采用低温固相燃烧法快速制备了一种具有{111}、{110}和{100}晶面的去顶角八面体LiNi_(0.08)Mn_(1.92)O_(4)(LNMO)正极材料,其高暴露{111}晶面可以减少充放电过程中Mn的溶解,面积相对较小的{110}和{100}晶面可增加Li^(+)快速扩散的通道....采用低温固相燃烧法快速制备了一种具有{111}、{110}和{100}晶面的去顶角八面体LiNi_(0.08)Mn_(1.92)O_(4)(LNMO)正极材料,其高暴露{111}晶面可以减少充放电过程中Mn的溶解,面积相对较小的{110}和{100}晶面可增加Li^(+)快速扩散的通道.测试结果表明,所合成的LNMO具有LiMn_(2)O_(4)特有的立方晶系结构,其颗粒尺寸为亚微米级.LNMO的高温电化学性能优异,在55℃,1和5 C的首次放电比容量分别为109.9和98.0 m Ah/g,分别循环300次后容量保持率为75.8%和80.5%;即使在55℃,10和15 C下分别循环1000次后仍具有48.4%和49.4%的容量保持率,而未掺杂的LiMn_(2)O_(4)于15 C循环1000次后容量损失高达98%.LNMO在55℃有较高的Li^(+)扩散系数(D=3.86×10^(-15)cm^(2)/s)和较小的电荷转移阻抗(循环前、后R_(ct)=158.0和279.8Ω)以及较低的表观活化能(E_(a)=17.63 k J/mol),说明Ni掺杂能够提高Li^(+)在尖晶石型LiMn_(2)O_(4)内的扩散速率及减小锂离子在脱嵌过程中的能垒,从而提高锂离子的扩散速率和倍率性能.对LNMO于55℃循环1000次后的极片进行X射线衍射(XRD)分析,发现LNMO电极材料的晶体结构基本保持不变,表明Ni掺杂提高了锰酸锂材料在55℃长循环过程中的晶体结构稳定性,有效抑制了Jahn-Teller效应及Mn的溶解,显著提升了其高温电化学性能.本工作为尖晶石LiMn_(2)O_(4)电极材料在高温方面的应用提供了借鉴.展开更多
Hepatitis B virus （HBV） reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor （TNF） blockage therapy is effective for the treatment of many autoimmune infla...Hepatitis B virus （HBV） reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor （TNF） blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-a blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-a blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose- and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-a blockage therapy occurred at early time points after HBV infection. In addition, TNF-a blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death （PD）- 1highCD127low exhausted T cells. Furthermore, TNF-a blockade abolished Toll-like receptor 9 （TLR9） ligand-induced facilitation of HBV viral clearance. Taken together, TNF-a blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-a blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during theraoy with TNF-a-blocking agents.展开更多
Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa,leading to chronic gastritis,peptic ulcers,gastric carcinoma and gastric mucosa-associated lymphoid tissue(MALT)lymphomas...Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa,leading to chronic gastritis,peptic ulcers,gastric carcinoma and gastric mucosa-associated lymphoid tissue(MALT)lymphomas.Recent studies have shown that apoptosis of gastric epithelial cells is increased during H.pylori infection.Apoptosis induced by microbial infections are factors implicated in the pathogenesis of H.pylori infection.The enhanced gastric epithelial cell apoptosis in H.pylori infection has been suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology.In addition to directly triggering apoptosis,H.pylori induces sensitivity to tumor-necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis in gastric epithelial cells via modulation of TRAIL apoptosis signaling.Moreover,H.pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis.In H.pylori infection,there was significantly increased CCR61CD31 T-cell infiltration in the gastric mucosa,and the CCR6 ligand,CCL20 chemokine,was selectively expressed in inflamed gastric tissues.These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting T cells to the sites of inflammation in the gastric mucosa during Helicobacter infection.Through these mechanisms,chemokine-mediated T lymphocyte trafficking into inflamed epithelium is initiated and the mucosal injury in Helicobacter infection is induced.This article will review the recent novel findings on the interactions of H.pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology,including gastric inflammation,mucosal damage and development of MALT lymphomas.展开更多
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation ofinflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocyte...Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation ofinflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocytes andinfiltrating lymphocytes. The aim of this study was to investigate the immunomodulatory mechanism and role ofTRAIL in inflammatory arthritis. We created an animal model of inflammatory arthritis and demonstrated that TRAILsignificantly inhibited joint inflammation and reduced the severity of arthritis. The suppression of joint inflammationwas not due to the TRAIL-mediated induction of apoptosis in T cells, macrophages or synovial fibroblasts. Incontrast, TRAIL directly inhibited T-cell proliferation and suppressed the production of cytokines, which indicatedthat TRAIL exerted its anti-inflammatory effects by direct inhibition of T-cell activation. Moreover, TRAIL receptor(TRAIL-R)-knockout mice developed more severe disease, and the protective effects of TRAIL were abolished in theexperimental arthritis model in TRAIL-R knockout mice. From these results, we conclude that TRAIL suppressesjoint inflammation via an apoptosis-independent pathway and directly inhibits T-cell activation. Our results providea novel apoptosis-independent, immune regulatory role for TRAIL in suppressing inflammatory arthritis and shedlight on the development of effective new therapies for autoimmune inflammatory diseases.展开更多
Persistent hepatitis B virus(HBV)infection results in chronic liver diseases that may progress to chronic hepatitis,liver cirrhosis,and subsequent hepatocellular carcinoma.Previous studies demonstrated that adaptive i...Persistent hepatitis B virus(HBV)infection results in chronic liver diseases that may progress to chronic hepatitis,liver cirrhosis,and subsequent hepatocellular carcinoma.Previous studies demonstrated that adaptive immunity,in particular CD8 T cells,is critical in HBV elimination.Recent studies have revealed a distinct tissue-localized T cell lineage,tissue-resident memory(TRM)cells,that is crucial for protective immunity in peripheral tissues.In this study,we showed that treatment with an anti-asialo GM1(ASGM1)antibody(Ab),which depletes NK cells,led to impairment of HBV clearance in a mouse animal model.Unexpectedly,the ability to clear HBV was not significantly impaired in NFIL3 KO mice,which are deficient in NK cells,implying that other non-NK ASGM1-positive immune cells mediate HBV clearance.We isolated intrahepatic ASGM1-positive cells from NFIL3 KO mice and analyzed the immune phenotype of these cells.Our results demonstrated a distinct population of CD44+LFA-1hi CD8 T cells that were the major intrahepatic ASGM1-positive immune cells in NFIL3 KO mice.Importantly,transcriptome analysis revealed that these ASGM1-positive CD8 T cells had distinct gene profiles and shared a similar core gene signature with TRM cells.In addition to both transcriptional and phenotypic liver residency characteristics,ASGM1-positive CD8 T cells were able to home to and be retained in the liver after adoptive transfer.Taken together,our study results indicate that these ASGM1-positive liver-resident CD8 T cells are the major effector immune cells mediating anti-HBV immunity.展开更多
The immunopathogenesis of hepatitis B virus(HBV)involves a complex interaction of innate and adaptive immune response associated with several cytokines.However,due to experimental limitations,very limited and even no ...The immunopathogenesis of hepatitis B virus(HBV)involves a complex interaction of innate and adaptive immune response associated with several cytokines.However,due to experimental limitations,very limited and even no activation of the innate immune response can be demonstrated in acute HBV infection.The role of innate immunity and the key innate effectors for HBV clearance is still uncertain.It is also not clear whether clinical use of TNF inhibitors in treating rheumatoid arthritis and other autoimmune disease patients with chronic HBV infection would affect viral reactivation.However,in a recent paper in Cell Mol Immunol,Chyuan et al.reported that under TNF-αblockade,HBV viral clearance was impaired with persistent elevated HBV viral load in a dose and temporal-dependent manner.1 It demonstrates that a deficiency of TNF-αreduces viral clearance and promotes HBV persistence in a mouse model,and the impairment of HBV clearance under anti-TNF-αoccurs at an early time point of HBV infection,suggesting that HBV may reactivate during therapy with TNF inhibitors.The results together with previous reports support that TNF is a key innate cytokine required to clear HBV.2,3 It also provides evidence that therapy with TNF inhibitors may impair immune response to HBV clearance.展开更多
文摘采用低温固相燃烧法快速制备了一种具有{111}、{110}和{100}晶面的去顶角八面体LiNi_(0.08)Mn_(1.92)O_(4)(LNMO)正极材料,其高暴露{111}晶面可以减少充放电过程中Mn的溶解,面积相对较小的{110}和{100}晶面可增加Li^(+)快速扩散的通道.测试结果表明,所合成的LNMO具有LiMn_(2)O_(4)特有的立方晶系结构,其颗粒尺寸为亚微米级.LNMO的高温电化学性能优异,在55℃,1和5 C的首次放电比容量分别为109.9和98.0 m Ah/g,分别循环300次后容量保持率为75.8%和80.5%;即使在55℃,10和15 C下分别循环1000次后仍具有48.4%和49.4%的容量保持率,而未掺杂的LiMn_(2)O_(4)于15 C循环1000次后容量损失高达98%.LNMO在55℃有较高的Li^(+)扩散系数(D=3.86×10^(-15)cm^(2)/s)和较小的电荷转移阻抗(循环前、后R_(ct)=158.0和279.8Ω)以及较低的表观活化能(E_(a)=17.63 k J/mol),说明Ni掺杂能够提高Li^(+)在尖晶石型LiMn_(2)O_(4)内的扩散速率及减小锂离子在脱嵌过程中的能垒,从而提高锂离子的扩散速率和倍率性能.对LNMO于55℃循环1000次后的极片进行X射线衍射(XRD)分析,发现LNMO电极材料的晶体结构基本保持不变,表明Ni掺杂提高了锰酸锂材料在55℃长循环过程中的晶体结构稳定性,有效抑制了Jahn-Teller效应及Mn的溶解,显著提升了其高温电化学性能.本工作为尖晶石LiMn_(2)O_(4)电极材料在高温方面的应用提供了借鉴.
基金supported by the University of Macao(SRG2014-00019-FHSMYRG2015-00230-FHS+4 种基金MYRG2016-00005-FHS)the Affiliated Brain Hospital of Guangzhou Medical University(2016YFC09063022014Y2-001052015BAI13B02)Science and Technology Department of Guangdong Province major science and technology(2016B010108003)
文摘Hepatitis B virus （HBV） reactivation and recurrence are common in patients undergoing immunosuppression therapy. Tumor necrosis factor （TNF） blockage therapy is effective for the treatment of many autoimmune inflammatory diseases. However, the role of TNF-a blockage therapy in the innate and adaptive immune responses against HBV is still not clear. A detailed analysis of HBV infection under TNF-a blockage therapy is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV clearance and T-cell responses were analyzed in a HBV-transfected mouse model under anti-TNF blockage therapy. Our results demonstrated that under TNF-a blockage therapy, HBV viral clearance was impaired with persistent elevated HBV viral load in a dose- and temporal-dependent manner. The impairment of HBV clearance under anti-TNF-a blockage therapy occurred at early time points after HBV infection. In addition, TNF-a blockade maintained a higher serum HBV viral load and increased the number of intrahepatic programmed cell death （PD）- 1highCD127low exhausted T cells. Furthermore, TNF-a blockade abolished Toll-like receptor 9 （TLR9） ligand-induced facilitation of HBV viral clearance. Taken together, TNF-a blockade impairs HBV clearance and enhances viral load, and these effects depend on early administration after HBV infection. Our results here demonstrate that early TNF-a blockade reduces viral clearance and persistently maintains elevated HBV viral load in a mouse model, suggesting that HBV may reactivate during theraoy with TNF-a-blocking agents.
基金supported by grants from the National Health Research Institute(NHRI-EX95-9532SI)National Science Council,Taiwan(NSC90-2314B075B003 and NSC91-2320B-002)China Medical University(CMU96-266,CMU97-299).
文摘Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa,leading to chronic gastritis,peptic ulcers,gastric carcinoma and gastric mucosa-associated lymphoid tissue(MALT)lymphomas.Recent studies have shown that apoptosis of gastric epithelial cells is increased during H.pylori infection.Apoptosis induced by microbial infections are factors implicated in the pathogenesis of H.pylori infection.The enhanced gastric epithelial cell apoptosis in H.pylori infection has been suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology.In addition to directly triggering apoptosis,H.pylori induces sensitivity to tumor-necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis in gastric epithelial cells via modulation of TRAIL apoptosis signaling.Moreover,H.pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis.In H.pylori infection,there was significantly increased CCR61CD31 T-cell infiltration in the gastric mucosa,and the CCR6 ligand,CCL20 chemokine,was selectively expressed in inflamed gastric tissues.These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting T cells to the sites of inflammation in the gastric mucosa during Helicobacter infection.Through these mechanisms,chemokine-mediated T lymphocyte trafficking into inflamed epithelium is initiated and the mucosal injury in Helicobacter infection is induced.This article will review the recent novel findings on the interactions of H.pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology,including gastric inflammation,mucosal damage and development of MALT lymphomas.
基金This work was supported by grants from the National Science Council,Taiwan(NSC 101-2321-B-002-008 and 104-2314-B-281-002-,MOST 105-2320-B-002-034-and 105-2320-B-038-065-)。
文摘Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been implicated in the regulation ofinflammation in rheumatoid arthritis (RA), primarily due to its ability to promote apoptosis in synoviocytes andinfiltrating lymphocytes. The aim of this study was to investigate the immunomodulatory mechanism and role ofTRAIL in inflammatory arthritis. We created an animal model of inflammatory arthritis and demonstrated that TRAILsignificantly inhibited joint inflammation and reduced the severity of arthritis. The suppression of joint inflammationwas not due to the TRAIL-mediated induction of apoptosis in T cells, macrophages or synovial fibroblasts. Incontrast, TRAIL directly inhibited T-cell proliferation and suppressed the production of cytokines, which indicatedthat TRAIL exerted its anti-inflammatory effects by direct inhibition of T-cell activation. Moreover, TRAIL receptor(TRAIL-R)-knockout mice developed more severe disease, and the protective effects of TRAIL were abolished in theexperimental arthritis model in TRAIL-R knockout mice. From these results, we conclude that TRAIL suppressesjoint inflammation via an apoptosis-independent pathway and directly inhibits T-cell activation. Our results providea novel apoptosis-independent, immune regulatory role for TRAIL in suppressing inflammatory arthritis and shedlight on the development of effective new therapies for autoimmune inflammatory diseases.
基金supported by grants from the Ministry of Science and Technology(MOST 105-2320-B-038-065,MOST 106-2320-B-038-0193,MOST 107-2321-B-002-003,and MOST 108-2320-B-002-036-MY3).
文摘Persistent hepatitis B virus(HBV)infection results in chronic liver diseases that may progress to chronic hepatitis,liver cirrhosis,and subsequent hepatocellular carcinoma.Previous studies demonstrated that adaptive immunity,in particular CD8 T cells,is critical in HBV elimination.Recent studies have revealed a distinct tissue-localized T cell lineage,tissue-resident memory(TRM)cells,that is crucial for protective immunity in peripheral tissues.In this study,we showed that treatment with an anti-asialo GM1(ASGM1)antibody(Ab),which depletes NK cells,led to impairment of HBV clearance in a mouse animal model.Unexpectedly,the ability to clear HBV was not significantly impaired in NFIL3 KO mice,which are deficient in NK cells,implying that other non-NK ASGM1-positive immune cells mediate HBV clearance.We isolated intrahepatic ASGM1-positive cells from NFIL3 KO mice and analyzed the immune phenotype of these cells.Our results demonstrated a distinct population of CD44+LFA-1hi CD8 T cells that were the major intrahepatic ASGM1-positive immune cells in NFIL3 KO mice.Importantly,transcriptome analysis revealed that these ASGM1-positive CD8 T cells had distinct gene profiles and shared a similar core gene signature with TRM cells.In addition to both transcriptional and phenotypic liver residency characteristics,ASGM1-positive CD8 T cells were able to home to and be retained in the liver after adoptive transfer.Taken together,our study results indicate that these ASGM1-positive liver-resident CD8 T cells are the major effector immune cells mediating anti-HBV immunity.
基金financially supported by a grant from the Ministry of Science and Technology(MOST),Taiwan。
文摘The immunopathogenesis of hepatitis B virus(HBV)involves a complex interaction of innate and adaptive immune response associated with several cytokines.However,due to experimental limitations,very limited and even no activation of the innate immune response can be demonstrated in acute HBV infection.The role of innate immunity and the key innate effectors for HBV clearance is still uncertain.It is also not clear whether clinical use of TNF inhibitors in treating rheumatoid arthritis and other autoimmune disease patients with chronic HBV infection would affect viral reactivation.However,in a recent paper in Cell Mol Immunol,Chyuan et al.reported that under TNF-αblockade,HBV viral clearance was impaired with persistent elevated HBV viral load in a dose and temporal-dependent manner.1 It demonstrates that a deficiency of TNF-αreduces viral clearance and promotes HBV persistence in a mouse model,and the impairment of HBV clearance under anti-TNF-αoccurs at an early time point of HBV infection,suggesting that HBV may reactivate during therapy with TNF inhibitors.The results together with previous reports support that TNF is a key innate cytokine required to clear HBV.2,3 It also provides evidence that therapy with TNF inhibitors may impair immune response to HBV clearance.
