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In vivo testing of mucus-permeating nanoparticles for oral insulin delivery using Caenorhabditis elegans as a model under hyperglycemic conditions

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Acta Pharmaceutica Sinica B 2021年第4期11卷 989-1002页

作者： Ana LMartínez-López carlos JGonzález-Navarro Paula Aranaz JoséLVizmanos juan MIrache NANO-VAC Research Group Department of Chemistry and Pharmaceutical TechnologySchool of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Center for Nutrition Research School of Pharmacy and NutritionUniversity of NavarraPamplona 31080Spain Department of Biochemistry&Genetics School of ScienceUniversity of NavarraPamplona 31080Spain Navarra Institute for Health Research(IdiSNA) Pamplona 31080Spain

The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral administration of *** nanocarriers,based on the coating of zein nanoparticles with a polymer conjugate containing PEG,displayed a size of 260 nm with a negative surface charge and an insulin payload of 77 mg/*** intestinal pig mucus,the diffusivity of these nanoparticles(PPA-NPs)was found to be 20-fold higher than bare nanoparticles(NPs).These results were in line with the biodistribution study in rats,in which NPs remained trapped in the mucus,whereas PPA-NPs were able to cross this layer and reach the epithelium *** therapeutic effcacy was evaluated in Caenorhabditis elegans grown under high glucose *** this model,worms treated with insulin-loaded in PPA-NPs displayed a longer lifespan than those treated with insulin free or nanoencapsulated in *** finding was associated with a signifcant reduction in the formation of reactive oxygen species(ROS)as well as an important decrease in the glucose and fat content in *** effects would be related with the mucus-permeating ability of PPA-NPs that would facilitate the passage through the intestinal peritrophic-like dense layer of worms(similar to mucus)and,thus,the absorption of insulin.

关键词： Nanoparticles Oral delivery Mucus-permeating Biodistribution Insulin Caenorhabditis elegans ROS

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Influence of postoperative complications on long-term survival in liver transplant patients

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World Journal of Gastrointestinal Surgery 2020年第8期12卷 336-345页

作者： Sonia Castanedo Enrique Toledo Roberto Fernández-Santiago Federico Castillo juan Echeverri juan carlos Rodríguez-Sanjuán Department of General Surgery University Hospital Marqués de ValdecillaUniversity of CantabriaSantander 39008Spain

BACKGROUND Liver transplant(LT)is a complex procedure with frequent postoperative *** other surgical procedures such as gastrectomy,esophagectomy or resection of liver metastases,these complications are associated with poorer long-term *** is possible this happens in LT but there are not enough data to establish this *** To analyze the possible influence of postoperative complications on long-term survival and the ability of the comprehensive complication index(CCI)to predict *** Retrospective study in a tertiary-level university *** 164 participants were all patients who received a LT from January 2012 to July *** follow-up was done in the hospital until the end of the study or *** and risk after transplantation were calculated using the Charlson and balance of risk(BAR)scores,*** complications were graded according to the Clavien-Dindo classification and the *** assess the CCI cut-off value with greater prognostic accuracy a receiver operating characteristic(ROC)curve was built,with calculation of the area under the curve(AUC).Overall survival was estimated according to the Kaplan-Meier test and log-rank *** were compared by the Mann-Whitney *** the multivariable analysis the Cox regression was *** The mean follow-up time of the cohort was 37.76(SD=24.5)mo.A ROC curve of CCI with 5-year survival was *** AUC was 0.826(0.730-0.922),P33.5(33.5=median CCI value)showed estimate

关键词： Liver transplant Complication Survival Comprehensive complication index Clavien Prognosis

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MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

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Research 2024年第2期2023卷 239-257页

作者： Cui Wang Kuan Yang Xiaoqian Liu Si Wang Moshi Song juan carlos Izpisua Belimonte Jing Qu Guang-Hui Liu Weiqi Zhang CAS Key Laboratory of Genomic and Precision Medicine Beijng Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Bejing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ ***,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell *** answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell *** found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence *** uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence *** together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

关键词： CRISPR/Cas9 homeostasis Mitochondrial

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A novel induction motor control scheme using IDA-PBC

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控制理论与应用（英文版） 2008年第1期6卷 59-68页

作者： Humberto GONZLEZ Manuel A. DUARTE-MERMOUD Ian PELISSIER juan carlos TRAVIESO-TORRES Romeo ORTEGA Department of Electrical Engineering University of ChileCasilla 412-3 Santiago Chile Laboratoire des Signaux et Systèmes Plateau de Moulon 91192 Gif-sur-Yvette France

A new control scheme for induction motors is proposed in the present paper, applying the interconnection and damping assignment-passivity based control （IDA-PBC） method. The scheme is based exclusively on passivity based control, without restricting the input frequency as it is done in field oriented control （FOC）. A port-controlled Hamiltonian （PCH） model of the induction motor is deduced to make the interconnection and damping of energy explicit on the scheme. The proposed controller is validated under computational simulations and experimental tests using an inverter prototype.

关键词： Induction motor Passivity based control Energy shaping control Interconnection and damping assignment IDA-PBC Port-controlled Hamiltonian PCH

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Hydration status,body composition,and anxiety status in aeronautical military personnel from Spain:a crosss-ectional study

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Military Medical Research 2022年第2期9卷 184-192页

作者： Alejandra Carretero-Krug Nataliaúbeda carlos Velasco juan Medina-Font Trinidad Trujillo Laguna Gregorio Varela-Moreiras Ana Montero Departamento Ciencias Farmacéuticas y de la Salud Facultad de FarmaciaUniversidad San Pablo-CEUCEU UniversitiesUrbanización Montepríncipe28660 Boadilla del MonteSpain Centro de Instrucción de Medicina Aeroespacial Ejército del Aire28850 Torrejón de ArdozMadridSpain

Background: An adequate hydration status is critical to ensure efficiency during mental and physical *** goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and ***: A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were ***: Of the total sample, 81% met the hydration criteria(urine color = well hydrated, water balance ≥0 ml, and total water intake/weight ≥35 ml/kg), and 19% did not meet the hydration criteria(urine color = not sufficiently hydrated or dehydrated, water balance <0 ml, and total water intake/weight <35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status(score=4 vs. 3, P=0.026), weight [(84.7±10.5) kg vs.(80.5±10.2) kg], body mass index [(26.3±3.1) kg/m;vs.(25.2±2.8) kg/m;], body fat [(22.3±5.6)% vs.(18.3±6.5)%], urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat(P=0.004), but no relation was found with age, comorbidities, or medications. Furthermore, total water intake/weight was positively correlated with percentage of body water(r=0.357, P=0.000) and negatively with body fat(kg)(r=–0.427, P=0.000), percentage of body fat(r=–0.405, P=0.000), and waist/hip ratio(r=–0.223, P=0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat(P=0.001) and percentage of body water content(P=0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or ***: These findings all suggest a relationship between hydration status and body composition but

关键词： Hydration status Military aeronautical personnel Body composition Anxiety status Water intake

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Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review

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World Journal of Gastrointestinal Oncology 2014年第8期6卷 301-310页

作者： William J Salyers Kenneth J Vega juan carlos Munoz Bruce W Trotman Silvio S Tanev Division of Gastroenterology University of Florida College of Medicine/Jacksonville Jacksonville FL 32207 United States Division of Digestive Diseases and Nutrition University of Oklahoma Health Sciences Center Oklahoma City OK 73104 United States Department of Medicine University of Maryland School of Medicine Baltimore MD 21201 United States Department of Pathology Manatee Memorial Hospital Bradenton FL 34208 United States

Neuroendocrine tumors(NET)previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid *** annual incidence of patients with NET is 8.4 per 100000;yet many NET remain asymptomatic and clinically undetected.A majority of NET follows a benign course;however,some will display malignant *** most commonly occur in the gastrointestinal tract(67%)and bronchopulmonary system(25%).Gastrointestinal NET occur within the stomach,small intestine,liver,and *** report a retrospective study of 11 subjects:Eight with benign carcinoid tumors:duodenal bulb(n=2),terminal ileum(n=1),sigmoid colon(n=2),and rectum(n=3);three with malignant carcinoid:liver(n=1)and intra-abdominal site(n=2).The diagnosis,endoscopic images,outcome,treatment and review of the literature are presented.

关键词： Neuroendocrine Carcinoid Gastrointestinal Tumors

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Kinematic calibration of precise 6-DOF Stewart platform-type positioning systems for radio telescope applications

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Frontiers of Mechanical Engineering 2013年第3期8卷 252-260页

作者： juan carlos JUREGUI Eusebio E.HERNNDEZ Marco CECCARELLI carlos LOPEZ-CAJUN Alejandro GARCIA División de Estudios de Posgrado Facultad de IngenieríaUniversidad Autónoma de Quéretaro QuéretaroQro.Mexico National Polytechnic Institute IPNSection of Graduate Studies and ResearchESIME-UPTMéxico D.F.Mexico Laboratory of Robotics and Mechatronics University of Cassino Italy Universidad Autónoma de Quéretaro Querétaro Qro.México CIATEQ A.C.AguascalientesAgs.México

The pose accuracy of a parallel robot is a function of the mobile platform ***,there is no a single value of the robot’s *** this paper,two novel methods for estimating the accuracy of parallel robots are *** the frst method,the pose accuracy estimation is calculated by considering the propagation of each error,i.e.,error variations are considered as a function of the actuator’s *** the second method,it is considered that each actuator has a constant error at any *** methods can predict pose accuracy of precise robots at design stages,and/or can reduce calibration time of existing *** example of a six degree-of-freedom parallel manipulator is included to show the application of the proposed methods.

关键词： pose errors error estimation parallel robot radio telescopes

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Effect of Noisy Fitness in Real-Time Strategy Games Player Behaviour Optimisation Using Evolutionary Algorithms

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Journal of Computer Science & Technology 2012年第5期27卷 1007-1023页

作者： Antonio M. Mora Antonio Fernndez-Ares juan J. Merelo Pablo García-Snchez carlos M. Fernandes Computer Architecture and Technology Department University of Granada Institute for Systems and Robotics Technical University of Lisbon

This paper investigates the performance and the results of an evolutionary algorithm （EA） specifically designed for evolving the decision engine of a program （which, in this context, is called bot） that plays Planet Wars. This game, which was chosen for the Google Artificial Intelligence Challenge in 2010, requires the bot to deal with multiple target planets, while achieving a certain degree of adaptability in order to defeat different opponents in different scenarios. The decision engine of the bot is initially based on a set of rules that have been defined after an empirical study, and a genetic algorithm （GA） is used for tuning the set of constants, weights and probabilities that those rules include, and therefore, the general behaviour of the bot. Then, the bot is supplied with the evolved decision engine and the results obtained when competing with other bots （a bot offered by Google as a sparring partner, and a scripted bot with a pre-established behaviour） are thoroughly analysed. The evaluation of the candidate solutions is based on the result of non-deterministic battles （and environmental interactions） against other bots, whose outcome depends on random draws as well as on the opponents＇ actions. Therefore, the proposed GA is dealing with a noisy fitness function. After analysing the effects of the noisy fitness, we conclude that tackling randomness via repeated combats and reevaluations reduces this effect and makes the GA a highly valuable approach for solving this problem.

关键词： real-time strategy game genetic algorithm noisy fitness player behaviour optimisation parameter adaptation

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Direct conversion of human fibroblasts into retinal pigment epithelium-like cells by defined factors

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Protein & Cell 2014年第1期5卷 48-58页

作者： Kejing Zhang Guang-Hui Liu Fei Yi Nuria Montserrat Tomoaki Hishida Concepcion Rodriguez Esteban juan carlos Izpisua Belmonte] Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Department of Molecular and Cellular Physiology Stanford University School of Medicine 265 Campus Drive StanfordCA 94305 USA Center for Regenerative Medicine in Barcelona Dr. Aiguader 88 08003 Barcelona Spain Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN) BarcelonaSpain

The generation of functional retinal pigment epithelium （RPE） is of great therapeutic interest to the field of regenerative medicine and may provide possible cures for retinal degenerative diseases, including age-related macular degeneration （AMD）. Although RPE cells can be produced from either embryonic stem cells or induced pluripotent stem cells, direct cell reprogramming driven by lineage-determining transcription factors provides an immediate route to their generation. By monitoring a human RPE specific Bestl：：GFP reporter, we report the conversion of human fibroblasts into RPE lineage using defined sets of transcription factors. We found that Bestl：：GFP positive cells formed colonies and exhibited morphological and molecular features of early stage RPE cells. Moreover, they were able to obtain pigmen- tation upon activation of Retinoic acid （RA） and Sonic Hedgehog （SHH） signaling pathways. Our study not only established an ideal platform to investigate the tran- scriptional network regulating the RPE cell fate deter- mination, but also provided an alternative strategy to generate functional RPE cells that complement the useof pluripotent stem cells for disease modeling, drug screening, and cell therapy of retinal degeneration.

关键词： retinal pigment epithelium fibroblasts,direct conversion

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The significance of U-Pb zircon ages in zoned plutons:the case of the Flamenco pluton, Coastal Range batholith, northern Chile

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Geoscience Frontiers 2019年第3期10卷 1073-1099页

作者： Natalia Rodríguez juan Díaz-Alvarado carlos Fernández Paulina Fuentes Christoph Breitkreuz Colombo Celso Gaeta Tassinari Departamento de Geología Universidad de Atacama Departamento de Ciencias de la Tierra Universidad de Huelva Institut für Geologie TU Bergakademie Freiberg High Resolution Geochronological Laboratory University of S?o Paulo

Compositionally zoned plutons, both layered and concentrically arranged, provide granitic exposures where the mechanisms and timing of the magmatic emplacement processes can be studied. The importance of in-situ geochemical differentiation and the magma replenishment rates are revealed by geochemistry and field relations, together with the increasingly accurate U-Pb geochronology, which has promoted the knowledge about the pluton incremental assembly *** Flamenco pluton, located in the Coastal Range of northern Chile, is part of the Upper Triassic to Early Cretaceous Andean intrusives formed in the western active margin of South America, and present a normal zoned structure with mafic magmatic facies(mostly gabbros and Qtz-diorites) close to the contacts with the host metasediments, and tonalites, granodiorites and granites in the inner areas. A combined study of the field relations, geochemistry and zircon geochronology of the magmatic facies was applied to determine the emplacement sequence of the Flamenco pluton, revealing three distinguishable domains separated by metasedimentary septa. The SW area is constituted by mostly homogeneous leucocratic granodiorites that yielded an age of 213 Ma as the best estimation for their emplacement age. Distinctive geochemical characteristics, such as the absence of an Eu anomaly, the depletion in HREE, or the highest Sr, Sr/Y and Ce/Yb values among the granodioritic facies of the pluton,involve lower T and/or higher P conditions at the magmatic source according to experimental *** conditions were established during an early stage of the Andean magmatic arc building that is firstly defined here as Upper Triassic. The NW and E domains of the pluton were sequentially emplaced between 194 Ma and 186 Ma and both the field relations and the detailed geochronological results suggest that the mafic facies intruded latter in the emplacement sequence. To the NW, Qtz-dioritic and gabbroic externally emplaced pulses ga

关键词： Zircon U-Pb geochronology Zoned plutons Andean magmatic arc Sequential emplacement Individual and statistical zircon ages

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