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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij j.p.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia j.Santegoets Timo Oosenbrug Annemarthe van der Veen joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz jacobs Sjoerd H.van der Burg jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to pD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to pD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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HI in High Gas-phase Metallicity Dwarf Galaxy WISEA j230615.06+143927.9

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Research in Astronomy and Astrophysics 2024年第1期24卷 292-299页

作者： Yan Guo C.Sengupta T.C.Scott p.Lagos Y.Luo purple Mountain Observatory Chinese Academy of SciencesNanjing 210023China School of Astronomy and Space Sciences University of Science and Technology of ChinaHefei 230026China Institute of Astrophysics and Space Sciences(IA porto) Rua das Estrelas4150-762PortoPortugal

We present resolved Giant Metrewave Radio Telescope H I observations of the high gas-phase metallicity dwarf galaxy WISEA j230615.06+143927.9(z = 0.005)(hereafter j2306) and investigate whether it could be a Tidal Dwarf Galaxy(TDG) candidate. TDGs are observed to have higher metallicities than normal dwarfs. j2306 has an unusual combination of a blue g-r color of 0.23 mag, irregular optical morphology and high-metallicity(12 +log(O/H) = 8.68 ± 0.14), making it an interesting galaxy to study in more detail. We find j2306 to be an H I rich galaxy with a large extended, unperturbed rotating H I disk. Using our H I data we estimated its dynamical mass and found the galaxy to be dark matter(DM) dominated within its H I radius. The quantity of DM, inferred from its dynamical mass, appears to rule out j2306 as an evolved TDG. A wide area environment search reveals j2306 to be isolated from any larger galaxies which could have been the source of its high gas metallicity. Additionally, the H I morphology and kinematics of the galaxy show no indication of a recent merger to explain the *** detailed optical spectroscopic observations of j2306 might provide an answer to how a seemingly ordinary irregular dwarf galaxy achieved such a high level of metal enrichment.

关键词： galaxies:abundances galaxies:dwarf galaxies:irregular radio lines:galaxies radio lines:ISM

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili patricia Graham Adriana Brooks Risset Silvera Alexander j.p.Goldschmidt Damien D.pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami project to Cure paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Macroinvertebrate Community Index (MCI) and Quantitative Macroinvertebrate Community Index (QMCI) Analysis: A Comparative Study between Le Afe and Mulivaifagatoloa Rivers, Upolu Island, Samoa

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journal of Geoscience and Environment protection 2024年第8期12卷 149-167页

作者： S. Taupega-Satau p. Amosa A. Leauga j. Nunufolau T. Veni Nun Yan Department of Science National University of Samoa Apia Samoa Office of The Vice Chancellor National University of Samoa Apia Samoa Department of Information Technology and Systems National University of Samoa Apia Samoa

The diversity of Samoa’s freshwater macroinvertebrates remains largely unexplored, with past studies focusing on specific species without comprehensive cataloguing. This research evaluated the health of Upolu Island’s rural rivers through macroinvertebrate analysis, particularly in the Le Afe and Mulivaifagatoloa Rivers. Collaborating with Samoa’s Water Resources Division in the Ministry of Natural Resources and Environment (MNRE), three sites along each river were sampled, representing a gradient from pristine to anthropogenically impacted areas. A total of 2953 macroinvertebrates were collected and classified into five categories using established identification keys. The Macroinvertebrate Community Index (MCI) and Quantitative Macroinvertebrate Community Index (QMCI) were applied for analysis. The results showed no clear pattern of pollutant-sensitive species prevalence or decline in less disturbed rivers. High MCI scores with low QMCI values indicated numerous low-scoring species, while the opposite suggested a richness of high-scoring taxa. Although MCI and QMCI are tools for monitoring freshwater health, this study lays the groundwork for future research to categorize Samoan macroinvertebrates and assign tolerance scores based on their presence in varying river conditions. .

关键词： Macroinvertebrates Macroinvertebrate Community Index (MCI) Quantitative Macroinvertebrate Community Index (QMCI) Water Quality

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Integrated Single-cell Multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

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Genomics, proteomics & Bioinformatics 2024年第1期22卷 67-88页

作者： Manickam Ashokkumar Wenwen Mei jackson j.peterson Yuriko Harigaya David M.Murdoch David M.Margolis Caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia D.Rudin Yuchao jiang Edward p.Browne Department of Medicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA Department of Medicine Duke UniversityDurhamNC 27708USA Department of Computer Science Duke UniversityDurhamNC 27708USA Department of Statistics Texas A&M UniversityCollege StationTX 77843USA Department of Biology Texas A&M UniversityCollege StationTX 77843USA Department of Biomedical Engineering Texas A&M UniversityCollege StationTX 77843USA

Despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXp1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal primary CD4þT cell Single-cell multiomics HIV-regulating factor Machine learning

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A REDUCED ORDER SCHWARZ METHOD FOR NONLINEAR MULTISCALE ELLIpTIC EQUATIONS BASED ON TWO-LAYER NEURAL NETWORKS

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journal of Computational Mathematics 2024年第2期42卷 570-596页

作者： Shi Chen Zhiyan Ding Qin Li Stephen j.Wright Mathematics Department University of Wisconsin-MadisonMadisonWI 53706USA Department of Mathematics University of California-BerkeleyBerkeley CA 94720USA Mathematics Department and Discovery Institute University of Wisconsin-Madison MadisonWI 53706USA Computer Sciences Department University of WisconsinMadisonWI 53706USA

Neural networks are powerful tools for approximating high dimensional data that have been used in many contexts,including solution of partial differential equations(pDEs).We describe a solver for multiscale fully nonlinear elliptic equations that makes use of domain decomposition,an accelerated Schwarz framework,and two-layer neural networks to approximate the boundary-to-boundarymap for the subdomains,which is the key step in the Schwarz ***,the boundary-to-boundary map requires solution of boundary-value elliptic problems on each *** leveraging the compressibility of multiscale problems,our approach trains the neural network offline to serve as a surrogate for the usual implementation of the boundary-to-boundary *** method is applied to a multiscale semilinear elliptic equation and a multiscale p-Laplace *** both cases we demonstrate significant improvement in efficiency as well as good accuracy and generalization performance.

关键词： Nonlinear homogenization Multiscale elliptic problem Neural networks Do-main decomposition

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On an isotropic porous solid cylinder:the analytical solution and sensitivity analysis of the pressure

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Applied Mathematics and Mechanics(English Edition) 2024年第9期45卷 1499-1522页

作者： H.ASGHARI L.MILLER R.pENTA j.MERODIO Departamento de Matematica Aplicada a las TIC ETS de Ingenieria de Sistemas InformaticosUniversidad Politecnica de MadridMadrid 28031Spain School of Mathematics and Statistics University of GlasgowGlasgow G128QQU.K.

Within this work,we perform a sensitivity analysis to determine the influence of the material input parameters on the pressure in an isotropic porous solid *** provide a step-by-step guide to obtain the analytical solution for a porous isotropic elastic cylinder in terms of the pressure,stresses,and elastic *** obtain the solution by performing a Laplace transform on the governing equations,which are those of Biot's poroelasticity in cylindrical polar *** enforce radial boundary conditions and obtain the solution in the Laplace transformed domain before reverting back to the time *** sensitivity analysis is then carried out,considering only the derived pressure *** analysis finds that the time t,Biot's modulus M,and poisson's ratio ν have the highest influence on the pressure whereas the initial value of pressure p_(0) plays a very little role.

关键词： sensitivity analysis Laplace transform cylindrical polar coordinate Biot's modulus cylinder

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Universal insertion of molecules in ionic compounds under pressure

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National Science Review 2024年第1期11卷 120-128页

作者： Feng peng Yanming Ma Chris j.pickard Hanyu Liu Maosheng Miao College of physics and Electronic Information Luoyang Normal University Department of Chemistry and Biochemistry California State University Northridge State Key Laboratory of Superhard Materials & Key Laboratory of Material Simulation Methods and Software of Ministry of Education College of Physics Jilin University International Center of Future Science Jilin University Department of Materials Science & Metallurgy University of Cambridge Advanced Institute for Materials Research Tohoku University Department of Earth Science University of California Santa Barbara

Using first-principles calculations and crystal structure search methods, we found that many covalently bonded molecules such as H2, N2, CO2, NH3, H2O and CH4may react with NaC l, a prototype ionic solid,and form stable compounds under pressure while retaining their molecular structure. These molecules,despite whether they are homonuclear or heteronuclear, polar or non-polar, small or large, do not show strong chemical interactions with surrounding Na and Cl ions. In contrast, the most stable molecule among all examples, N2, is found to transform into cyclo-N5-anions while reacting with NaC l under high pressures. It provides a new route to synthesize pentazolates, which are promising green energy materials with high energy density. Our work demonstrates a unique and universal hybridization propensity of covalently bonded molecules and solid compounds under pressure. This surprising miscibility suggests possible mixing regions between the molecular and rock layers in the interiors of large planets.

关键词： molecule-solid hybrid materials high-pressure crystal structure prediction density functional theory planet interior

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Seasonal changes in Hermit Thrush (Catharus guttatus) song syntax

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Avian Research 2024年第2期15卷 172-179页

作者： Sean p.Roach Luke C.McLean jeff W.MacLeod Leslie S.phillmore psychology Department University of New Brunswick Saint John100 Tucker Park RoadSaint JohnNBCanada Department of psychology and Neuroscience Dalhousie University1355 Oxford StHalifaxNSB3H 4J1Canada

In many songbird species,birdsong features phonological syntax,meaning that the units within their vocal se-quences are ordered in a non-random way that adheres to a *** such syntactical patterns have been richly described in many species,comparatively little is known about how those patterns contribute to song achieving its important *** each of song’s main functions,territorial defense and mate attraction,evidence of a role for syntax is *** species for which syntax has been thoroughly described is the Hermit Thrush(Catharus guttatus),which presents song types from their repertoires in a semi-predictable order and,in doing so,rapidly cycle up and down the frequency *** objective of the present study was to explore the importance of song syntax in the Hermit Thrush through a within-subject examination of how measures of syntax,such as the predictability of song type order within song sequences,shift over the breeding *** hypothesized that,if such syntactical characteristics are important to breeding behaviour,they would be most prominent at the start of the breeding season when activity associated with territory establishment and mate attraction is most *** revealed that,as predicted,the rigidness of song type ordering within se-quences was highest at the start of the season and declined *** song type sequences were most predictable at the vitally important early part of the breeding season fit our hypothesis that this aspect of song syntax is important to song’s functions related to territory establishment and/or mate *** work will clarify whether that role relates to one of song’s two main functions or serves song transmission in some broader way.

关键词： Birdsong Hermit Thrush Seasonal change Stereotypy Syntax

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Simulated Microbe Removal around Finger Rings Using Different Hand Sanitation Methods

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International journal of Oral Science 2009年第3期1卷 136-142页

作者： Archana A. Alur Madhavi j. Rane james p. Scheetz Douglas j. Lorenz lawrence Gettleman Ballard High School Louisville Kentucky USA School of Medicine University of Louisville Louisville Kentucky USA School of Dentistry University of Louisville Louisville Kentucky USA School of public Health & Information Sciences University of Louisville Louisville Kentucky USA

Aim It is our opinion that the CDC and the WHO have underestimated cross-contamination under examination gloves in dental clinics while wearing jewelry, such as finger rings. These agencies only ＂recommend＂ removing jewelry, and only washing hands for 15 seconds with soap and warm water before donning gloves. This study examined several washing procedures and finger rings using simulated microbes. Methodology A gloved robber hand manikin was made and fitted with a flesh disposable vinyl glove. Four fingers were fitted with rings or no ring, dusted with simulated microbes, and washed with a scrub brush for 5, 15, and 25 seconds under 20℃ and 40℃ water alone, or with liquid hand soap. Light levels （in lux） of fluorescent powder before and after washing were measured and delta scores calculated for changes in light levels, equivalent to effectiveness of hand washing procedures. A full-factorial, 3-factor analysis of variance （ANOVA） was used to test for differences among levels of the three study factors-time, temperature, and soap use. Tukey＇s post hoc honestly significant difference （HSD） test was applied to significant factors to examine pair-wise differences between factor levels. Results It was found that the longer the hands with rings were washed with a scrub brush under flowing water, the more simulated microbes were removed. By 25 seconds, all methods were essentially the same. Simulated microbes were more difficult to remove from the palm compared to the back of the hand. The liquid hand soap used in this study was more effective with warm water than cold. When given a choice of washing with cold water up to 15 seconds, it would be preferable not to use soap to remove simulated microbes. Qualitatively, the outer surface of finger rings were more effectively cleaned than the crevice below the ring, and the ring with a stone setting appeared to accumulate and retain simulated microbes more than other rings. Conclusion The most effective treatment was washing wi

关键词： dental exam gloves finger ring jewelry crosscontamination hand hygiene microbes fluorescent powder dental health care workers

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