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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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Drosophila X virus-like particles as delivery carriers for improved oral insecticidal efficacy of scorpion Androctonus australis peptide against the invasive fruit fly,Drosophila suzukii

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Insect Science 2024年第3期31卷 847-858页

作者： Qi Xue luc Swevers Clauvis Nji Tizi Taning Faculty of Bioscience Engineering Department of Plants and CropsGhent UniversityGhentBelgium Insect Molecular Genetics and Biotechnology Institute of Biosciences and ApplicationsNational Centre for Scientific Research"Demokritos"AthensGreece

Insect-specific neurotoxic peptides derived from the venoms of scorpions and spiders can cause acute paralysis and death when injected into insects,offering a promising insecticidal component for insect pest ***,effective delivery systems are required to help neurotoxic peptides pass through the gut barrier into the hemolymph,where they can ***,we investigated the potential of a novel nanocarrier,Drosophila X virus-like particle(DXV-VLP),for delivering a neurotoxin from the scorpion Androctonus australis Hector(AaIT)against the invasive pest fruit fly,Drosophila *** results show that the fusion proteins of DXV polyproteins with AalT peptide at their Ctermini could be sufficiently produced in Lepidoptera Hi5 cells in a soluble form using the recombinant baculovirus expression system,and could self-assemble into VLPs with similar particle morphology and size to authentic DXV *** addition,the AalT peptides displayed on DXV-VLPs retained their toxicity,as demonstrated in injection bioassays that resulted in severe mortality(72%)in adults after 72 *** fed to adults,mild mortality was observed in the group treated with DXV-AalT(38%),while no mortality occurred in the group treated with AaIT peptide,thus indicating the significant role of DXV-VLPs in delivering AalT ***,this proof-of-concept study demonstrates for the first time that VLPs can be exploited to enhance oral delivery of insect-specific neurotoxic peptides in the context of pest ***,it provides insights for further improvements and potentially the development of neurotoxin-based bioinsecticides and/or transgenic crops for insect pest control.

关键词： AalT Drosophila suzuki nanocarrier neurotoxic peptides pest control virus-like particle(VLP)

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tRNA^(Glu)-derived fragments from embryonic extracellular vesicles modulate bovine embryo hatching

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1559-1566页

作者： Yuan Fan Krishna Chaitanya Pavani Katrien Smits Ann Van Soom luc Peelman Department of Veterinary and Biosciences Faculty of Veterinary MedicineGhent UniversityHeidestraat 199820 MerelbekeBelgium Department of Internal Medicine Reproduction and Population MedicineFaculty of Veterinary MedicineGhent UniversitySalisburylaan 1339820 MerelbekeBelgium Department for Reproductive Medicine Ghent University HospitalCorneel Heymanslaan 109000 GhentBelgium

Transfer RNA-derived small RNAs(tsRNAs)have been shown to be involved in early embryo development and repression of endogenous retroelements in embryos and stem ***,it is unknown whether tsRNAs also regulate embryo *** this study,we mined the sequencing data of a previous experiment in which we demonstrated that the microRNA(miRNA)cargo of preimplantation embryonic extracellular vesicles(EVs)influences embryo *** thus profiled the tsRNA cargo of EVs secreted by blastocysts and *** majority of tsRNAs was identified as tRNA halves originating from the 5'ends of *** the 148 differentially expressed tsRNAs,the 19 nt tRNA fragment(tRF)tDR-14:32-Glu-CTC-1 was found to be significantly up-regulated in EVs derived from ***-qPCR assays confirmed its significant up-regulation in non-blastocyst embryos and their conditioned medium compared to the blastocyst group(P<0.05).Inhibition of tDR-14:32-Glu-CTC-1 by supplementing antagomirs to the conditioned medium improved embryo hatching(P<0.05).Transcriptomic analysis of embryos treated with tDR-14:32-Glu-CTC-1 antagomirs further showed differential expression of genes that are associated with embryo hatching and *** summary,tDR-14:32-Glu-CTC-1 is up-regulated in non-blastocyst embryos and their secretions,and inhibition of tDR-14:32-Glu-CTC-1 promotes embryo hatching,while influencing embryo implantation-related genes and *** results indicate that embryonic EVs containing specific tRFs may regulate preimplantation embryo development.

关键词： Embryo Extracellular vesicles Hatching tRNA fragments ts RNAs

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Vision Transformers with Hierarchical Attention

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Machine Intelligence Research 2024年第4期21卷 670-683页

作者： Yun Liu Yu-Huan Wu Guolei Sun Le Zhang Ajad Chhatkuli luc Van Gool Institute for Infocomm Research(I2R) A*STARSingapore 138632Singapore Institute of High Performance Computing(IHPC) A*STARSingapore 138632Singapore Computer Vision Lab ETH ZürichZürich 8092Switzerland School of Information and Communication Engineering University of Electronic Science and Technology of China(UESTC)Chengdu 611731China

This paper tackles the high computational/space complexity associated with multi-head self-attention(MHSA)in vanilla vision *** this end,we propose hierarchical MHSA(H-MHSA),a novel approach that computes self-attention in a hierarchical ***,we first divide the input image into patches as commonly done,and each patch is viewed as a ***,the proposed H-MHSA learns token relationships within local patches,serving as local relationship ***,the small patches are merged into larger ones,and H-MHSA models the global dependencies for the small number of the merged *** last,the local and global attentive features are aggregated to obtain features with powerful representation *** we only calculate attention for a limited number of tokens at each step,the computational load is reduced ***,H-MHSA can efficiently model global relationships among tokens without sacrificing fine-grained *** the H-MHSA module incorporated,we build a family of hierarchical-attention-based transformer networks,namely *** demonstrate the superiority of HAT-Net in scene understanding,we conduct extensive experiments on fundamental vision tasks,including image classification,semantic segmentation,object detection and instance ***,HAT-Net provides a new perspective for vision *** and pretrained models are available at https://***/yun-liu/HAT-Net.

关键词： Vision transformer hierarchical attention global attention local attention scene understanding.

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Rethinking Global Context in Crowd Counting

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Machine Intelligence Research 2024年第4期21卷 640-651页

作者： Guolei Sun Yun Liu Thomas Probst Danda Pani Paudel Nikola Popovic luc Van Gool Computer Vision Lab ETH ZürichZürich 8092Switzerland Institute for Infocomm Research A*STARSingapore 138632Singapore Magic Leap Zürich 8050Switzerland

This paper investigates the role of global context for crowd ***,a pure transformer is used to extract features with global information from overlapping image *** by classification,we add a context token to the input sequence,to facilitate information exchange with tokens corresponding to image patches throughout transformer *** to the fact that transformers do not explicitly model the tried-and-true channel-wise interactions,we propose a token-attention module(TAM)to recalibrate encoded features through channel-wise attention informed by the context *** that,it is adopted to predict the total person count of the image through regression-token module(RTM).Extensive experiments on various datasets,including ShanghaiTech,UCFQNRF,JHU-CROWD++and NWPU,demonstrate that the proposed context extraction techniques can significantly improve the performanceover the baselines.

关键词： Crowd counting vision transformer global context attention density map.

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Editorial for Special Issue on Multi-modal Representation Learning

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Machine Intelligence Research 2024年第4期21卷 615-616页

作者： Deng-Ping Fan Nick Barnes Ming-Ming Cheng luc Van Gool Nankai University China&ETH ZürichSwitzerland Australian National University Australia Nankai University China ETH Zürich Switzerland

The past decade has witnessed the impressive and steady development of single-modal AI technologies in several fields,thanks to the emergence of deep *** studied,however,is multi-modal AI-commonly considered the next generation of AI-which utilizes complementary context concealed in different-modality inputs to improve *** naturally learn to form a global concept from multiple modalities(i.e.,sight,hearing,touch,smell,and taste),even when some are incomplete or ***,in addition to the two popular modalities(vision and language),other types of data such as depth,infrared information,and events are also important for multi-modal learning in real-world scenes.

关键词： modal utilize incomplete

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The shear strength of the interface between artificial rock and printed concrete at super-early ages

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Frontiers of Structural and Civil Engineering 2024年第1期18卷 51-65页

作者： Yong Yuan Xiaoyun Wang Jiao-Long Zhang Yaxin Tao Kim Van Tittelboom luc Taerwe Geert De Schutter College of Civil Engineering Tongji UniversityShanghai 200092China State Key Laboratory of Disaster Reduction in Civil Engineering Tongji UniversityShanghai 200092China Belgium-China Joint Laboratory for Industrialized Construction Tongji UniversityShanghai 200092China Magnel-Vandepitte Laboratory for Structural Engineering and Building Materials Ghent UniversityGhent 9052Belgium

3D concrete printing has the potential to replace shotcrete for construction of linings of tunnels in hard *** shear strength of the interface between rock and printed concrete is vital,especially at super-early ***,traditional methods for testing the shear strength of the interface,e.g.,the direct shear test,are time-consuming and result in a high variability for fast-hardening printed *** this paper,a new fast bond shear test is *** test can be completed in 1 min,with another 2 min for preparing the next *** influence of the matrix composition,the age of the printed matrices,and the interface roughness of the artificial rock substrate on the shear strength of the interface was experimentally *** tests were conducted at the age of the matrices at the 1st,the 4th,the 8th,the 16th,the 32nd,and the 64th min after its final setting.A dimensionless formula was established to calculate the shear strength,accounting for the age of the printed matrices,the interface roughness,and the shear failure *** was validated by comparing the calculated results and the experimental results of one group of samples.

关键词： rock tunnel printed concrete interface fast bond shear test shear strength

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Elevated fluid and glycosaminoglycan content in the Achilles tendon contribute to higher intratendinous pressures:Implications for Achilles tendinopathy

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Journal of Sport and Health Science 2024年第6期13卷 863-871页

作者： Lauren Pringels Gert-Jan Van Valckenborgh Patrick Segers Amelie Chevalier Hedwig Stepman Evi Wezenbeek Arne Burssens luc Vanden Bossche Department of Physical and Rehabilitation Medicine Ghent University HospitalGhent 9000Belgium Department of Rehabilitation Sciences and Physiotherapy Ghent UniversityGhent 9000Belgium Department of Electronics and Information Systems Ghent UniversityGhent 9000Belgium Department of Electromechanics University of AntwerpAntwerp 2020Belgium Department of Laboratory Medicine Ghent University HospitalGhent 9000Belgium Department of Orthopedic Surgery Ghent University HospitalGhent 9000Belgium

Background:Tendinopathy alters the compositional properties of the Achilles tendon by increasing fluid and glycosaminoglycan *** has been speculated that these changes may affect intratendinous pressure,but the extent of this relationship remains ***,we aimed to investigate the impact of elevated fluid and glycosaminoglycan content on Achilles tendon intratendinous pressure and to determine whether hyaluronidase(HYAL) therapy can intervene in this potential ***:Twenty paired fresh-frozen cadaveric Achilles tendons were mounted in a tensile-testing machine and loaded up to 5% *** resting(at 0% strain) and dynamic pressure(at 5% strain) were assessed using the microcapillary infusion ***,intratendinous pressure was measured under native conditions before and after infusion of 2 mL physiological ***,80 mg of glycosaminoglycans were administered bilaterally to the paired *** right tendons were additionally treated with 1500 units of ***,both groups were retested,and the glycosaminoglycan content was ***:It was found that both elevated fluid and glycosaminoglycan content resulted in higher intratendinous resting and dynamic pressures(p <0.001).HYAL treatment induced a 2.3-fold reduction in glycosaminoglycan content(p=0.002) and restored intratendinous ***:The results of this study demonstrated that elevated fluid and glycosaminoglycan content in Achilles tendinopathy contribute to increased intratendinous re sting and dynamic pressures,which can be explained by the associated increased volume and reduced permeability of the tendon matrix,*** degrades glycosaminoglycans sufficiently to lower intratendinous pressures and may,therefore,serve as a promising treatment.

关键词： Achilles tendon Achilles tendinopathy Intratendinous pressure Glycosaminoglycans Tendon fluid

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It’s not all in your feet: Improving penalty kick performance with humanavatar interaction and machine learning

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The Innovation 2024年第2期5卷 115-121页

作者： Jean-luc Bloechle Julien Audiffren Thibaut Le Naour Andrea Alli Dylan Simoni Gabriel Wüthrich Jean-Pierre Bresciani Control and Perception Laboratory University of FribourgBd Perolles 901700 FribourgSwitzerland Motion-up Le PrismePlace Albert Einstein56000 VannesFrance FC Basel 1893 Birsstrasse 320A4002 BaselSwitzerland

Penalty kicks are increasingly decisive in major international football ***,over 30%of shootout kicks are *** outcome of the kick often relies on the ability of the penalty taker to exploit anticipatory movements of the goalkeeper to redirect the kick toward the open side of the ***,this ability is difficult to train using classical *** used an augmented reality simulator displaying an holographic goalkeeper to test and train penalty kick performance with 13 young elite *** learning algorithms were used to optimize the learning rate by maintaining an optimal level of training *** training sessions of 20 kicks reduced the redirection threshold by 120 ms,which constituted a 28%reduction with respect to the baseline ***,redirection threshold reduction was observed for all trained players,and all things being equal,it corresponded to an estimated 35%improvement of the success rate.

关键词： kick penalty learning

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Phage lytic proteins: a natural approach to agro-food safety

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Food Science and Human Wellness 2024年

作者： Seila Agún lucía Fernández Ana Rodríguez Pilar García Instituto de Productos Lácteos de Asturias (IPLA-CSIC). DairySafe Group.Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)

Sustainability is a leading trend in the context of food production. Additionally， consumers increasingly demand safer and less-processed products. Among the different technologies used to maintain the quality and extend the shelf-life of fresh and minimally-processed food， natural antimicrobial agents offer a promising strategy to replace conventional compounds. In this regard， phage lytic proteins or lysins， such as endolysins and virion-associated peptidoglycan hydrolases (VAPGHs)， have been proposed as a viable option for the avoidance and elimination of undesirable bacteria within the food production chain. Even when applied exogenously， these proteins can degrade the bacterial cell wall maintaining their lytic activity. This feature， alongside their modular structure， which can be exploited for bioengineering， provides significant biotechnological potential. However， despite the promising properties of lysins， the main obstacle for their commercialization is the limited legal information regulating their use. This challenge underscores the need to navigate complex regulatory pathways. The primary objective of this review is to address this crucial gap and summarize the many prospective applications of endolysins during the different stages of food production. By doing so， we aim to provide clarity and insight into the regulatory challenges that must be overcome for the successful utilization of lysins.

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