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| 1 | Single-cell Analysis of CAR-T Cell Activation Reveals A Mixed T_H1/T_H2 Response Independent of Differentiation显示文摘The activation mechanism of chimeric antigen receptor (CAR)-engineered T cells may differ substantially from T cells carrying native T cell receptor,but this difference remains poorly understood. We present the first comprehensive portrait of single-cell level transcriptional and cyto-kine signatures of anti-CD19/4-1BB/CD28/CD3ζ CAR-T cells upon antigen-specific stimulation. Both CD4+helper T (TH) cells and CD8+cytotoxic CAR-T cells are equally effective in directly killing target tumor cells and their cytotoxic activity is associated with the elevation of a range of TH1 and TH2 signature cytokines,e.g.,interferon γ,tumor necrotic factor α,interleukin 5 (IL5),and IL13,as confirmed by the expression of master transcription factor genes TBX21 and GATA3. However,rather than conforming to stringent TH1 or TH2 subtypes,single-cell analysis reveals that the predominant response is a highly mixed TH1/TH2 function in the same cell. The reg-ulatory T cell activity,although observed in a small fraction of activated cells,emerges from this hybrid TH1/TH2 population. Granulocyte-macrophage colony stimulating factor (GM-CSF) is pro-duced from the majority of cells regardless of the polarization states,further contrasting CAR-T to classic T cells. Surprisingly,the cytokine response is minimally associated with differentiation status,although all major differentiation subsets such as na?ve,central memory,effector memory,and effector are detected. All these suggest that the activation of CAR-engineered T cells is a canon-ical process that leads to a highly mixed response combining both type 1 and type 2 cytokines together with GM-CSF,supporting the notion that polyfunctional CAR-T cells correlate with objective response of patients in clinical trials. This work provides new insights into the mechanism of CAR activation and implies the necessity for cellular function assays to characterize the quality of CAR-T infusion products and monitor therapeutic responses in patients. | Iva Xhangolli Burak Dura GeeHee Lee Dongjoo Kim Yang Xiao Rong Fan | 2019 | Genomics, Proteomics & Bioinformatics2019，17，2： | 7 |
| 2 | Integrating geochemical(surface waters, stream sediments)and biological(diatoms) approaches to assess AMD environmental impact in a pyritic mining area: Aljustrel(Alentejo, Portugal)显示文摘Aljustrel mines were classified as having high environmental hazard due to their large tailings volume and high metal concentrations in waters and sediments.To assess acid mine drainage impacted systems whose environmental conditions change quickly,the use of biological indicators with short generation time such as diatoms is advantageous.This study combined geochemical and diatom data,whose results were highlighted in 3 groups:Group 1,with low p H(1.9–5.1)and high metal/metalloid(Al,As,Cd,Co,Cu,Fe,Mn,Ni,Pb,Zn;0.65–1032 mg/L)and SO_4(405–39124 mg/L)concentrations.An acidophilic species,Pinnularia aljustrelica,was perfectly adapted to the adverse conditions;in contrast,teratological forms of Eunotia exigua were found,showing that metal toxicity affected this species.The low availability of metals/metalloids in sediments of this group indicates that metals/metalloids of the exchangeable fractions had been solubilized,which in fact enables metal/metalloid diatom uptake and consequently the occurrence of teratologies;Group 2,with sites of near neutral p H(5.0–6.8)and intermediate metal/metalloid(0.002–6 mg/L)and SO_4(302–2179 mg/L)concentrations;this enabled the existence of typical species of uncontaminated streams(Brachysira neglectissima,Achnanthidium minutissimum);Group 3,with samples from unimpacted sites,showing low metal/metalloid(0–0.8 mg/L)and SO_4(10–315 mg/L)concentrations,high pH(7.0–8.4)and Cl contents(10–2119 mg/L)and the presence of brackish to marine species(Entomoneis paludosa).For similar conditions of acidity,differences in diversity,abundance and teratologies of diatoms can be explained by the levels of metals/metalloids. | Ana Teresa Luís Nuno Duraes SaloméFernandes Pinheiro de Almeida Eduardo Ferreira da Silva | 2016 | Journal of Environmental Sciences2016，28，4： | 4 |
| 3 | Potential applications of laecase in the food industry显示文摘 | Minussi R C Pastore G M Dura N | 2002 | Trends in Food Science & Technology2002，13，： | 1 |
| 4 | Evaluation of boron removal from water by hydrotalcite-like compounds 显示文摘 | O P Ferreira S G de Moraes0 Nelson Dura'n | 2006 | Chemosphere2006，62，1： | 1 |
| 5 | Effects of Fungal Laccase Immobilization Procedures for the Development of a Biosensor for Phenol Compounds显示文摘 | Renato S Freire Nelson Dura′n Lauro T | 2001 | Talanta2001，，54： | 1 |
| 6 | Localized ridge augmentationwith autografts and barrier membranes 显示文摘 | Buser D Dura K Hess D | 1999 | Periodontol 20001999，19，： | 1 |
| 7 | Tumor necrosis factor alpha extended haplotypes and risk of gastric carcinoma显示文摘 | Canedo P Duraes C Pereira F | 2008 | Cancer Epidemiol Biomarkers Prey2008，17，9： | 1 |
| 8 | Ryks: new partners for Wnts in the developing and regenerating nervous system 显示文摘 | Fradkin LG Dura JM Noordermeer JN | 2010 | Trends Neurosci2010，33，： | 1 |
| 9 | Functionality of porous starch obtained by amylase or amyloglucosidase treatments显示文摘 | Dura A Baszczak W Rosell C M | 2014 | Carbohydrate Polymers2014，101，： | 1 |
| 10 | Functionality of porous starch obtained by amylase or amyloglucosidase treatments 显示文摘 | Dura A Blaszczak W Rosell C M | 2014 | Carbohydrate Polymers2014，101，： | 1 |
| 11 | 显示文摘 | Hjorvarsson B Dura J A Isberg P | 1997 | Phys Rev Lett1997，79，： | 1 |
| 12 | Emulation of software faults: a field data study and a practical approach 显示文摘 | Duraes J Madeira H | 2006 | IEEE Transactions on Software Engineering2006，32，11： | 1 |
| 13 | Tyrosine hydroxylase deficit in the che- moafferent and the sympathoadrenergic pathways of the Meep2 defi- cient mouse显示文摘 | Roux JC Dura E Villard L | 2007 | Neumsci Lett2007，447，1： | 1 |
| 14 | The choice of the best among the shortest routes in transparent opti- cal networks 显示文摘 | Duraes G M Soares A Amazonas J R | 2010 | Computer Networks2010，54，14： | 1 |
| 15 | Spousal caregiv- ers of dementia victims: Longitudinal changes in immunity and health显示文摘 | Kiecolt -Glaser JK Dura JR Speicher CE | 1991 | Psychosom Med1991，53，4： | 1 |
| 16 | Oral embryonal rhabdomyosarcoma in a child:a case report with immunohistochemical analysis显示文摘 | Duraes GV Jham BC Mesquita ATM | 2006 | Oral Oncology Extra2006，42，3： | 1 |
| 17 | Pancreatic trauma显示文摘 | Rupert K Spidlen V Duras P | 2011 | Rozhl Chir2011，90，9： | 1 |
| 18 | Toward a Psychology of Human Agency显示文摘 | BAN DURA A | 2006 | Perspectives on Psychological Science2006，1，2： | 1 |
| 19 | IL-12 and TNF-α production by dendritic ceils stimulated with Schistosoma mansoni schistosomula tegument is TLR4- and MyD88-dependent显示文摘 | Duraes FV Carvalho NB Melo TF | 2009 | Immunol Lett2009，125，1： | 1 |
| 20 | Localized ridge augmentation using guided bone regeneration显示文摘 | Buser D Dura K Belser U | 1993 | Intern J Periodont Restorat Dent1993，1329，： | 1 |
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