, followed by 10Be, 14C, 50V and many others. Before Bi, 12 cosmogenic radioisotopes are listed. They are those continuously produced by nuclear reactions among light elements present in earthly atmosphere and radiations coming from the outside space. Eighteen additional primordial radioisotopes are listed. They were created at the same time that the non-radioactive isotopes composing the 92 natural elements in the periodic table. From Bi on, every isotope is radioactive, up to U. Then follow the artificial elements produced by laboratory nuclear reactions from Np to element with atomic number 118. In this way, from 118 known elements, 64 are radioactive, which amount 55% of all those units forming the chemical compounds. Therefore, the complete understanding of radioactivity should be a suitable tool to advance our knowledge of Universe, and consequent applications to get better living conditions. So, this paper deals with radioisotopes as suitable instruments for chemical analysis.

关键词： Radioisotopes Radiations Chemical Quantitative Analysis

Study of Functionalized Gold Nanoparticles with Anti-gp63 IgG Antibody for the Detection of Glycoprotein gp63 in Membrane Surface of <i>Leishmania</i>Genus Parasites

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American Journal of Analytical Chemistry 2013年第7期4卷 100-108页

作者： Pedro Rodríguez Humberto Rojas Miguel Medina Jazzmin Arrivillaga Yosue Francisco Fracehuli Dager Vincent Piscitelli Manuel Caetano alberto fernández Jimmy Castillo Centro de Microscopia Electrónica Facultad de Ciencias Universidad Central de Venezuela Caracas Venezuela Departamento de Biología Universidad Simón Bolívar Caracas Venezuela Escuela de Biología Facultad de Ciencias Universidad Central de Venezuela Caracas Venezuela Laboratorio de Espectroscopia Laser Facultad de Ciencias Universidad Central de Venezuela Caracas Venezuela

In this work we present the preparation and functionalization of gold nanoparticles (AuNPs) for the detection of presence of gp63 glycoprotein in the surface of Leishmania genus parasites. AuNPs were prepared by induced laser ablation in a clean and biologically suitable media. The nanoparticles were functionalized with anti-gp63 lgG antibody in order to study the interaction with the glycoprotein component gp63 (63 kDa) present on the membrane surface of Leishmania genus parasites. The functionalized AuNPs showed potential as a spectrometric indicator of the parasite existence, both by the detection of the presence of the gp63 in solution and through the specific interaction with the parasites in vitro. The specificity of the study opens a new line of research on the use of modified nanoparticles in the development of a fast and easy assay for Leishmaniosis diagnostics.

关键词： Leishmania Nanoparticles Surface Plasmon Resonance gp63 Protein

基于本征正交分解的环境温度分布快速预测模型研究

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制冷技术 2018年第6期38卷 54-60,67页

作者：芮庆王路瑶 José alberto García fernández 杜志敏晋欣桥上海交通大学制冷与低温工程研究院上海200240

本文基于Karhunen-Loeve分解的原理,使用本征正交分解方法(Proper Orthogonal Decomposition,POD)对高维非线性的流动及传热过程进行降阶,获得研究对象所处流场的各阶模态以用于温度场的重构预测。将本征正交分解模型预测温度分布的准... 详细信息

本文基于Karhunen-Loeve分解的原理,使用本征正交分解方法(Proper Orthogonal Decomposition,POD)对高维非线性的流动及传热过程进行降阶,获得研究对象所处流场的各阶模态以用于温度场的重构预测。将本征正交分解模型预测温度分布的准确度及响应速度和通过流动及传热控制方程的离散求解获取温度分布的过程进行对比,对比结果显示本征正交分解具有较高的准确度和更加敏捷的温度预测响应速度,并且其预测过程占用更少的计算资源。结果显示,每次离散求解流动及传热控制方程约耗时93 s,而使用本征正交分解模型获取热环境所需的时间约为6 ms,并且后者的平均泛化误差小于5%。

关键词：本征正交分解降阶空调系统温度分布重构预测模态