Using density functional theory with generalized gradient approximation and hybrid functional, we studied the properties of energy, charge population, and vibration of CH2 and CH3 adsorbed on Cun （n=1-6） clusters. T...Using density functional theory with generalized gradient approximation and hybrid functional, we studied the properties of energy, charge population, and vibration of CH2 and CH3 adsorbed on Cun （n=1-6） clusters. The results show that the DFT calculation with the hybrid functional matches the experimental results better in both cases. The calculation results indicate that the adsorption of CH2 is stronger than that of CH3. During adsorption, the charges transfer from Cu to CH2 or CH3. The obtained vibrational frequencies for different modes of CH2 and CH3 adsorbed on Cun agree well with the experimental results for the adsorption on Cu（111） surface.展开更多
Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblast...Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells,and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations,e.g.,CD8+T cells and natural killer (NK) cells,in the bone marrow. Additionally,CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways,including the NK cell mediated cytotoxicity and NOD-like recep-tor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g.,miR-148a-3p and miR-375),acting as oncogenes or tumor suppressors,could regulate the crosstalk between the genes encoding transcription factors (TFs,e.g.,JUN and FOS) and histones (e.g.,HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore,many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g.,FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for fur-ther understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.展开更多
基金This work was supported by the Chinese Academy of Engineering Physics （No.51480030105JW1301） and the National Natural Science Foundation of China （No.10534010, No.10374036, and No.10374037）.
文摘Using density functional theory with generalized gradient approximation and hybrid functional, we studied the properties of energy, charge population, and vibration of CH2 and CH3 adsorbed on Cun （n=1-6） clusters. The results show that the DFT calculation with the hybrid functional matches the experimental results better in both cases. The calculation results indicate that the adsorption of CH2 is stronger than that of CH3. During adsorption, the charges transfer from Cu to CH2 or CH3. The obtained vibrational frequencies for different modes of CH2 and CH3 adsorbed on Cun agree well with the experimental results for the adsorption on Cu（111） surface.
基金the National Natural Science Foundation of China (Grant Nos. 31822030, 31801113, and 31771458)the National Key R&D Program of China (Grant No. 2017YFA0700403)China Postdoctoral Science Foundation (Grant No. 2018M632830)
文摘Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells,and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations,e.g.,CD8+T cells and natural killer (NK) cells,in the bone marrow. Additionally,CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways,including the NK cell mediated cytotoxicity and NOD-like recep-tor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g.,miR-148a-3p and miR-375),acting as oncogenes or tumor suppressors,could regulate the crosstalk between the genes encoding transcription factors (TFs,e.g.,JUN and FOS) and histones (e.g.,HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore,many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g.,FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for fur-ther understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
