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Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

World Journal of Stem Cells 2014年第3期6卷 322-343页

作者： antonio garcia-gomez Fermin Sanchez-Guijo M Consuelo del Caizo Jesus F San Miguel Mercedes Garayoa Cancer Research Center IBMCC(University of Salamanca-CSIC) Institute of Biomedical Research of Salamanca University Hospital Network of Centers for Regenerative Medicine and Cellular Therapy fromCastilla y León Spanish Cooperative Research Network in Cellular Therapy Center for Applied Biomedical Research Clinic University of Navarra

Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.

关键词： Mesenchymal stromal cells Multiple myelo-ma Osteolytic lesions Myeloma bone disease Bone-directed therapy Bone-anabolic drugs

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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

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King's College criteria and the Clichy-Villejuif criteria require adjustments for assessing acute liver failure due to yellow fever

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World Journal of Transplantation 2025年第1期15卷 124-134页

作者： Bruno da Silva Athanasio antonio Marcio de Faria Andrade Vivian Vasconcelos Costa Juliano Felix Castro Silverio Leonardo Macedo garcia Mauro Martins Teixeira Daniele da Gloria Souza Paula Vieira Teixeira Vidigal Cristiano Xavier Lima Department of Surgery Federal University of Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil Liver Transplantation Unit Felicio Rocho HospitalBelo Horizonte 30110-934Minas GeraisBrazil Department of Morphology Federal University of Minas GeraisBelo Horizonte 31270-901Minas GeraisBrazil Department of Biochemistry and Immunology Federal University of Minas GeraisBelo Horizonte 31270-901Minas GeraisBrazil Department of Pathology Federal University of Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver *** transplantation(LT)is the most impactful *** fever(YF)is an infectious disease that primarily affects the liver and has a high mortality ***,LT can be a viable option for treating rare cases with extensive liver ***,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by *** To present necessary adjustments to established scoring systems for ALF secondary to *** This was an observational,retrospective,single-center *** consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in *** hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver *** is considered a viable measure for patients with signs of end-stage liver *** Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital *** patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient *** To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Vill

关键词： Yellow fever Acute liver failure Liver transplantation King's College criteria Clichy-Villejuif criteria

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Recent Advances to Understand Morphology Stability of Organic Photovoltaics

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Nano-Micro Letters 2017年第1期9卷 39-54页

作者： antonio Guerrero Germà garcia-Belmonte Institute of Advanced Materials(INAM) Universitat Jaume I12006 Castello´Spain

Organic photovoltaic devices are on the verge of commercialization with power conversion efficiencies exceeding 10 % in laboratory cells and above 8.5 % in modules. However, one of the main limitations hindering their mass scale production is the debatable inferior stability of organic photovoltaic devices in comparison to other *** donor/acceptor morphology of the active layer is required to provide carrier separation and transport to the electrodes. Unfortunately, the beneficial morphology for device performance is usually a kinetically frozen state which has not reached thermodynamic equilibrium. During the last 5 years, special efforts have been dedicated to isolate the effects related to morphology changes taking place within the active layer and compare to those affecting the interfaces with the external electrodes. The current review discusses some of the factors affecting the donor/acceptor morphology evolution as one of the major intrinsic degradation pathways. Special attention is paid to factors in the nano- and microscale *** example, phase segregation of the polymer and fullerene domains due to Ostwald ripening is a major factor in the microscale domain and is affected by the presence of additives, glass transition temperature of the polymers or use of crosslinkers in the active layer. Alternatively, the role of vertical segregation profile toward the external electrodes is key for device operation, being a clear case of nanoscale morphology evolution. For example, donor and acceptor molecules actually present at the external interfaces will determine the leakage current of the device, energy-level alignment, and interfacial recombination processes. Different techniques have been developed over the last few years to understand its relationship with the device efficiency. Of special interest are those techniques which enable in situ analysis being nondestructive as they can be used to study accelerated degradation experiments and

关键词： Organic photovoltaics Intrinsic degradation Morphology Thermal degradation Interface

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Influence of metal support in-plane symmetry on the corrugation of hexagonal boron nitride and graphene monolayers

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Nano Research 2018年第9期11卷 4643-4653页

作者： antonio d. Martinez-Galera Jose M. gomez-Rodriguez Departamento de Fisica de la Matefia Condensada Universidad Autonoma de Madrid Madrid E-28049 Spain Condensed Matter Physics Center (IFIMAC) UniversidadAutdnoma de Madrid Madrid E-28049 Spain Instituto Nicolds Cabrera Universidad Autonoma de Madrid Madrid E-28049 Spain

Predicting the properties of two-dimensional （2D） materials as graphene and hexagonal boron nitride （h-BN） monolayers after their growth on any given substrate is a major challenge. While the influence of the electron configuration of the atoms of the underlying surface is well-understood, the effect of substrate geometry still remains unclear. The structural properties of h-BN monolayers grown on a rectangularly packed Rh（110） surface were characterized in situ by ultrahigh vacuum scanning tunneling microscopy and were compared to those that this material exhibits when grown on substrates showing different crystallographic orientations. Although the h-BN monolayer grown on Rh（110） was dominated by a unique quasiunidimensional moir6 pattern, suggesting considerable interface interaction, the moir6 corrugation was unexpectedly smaller than those reported for strongly interacting interfaces with hexagonal-terminated substrates, owing to differences in the possible binding landscapes at interfaces with differently oriented substrates. Moreover, a rule was derived for predicting how interface corrugation and the existence and extent of subregions within moir6 supercells containing favorable sites for orbital mixing between h-BN monolayers and their supports depend on substrate symmetry. These general symmetry considerations can be applied to numerous 2D materials, including graphene, thereby enabling the prediction of how substrate choice determines the properties of these materials. Furthermore, they could also provide new routes for tuning 2D material properties and for developing nanotemplates showing different geometries for Krowing adsorbate superlattices.

关键词： hexagonal boron nitride graphene two-dimensional materials scanning tunneling microscopy moire superstructures nanotemplates

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A SHORT NOTE ABOUT EXPOSED POINTS IN REAL BANACH SPACES

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Acta Mathematica Scientia 2008年第4期28卷 797-800页

作者： antonio Aizpuru Francisco J garcia-Pacheco Departamento de Matemá ticas Universidad de Cá diz Department of Mathematical Sciences Kent State University

We express the set of exposed points in terms of rotund points and non-smooth *** long as we have Banach spaces each time＂bigger＂,we consider sets of non-smooth points each time＂smaller＂.

关键词： Exposed point exposed face rotund point smooth point

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Guest Editorial: State Estimation for Future Cyber-physical Power and Energy Systems:Challenges and Solutions

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Journal of Modern Power Systems and Clean Energy 2020年第4期8卷 595-596页

作者： antonio gomez-Exposito Lamine Mili Wenchuan Wu Universidad de Sevilla Virginia Tech Tsinghua University

LARGE-SCALE renewable power plants and distributed generators are integrated in the electric power systems on the generation side,meanwhile new demand-response technologies are being deployed on the demand side,such a... 详细信息

关键词： power Power energy

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Optimal heat release shaping in a reactivity controlled compression ignition （RCCI） engine

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Control Theory and Technology 2017年第2期15卷 117-128页

作者： Carlos GUARDIOLA Benjamin PLA antonio garcia Vicente BORONAT CMT-Motores Termicos Universitat Politecnica de Valencia Valencia Spain

The present paper addresses the optimal heat release （HR） law in a single cylinder engine operated under reactivity controlled compression ignition （RCCl） combustion mode to minimise the indicated specific fuel consumption （ISFC） subject to different constraints including pressure related limits （maximum cylinder pressure and maximum cylinder pressure gradient）. With this aim, a 0-dimensional （OD） engine combustion model has been identified with experimental data. Then, the optimal control problem of minimising the ISFC of the engine at different operating conditions of the engine operating map has been stated and analytically solved. To evaluate the method viability a data-driven model is developed to obtain the control actions （gasoline fraction） leading to the calculated optimal HR, more precisely to the optimal ratio between premixed and diffusive combustion. The experimental results obtained with such controls and the differences with the optimal HR are finally explained and discussed.

关键词： Diesel engine RCCI combustion analysis optimal control

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Endoscopic techniques for the diagnosis of pancreatic cystic lesions

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World Journal of Gastroenterology 2025年第1期31卷 1-7页

作者： Sahib Singh Saurabh Chandan Rakesh Vinayek Jahnvi Dhar Jayanta Samanta Gabriele Capurso Ivo Boskoski Cristiano Spada Jorge D Machicado Stefano Francesco Crinò antonio Facciorusso Department of Internal Medicine Sinai HospitalBaltimoreMD 21215United States Division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States Department of Gastroenterology Sinai Hospital of BaltimoreBaltimoreMD 21215United States Department of Gastroenterology Postgraduate Institute of Medical Education and ResearchChandigarh 160012India Division of Pancreato-Biliary Endoscopy and Endosonography Pancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilano 20132Italy Digestive Endoscopy Unit Fondazione Policlinico Universitario Agostino Gemelli IRCSSUniversitàCattolica del Sacro Cuore di RomaCenter for Endoscopic Research Therapeutics and TrainingRoma 00168Italy Department of Gastroenterology and Endoscopy Catholic UniversityRoma 00168Italy Department of Gastroenterology University of Michigan HealthAnn ArborMI 48107United States Department of Endoscopy University of VeronaVerona 37121VenetoItaly Gastroenterology Unit Department of Medical and Surgical SciencesUniversity of FoggiaFoggia 71122Italy

Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other *** accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced *** studies have reported varying diagnostic and adverse event rates with these *** addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different *** this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.

关键词： Endoscopic ultrasound Fine needle aspiration Needle confocal laser endomicroscopy Through-the-needle biopsy Contrast-enhanced endoscopic ultrasound

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Local Phase Portraits through the Newton Diagram of a Vector Field

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Acta Mathematica Sinica,English Series 2015年第6期31卷 1015-1034页

作者： antonio ALGABA Isabel CHECA Cristóbal garcia Manuel REYES Department of Mathematics Faculty of Experimental Sciences

The Newton diagram and, in particular, the lowest-degree quasi-homogeneous terms of an analytic planar vector field allow us to determine the existence of characteristic orbits and separatrices of an isolated singular point. We give an easy algorithm for obtaining the local phase portrait near the origin of a bi-dimensional differential system and we provide several examples.

关键词： Monodromy separatrices phase portraits quasi-homogeneous vector field

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