We investigate the dynamics of the entanglement and quantum discord of two qubits in liquid state homonuclear nuclear magnetic resonance. Applying a phenomenological description for nuclear magnetic resonance under a ...We investigate the dynamics of the entanglement and quantum discord of two qubits in liquid state homonuclear nuclear magnetic resonance. Applying a phenomenological description for nuclear magnetic resonance under a relaxation process, and taking a group of typical parameters of nuclear magnetic resonance, we show that when a zero initial state experiences a relaxation process, its entanglement disappears completely after a sequence of so-called sudden deaths and revivals, while the quantum discord retains remarkable values after a sequence of oscillations. That is to say, the quantum discord is more robust than entanglement.展开更多
Colorectal carcinogenesis(CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severit...Colorectal carcinogenesis(CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APC^(min/+) mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.展开更多
Nuclear domain 10(ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found i...Nuclear domain 10(ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found in the nucleus. They are known by a number of other names, including Promyelocytic Leukemia bodies(PML bodies), Kremer bodies, and PML oncogenic domains. ND10 are frequently associated with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating gene transcription. ND10 were originally characterized using human autoantisera, which recognizes Speckled Protein of 100 kD a, from patients with primary biliary cirrhosis. At the immunohistochemical level, ND10 appear as nuclear punctate structures, with 10 indicating the approximate number of dots per nucleus observed. ND10 do not colocalize with kinetochores, centromeres, sites of mR NA processing, or chromosomes. Resistance of ND10 antigens to nuclease digestion and salt extraction suggest that ND10 are associated with the nuclear matrix.They are often identified by immunofluorescent assay using specific antibodies against PML, Death domainassociated protein, nuclear dot protein(NDP55), and so on. The role of ND10 has long been the subject of investigation, with the specific connection of ND10 and viral infection having been a particular focus for almost 20 years. This review summarizes the relationship of ND10 and viral infection. Some future study directions are also discussed.展开更多
OBJECTIVE To evaluate whether the IDO1 inhibitor 1-methyl-L-tryptophan(1-MT)combine calcium influx inhibitor carboxyamidotriazole(CAI)could further enhance the suppression of programmed death 1(PD-1)in CD8^+T cells an...OBJECTIVE To evaluate whether the IDO1 inhibitor 1-methyl-L-tryptophan(1-MT)combine calcium influx inhibitor carboxyamidotriazole(CAI)could further enhance the suppression of programmed death 1(PD-1)in CD8^+T cells and investigate the curative effect of the combined use.METHODS CD8^+T cells were isolated from normal mice spleen by negative selection using magnetic cell separation.The isolated CD8^+T cells were cultured in RPMI 1640 medium containing 10%FBS and 100 U·mL^(-1)IL-2 and activated by the addition of anti-CD3 and anti-CD28(1 g·L^(-1) each mabs).CD8^+T cells were pretreated for 48 h with drug and the fluo-3 as a marker of intracellular calcium concentration was detected by flow cytometry.The calcineurin(Ca N)levels were assayed with ELISA in CD8^+T cells after 48 h incubation with 10μm CAI.The nuclear translocations of NFAT and AHR were detected by immunofluorescent staining after 48 h of drug treatment.The expression of PD-1 in CD8^+T cells was analyzed by flow cytometry.RESULTS Intracellular fluorescent intensity was markedly debase due to CAI treatment(P<0.01).Meanwhile,the changes of CaN content had a resembled correlation(P<0.01).Immunofluorescence experiment showed that after combination therapy the transfer of NFAT and AHR in nuclear substantially reduced.Flow cytometry revealed that after the combination caused a significant decrease in PD-1 expression in CD8^+T cells.CONCLUSION CAI and 1-MT could inhibit markedly the expression of PD-1 in CD8^+T cells by inhibiting the nuclear translocation of NFAT and AHR,respectively and the combination of them has synergetic effect.展开更多
目的探讨程序性死亡蛋白配体-1(programmed death ligand-1,PD-L1)过表达对子宫内膜癌细胞Ishikawa上皮间质转化的影响及可能机制。方法使用实验室构建的PD-L1过表达稳转细胞株Ishikawa/PD-L1及稳转空载对照组Ishikawa/EV,qPCR及Western...目的探讨程序性死亡蛋白配体-1(programmed death ligand-1,PD-L1)过表达对子宫内膜癌细胞Ishikawa上皮间质转化的影响及可能机制。方法使用实验室构建的PD-L1过表达稳转细胞株Ishikawa/PD-L1及稳转空载对照组Ishikawa/EV,qPCR及Western blot法检测PD-L1过表达效率,Transwell和划痕实验检测细胞迁移能力和侵袭活性,Western blot法检测上皮间质转化相关蛋白表达和核转录因子-κB(nuclear factor kappa-B,NF-κB)磷酸化水平。结果与对照组相比,Ishikawa/PD-L1迁移能力与侵袭活性显著增强,Vimentin、N-cadherin、p-p65蛋白表达明显升高,E-cadherin表达明显下调。结论PD-L1可通过诱导NF-κB信号通路激活,促进上皮间质转化,进而增强子宫内膜癌细胞的迁移、侵袭能力。展开更多
目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。...目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。方法选择2021年1月至2023年12月于南阳市第一人民医院治疗的62例胃癌患者手术切除后组织标本及癌旁正常组织标本分别作为胃癌组及癌旁组。62例患者中,男39例,女23例,年龄(61.86±2.31)岁,肿瘤长径(4.92±0.53)cm。采用免疫组织化学染色法检测NF-κB、PD-1、PD-L1表达情况。比较两组NF-κB、PD-1、PD-L1表达阳性率,分析其与胃癌临床病理特征的关系。采用χ^(2)检验。结果胃癌组NF-κB、PD-1、PD-L1表达阳性率高于癌旁组[83.87%(52/62)比33.87%(21/62)、75.81%(47/62)比30.65%(19/62)、80.65%(50/62)比40.32%(25/62)],差异均有统计学意义(χ^(2)=32.008、25.396、21.088,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者NF-κB表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[92.68%(38/41)比66.67%(14/21)、94.74(36/38)比66.67%(16/24)、92.31%(36/39)比69.57%(16/23)],差异均有统计学意义(χ^(2)=5.158、6.619、3.978,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-1表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[85.37%(35/41)比57.14%(14/21)、89.47%(34/38)比54.17%(13/24)、89.74%(35/39)比52.17%(12/23)],差异均有统计学意义(χ^(2)=6.031、9.998、11.135,均P<0.05);低分化、肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-L1表达阳性率高于高中分化、黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[96.00%(24/25)比70.27%(26/37)、90.24%(37/41)比61.90%(13/21)、92.11%(35/38)比62.50%(15/24)、94.87%(37/39)比56.52%(13/23)],差异均有统计学意义(χ^(2)=4.787、5.445、6.472、11.286,均P<0.05)。结论胃癌组织中NF-κB、PD-1、PD-L1表达阳性率升高,且NF-κB、PD-1表达与胃癌浸润深度、淋巴结转移及TNM分期有关,PD-L1表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期有关。展开更多
程序性死亡配体1(Programmed cell death ligand 1,PD-L1)是一种Ⅰ型跨膜蛋白,与程序性死亡受体1(Programmed cell death protein 1,PD-1)结合,诱导肿瘤免疫逃逸。靶向PD-1/PD-L1通路的临床免疫治疗逐渐开展,但在部分肿瘤治疗中未能取...程序性死亡配体1(Programmed cell death ligand 1,PD-L1)是一种Ⅰ型跨膜蛋白,与程序性死亡受体1(Programmed cell death protein 1,PD-1)结合,诱导肿瘤免疫逃逸。靶向PD-1/PD-L1通路的临床免疫治疗逐渐开展,但在部分肿瘤治疗中未能取得满意的效果。近年来研究发现PD-L1不仅定位于细胞膜,还定位在细胞质、细胞核或者细胞外,并且发挥相应的功能。本文结合近年来国内外的研究,从细胞核PD-L1(Nuclear PD-L1,nPD-L1)的表达、转运、功能、检测及临床意义等方面进行综述。文献复习结果表明,PD-L1在多种肿瘤细胞核中表达。在外界刺激因素作用下,PD-L1可通过核转运蛋白、信号转导及转录激活蛋白3、蛋白激酶B、细胞外调节蛋白激酶等多个信号通路转运至细胞核内,调控肿瘤增殖和死亡、免疫、血管及干细胞生成。通过免疫组化等方法检测nPD-L1的表达,对肿瘤诊断、治疗、预后、监测及随访均有重要意义,nPD-L1有可能成为新的治疗靶点并进入临床应用。展开更多
基金supported by the Fundamental Research Funds for the Central Universities of China (Grant No. 2010scu23002)
文摘We investigate the dynamics of the entanglement and quantum discord of two qubits in liquid state homonuclear nuclear magnetic resonance. Applying a phenomenological description for nuclear magnetic resonance under a relaxation process, and taking a group of typical parameters of nuclear magnetic resonance, we show that when a zero initial state experiences a relaxation process, its entanglement disappears completely after a sequence of so-called sudden deaths and revivals, while the quantum discord retains remarkable values after a sequence of oscillations. That is to say, the quantum discord is more robust than entanglement.
基金Council of Scientific and Industrial research (CSIR),New Delhi for funding Colon cancer project [37(1364)/09/EMR-Ⅱ]
文摘Colorectal carcinogenesis(CRC) imposes a major health burden in developing countries. It is the third major cause of cancer deaths. Despite several treatment strategies, novel drugs are warranted to reduce the severity of this disease. Adenomatous polyps in the colon are the major culprits in CRC and found in 45% of cancers, especially in patients 60 years of age. Inflammatory polyps are currently gaining attention in CRC, and a growing body of evidence denotes the role of inflammation in CRC. Several experimental models are being employed to investigate CRC in animals, which include the APC^(min/+) mouse model, Azoxymethane, Dimethyl hydrazine, and a combination of Dextran sodium sulphate and dimethyl hydrazine. During CRC progression, several signal transduction pathways are activated. Among the major signal transduction pathways are p53, Transforming growth factor beta, Wnt/β-catenin, Delta Notch, Hippo signalling, nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathways. These signalling pathways collaborate with cell death mechanisms, which include apoptosis, necroptosis and autophagy, to determine cell fate. Extensive research has been carried out in our laboratory to investigate these signal transduction and cell death mechanistic pathways in CRC. This review summarizes CRC pathogenesis and the related cell death and signal transduction pathways.
基金Supported by A Pilot Grant from the National Center for Research Resources(G12 RR003050)the National Institute on Minority Health and Health Disparities(8G12MD007579-27)+2 种基金the National Institutes of Health(To Tang Q)an American Cancer Society Grant(117448-RSG-09-289-01-MPC)(To Tang Q)NIH/NCRR U54RR022762(To Tang Q)
文摘Nuclear domain 10(ND10) are spherical bodies distributed throughout the nucleoplasm and measuring around 0.2-1.0 μm. First observed under an electron microscope, they were originally described as dense bodies found in the nucleus. They are known by a number of other names, including Promyelocytic Leukemia bodies(PML bodies), Kremer bodies, and PML oncogenic domains. ND10 are frequently associated with Cajal bodies and cleavage bodies. It has been suggested that they play a role in regulating gene transcription. ND10 were originally characterized using human autoantisera, which recognizes Speckled Protein of 100 kD a, from patients with primary biliary cirrhosis. At the immunohistochemical level, ND10 appear as nuclear punctate structures, with 10 indicating the approximate number of dots per nucleus observed. ND10 do not colocalize with kinetochores, centromeres, sites of mR NA processing, or chromosomes. Resistance of ND10 antigens to nuclease digestion and salt extraction suggest that ND10 are associated with the nuclear matrix.They are often identified by immunofluorescent assay using specific antibodies against PML, Death domainassociated protein, nuclear dot protein(NDP55), and so on. The role of ND10 has long been the subject of investigation, with the specific connection of ND10 and viral infection having been a particular focus for almost 20 years. This review summarizes the relationship of ND10 and viral infection. Some future study directions are also discussed.
基金supported by National Natural Science Foundation of China(81402943)CAMS Major Collaborative Innovation Project(2016-I2M-1-011)PUMC Youth Fund(3332015168)
文摘OBJECTIVE To evaluate whether the IDO1 inhibitor 1-methyl-L-tryptophan(1-MT)combine calcium influx inhibitor carboxyamidotriazole(CAI)could further enhance the suppression of programmed death 1(PD-1)in CD8^+T cells and investigate the curative effect of the combined use.METHODS CD8^+T cells were isolated from normal mice spleen by negative selection using magnetic cell separation.The isolated CD8^+T cells were cultured in RPMI 1640 medium containing 10%FBS and 100 U·mL^(-1)IL-2 and activated by the addition of anti-CD3 and anti-CD28(1 g·L^(-1) each mabs).CD8^+T cells were pretreated for 48 h with drug and the fluo-3 as a marker of intracellular calcium concentration was detected by flow cytometry.The calcineurin(Ca N)levels were assayed with ELISA in CD8^+T cells after 48 h incubation with 10μm CAI.The nuclear translocations of NFAT and AHR were detected by immunofluorescent staining after 48 h of drug treatment.The expression of PD-1 in CD8^+T cells was analyzed by flow cytometry.RESULTS Intracellular fluorescent intensity was markedly debase due to CAI treatment(P<0.01).Meanwhile,the changes of CaN content had a resembled correlation(P<0.01).Immunofluorescence experiment showed that after combination therapy the transfer of NFAT and AHR in nuclear substantially reduced.Flow cytometry revealed that after the combination caused a significant decrease in PD-1 expression in CD8^+T cells.CONCLUSION CAI and 1-MT could inhibit markedly the expression of PD-1 in CD8^+T cells by inhibiting the nuclear translocation of NFAT and AHR,respectively and the combination of them has synergetic effect.
文摘目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。方法选择2021年1月至2023年12月于南阳市第一人民医院治疗的62例胃癌患者手术切除后组织标本及癌旁正常组织标本分别作为胃癌组及癌旁组。62例患者中,男39例,女23例,年龄(61.86±2.31)岁,肿瘤长径(4.92±0.53)cm。采用免疫组织化学染色法检测NF-κB、PD-1、PD-L1表达情况。比较两组NF-κB、PD-1、PD-L1表达阳性率,分析其与胃癌临床病理特征的关系。采用χ^(2)检验。结果胃癌组NF-κB、PD-1、PD-L1表达阳性率高于癌旁组[83.87%(52/62)比33.87%(21/62)、75.81%(47/62)比30.65%(19/62)、80.65%(50/62)比40.32%(25/62)],差异均有统计学意义(χ^(2)=32.008、25.396、21.088,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者NF-κB表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[92.68%(38/41)比66.67%(14/21)、94.74(36/38)比66.67%(16/24)、92.31%(36/39)比69.57%(16/23)],差异均有统计学意义(χ^(2)=5.158、6.619、3.978,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-1表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[85.37%(35/41)比57.14%(14/21)、89.47%(34/38)比54.17%(13/24)、89.74%(35/39)比52.17%(12/23)],差异均有统计学意义(χ^(2)=6.031、9.998、11.135,均P<0.05);低分化、肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-L1表达阳性率高于高中分化、黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[96.00%(24/25)比70.27%(26/37)、90.24%(37/41)比61.90%(13/21)、92.11%(35/38)比62.50%(15/24)、94.87%(37/39)比56.52%(13/23)],差异均有统计学意义(χ^(2)=4.787、5.445、6.472、11.286,均P<0.05)。结论胃癌组织中NF-κB、PD-1、PD-L1表达阳性率升高,且NF-κB、PD-1表达与胃癌浸润深度、淋巴结转移及TNM分期有关,PD-L1表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期有关。
文摘程序性死亡配体1(Programmed cell death ligand 1,PD-L1)是一种Ⅰ型跨膜蛋白,与程序性死亡受体1(Programmed cell death protein 1,PD-1)结合,诱导肿瘤免疫逃逸。靶向PD-1/PD-L1通路的临床免疫治疗逐渐开展,但在部分肿瘤治疗中未能取得满意的效果。近年来研究发现PD-L1不仅定位于细胞膜,还定位在细胞质、细胞核或者细胞外,并且发挥相应的功能。本文结合近年来国内外的研究,从细胞核PD-L1(Nuclear PD-L1,nPD-L1)的表达、转运、功能、检测及临床意义等方面进行综述。文献复习结果表明,PD-L1在多种肿瘤细胞核中表达。在外界刺激因素作用下,PD-L1可通过核转运蛋白、信号转导及转录激活蛋白3、蛋白激酶B、细胞外调节蛋白激酶等多个信号通路转运至细胞核内,调控肿瘤增殖和死亡、免疫、血管及干细胞生成。通过免疫组化等方法检测nPD-L1的表达,对肿瘤诊断、治疗、预后、监测及随访均有重要意义,nPD-L1有可能成为新的治疗靶点并进入临床应用。
