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cD4^(+)T cells produce IFN-I to license cDc1s for induction of cytotoxic T-cell activity in human tumors

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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

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

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Neural Regeneration Research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-chaves Zainab Maastor carlos Spuch José Antonio Lamas Lucas c.González-Matías Federico Mallo Biomedical Research centre(cINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience Research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical Research centre(cINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and ***-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain ***-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural *** glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous *** brain insult,microglia are the first cells to respond,followed by reactive *** activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the ***,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many *** processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control *** glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry *** review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkins

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

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cancer-associated fibroblasts express cD1d and activate invariant natural killer T cells under cellular stress

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cellular & Molecular Immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael c.I.Karlsson Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden Division of Translational cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHc class I like molecule cD1^([1]).In humans there are five cD1 molecules named cD1a to cD1e,whereas mice use only cD1d for lipid ***,iNKT cells can elicit both cytotoxicity similarly to conventional cD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor *** iNKT cells use a restricted TcR repertoire and cD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer cD1d cancer

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亚里士多德的善和恶

世界哲学 2024年第2期 68-78页

作者： [爱尔兰]c.D.c.里夫孔祥润(译) 美国北卡罗来纳大学教堂山分校哲学系天津理工大学马克思主义学院

亚里士多德确实有一种关于恶的理论。善在定义上优先于恶,这是由善所需要的本体论边界决定的。如果善实际上就是卓越的存在,那么恶必定是这种存在的缺乏。在实体范畴中,亚里士多德的善是一种活的存在,在对自身的沉思中,第一性的神获得... 详细信息

亚里士多德确实有一种关于恶的理论。善在定义上优先于恶,这是由善所需要的本体论边界决定的。如果善实际上就是卓越的存在,那么恶必定是这种存在的缺乏。在实体范畴中,亚里士多德的善是一种活的存在,在对自身的沉思中,第一性的神获得了善并且是幸福的。由此类推,如果存在一种实体范畴上的恶,那么它必定是一种能对自身加以沉思的活的存在。然而在亚里士多德勾勒的事物体系中,这种观念是无法实现的。亚里士多德的善的理论排除了把一种恶(即实体性的巨大的恶)等同于善的可能性。这种理论认真对待伦理上的恶,把它当作心理学、政治学问题,而不是当作本体论问题。无条件的恶说的不是理性的神灵,而是心理变态之人或反社会之人,说的是一位恶人,尽管这个人处在一种特定的社会,即良好的社会之中。

关键词：亚里士多德善恶幸福

Harnessing marine microbiomes to develop a sustainable,all-Atlantic bioeconomy

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mLife 2024年第2期3卷 163-166页

作者： cristiane Thompson Alice c.Ortmann Henk Bolhuis Thulani Makhalanyane Fabiano Thompson Institute of Biology Federal University of Rio de Janeiro(UFRJ)Rio de JaneiroBrazil Fisheries and Oceans canada Bedford Institute of OceanographyDartmouthNova ScotiaCanada Department of Marine Microbiology and Biogeochemistry Royal Netherlands Institute for Sea Research(NIOZ)The Netherlands Department of Microbiology School of Data Science and Computational ThinkingStellenbosch UniversityStellenboschSouth Africa

Marine microbiomes are integral to the functioning of a healthy ocean and have the potential to be key contributors toward an all-Atlantic sustainable blue bioeconomy(Figure 1).New compounds may be developed based on these *** Atlantic Ocean is a biodiversity *** All-Atlantic Ocean Research and Innovation Alliance(AAORIA)Declaration,signed in 2022 in Washington,Dc,is a promising mechanism to move forward marine microbiome science,technology,and innovation.

关键词： Atlantic marine ocean

福建紫金山矿田悦洋银多金属矿床银的赋存状态和沉淀机制

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岩石学报 2024年第3期40卷 987-1002页

作者：刘兰海陈静周涛发孙艺 WHITE Noel c 合肥工业大学资源与环境工程学院合肥工业大学矿床成因与勘查技术研究中心(ODEC)合肥230009 安徽省矿产资源与矿山环境工程技术研究中心合肥230009 centre of Excellence in Ore Deposits(cODES) University of TasmaniaHobart 7001

浅成低温热液矿床是世界上银矿的重要矿床类型,伴生有金铜铅锌等多种金属。银的赋存状态研究可以为矿床资源禀赋、选冶成本以及经济价值的综合评价提供重要的依据。近年来,矿物自动定量分析系统越来越多地应用到贵金属的赋存状态研究中... 详细信息

浅成低温热液矿床是世界上银矿的重要矿床类型,伴生有金铜铅锌等多种金属。银的赋存状态研究可以为矿床资源禀赋、选冶成本以及经济价值的综合评价提供重要的依据。近年来,矿物自动定量分析系统越来越多地应用到贵金属的赋存状态研究中,相比传统方法而言其能提供精确定量的矿物学信息。悦洋银多金属矿床位于福建省紫金山矿田,是典型的浅成低温热液矿床,是研究银赋存状态的理想选区。通过野外地质调查研究发现,矿体主要受控于岩性边界和断裂构造,主要矿石类型为热液角砾岩型和石英脉型。成矿作用可以分为石英-黄铁矿、石英-黄铁矿-黄铜矿、石英-银多金属、石英-碳酸盐等四个阶段,其中银在石英-银多金属阶段沉淀,可以进一步划分为石英伊利石硫化物亚阶段和石英冰长石硫化物亚阶段。本文在野外地质调查的基础上,针对不同的矿石类型使用TIMA(TEScAN Integrated Mineral Analyzer)自动矿物分析系统,结合显微镜下观察、扫描电镜和电子探针分析手段,对银的赋存形式和分布情况进行了定量化研究,根据矿物共生组合对银沉淀机制及成矿过程进行了探讨。研究结果显示,悦洋矿床中的银90%以上以独立矿物的形式存在,主要是硫化银和自然银,且粒径大多在10~50μm之间;少部分银以次显微包裹体形式存在于黄铜矿中,或以显微包裹体和类质同相形式存在于黄铁矿和闪锌矿中。成矿热液中银主要以硫氢络合物形式运移,主成矿期大量的冰长石与银矿物共生表明沸腾作用是主要的沉淀机制。

关键词：银的赋存状态矿物定量分析银的沉淀机制浅成低温热液矿床紫金山矿田

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Deformable microlaser force sensing

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Light(Science & Applications) 2024年第6期13卷 1196-1209页

作者： Eleni Dalaka Joseph SHill Jonathan H.H.Booth Anna Popczyk Stefan R.Pulver Malte c.Gather Marcel Schubert centre of Biophotonics SUPASchool of Physics and AstronomyUniversity of St AndrewsNorth HaughSt AndrewsUK Humboldt centre for Nano-and Biophotonics Department of ChemistryUniversity of CologneKölnGermany School of Psychology and Neuroscience University of St AndrewsSt Mary’s QuadSouth StreetSt AndrewsUK Institute for Bioengineering of catalonia BarcelonaSpain

Mechanical forces are key regulators of cellular behavior and function,affecting many fundamental biological processes such as cell migration,embryogenesis,immunological responses,and pathological *** force sensors and imaging techniques have been developed to quantify these otherwise invisible forces in single cells and in ***,current techniques rely heavily on high-resolution microscopy and do not allow interrogation of optically dense tissue,reducing their application to 2D cell cultures and highly transparent biological ***,we introduce DEFORM,deformable microlaser force sensing,a spectroscopic technique that detects sub-nanonewton forces with unprecedented spatio-temporal *** is based on the spectral analysis of laser emission from dye-doped oil microdroplets and uses the force-induced lifting of laser mode degeneracy in these droplets to detect nanometer *** validation by atomic force microscopy and development of a model that links changes in laser spectrum to applied force,DEFORM is used to measure forces in 3D and at depths of hundreds of microns within tumor spheroids and late-stage Drosophila *** furthermore show continuous force sensing with single-cell spatial and millisecond temporal resolution,thus paving the way for non-invasive studies of biomechanical forces in advanced stages of embryogenesis,tissue remodeling,and tumor invasion.

关键词： invasion otherwise hundreds

Are school uniforms associated with gender inequalities in physical activity? A pooled analysis of population-level data from 135 countries/regions

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Journal of Sport and Health Science 2024年第4期13卷 590-598页

作者： Mairead Ryan Luiza I.c.Ricardo Nicole Nathan Riikka Hofmann Esther van Sluijs Medical Research council Epidemiology Unit University of CambridgeCambridge CB20QQUK Faculty of Education University of CambridgeCambridge CB28PQUK Hunter New England Population Health WallsendNSW 2287Australia School of Medicine and Public Health College of HealthMedicine and WellbeingUniversity of NewcastleCallaghanNSW 2308Australia Hunter Medical Research Institute New Lambton HeightsNSW 2305Australia National centre of Implementation Science University of NewcastleCallaghanNSW 2308Australia

Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment ***:An ecological study design was *** collected data about global uniform practices using an online *** searched for country/region-level estimates of school-aged youth meeting physical activity guidelines from international surveillance *** selection was conducted in duplicate using a systematic process,and a random sample of all data was checked to ensure extraction and pooling processes were *** calculated absolute and relative gender inequalities in physical activity for each *** regression examined associations between country/region-level uniform practices(binary yes/no exposure variable) and country/region-level gender inequalities in physical activity guideline compliance(absolute and relative inequalities).We investigated moderation by school level,stratified analyses by income group,and repeated primary analyses using device-measured ***:Pooling data from 135 countries/regions(n=1,089,852),we found no association between population-level uniform practices and gender inequalities in physical activity across all ages(absolute:β=-0.2;95% confidence interval(95%cI):-1.7 to 1.3,p=0.74;relative:β=0.1;95%cI:-0.1 to 0.2,p=0.51).Subgroup analysis suggested a positive association in primary school settings(absolute:β=4.3;95%cI:-0.0 to 8.6,p=0.05).Among high-income countries,absolute inequalities were significantly greater in countries/regions with uniform practices(N=37) compared to those without(N=48)(9.1(SD=3.6) vs.7.8 percentage points(SD=4.3)).Repeating analyses using device-measured data(n=32,130;N=24) did not alter our primary *** initial descriptive statistics,we found that in countries/regions where a maj ority of schools(>50%) reportedly use uniforms,there was lower compli

关键词： School policy clothing child Adolescent Accelerometer

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Post-urethroplasty complications in hypospadias repair: a systematic review and meta-analysis comparing, polydioxanone and polyglactin sutures

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World Journal of Pediatric Surgery 2024年第1期7卷 1-9页

作者： Nitinkumar Borkar charu Tiwari Debajyoti Mohanty Tridip Dutta Baruah Manoj Mohanty c K Sinha Pediatric Surgery All India Instituteof Medical Sciences-RaipurRaipurChhattisgardhIndia General Surgery All India Institute of Medical Sciences-RaipurRaipurChhattisgardhIndia Pediatric Surgery All India Institute of Medical Sciences-BhubaneswarBhubaneswarOrissaIndia St George's University of London LondonUK

Background Polyglactin(PG)and polydioxanone(PDS)sutures are extensively used based on the surgeon's *** development of post-reconstruction urethrocutaneous fistula(UcF)is variably attributed to the choice of suture material for *** meta-an alysiscompares complications of hypospadia srepair using PGand PDS *** The systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses *** authors conducted thorough searches in databases including MEDLINE,EMBASE,cENTRAL,Scopus,Google Scholar,and clinical trial *** measures included UcF,meatal stenosis,wound infection,urethral stricture,glans dehiscence,and overall *** analysis was used with fixed or random-effect models to find the pooled risk ratio and I2 *** The criteria for inclusion were met by five comparative studies with the inclusion of 1244 children *** analysis failed to show a statistically significant difference in the incidence of meatal stenosis,urethral stricture,wound infection,and total complications using PG and PDS ***,it showed a reduction in the incidence of UcF with PDS suture hypospadias repairs(risk ratio=0.66,95%cl 0.48 to 0.92).conclusions PDS sutures are associated with decreased incidence of UcF than PG after hypospadias *** incidence of meatal stenosis,urethral stricture,wound infection,and total complications was not affected by the type of suture material used for *** implications This meta-analysis suggests decreased incidence of UcF when PDS sutures are used for hypospadias repair which may impact the choice of suturematerialforrepair.

关键词： complications wound suture