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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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Glacier Changes at Svartisen,Northern Norway,during the Last 125 Years:Influence of Climate and Other Factors

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Journal of Earth Science 2010年第2期21卷 123-136页

作者： Wilfred H Theakstone school of Environment and Development University of Manchester

The two ice caps of Svartisen, at the latitude of the Arctic Circle in Norway, supply 60 glaciers, ranging in size from 〉50 to 〈1 km^2. Until the last two decades of the 19th century, the glaciers remained close to their maximum recent （Little Ice Age） size. In response to the prevailing 20th century climate, they have become smaller, but the changes have varied between glaciers. Climatic factors have not been the sole control of the variations. The response times of small, steep glaciers are shorter than those of the longer, more gently sloping outlet glaciers. Topographic factors may moderate the response of individual glaciers to climate. The 20th century mass balance of several of the larger glaciers was dominated by calving into marginal lakes. The mass balance of Engabreen, the largest outlet of the western ice cap, has been measured every year since 1970 and the cumulative balance to 2008 was a gain of 22.7 m water equivalent. Although the pattern of annual variations probably applies to the other glaciers of Svartisen, it does not indicate their actual changes （gain or loss）. Thus, the Engabreen record is of little utility in water resource planning for the whole area.

关键词： Svartisen climatic change glacier variation calving mass balance.

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The Human Ankle-Foot Complex as a Multi-Configurable Mechanism during the Stance Phase of Walking

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Journal of Bionic Engineering 2010年第3期7卷 211-218页

作者： Amaraporn Boonpratatong school of Mechanical Aerospace and Civil EngineeringUniversity of Manchester

The objective of this study is to investigate the biomechanical functions of the human ankle-toot complex during the stancephase of walking. The three-dimensional (3D) gait measurement was conducted by using a 3D infrared multi-camera system anda force plate array to record the Ground Reaction Forces (GRF) and segmental motions simultaneously. The ankle-foot complexwas modelled as a four-segment system, connected by three joints: talocrural joint, sub-talar joint and metatarsophalangeal *** subject-specific joint orientations and locations were determined using a functional joint method based on the particleswarm optimisation algorithm. The GRF moment arms and joint moments acting around the talocrural and sub-talar joints werecalculated over the entire stance phase. The estimated talocrural and sub-talar joint locations show noticeable obliquity. Thekinematic and kinetic results strongly suggest that the human ankle-foot complex works as a mechanical mechanism with twodifferent configurations in stance phase of walking. These lead to a significant decrease in the GRF moment arms therebyincreasing the effective mechanical advantages of the ankle plantarflexor muscles. This reconfigurable mechanism enhancesmuscle effectiveness during locomotion by modulating the gear ratio of the ankle plantarflexor muscles in stance. This studyalso reveals many factors may contribute to the locomotor function of the human ankle-foot complex, which include not only itsre-configurable structure, but also its obliquely arranged joints, the characteristic heel-to-toe Centre of Pressure (COP) motionand also the medially acting GRF pattern. Although the human ankle-foot structure is immensely complex, it seems that itsconfiguration and each constitutive component are well tuned to maximise locomotor efficiency and also to minimise risk ofinjury. This result would advance our understanding of the locomotor function of the ankle-foot complex, and also the intrinsicdesign of the ankle-

关键词： ankle foot talocrural joint sub-talar joint metatarsophalangeal joint ground reaction force moment arm reconfigurable mechanism

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50 years change in urban land use and ecological planning globally in the era of design with nature

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Ecosystem Health and Sustainability 2019年第1期5卷 185-198,I0001页

作者： Ian Douglas school of Environment Education and DevelopmentUniversity of ManchesterManchesterUK

Ian McHarg’s 1969 book,Design with Nature,was grounded in earlier good practice,especially the European vision of fitting cities into the regional landscape and carrying thorough surveys before planning *** book emerged in the wake of publications that worried about the ability of the earth to support expanding populations and their growing impact on the *** argued that ecological design should follow planning based on detailed site *** McHarg advised many urban authorities in the USA and other countries,especially in Africa,Asia and Europe,and his ideas had influenced some British new towns,they had little attention in the planning of Milton Keynes,England’s largest new urban settlement,where the initial geological surveys were inadequate,but a successful large tree-planting programhas created a“city in the forest.”McHarg was however closely involved in planning the Nigerian Capital city,Abuja,but his sound master plan was ill-equipped to provide for a nation undergoing post-conflict rebuilding and a local population more concerned with access to land than ecological ***,McHarg helped us to promote,protect,and preserve urban green *** teams from different disciplines now work well together,the integrated thinking advocated by McHarg remains sometimes in short supply in local practice.

关键词： Planning design urban nature garden city site investigation

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Assessment of spongy moth infestation impacts on forest productivity and carbon loss using the Sentinel-2 satellite remote sensing and eddy covariance flux data

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Ecological Processes 2024年第2期13卷 231-245页

作者： Nur Hussain Alemu Gonsamo Shusen Wang M.Altaf Arain school of Earth Environment and Society and McMaster Centre for Climate Change Mc Master University Canada Centre for Remote Sensing Natural Resources Canada

Background Deciduous forests in eastern North America experienced a widespread and intense spongy moth（Lymantria dispar） infestation in 2021. This study quantified the impact of this spongy moth infestation on carbon（C） cycle in forests across the Great Lakes region in Canada, utilizing high-resolution（10 × 10 m2） Sentinel-2 satellite remote sensing images and eddy covariance（EC） flux data. Study results showed a significant reduction in leaf area index（LAI） and gross primary productivity（GPP） values in deciduous and mixed forests in the region in *** Remote sensing derived, growing season mean LAI values of deciduous（mixed） forests were 3.66（3.18）, 2.74（2.64）, and 3.53（2.94） m2m-2in 2020, 2021 and 2022, respectively, indicating about 24（14）% reduction in LAI, as compared to pre-and post-infestation years. Similarly, growing season GPP values in deciduous（mixed） forests were 1338（1208）, 868（932）, and 1367（1175） g C m-2, respectively in 2020, 2021 and 2022, showing about 35（22）% reduction in GPP in 2021 as compared to pre-and post-infestation years. This infestation induced reduction in GPP of deciduous and mixed forests, when upscaled to whole study area（178,000 km2）, resulted in 21.1（21.4） Mt of C loss as compared to 2020（2022）, respectively. It shows the large scale of C losses caused by this infestation in Canadian Great Lakes *** The methods developed in this study offer valuable tools to assess and quantify natural disturbance impacts on the regional C balance of forest ecosystems by integrating field observations, high-resolution remote sensing data and models. Study results will also help in developing sustainable forest management practices to achieve net-zero C emission goals through nature-based climate change solutions.

关键词： Spongy moth Infestation Carbon Gross ecosystem productivity Leaf area index Temperate forest Remote sensing Sentinel-2 Eddy covariance

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Decision Support System for Evaluating Impact of Product Carbon Labeling Scheme

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Frontiers of Engineering Management 2014年第1期1卷 89-104页

作者： Dong-ling Xu Chris Foster Ying Hu Jian-bo Yang manchester business school The University of Manchester

In this paper a decision support system for systematically evaluating the impact of labeling products with their carbon footprints is developed and applied to prioritize products for carbon labeling in a large supermarket chain in the *** labels may change consumers’ behavior and encourage suppliers to implement carbon-reduction *** changes may,however,lead to unintended *** handle the challenges of uncertainties in the evaluation,the Evidential Reasoning approach and the Intelligent Decision System software for multi-criteria decision analysis are applied to support the *** system developed can be applied to assessing the impact of sustainable development policies to maximize their benefits and minimize their risks.

关键词： impact assessment multiple criteria decision analysis risk analysis carbon footprint decision support system product carbon labeling

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Composite Hierachical Linear Quantile Regression

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Acta Mathematicae Applicatae Sinica 2014年第1期30卷 49-64页

作者： Yan-liang CHEN Mao-zai TIAN Ke-ming YU Jian-xin PAN Center for Applied Statistics School of StatisticsRenmin University of China school of business Shihezi University Mathematical Sciences John Crank 209Brunel University school of Mathematics The University of Manchester school of Statistics and Mathematics Yunnan University of Finance and Economics

Multilevel （hierarchical） modeling is a generalization of linear and generalized linear modeling in which regression coefficients are modeled through a model, whose parameters are also estimated from data. Multilevel model fails to fit well typically by the use of the EM algorithm once one of level error variance （like Cauchy distribution） tends to infinity. This paper proposes a composite multilevel to combine the nested structure of multilevel data and the robustness of the composite quantile regression, which greatly improves the efficiency and precision of the estimation. The new approach, which is based on the Gauss-Seidel iteration and takes a full advantage of the composite quantile regression and multilevel models, still works well when the error variance tends to infinity, We show that even the error distribution is normal, the MSE of the estimation of composite multilevel quantile regression models nearly equals to mean regression. When the error distribution is not normal, our method still enjoys great advantages in terms of estimation efficiency.

关键词： multilevel model composite quantile regression E-CQ algorithm, fixed effects, random effects

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Rare tau decays from BABAR

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Chinese Physics C 2010年第6期34卷 907-911页

作者： G.D.Lafferty school of Physics and Astronomy The University of Manchester

The BABAR experiment has now completed data taking and with an integrated luminosity of 531 fb^-1 of e^＋e^- collision data has recorded some 480 million tau-pair events. Various studies of suppressed, rare and forbidden decays of the tau have been conducted, including searches for high-multiplicity decays, for second-class hadronic weak currents, and for lepton-flavour violation.

关键词： particle physics tau leptons rare decays

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Temporal pattern mining from user-generated content

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Digital Communications and Networks 2022年第6期8卷 1027-1039页

作者： Adnan Ali Jinlong Li Huanhuan Chen Ali Kashif Bashir school of Computer Science and Technology University of Science and Technology of ChinaHefei230026AnhuiChina Department of Computing and Mathematics Manchester Metropolitan UniversityManchesterM156BHUnited Kingdom Department of Computer Science and Mathematics Lebanese American UniversityBeirutLebanon Woxsen school of business Woxsen UniversityIndia

Faster internet, IoT, and social media have reformed the conventional web into a collaborative web resulting in enormous user-generated content. Several studies are focused on such content;however, they mainly focus on textual data, thus undermining the importance of metadata. Considering this gap, we provide a temporal pattern mining framework to model and utilize user-generated content's metadata. First, we scrap 2.1 million tweets from Twitter between Nov-2020 to Sep-2021 about 100 hashtag keywords and present these tweets into 100 User-Tweet-Hashtag (UTH) dynamic graphs. Second, we extract and identify four time-series in three timespans (Day, Hour, and Minute) from UTH dynamic graphs. Lastly, we model these four time-series with three machine learning algorithms to mine temporal patterns with the accuracy of 95.89%, 93.17%, 90.97%, and 93.73%, respectively. We demonstrate that user-generated content's metadata contains valuable information, which helps to understand the users' collective behavior and can be beneficial for business and research. Dataset and codes are publicly available;the link is given in the dataset section.

关键词： Social media analysis Collaborative computing Social data Twitter data Temporal patterns mining Dynamic graphs

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Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

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Food Science and Human Wellness 2024年第5期13卷 2917-2936页

作者： Peng Ma Jie Xiao Biyu Hou Ping He Xinyu Yang Yisa Wang Zijing Wang Tianshu Xu Xiuying Yang Xuan Zhu Shasha Xiang Song Li Guanhua Du Jian Ying Guifen Qiang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening ResearchBeijing 100050China COFCO Nutrition and Health Research Institute Beijing 102209China Department of Pharmacy The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China Faculty of Biology Medicine and Health SciencesThe University of ManchesterManchester M139PLUnited Kingdom Changchun University of Chinese Medicine Changchun 130117China school of Food Science and Biotechnology Zhejiang Gongshang UniversityHangzhou 310018China China Tea Technology(Beijing)Co. Ltd.Beijing 102209China Beijing Key Laboratory of Nutrition Health and Food SafetyBeijing 102209China

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a“disease”.Brown adipose tissue(BAT)thermogenesis and white adipose tissue(WAT)browning emerge as a potential strategy of anti-obesity by dissipating energy as ***,drugs based on adipose tissue thermogenesis have not been successfully approved *** current study,we found that black tea extract(BTE)obtained by patentauthorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity,improvement of adipose distribution,and glucose metabolism improvement in diet-induced obesity ***,anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1(UCP1),especially visceral adipose tissue(VAT)with browning ***,utilizing in silico approach of network pharmacology and molecular docking,we identified carbonic anhydrase 2(CA2)in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B(AKT)signaling pathway linked CA2 and *** gut microbiota regulation may prompt the CA2-dependent thermogenesis *** findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway,which could be developed as promising anti-obesity agent with good safety and efficacy.

关键词： Obesity Black tea Thermogenesis Browning Adipose tissue

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