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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

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The Role of PIN Auxin Efflux Carriers in Polar Auxin Transport and Accumulation and Their Effect on Shaping Maize Development

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Molecular Plant 2012年第4期5卷 787-798页

作者： cristian Forestan Serena Varotto Department of Environmental Agronomy and Crop Science--University of Padova Viale dell'Universita 16 35020 Legnaro (PD) Italy

In plants, proper seed development and the continuing post-embryonic organogenesis both require that dif- ferent cell types are correctly differentiated in response to internal and external stimuli. Among internal stimuli, plant hormones and particularly auxin and its polar transport （PAT） have been shown to regulate a multitude of plant phys- iological processes during vegetative and reproductive development. Although our current auxin knowledge is almost based on the results from researches on the eudicot Arabidopsis thaliana, during the last few years, many studies tried to transfer this knowledge from model to crop species, maize in particular. Applications of auxin transport inhibitors, mutant characterization, and molecular and cell biology approaches, facilitated by the sequencing of the maize genome, allowed the identification of genes involved in auxin metabolism, signaling, and particularly in polar auxin transport. PIN auxin efflux carriers have been shown to play an essential role in regulating PAT during both seed and post-embryonic development in maize. In this review, we provide a summary of the recent findings on PIN-mediated polar auxin transport during maize development. Similarities and differences between maize and Arabidopsis are analyzed and discussed, also considering that their different plant architecture depends on the differentiation of structures whose development is con- trolled by auxins.

关键词： auxin PIN-formed auxin efflux carrier PAT Polar Auxin Transport kernel development meristem organ-ogenesis Zea mays.

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Degenerate Nonlinear Elliptic Equations Lacking in Compactness

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Chinese Annals of Mathematics,Series B 2016年第1期37卷 53-72页

作者： Maria MALIN cristian UDREA Department of Mathematics University of Craiova

In this paper, the authors prove the existence of solutions for degenerate elliptic equations of the form-div(a(x)▽_p u(x)) = g(λ, x, |u|^(p-2)u) in R^N, where ▽_pu =|▽u|^(p-2)▽u and a(x) is a degenerate nonnegative weight. The authors also investigate a related nonlinear eigenvalue problem obtaining an existence result which contains information about the location and multiplicity of eigensolutions. The proofs of the main results are obtained by using the critical point theory in Sobolev weighted spaces combined with a Caffarelli-Kohn-Nirenberg-type inequality and by using a specific minimax method, but without making use of the Palais-Smale condition.

关键词： Degenerate equations p-Laplacian Sobolev weighted spaces Mountain-pass theorem

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Dynamic Analysis for the Global Performance of An SPM-Feeder-Cage System Under Waves and Currents

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China Ocean Engineering 2015年第3期29卷 415-430页

作者： cristian CIFUENTES M.H.KIM Ocean Engineering Program Department of Civil Engineering Texas A&M University College Station

In the present study, the dynamic response of a coupled SPM-feeder-cage system under irregular waves and shear currents is analyzed. A numerical model is developed by using the commercial software Orca Flex. Hydrodynamics coefficients of the vessel are calculated by using a 3D diffraction/radiation panel program. First- and second-order wave forces are included in the calculations. Morison equation is used to compute the drag force on line elements representing the net. Drag coefficients are determined at every time step in the simulation considering the relative normal velocity between the structural elements and the fluid flow. The dynamic response of the coupled system is analyzed for various environments and net materials. The results of the study show the effects of solidity ratio of the net and vertical positions of the cage on the overall dynamic response of the system, confirming the viability of this type of configuration for future development of offshore aquaculture in deep waters.

关键词： offshore aquaculture SPM(single point mooring) feeder vessel connecting lines operational/survival environment drag force equivalent net cage grouping net modeling line tensions solidity ratio

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A high Q terahertz metamaterial absorber using concentric elliptical ring resonators for harmful gas sensing applications

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Defence Technology（防务技术） 2023年第4期22卷 69-73页

作者： Bhargav Appasani Avireni Srinivasulu cristian Ravariu Department of Electronics Engineering Kalinga Institute of Industrial TechnologyBhubaneswarIndia Department of Electronics Engineering K R Mangalam UniversityGurgaonIndia Department of Electronic Devices Circuits and ArchitecturesPolytechnic University of BucharestBucharestRomania

A nearly perfect metamaterial absorber is proposed that can find utility in terahertz sensing *** design consists of two concentric elliptical ring resonators(ERRs)whose parameters are appropriately set to achieve dual band absorption with near perfect *** first absorption band at 3.62 THz having a Q-factor of 51.7 was caused due to the currents in the outer and inner *** second absorption peak at 3.814 THz having a Q factor of 1411.11 was a consequence of currents flowing across the gap between the two concentric ***,it is observed that the absorption bands are sensitive to the variation in refractive index of the surrounding *** sensitivity's in the absorption bands are 3 THz/RIU and 3.59 THz/RIU respectively.A sensor is proposed based on this design to detect harmful gases,which is demonstrated for detection of Methane and *** Q-factor and high sensitivity of the narrow band makes the design an excellent sensor for detecting variations in the refractive index.

关键词： Refractive index Plasma frequency Metamaterials Terahertz absorption Q-factor Gas sensing

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Redox regulation of mammalian sperm capacitation

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Asian Journal of Andrology 2015年第4期17卷 583-590页

作者： cristian O'Flaherty Urology Research Laboratory Surgery Department (Urology Division) Faculty of Medicine McGill University Montreal Quebec Canada The Research Institute McGillUniversity Health Centre Montreal Quebec Canada.

Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species （ROS） that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD （P） H for sperm capacitation. Peroxiredoxins （PRDXs） are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

关键词： dehydrogenases oxidases peroxiredoxins reactive oxygen species spermatozoa thiols thioredoxins

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Dispersed multiphase flows:advances in measuring,simulation and modeling

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Acta Mechanica Sinica 2022年第8期38卷 1-3页

作者： cristian Marchioli Lihao Zhao Department of Engineering and Architecture University of UdineUdine33100Italy Key Laboratory of Applied Mechanics Department of Engineering MechanicsTsinghua UniversityBeijing100084China

Dispersed multiphase flows are commonly encountered in a wide variety of natural and industrial applications,from sedimentation in rivers and plankton surfacing in oceanic flows to fluidized bed in chemical reactors and pneumatic conveying *** these flows,a dispersed phase(con-sisting of particles,droplets and/or bubbles)is transported by a carrier *** interaction between the phases re-sults in complex dynamics(e.g.,transport,spatial clustering,and deformation or break-up)that is rich in physics and poses a wide spectrum of theoretical,computational,and experimental *** challenges are at the very core of the research efforts made by the multiphase flow community over the past decades.

关键词： multiphase flows dispersed

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In vivo oxidative stress alters thiol redox status of peroxiredoxin 1 and 6 and impairs rat sperm quality

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Asian Journal of Andrology 2017年第1期19卷 73-79页

作者： Yannan Liu cristian O'Flaherty The Research Institute of the McGill University Health Centre Montreal QC H4A 3J1 Canada Department of Surgery (Urology Division) McGill University Montreal QC H4A 3J1 Canada Department of Obstetrics and Gynecology McGill University Montreal QC H4A 3J1 Canada Department of Pharmacology and Therapeutics McGill University Montreal QC H3G 1Y6 Canada

Oxidative stress, the imbalance between the production of reactive oxygen species （ROS） and antioxidant activity is a major culprit of male infertility. Peroxiredoxins （PRDXs） are major antioxidant enzymes of mammalian spermatozoa and are thiol oxidized and inactivated by ROS in a dose-dependent manner. Their deficiency and/or inactivation have been associated with men infertility. The aim of this study was to elucidate the impact of oxidative stress, generated by the in vivo tert-butyl hydroperoxide （tert-BHP） treatment on rat epididymal spermatozoa during their maturation process. Adult Sprague-Dawley males were treated with 300 -moles tert-BHP/kg or saline （control） per day intraperitoneal for 15 days. Lipid peroxidation （2-thibarbituric acid reactive substances assay）, total amount and thiol oxidation of PRDXs along with the total amount of superoxide dismutase （SOD）, motility and DNA oxidation （8-hydroxy-deoxyguanosine） were determined in epididymal spermatozoa. Total amount of PRDXs and catalase and thiol oxidation of PRDXs were determined in caput and cauda epididymis. While animals were not affected by treatment, their epididymal spermatozoa have decreased motility, increased levels of DNA oxidation and lipid peroxidation along with increased PRDXs （and not SOD） amounts. Moreover, sperm PRDXs were highly thiol oxidized. There was a differential regulation in the expression of PRDX1 and PRDX6 in the epididymis that suggests a segment-specific role for PRDXs. In conclusion, PRDXs are increased in epididymal spermatozoa in an attempt to fight against the oxidative stress generated by tert-BHP in the epididymis. These findings highlight the role of PRDXs in the protection of sperm function and DNA integrity during epididymal maturation.

关键词： antioxidant enzymes DNA oxidation epididymis reactive oxygen species spermatozoa thiol oxidation

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Evaluation of left atrial remodelling following percutaneous left atrial appendage closure

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Journal of Geriatric Cardiology 2017年第8期14卷 496-500页

作者： Zakaria Jalal Xavier iriart Marie-Lou Dinet Olivier Comeloup Xavier Pillois Hubert Cochet Jean-Benoit Thambo Department of Paediatric and Adult Congenital Cardiology Bordeaux University Hospital Pessac France Electrophysiology and Heart Modeling Institute IHU Lirye Fondation Bordeaux UniversitO Pessac-Bordeaux France Centre de recherche Cardio-Thoracique de Bordeaux INSERM Bordeaux France Department of Radiology Bordeaux University Hospital Pessac France

Atrial fibrillation prevalence is increasing with age, reaching up to 5% of patients older than 65 years, and is associated with 20%-30% of stroke episodes in that population.

关键词： Atrial fibrillation Left atrial appendage Left atrial remodeling Percutaneous closure

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Effect of particle shape and size on flow properties of lactose powders

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Particuology 2012年第2期10卷 203-208页

作者： Xiaowei Fu Deborah huck Lisa Makein Brian Armstrong Ulf Willen Tim Freeman Freeman Technology I Miller Court Severn Drive Tewkesbury Gloucestershire G1208DN UK Malvern Instruments Ltd Enigma Business Park Crovewood Rd. Malvern Worcestershire WRI4 IX.Z UK

The shape and size of particles are understood to affect the bulk behaviour of powders, though there are but few studies that present quantitative information on the relationship between particle shape and the flow properties of powder. This is due in part to the lack of techniques for rapidly determining both particle shape and the range of flow characteristics that describe the response of powders to the stress and shear experienced during their processing. This study presents data that quantifies the influence of particle shapeJsize of three different lactose powders on their respective flow and bulk characteristics. Two of the samples differ in size but have similar shapes; the third sample is more spherical but similar in size to one of the other two samples, The results demonstrate that in addition to particle size, particle shape significantly affect the flow characteristics of a powder over a wide range of stress conditions.

关键词： ParticleShapeSizePowder flowFlowability

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