Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8+CD28+ cytotoxic T lymphocyte（CTL） responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated wit...Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8+CD28+ cytotoxic T lymphocyte（CTL） responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated with H-2Kb:Ig-TRP2(181111K and anti-CD28 antibody were used as artificial antigen-presenting cells（aAPCs） lo induce melanoma-specific CD8*CD28’ CTL responses with the help of IL-2I and IL-I5.Dimer staining,proliferation,ELISPOT,and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.Results:Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8CD28' CTLs.Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- y under the slimulalion of H-2K:Ig-TRP2-aAPCs,TL-15,and IL-21.In addition,cytoloxicily experiments showed lhat induced CTLs have specific killing activity of target cells.Conclusions:The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8+CD28+ CTLs against the melanoma.Our study provides evidence for a novel adoptive immunotherapy against tumors.展开更多
BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortal...BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortality during early sepsis.METHODS:In total,40 healthy controls and 198 patients with sepsis were included in this study.Peripheral blood was collected within the first 24 h after the diagnosis of sepsis.The expression of PDL1 and PD-1 was determined on APCs,such as B cells,monocytes,and dendritic cells(DCs),by flow cytometry.Cytokines in plasma,such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-6,IL-10,and IL-17A were determined by Luminex assay.RESULTS:PD-1 expression decreased significantly on B cells,monocytes,myeloid DCs(mDCs),and plasmacytoid DCs(pDCs)as the severity of sepsis increased.PD-1 expression was also markedly decreased in non-survivors compared with survivors.In contrast,PD-L1 expression was markedly higher on mDCs,pDCs,and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors.The PD-L1 expression on APCs(monocytes and DCs)was weakly related to organ dysfunction and infl ammation.The area under the receiver operating characteristic curve(AUC)of the PD-1 percentage of monocytes(monocyte PD-1%)+APACHE II model(0.823)and monocyte PD-1%+SOFA model(0.816)had higher prognostic value than other parameters alone.Monocyte PD-1%was an independent risk factor for 28-day mortality.CONCLUSION:The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs.PD-L1 in monocytes and DCs was weakly correlated with infl ammation and organ dysfunction during early sepsis.The combination of SOFA or APACHE II scores with monocyte PD-1%could improve the prediction ability for mortality.展开更多
Severe damage to suspended ceilings of metal grids and lay-in panels was observed in public buildings during the 2013 M7.0 Lushan earthquake in China. Over the past several years, suspended ceilings have been widely u...Severe damage to suspended ceilings of metal grids and lay-in panels was observed in public buildings during the 2013 M7.0 Lushan earthquake in China. Over the past several years, suspended ceilings have been widely used practice in public buildings throughout China, including government offices, schools and hospitals. To investigate the damage mechanism of suspended ceilings, a series of three-dimensional shake table tests was conducted to reproduce the observed damage. A full-scale reinforced concrete frame was constructed as the testing frame for the ceiling, which was single-story and infilled with brick masonry walls to represent the local construction of low-rise buildings. In general, the ceiling in the tests exhibited similar damage phenomena as the field observations, such as higher vulnerability of perimeter elements and extensive damage to the cross runners. However, it exhibited lower fragility in terms of peak ground/roof accelerations at the initiation of damage. Further investigations are needed to clarify the reasons for this behavior.展开更多
基金supported,in part,by grants from the Program for New Century Excellent Talents in University(NECT-10-0098)the National Natural Scientific Foundation of China(Nos.81072161.81000769.81172139.and 81060183)+3 种基金Programs for Changjiang Scholars and Innovative Research Team in University(No. IRT1119)Innovative Research Team in Guangxi Natural Science Foundation (No.2011-18-5)Fund for Distinguished Young Scholars in Guangxi Natural Science Foundation(2012jjFA40005)Project of science and technology of Guangxi (1140003A-17)
文摘Objective:To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8+CD28+ cytotoxic T lymphocyte（CTL） responses.Methods:Cell-sized Dynabeads? M-450 Epoxy beads coated with H-2Kb:Ig-TRP2(181111K and anti-CD28 antibody were used as artificial antigen-presenting cells（aAPCs） lo induce melanoma-specific CD8*CD28’ CTL responses with the help of IL-2I and IL-I5.Dimer staining,proliferation,ELISPOT,and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.Results:Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8CD28' CTLs.Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- y under the slimulalion of H-2K:Ig-TRP2-aAPCs,TL-15,and IL-21.In addition,cytoloxicily experiments showed lhat induced CTLs have specific killing activity of target cells.Conclusions:The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8+CD28+ CTLs against the melanoma.Our study provides evidence for a novel adoptive immunotherapy against tumors.
文摘BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortality during early sepsis.METHODS:In total,40 healthy controls and 198 patients with sepsis were included in this study.Peripheral blood was collected within the first 24 h after the diagnosis of sepsis.The expression of PDL1 and PD-1 was determined on APCs,such as B cells,monocytes,and dendritic cells(DCs),by flow cytometry.Cytokines in plasma,such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-6,IL-10,and IL-17A were determined by Luminex assay.RESULTS:PD-1 expression decreased significantly on B cells,monocytes,myeloid DCs(mDCs),and plasmacytoid DCs(pDCs)as the severity of sepsis increased.PD-1 expression was also markedly decreased in non-survivors compared with survivors.In contrast,PD-L1 expression was markedly higher on mDCs,pDCs,and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors.The PD-L1 expression on APCs(monocytes and DCs)was weakly related to organ dysfunction and infl ammation.The area under the receiver operating characteristic curve(AUC)of the PD-1 percentage of monocytes(monocyte PD-1%)+APACHE II model(0.823)and monocyte PD-1%+SOFA model(0.816)had higher prognostic value than other parameters alone.Monocyte PD-1%was an independent risk factor for 28-day mortality.CONCLUSION:The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs.PD-L1 in monocytes and DCs was weakly correlated with infl ammation and organ dysfunction during early sepsis.The combination of SOFA or APACHE II scores with monocyte PD-1%could improve the prediction ability for mortality.
基金Research fund for earthquake engineering of China Earthquake Administration(201508023)a project of the National Science&Technology Support Program during the Twelfth Five-year Plan Period of China(2015BAK17B03)a general program of National Natural Science Foundation of China(51578515)
文摘Severe damage to suspended ceilings of metal grids and lay-in panels was observed in public buildings during the 2013 M7.0 Lushan earthquake in China. Over the past several years, suspended ceilings have been widely used practice in public buildings throughout China, including government offices, schools and hospitals. To investigate the damage mechanism of suspended ceilings, a series of three-dimensional shake table tests was conducted to reproduce the observed damage. A full-scale reinforced concrete frame was constructed as the testing frame for the ceiling, which was single-story and infilled with brick masonry walls to represent the local construction of low-rise buildings. In general, the ceiling in the tests exhibited similar damage phenomena as the field observations, such as higher vulnerability of perimeter elements and extensive damage to the cross runners. However, it exhibited lower fragility in terms of peak ground/roof accelerations at the initiation of damage. Further investigations are needed to clarify the reasons for this behavior.
