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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana m.lópez-Estévez Y.Zhang maría medel Iker Arriaga lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia maría J.Vicent Defang Ouyang Dolores Torres maría José Alonso Center for Research in molecular medicine and Chronic Diseases(CimUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key laboratory of Quality Research in Chinese medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain AlBA Synchrotron light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEm),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

On an isotropic porous solid cylinder:the analytical solution and sensitivity analysis of the pressure

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Applied mathematics and mechanics(English Edition) 2024年第9期45卷 1499-1522页

作者： H.ASGHARI l.mIllER R.PENTA J.mERODIO Departamento de matematica Aplicada a las TIC ETS de Ingenieria de Sistemas InformaticosUniversidad Politecnica de MadridMadrid 28031Spain School of mathematics and Statistics University of GlasgowGlasgow G128QQU.K.

Within this work,we perform a sensitivity analysis to determine the influence of the material input parameters on the pressure in an isotropic porous solid *** provide a step-by-step guide to obtain the analytical solution for a porous isotropic elastic cylinder in terms of the pressure,stresses,and elastic *** obtain the solution by performing a laplace transform on the governing equations,which are those of Biot's poroelasticity in cylindrical polar *** enforce radial boundary conditions and obtain the solution in the laplace transformed domain before reverting back to the time *** sensitivity analysis is then carried out,considering only the derived pressure *** analysis finds that the time t,Biot's modulus m,and Poisson's ratio ν have the highest influence on the pressure whereas the initial value of pressure P_(0) plays a very little role.

关键词： sensitivity analysis laplace transform cylindrical polar coordinate Biot's modulus cylinder

Oligodendroctyes:the forgotten players of diabetes pathophysiology

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Neural Regeneration Research 2024年第11期19卷 2349-2350页

作者： Juan Antonio lópez-Villodres Beatriz García-Díaz Departamento Fisiología Humana Histología HumanaAnatomía Patológica y Educación Física y DeportivaFacultad de MedicinaUniversidad de MálagaMálagaSpain UGC Neurociencia.Instituto de Investigación Biomédica de málaga y Plataforma en Nanomedicina(IBImA Plataforma Bionand) MálagaSpain

Oligodendrocytes(Ols),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual ***,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action *** and not less important,Ols provide trophic support to neurons and ***,Ol metabolism is important for Ol well-being and the proper accomplishment of their functions,and Ol metabolism energetics directly affect the energy metabolism of neighboring neurons.

关键词： metabolism nerves myelin

living in a Condominium Regime:Neighborhood Conflicts in low-Income Housing,Tijuana,Baja California-A Secondary Publication

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Journal of World Architecture 2024年第2期8卷 96-107页

作者： m.Zárate lópez A.Almejo Ornelas m.Sahagún Valenzuela Autonomous University of Baja California Mexico

This paper analyzes neighborhood conflicts arising from the condominium property regime,under which social housing promoted by mexican government institutions and private developers is *** regime has facilitated access to housing for the salaried population,but it is far from contributing to the attainment of the right to *** research takes as case studies housing complexes located in the city of Tijuana,Baja California,*** analysis included a mixed ***,similar case studies were analyzed;secondly,a review of the Condominium Property Regime law was carried out in order to understand its *** view of the pandemic situation,a virtual survey was applied to the inhabitants of these areas,as well as interviews with presidents of neighborhood committees of these *** the above,it was found that this form of ownership generates conflicts,reflected in the dissatisfaction of the inhabitants with their housing,disagreements and controversies in their organization and *** inhabitants have to collectively solve the problems they face,related to the maintenance and use of common areas,insecurity,and cleanliness,among *** addition,there is a lack of support from local *** this,it is concluded that although the inhabitants have a space that solves their housing problem,it does not manage to be a space that adequately guarantees their right to housing.

关键词： Neighborhood conflicts Right to housing Condominium property Social interest Affordable housing

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany m.Zúñiga Forrest l.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA laboratory medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

Prompt neutron emission in ^(250)No spontaneous fission associated with ground and isomeric state decays

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Chinese Physics C 2024年第6期48卷 112-117页

作者： R.S.mukhin A.V.Isaev A.V.Andreev m.l.Chelnokov V.I.Chepigin H.m.Devaraja I.N.Izosimov A.A.Kuznetsova O.N.malyshev A.G.Popeko Yu.A.Popov A.Rahmatinejad B.Sailaubekov T.m.Shneidman E.A.Sokol A.I.Svirikhin m.S.Tezekbayeva m.A.Bychkov A.V.Yeremin O.Dorvaux B.Gall K.Kessaci K.Hauschild A.lopez-martens Joint Institute for Nuclear Research Dubna141980Russia Dubna State University Dubna141982Russia Institute of Nuclear Physics Almaty050032Kazakhstan l.N.Gumilyov Eurasian National University Astana010008Kazakhstan Kazan Federal University Kazan420008Russia Universitéde Strasbourg CNRSStrasbourg67000France IJClab IN2P3-CNRSUniversitéParis-SaclayOrsay91400France

The complete-fusion reaction^(204)Pb(^(48)Ca,2n)^(250)No was used to study two activities of^(250)No with distinct half-lives.A total of 1357 events were observed in the SFiNx neutron detection *** average number of neutrons emitted per spontaneous fission of^(250)No was determined to be(4.1±0.1).The unusually symmetrical shape of the prompt neutron multiplicity distribution was restored and presented for the first *** tests were performed to compare the prompt neutron multiplicity distributions associated with the ground state and K-isomer state decays.

关键词： spontaneous fission prompt neutrons actinide

Development of an ultrathin liquid sheet target for laser ion acceleration at high repetition rates in the kilohertz range

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High Power laser Science and Engineering 2024年第3期 139-150页

作者： m.Füle A.P.Kovács T.Gilinger m.Karnok P.Gaál S.Figul G.marowsky K.Osvay National laser-Initiated Transmutation laboratory University of Szeged Department of Experimental Physics University of Szeged ElI AlPS ELI-HU Non-Profit Ltd. Department of Optics and Quantum Electronics University of Szeged Advanced microfluidic Systems GmbH

A colliding microjet liquid sheet target system was developed and tested for pairs of round nozzles of 10, 11 and 18 μm in diameter. The sheet's position stability was found to be better than a few micrometers. Upon interaction with 50 mJ laser pulses, the 18 μm jet has a resonance amplitude of 16 μm at a repetition rate of 33 Hz, while towards 100 Hz it converges to 10 μm for all nozzles. A white-light interferometric system was developed to measure the liquid sheet thickness in the target chamber both in air and in vacuum, with a measurement range of 182 nm±1 μm and an accuracy of±3%. The overall shape and 3D shape of the sheet follow the Hasson±Peck model in air. In vacuum versus air, the sheet gradually loses 10% of its thickness, so the thinnest sheet achieved was below 200 nm at a vacuum level of 10±4mbar,and remained stable for several hours of operation.

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola mavillard Javier Perez-Florido Francisco m.Ortuño Amador Valladares miren l.Álvarez-Villegas Gema Roldán Rosario Carmona manuel Soriano Santiago Susarte Pilar Fuentes Daniel lópez-lópez Ana maría Nuñez-Negrillo Alejandra Carvajal Yolanda morgado Daniel Arteaga Rosa Ufano Pablo mir Juan F.Gamella Joaquín Dopazo Carmen Paradas macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

Increasing the maximum Capacity Path in a Network and Its Application for Improving the Connection Between Two Routers

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Tsinghua Science and Technology 2024年第3期29卷 753-765页

作者： Adrian m.Deaconu Javad Tayyebi Department of mathematics and Computer Science Transilvania University of BrasovBrasov 500036Romania Department of Industrial Engineering Birjand University of TechnologyBirjand 000097Iran

Abstract:This paper addresses the problem of improving the optimal value of the maximum Capacity Path(mCP)through expansion in a flexible network,and minimizing the involved *** only condition applied to the cost functions is to be non-decreasing *** is a non-restrictive condition,reflecting the reality in practice,and is considered for the first time in the ***,the total cost of expansion is a combination of max-type cost(e.g.,for supervision)and sum-type cost(*** building infrastructures,price of materials,price of labor,etc.).For this purpose,two types of strategies are combined:(l)increasing the capacity of the existing arcs,and(l)adding potential new *** different problems are introduced and *** the problems have immediate applications in Internet routing *** first one is to extend the network,so that the capacity of an mcP in the modified network becomes equal to a prescribed value,therefore the cost of modifications is minimized.A strongly polynomial-time algorithm is deduced to solve this *** second problem is a network expansion under a budget constraint,so that the capacity of an mcP is maximized.A weakly polynomial-time algorithm is presented to deal with *** the special case when all the costs are linear,a meggido's parametric search technique is used to develop an algorithm for solving the problem in strongly polynomial *** new approach has a time complexity of O(n^(4)),which is better than the time complexity of O(n4 log(n)of the previously known method from literature.

关键词： maximum Capacity Path(mCP) network expansion Internet routing polynomial-time algorithms