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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

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

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

Adaptive strategies of high and low nucleic acid prokaryotes in response to declining resource availability and selective grazing by protozoa

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Science China Earth Sciences 2024年第6期67卷 1872-1884页

作者： Chen hU Liuqian YU Xiaowei ChEN Jihua LIU Yao ZhANG john BATT Xilin XIAO Qiang ShI Rui ZhANG Tingwei LUO Nianzhi JIAO Dapeng XU College of the Environment and Ecology Xiamen UniversityXiamen 361102China State Key Laboratory of Marine Environmental Science College of Ocean and Earth SciencesFujian Key Laboratory of Marine Carbon SequestrationXiamen UniversityXiamen 361102China Joint Lab for Ocean Research and Education(LORE)of Dalhousie University Canadaand Shandong University and Xiamen UniversityXiamen 361102China Earth Ocean and Atmospheric Sciences ThrustThe Hong Kong University of Science and Technology(Guangzhou)Guangzhou 510000China Institute of Marine Science and Technology Shandong UniversityQingdao 266237China Department of Oceanography Dalhousie UniversityHalifaxNova Scotia B3H 4R2Canada Institute for Advanced Study Shenzhen UniversityShenzhen 518060China Carbon Neutral Innovation Research Center Xiamen UniversityXiamen 361102China

Prokaryotes play a fundamental role in global ocean biogeochemical ***,how the abundance and metabolic activity of ecologically distinct subgroups(i.e.,high nucleic acid(hNA)and low nucleic acid(LNA)cells),and their regulating factors,change in response to changing marine environmental conditions remains poorly ***,we delved into the time-evolving dynamic responses of the hNA and LNA prokaryotic subgroups to declining resource availability and selective grazing by protozoa by conducting a 73-day incubation experiment in a large-volume(117,000 L)macrocosm that facilitates community-level *** found that the metabolic activity of the hNA subgroup was higher than that of the LNA subgroup when the macrocosm was resource replete but that the hNA subgroup declined more rapidly than the LNA subgroup as the resources became increasingly scarce,leading to a steadily increasing contribution of LNA cells to prokaryotic ***,as resources in the macrocosm became limited,protozoan grazing preference shifted from the hNA to the LNA subgroup and the contributions of the LNA subgroup to the carbon flow within the macrocosm *** findings highlight the resilience of LNA cells in resource-limited environments,illuminate the critical role of selective grazing by protozoa in balancing distinct prokaryotic subgroups under changing resource conditions,and demonstrate the complex and adaptive interactions between protozoa and prokaryotes across diverse environmental contexts.

关键词： Microbial loop Macrocosm experiment Prokaryote Top-down and bottom-up controls Carbon flow

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Endoscopic ultrasound-guided portal pressure gradient identifies patients with previously undiagnosed clinically significant portal hypertension

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Portal hypertension & Cirrhosis 2024年第2期3卷 67-74页

作者： Jerome C.Edelson Scott F.D.Edelson john G.Quiles Cyrus V.Edelson Eric M.Montminy Christian L.horn john P.Magulick Don C.Rockey Department of Gastroenterology and hepatology Brooke Army Medical CenterFort Sam HoustonTexasUSA Department of Medicine Uniformed Services University of the Health SciencesBethesdaMarylandUSA Department of Medicine Brooke Army Medical CenterFort Sam HoustonTexasUSA john h.Stroger Jr.hospital of Cook County ChicagoIllinoisUSA Digestive Disease Research Center Medical University of South CarolinaCharlestonSouth CarolinaUSA

Aims:Portal hypertension(Ph)is a complication of cirrhosis that leads to hepatic *** the portal pressure gradient(PPG)provides valuable information for disease assessment,staging,and *** this study,we aimed to report the utilization of endoscopic ultrasound(EUS)-guided PPG(EUS-PPG)measurements in a real-world ***:This retrospective analysis included patients at a tertiary care center who underwent EUS-PPG between February 2021 and May *** most common indication was to establish or exclude the diagnosis of cirrhosis,followed by an assessment of surgical risk in the setting of suspected *** demographic and clinical data were collected,and statistical analysis was performed using the Student's t ***:Eighteen patients underwent *** success was achieved in 17 of the 18 *** complications were *** mean scores of Child-Pugh,Model for End-Stage Liver Disease-Sodium,and Fibrosis-4 scores were 5.1±0.5,9.0±3.0,and 3.7±4.5,*** the 18 patients,two presented with esophageal varices and six with portal hypertensive *** mean PPG was 5.8±4.5 mmhg,and five patients exhibited clinically significant Ph(CSPh).Of the 18 patients,15 underwent concurrent EUS-liver biopsy,which was 100%successful and provided diagnostic histology for all *** PPG data led to changes in the clinical management of 17 ***:EUS-PPG is safe and technically *** Child-Pugh score did not correlate well with the presence of CSPh;however,PPG measurements resulted in changes in the management of almost all *** studies correlating EUS-PPG with other assessments of liver diseases are required.

关键词： EUS portal hypertension portal pressure gradient

C19MC miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma

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Genes & Diseases 2024年第1期11卷 60-63页

作者： Goodwin G.Jinesh Marian T.Smallin Nino Mtchedlidze Isha Godwin Marco Napoli Nicole hackel Manali S.Phadke Avani A.Deshpande Xiaobo Li john h.Lockhart Jaden R.Baldwin Suehelay Acevedo-Acevedo Yifeng Gao Michelle A.Reiser Keiran S.M.Smalley Elsa R.Flores Andrew S.Brohl Department of Molecular Oncology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Molecular Medicine Program H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Saveetha Medical College ChennaiTamil Nadu 602105India Tumor Biology Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Sarcoma Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA

SP100 is an antiviral protein that restricts the productive stage of human papillomavirus(hPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(Table S1).Interferon(IFN)signaling could still produce more SP100 through transcription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.

关键词： SP100 melanoma stabilization

从h1N1血凝素序列提取的沙门氏菌传递的COBRA-hA1抗原对甲型流感亚型产生广谱保护作用

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Engineering 2024年第1期32卷 41-56页

作者： Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar john hwa Lee Department of Veterinary Public health College of Veterinary MedicineJeonbuk National UniversityIksan 54596Republic of Korea Department of Preventive Medicine College of Veterinary MedicineChungnam National UniversityDaejeon 34134Republic of Korea

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza *** this study,a strategy called computationally optimized broadly reactive antigen(COBRA)was used to generate a consensus sequence of the hemagglutinin globular head portion(hA1)of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed *** carrying different hA1regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNApolymerase(RdRp)-based eukaryotic expression system,*** protein expression was confirmed by Western blot and immunofluorescence *** immunized with the designed constructs produced a humoral response,with a significant increase in immunoglobulin G(IgG)levels,and a cell-mediated immune response,including a 1.5-fold increase in CD4^(+) and CD8^(+)T ***,constructs #1 and #5 increased the production of interferon-γ(IFN-γ)producing CD4^(+)and CD8^(+)T cells,skewing the response toward the T helper type 1 cell(Th1)***,interleukin-4(IL-4)-producing T cells were upregulated *** efficacy was demonstrated,with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer>40 against the selected viral *** designed constructs conferred a broadly protective immune response,resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34,A/Brisbane/59/2007,A/California/07/2009,KBPV VR-92,and NCCP 43021 *** discovery revolutionizes influenza vaccine design and delivery;Salmonella-mediated COBRA-hA1 is a highly effective in vivo antigen presentation *** approach can effectively combat seasonal h1N1 influenza strains and potential pandemic outbreaks.

关键词： COBRA Influenza A Salmonella Vaccine Broad spectral protection