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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

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Research 2024年第3期2023卷 35-50页

作者： June Li Danielle Karakas Feng Xue Yingyu Chen Guangheng Zhu Yeni h.Yucel Sonya A.MacParland haibo Zhang john W.Semple john Freedman Qizhen Shi heyu Ni Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Keenan Research Centre for Biomedical Science of St.Michael's hospital TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada Departments of Pediatrics Medical College of WisconsinMilwaukeeWIUSA Blood Research Institute Versiti WisconsinMilwaukeeWIUSA Departments of Ophthalmology and Vision Sciences Medicine University of TorontoTorontoONCanada Faculty of Engineering and Architectural Science Ryerson UniversityTorontoONCanada Multi-Organ Transplant Program Toronto General Hospital Research InstituteTorontoONCanada Department of Immunology University of TorontoTorontoONCanada Critical Care Medicine Department ofAnesthesiology and PainUniversity of TorontoTorontoONCanada Department of Physiology University of TorontoTorontoONCanada Department of Pharmacology University of TorontoTorontoONCanada. Division of hematology and Transfusion Medicine Lund UniversityLundSweden clinical Immunology and Transfusion Medicine Ofice of Medical ServicesRegion SkaneLundSweden Department of Medicine University of TorontoTorontoONCanada Children's Research Institute Children's WisconsinWauwatosaWIUSA Midwest Athletes Against Childhood Cancer Fund Research Center MilwaukeeWIUSA.

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. however, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell–Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

关键词： Platelet transfusion homeostasis

Optimizing oncolytic virus design:a“Swiss army knife”approach to create a systemically delivered therapeutic

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow john Cameron Bell Ottawa hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

Stable hydrogen isoscape in precipitation generated using data fusion for East China

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Science China Earth Sciences 2024年第9期67卷 2972-2988页

作者： Jiacheng ChEN Jie ChEN Xunchang john ZhANG Peiyi PENG State Key Laboratory of Water Resources Engineering and Management Wuhan UniversityWuhan 430072China hubei Key Laboratory of Water System Science for Sponge City Construction Wuhan UniversityWuhan 430072China USDA-ARS Oklahoma and Central Plains Agricultural Research Center El Reno OK 73036USA Southwest Research Institute for hydraulic and Water Transport Engineering Chongqing Jiaotong UniversityChongqing 400016China

The stable hydrogen isotope in precipitation is an effective environmental tracer for climatic and hydrologic ***,accurate and high-precision precipitation hydrogen isoscapes are currently unavailable in *** this study,a data fusion method based on Convolutional Neural Networks(CNN)is used to fuse the hydrogen isotopic composition(δ^(2)h_(p))of observations and isotope-equipped general circulation model(iGCM)simulations.A precipitation hydrogen isoscape with a temporal resolution of monthly and a spatial resolution of 50-60 km is established for East China for the 1969-2017 *** to building the isoscape,the performance of three data fusion methods(DFMs)and two bias correction methods(BCMs)is *** results indicate that the CNN fusion method performs the best with a correlation coefficient larger than 0.90 and root mean square error smaller than 10.5‰ when using observation as a *** fusion methods based on back propagation and long short-term memory neural network perform similarly,while slightly outperforming the bias correction ***,the CNN method is used to generate the hydrogen isoscape,and the temporal and spatial distribution characteristics of the hydrogen isotope in precipitation are analyzed based on this *** generated isoscape shows similar spatial and temporal distribution characteristics to *** general,the distribution pattern of δ^(2)h_(p) is consistent with the temperature effect in northern China,and consistent with the precipitation amount effect in southern *** trend of the δ^(2)h_(p) time series is consistent with that of observed precipitation and ***,the generated isoscape effectively reproduces the observations,and has the characteristics of time continuity and relative spatial regularity,which can provide valuable data support for tracking atmospheric and hydrological processes.

关键词： Precipitation Precipitation isotope General circulation model Data fusion Dataset

Nonuniform Dependence on the Initial Data for Solutions of Conservation Laws

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Communications on Applied Mathematics and Computation 2024年第1期6卷 489-500页

作者： john M.holmes Barbara Lee Keyfitz Department of Mathematics The Ohio State UniversityColumbusOH43210USA

In this paper,we study systems of conservation laws in one space *** prove that for classical solutions in Sobolev spaces h^(s),with s>3/2,the data-to-solution map is not uniformly *** results apply to all nonlinear s... 详细信息

关键词： Conservation laws Data-to-solution map Nonuniform dependence

Combining GLP-1 receptor agonists and SGLT-2 inhibitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with multiple network meta-regressions

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World Journal of Diabetes 2024年第10期15卷 2135-2146页

作者： Jing-Jing Zhu john P h Wilding Xiao-Song Gu Department of Endocrinology and Metabolic Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina Department of Cardiovascular and Metabolic Medicine University of LiverpoolLiverpool L697ZXUnited Kingdom Clinical Sciences Centre Liverpool University Hospitals NHS Foundation TrustLiverpool L97ALUnited Kingdom Department of Cardiovascular Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).however,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular *** To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in *** The systematic review was conducted according to PRISMA *** protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination *** modification of prior myocardial infarction(MI)and heart failure(hF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering *** instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(hF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for hF or cardiovascular death,irrespective of their history of T2D[5-8].however,similar car

关键词： Type 2 diabetes Glucagon-like peptide-1 receptor agonist Sodium-glucose co-transporter-2 inhibitor Combination treatment Cardiovascular outcome Systematic review Network meta-regression

Geochemistry and mineralogy of beach sediments in the northern Gulf of Mexico,Tamaulipas state,Mexico:implication for provenance

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Journal of Palaeogeography 2024年第3期13卷 375-400页

作者： Mayank Shukla Sanjeet K.Verma Mayla A.Ramos-Vázquez john S.Armstrong-Altrin Karla R.hernández-Martínez Sumit Mishra Vivek P.Malviya héctor hernández-Mendoza Posgrado de la Division de Geociencias Aplicadas Instituto Potosino de Investigacion Científica y Tecnologica(IPICYT)Camino a la Presa San José2055San Luis Potosí78216Mexico Division de Geociencias Aplicadas Instituto Potosino de Investigación Científica y Tecnologica(IPICYT)Camino a la Presa San Jose 2055San Luis Potosí78216Mexico Universidad Nacional Autonoma de México Instituto de Ciencias del Mar y LimnologíaUnidad de ProcesosOceanicos y CosterosCiudad UniversitariaCiudad de México 04510Mexico Department of Marine Sciences Bharathidasan UniversityTiruchirappalli620024Tamil NaduIndia Instituto de Geociencias Universidad Nacional Autonoma de MéxicoBoulevard Juriquilla 300176230JuriquillaQueretaroMexico Department of Applied Geology Dr.Harisingh Gour Central UniversitySagar470002Madhya PradeshIndia Instituto de Investigacion de Zonas Desérticas Universidad Autònoma de San Luis PotosíAltair 200CP 78377San LuisS.L.P.Mexico Universidad del Centro de Mexico Capitán Caldera 75CP 78250San LuisS.L.P.Mexico

Geochemical and mineralogical studies were performed in the La Pesca(LP)and Tesoro Altamira(TA)beach sediments,located in the Tamaulipas state,northern Gulf of *** main aim of this study is to infer the weathering history and provenance and to discriminate the tectonic environment of the beach *** sediments are composed of quartz with small amounts of accessory minerals such as plagioclase,calcite,orthoclase,microcline,and *** beach sediments are classified as fine-grained and very well sorted,however LP has coarse skewed and leptokurtic sediments,whereas TA has fine-skewed and very leptokurtic *** chemical index of weathering(CIW’)indicates intense weathering in the source *** quartz grain microtextures in the LP and TA are classified into mechanical,chemical,and mechanical/chemical *** features such as fractures,pits,percussion marks,abrasion fatigue,and V-shaped marks favor high-energy littoral,fluvial,subaqueous-marine,and aeolian *** chemical features indicate solution pits and crystalline overgrowth,which suggests a silica saturated marine *** mechanical/chemical features display adhering particles and elongated depressions suggest formation in a sub-aqueous nearshore marine *** and trace elements-based provenance discrimination diagrams indicate a felsic source derived from the Mesa Central(MC),Sierra Madre Oriental(SMOr)and Oaxaquia *** major and trace element concentrations imply a passive margin setting for the northern Gulf of Mexico,which is consistent with the general geology.

关键词： Beach sediments Geochemistry Mineralogy Provenance Tamaulipas Tectonic setting

The first record of a Konservat-Lagerstätten in which early post-settlement stages of fossil archaeobalanids(Cirripedia:Balanomorpha)are preserved

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Integrative Zoology 2024年第2期19卷 200-223页

作者： Tomáš KOCÍ Rok GAŠPARIC john BUCKERIDGE Martina KOCOVÁ VESELSKÁ Aleš ŠOSTER Ivancická581 PragueCzech Republic Palaeontological Department Natural History MuseumNational MuseumPragueCzech Republic Oertijdmuseum Bosscheweg 80Boxtel5293 WBThe Netherlands Institute for Palaeobiology and Evolution Novi TrgKamnikSlovenia Earth and Oceanic Systems Group RMIT UniversityMelbourneAustralia Museums Victoria CarltonVictoriaAustralia Department of Paleobiology and Paleoecology Institute of Geology of the Czech Academy of SciencesPragueCzech Republic Institute of Geology and Palaeontology Charles UniversityPragueCzech Republic Faculty of Natural Sciences and Engineering University of LjubljanaLjubljanaSlovenia

A diverse sessile barnacle fauna from a Miocene shallow-water deposit at Dolnja Stara vas in Slovenia is *** includes the first descriptions of early post settlement juveniles of Actinobalanus sloveniensis attached to mangrove *** represent three distinct growth phases,the earliest being interpreted as being less than 24 h post settlement,the others being 1 to 2 days post *** assessment of their taphonomy is *** adult balanomorphs are attached to a variety of organic substrates,including mangrove leaves and branches,fragments of the conifers?Taxodioxylon,Carapoxylon,pine cones,molluscs,and cetacean *** barnacles include ***,Amphibalanus venustus,and Perforatus perforatus—many with opercula retained within the *** retains some of the original shell *** is the second record of barnacle–plant associations from the Central Paratethys from Kamnik and *** paleoecology and paleogeography of the site are discussed.

关键词： acorn barnacles barnacle metamorphosis epibiont paleoecology taxonomy

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang howard h.W.Wong Leo C.h.Tsang Sara Chaothai Tsz Chun Kwan john K.C.Li Karl C.K.Chan Leo L.h.Luk Jenson C.h.ho Wing Yan Li Amos M.T.Lee Jennifer h.Y.Lam Sau Man Chan Wilfred h.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public health The University of Hong KongHong KongChina hKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

Optimization of Stealthwatch Network Security System for the Detection and Mitigation of Distributed Denial of Service (DDoS) Attack: Application to Smart Grid System

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Communications and Network 2024年第3期16卷 108-134页

作者： Emmanuel S. Kolawole Penrose S. Cofie john h. Fuller Cajetan M. Akujuobi Emmanuel A. Dada Justin F. Foreman Pamela h. Obiomon Electrical and Computer Engineering Department Prairie View A&M University Prairie View TX USA

The Smart Grid is an enhancement of the traditional grid system and employs new technologies and sophisticated communication techniques for electrical power transmission and distribution. The Smart Grid’s communication network shares information about status of its several integrated IEDs (Intelligent Electronic Devices). however, the IEDs connected throughout the Smart Grid, open opportunities for attackers to interfere with the communications and utilities resources or take clients’ private data. This development has introduced new cyber-security challenges for the Smart Grid and is a very concerning issue because of emerging cyber-threats and security incidents that have occurred recently all over the world. The purpose of this research is to detect and mitigate Distributed Denial of Service [DDoS] with application to the Electrical Smart Grid System by deploying an optimized Stealthwatch Secure Network analytics tool. In this paper, the DDoS attack in the Smart Grid communication networks was modeled using Stealthwatch tool. The simulated network consisted of Secure Network Analytic tools virtual machines (VMs), electrical Grid network communication topology, attackers and Target VMs. Finally, the experiments and simulations were performed, and the research results showed that Stealthwatch analytic tool is very effective in detecting and mitigating DDoS attacks in the Smart Grid System without causing any blackout or shutdown of any internal systems as compared to other tools such as GNS3, NeSSi2, NISST Framework, OMNeT++, INET Framework, ReaSE, NS2, NS3, M5 Simulator, OPNET, PLC & TIA Portal management Software which do not have the capability to do so. Also, using Stealthwatch tool to create a security baseline for Smart Grid environment, contributes to risk mitigation and sound security hygiene.

关键词： Smart Grid System Distributed Denial of Service (DDoS) Attack Intrusion Detection and Prevention Systems Detection Mitigation and Stealthwatch