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Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COvID-19 in nonhuman primates

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Cellular & Molecular Immunology 2022年第2期19卷 222-233页

作者： Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure robert v.blair Scott D.Boyd Rudolf P.Bohm Jay Rappaport François villinger Nathalie Landry Bali Pulendran Brian J.Ward Medicago Inc. QuébecQCCanada. Institute for Immunity Transplantation and InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA. Tulane National Primate Research Center CovingtonLAUSA. New Iberia Research Center University of Louisiana at LafayetteNew IberiaLAUSA. Department of Pathology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Department of Microbiology and Immunology Tulane University School of MedicineNew OrleansLAUSA. Department of Microbiology and Immunology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Institute for Immunity Transplantation&InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA Research Institute of the McGill University Health Centre MontrealQCCanada.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-Cov-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COvID-19)***-derived virus-like particle(vLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against ***,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a vLP bearing a SARS-Cov-2 spike protein(CovLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)*** a single dose of the unadjuvanted CovLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted *** micrograms of CovLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T *** were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of *** viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-Cov-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CovLP adjuvanted with *** clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated *** CovLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

关键词： SARS-Cov-2 virus-like particles Non-humane primates AS03 CpG1018

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A general mirror equivalence theorem for coset vertex operator algebras

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Science China Mathematics 2024年第10期67卷 2237-2282页

作者： robert McRae Yau Mathematical Sciences Center Tsinghua UniversityBeijing 100084China

We prove a general mirror duality theorem for a subalgebra U of a simple conformal vertex algebra A and its commutant v=ComA(U).Specifically,we assume that A≌■_(i∈I)U_(i)■v_(i) as a U■v-module,where the U-modules Uiare simple and distinct and are objects of a semisimple braided ribbon category of Umodules,and the v-modules viare semisimple and contained in a(not necessarily rigid) braided tensor category of *** also assume U=ComA(v).Under these conditions,we construct a braid-reversed tensor equivalence τ:u_(A)→v_(A),where u_(A)is the semisimple category of U-modules with simple objects Ui,i∈I,and v_(A)is the category of v-modules whose objects are finite direct sums of *** particular,the v-modules viare simple and distinct,and v_(A)is a rigid tensor *** an application,we find a rigid semisimple tensor subcategory of modules for the virasoro algebra at central charge 13+6p+6p^(-1),p∈Z_(≥2), which is braided tensor equivalent to an abelian 3-cocycle twist of the category of finite-dimensional ***,the virasoro vertex operator algebra at central charge 13+6p+6p^(-1)is the PSL_(2)(C)-fixed-point subalgebra of a simple conformal vertex algebra w(-p),analogous to the realization of the virasoro vertex operator algebra at central charge 13-6p-6p^(-1)as the PSL_(2)(C)-fixed-point subalgebra of the triplet algebra W(p).

关键词： vertex operator algebras coset conformal eld theory braid-reversed tensor equivalence virasoro algebra

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The Sigma-1 Receptor as a Pharmacologic Chaperone: Energetics

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Journal of Biosciences and Medicines 2024年第8期12卷 347-356页

作者： robert B. Raffa Joseph v. Pergolizzi Jr. School of Pharmacy (Emeritus) Temple University Philadelphia PA USA College of Pharmacy (Adjunct) University of Arizona Tucson AZ USA NEMA Research Naples FL USA

Initially thought to be an opioid receptor subtype, Sigma-1 receptors (S1R) are now known to be unique proteins that have chaperone-like properties. As such, they play critical roles in cellular signaling, homeostasis, and cell survival. These roles offer significant insight for understanding homeostasis of normal physiologic processes, and the pathophysiologic consequences of disruption of normal function. Because of the broad nature of chaperone action, S1R agonists and antagonists represent potential drug discovery goals for the pharmacotherapeutic treatment of a variety of disorders that result from dysfunctional proteins. The present study summarizes the S1R as a pharmacologic chaperone crucial for protein folding and cellular homeostasis. Through literature review and thermodynamic analysis, it explores how S1R stabilizes target proteins, influencing neuroprotection and potential drug therapies. The binding of chaperones to target proteins is thermodynamically favorable, offering insights into treating diseases linked to protein misfolding.

关键词： Chaperone Sigma-1 Receptor Energetics Thermodynamics Isothermal Titration Microcalorimetry

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Commentary on “Why people should run after positive affective experiences instead of health benefits”

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Journal of Sport and Health Science 2024年第4期13卷 451-452页

作者： Ting Wang Jinghua Chen robert Schinke Liye Zou Body-Brain-Mind Laboratory School of PsychologyShenzhen UniversityShenzhen 518060China School of Kinesiology and Health Sciences Laurentian UniversitySudburyON P3E 2C6Canada

Maltagliati et al.1 recently highlighted the vital role of affective experiences in promoting physical activity(PA).The authors suggested that positive affective experiences,rather than health benefits,can tip the balance in favor of PA over sedentary *** authors proposed a new formal decision model between PA and sedentary alternatives and reported that when health benefits are the unique reason to action,the costs of PA(e.g.,effort)and the subjective value(Sv)of sedentary alternatives(v_(sed))are the main drivers of decision-making processes.

关键词： benefits formal decision

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Effects of soil metal(loid)s pollution on microbial activities and environmental risks in an abandoned chemical smelting site

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Journal of Environmental Sciences 2024年第9期143卷 60-70页

作者： Hao Li Jun Yao Jianli Liu Ning Min Geoffrey Sunahara Dongyang Men robert Duran School of Water Resources and Environment Research Center of Environmental Science and EngineeringChina University of Geosciences(Beijing)Beijing 100083China Department of Natural Resource Sciences McGill University21111Lakeshore DriveSte-Anne-de-BellevueQuebecH9X 3V9Canada Equipe Environnement et Microbiologie MELODY groupUniversitéde Pau et des Pays de l’AdourE2S-UPPAIPREM UMR CNRS 5254BP 115564013 Pau CedexFrance

Abandoned chemical smelting sites containing toxic substances can seriously threaten and pose a risk to the surrounding ecological *** samples were collected from different depths(0 to 13 m)and analyzed for metal(loid)s content and fractionation,as well as microbial *** potential ecological risk indices for the different soil depths(ordered from high to low)were:1 m(D-1)>surface(S-0)>5 m(D-5)>13 m(D-13)>9 m(D-9),ranging between 1840.65-13,089.62,and representing extremely high environmental risks,of which Cd(and probably not arsenic)contributed to the highest environmental risk.A modified combined pollution risk index(MCR)combining total content and mobile proportion of metal(loid)s,and relative toxicities,was used to evaluate the degree of contamination and potential environmental *** the near-surface samples(S-0 and D-1 layers),the MCR considered that As,Cd,Pb,Sb,and Zn achieved high and alarming degrees of contamination,whereas Fe,Mn,and Ti were negligible or low to moderate pollution *** microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microbial metabolic activity *** analysis elucidated the relationship between metal(loid)s exchangeable fraction or content and microbial activity characteristics(pvity in the D-1 layer was low presumably due to heavy metal *** activity indicators and microcalorimetric growth rate(k)measurements were considered sensitive indicators to reflect the soil microbial activities in abandoned chemical smelting sites.

关键词： Abandoned chemical smelting sites Microbial activities Modified combined pollution risk Microcalorimetry Enzymatic activities

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Management of distal cholangiocarcinoma with arterial involvement: Systematic review and case series on the role of neoadjuvant therapy

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2689-2701页

作者： Lewis A Hall Duncan Loader Santiago Gouveia Marta Burak James Halle-Smith Peter Labib Moath Alarabiyat Ravi Marudanayagam Bobby v Dasari Keith J roberts Syed S Raza Michail Papamichail David C Bartlett robert P Sutcliffe Nikolaos A Chatzizacharias Department of Hepatopancreatobiliary Surgery and Liver Transplantation University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152TTUnited Kingdom College of Medical and Dental Sciences University of BirminghamBirmingham B152TTUnited Kingdom Institute of Clinical Sciences University of BirminghamBirmingham B152TTUnited Kingdom

BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is *** To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial *** A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received *** patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained *** characteristics,NAT type,progression to surgery and oncological outcomes were *** Twelve studies were *** definition of“unresectable”locally advanced dCCA was *** studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most *** studies considered either NAT in resectable dCCA or inclusive with extrahepatic *** presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced *** patients progressed to surgery and 2 were *** patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months *** Evidence for benefit of NAT is *** on criteria for uniform definition of resectability for dCCA is *** propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.

关键词： Cholangiocarcinoma Neoadjuvant therapy Arterial involvement Locally advanced Systematic review

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Long-Term Impact of Acute Retinoic Acid Supplementation at the Young Age on Testicular Architecture of Wistar Albino Rats

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Advances in Reproductive Sciences 2024年第1期12卷 1-13页

作者： Mama Sy Racha Kamenda Ibondou Fatoumata Bah robert Foko Ndiaga Diop Mame vénus Abdoulaye Séga Cheikh Diop Mamadou Fall Oumar Faye Laboratory of Histology Embryology and Cytogenetics Faculty of Medecine Cheikh Anta Diop University Dakar Senegal

Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p vel in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, d

关键词： vitamin A Retinyl Palmitate Spermatogenesis Testis-Wistar Albino Rats

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Storylines of family medicine Ⅱ:foundational building blocks—context,community and health

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Family Medicine and Community Health 2024年第S3期12卷 12-22页

作者： William B ventres Leslie A Stone Rupal Shah Tamala Carter Geoffrey M Gusoff Winston Liaw Bich-May Nguyen Joanna v Rachelson Mary Alice Scott Teresa L Schiff-Elfalan Seiji Yamada robert C Like Kathleen Zoppi A Peter Catinella Richard M Frankel Shailendra Prasad Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Bridge Lane Group Practice LondonUK Penn Center for Community Health Workers University of PennsylvaniaPhiladelphiaPennsylvaniaUSA National Clinician Scholars Program UCLA David Geffen School of MedicineLos AngelesCaliforniaUSA Health Systems and Population Health Sciences University of Houston Tilman J Fertitta Family College of MedicineHoustonTexasUSA Southern New Mexico Family Medicine Residency Program Las CrucesNew MexicoUSA New Mexico Primary Care Training Program Silver CityNew MexicoUSA Anthropology New Mexico State UniversityLas CrucesNew MexicoUSA Family Medicine and Community Health University of Hawai'i at Manoa John A Burns School of MedicineHonoluluHawaiiUSA Family Medicine and Community Health Rutgers Robert Wood Johnson Medical SchoolNew BrunswickNew JerseyUSA Family Medicine Indiana University School of MedicineIndianapolisIndianaUSA Family Medicine–Transmountain Texas Tech University Health Sciences CenterEl PasoTexasUSA Medicine Indiana University School of MedicineIndianapolisIndianaUSA Family Medicine and Community Health University of Minnesota Medical School-Twin Cities CampusMinneapolisMinnesotaUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅱ:foundational building blocks—context,community and health’,authors address the following themes:‘Context—grounding family medicine in time,place and being’,‘Recentring community’,‘Community-oriented primary care’,‘Embeddedness in practice’,‘The meaning of health’,‘Disease,illness and sickness—core concepts’,‘The biopsychosocial model’,‘The biopsychosocial approach’and‘Family medicine as social medicine.’May readers grasp new implications for medical education and practice in these essays.

关键词： thematic illustration dimensions

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A radical reinterpretation of the growth and form of the stromatolite Conophyton lituus(Maslov)from evidence of syngenetic biofilm mineralisation

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Journal of Palaeogeography 2022年第1期11卷 69-84页

作者： robert v.Burne Research School of Earth Sciences The Australian National University CanberraACT 0200Australia School of Earth and Environmental Sciences The University of QueenslandBrisbaneQLD 4072Australia

Conophyton(Maslov)is a cylindroidal stromatolite form-genus characterized by nested conical ***-preserved Conophyton,up to 4 m tall and with basal diameters of up to 50 cm,are exposed in the Proterozoic Atar Formation of Mauritania,where many occur together,in growth position,as fields of individual columns spaced between 5 and 70 cm *** uniformity of these forms and their regular distribution suggest that they grew in quiet-water environments below wave *** for their penecontemporaneous organomineralization is indicated by nearby toppled examples of undeformed Conophyton forms alongside eroded lithified Conophyton fragments in carbonate *** characteristics of Conophyton have been used to classify the structures-the form of the lamination and the nature of its axial structure.A mathematical/physical model provides an explanation for the growth pattern of *** predicts that coniform structures with thickened axial zones form when upward organic growth of a biofilm moderately exceeds the rate of its *** varying characteristics of these features between different forms of Conophyton are thought to reflect biomineralization of the decaying biofilm rather than differences in the composition of microbial communities.A modern example of a syngenetic mineralization process capable of producing similar structures has been observed in the contemporary sediments of Lake Preston,Western Australia,where benthic microbial mats are being transformed into coniform lithified *** initial biomineralization of the coniform mat forms magnesium silicate that first coats and permineralizes web-like microbial extracellular polymeric substances(EPS)and then coalesces into a uniform mass that provides mechanical strength to the *** a later stage,massive carbonate crystal growth occurs that over-prints much of this texture,leaving only small,remnant areas of the magnesium silicate *** fossil Conophyton are composed o

关键词： Conophyton Morphogenesis Proterozoic Stromatolite Microbialite Mineralisation Biofilm Lake Clifton Lake Preston Maslov

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Reducing intrathecal pressure after traumatic spinal cord injury: a potential clinical target to promote tissue survival

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Neural Regeneration Research 2015年第3期10卷 380-382页

作者： Anna v Leonard robert vink School of Medical Sciences University of Adelaide Division of Health Sciences University of South Australia

Spinal cord injury （SCI） is an unexpected event that is both devastating and debilitating, resulting in not just motor and sensory loss, but also autonomic dysfunction of the bladder, bowel and sexual organs. Currently, there are no treatments available to improve outcome follow- ing SCI, leaving individuals with permanent and lifelong physical disability. Worldwide it is estimated that more than 500,000 people sustain a SCI each year, with average lifetime cost of paraplegia and quadriplegia estimated at $5 million and $9.5 million respectively. We therefore urgently need effective therapies to improve quality of life following SCI, and this requires a greater understanding of how cell and axonal injury develops after the traumatic event.

关键词： ITP TBI a potential clinical target to promote tissue survival Reducing intrathecal pressure after traumatic spinal cord injury SCI

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