Al_(1-x)In_(x)N, a Ⅲ-nitride semiconductor material, is currently of great research interest due to its remarkable physical properties and chemical stability. When the Al and In compositions are tuned, its band-gap e...Al_(1-x)In_(x)N, a Ⅲ-nitride semiconductor material, is currently of great research interest due to its remarkable physical properties and chemical stability. When the Al and In compositions are tuned, its band-gap energy varies from 0.7 eV to 6.2 eV, which shows great potential for application in photodetectors. Here, we report the fabrication and performance evaluation of integrated Al_(1-x)In_(x)N on a free-standing GaN substrate through direct radio-frequency magnetron sputtering.The optical properties of Al_(1-x)In_(x)N will be enhanced by the polarization effect of a heterostructure composed of Al_(1-x)In_(x)N and other Ⅲ-nitride materials. An Al_(1-x)In_(x)N/Ga N visible-light photodetector was prepared by semiconductor fabrication technologies such as lithography and metal deposition. The highest photoresponsivity achieved was 1.52 A·W^(-1)under 365 nm wavelength illumination and the photodetector was determined to have the composition Al0.75In0.25N/GaN.A rise time of 0.55 s was observed after transient analysis of the device. The prepared Al_(1-x)In_(x)N visible-light photodetector had a low dark current, high photoresponsivity and fast response speed. By promoting a low-cost, simple fabrication method,this study expands the application of ternary alloy Al_(1-x)In_(x)N visible-light photodetectors in optical communication.展开更多
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved b...Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.展开更多
BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ru...BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.展开更多
Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in...Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in the National Comprehensive Cancer Network(NCCN)guidelines(version 2.2017)for CML.Indeed,various studies have confirmed the feasibility of discontinuing TKI therapy.In this study,we analyzed data from 45 CML patients who had discontinued TKI therapy.Univariate analysis was performed to predict factors that were potentially related to treatment-free remission(TFR)and identify the differences between early relapse and late relapse.Out of the 45 patients,20 exhibited molecular relapse after a median follow-up of 18 months(range,1-54 months),and the estimated TFR at 24 months was 40%.The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes.Our results indicate that TKI discontinuation could be successfully put into practice in China.展开更多
OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal dox...OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.展开更多
Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)rema...Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.展开更多
The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor ...The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36), is a novel variant of ERα (as known ER-α66) which can transduce both estrogenand antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 innerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P 0.01). Also, NF-κB subunit entered nuclear after transfection;Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.展开更多
To construct the recombinant expression vector for CD80-IgG fusion gene and to express it functionally in Chinese hamster ovary cells in order to be used as an effective method to eliminate the immune escape of leukem...To construct the recombinant expression vector for CD80-IgG fusion gene and to express it functionally in Chinese hamster ovary cells in order to be used as an effective method to eliminate the immune escape of leukemic cells, the cDNA encoding the signal and extracellular domains of murine CD80 was generated by PCR amplification from plasmid pcDNA/B7 containing the full length cDNA of murine CD80 and those of murine IgG1, in which the Fc fragment was obtained through RT-PCR amplification from murine spleen cells. These two cDNAs were then cloned in tandem into eukaryotic expression vector pcDNA3.0 and the resultant recombinant plasmid pcDNA/CD80-IgG was then transfected to Chinese hamster ovary cells with liposome transfection reagent. The cell clones constitutively expressing CD80-IgG fusion protein were obtained by G418 screening. Western blotting and dot ELISA assay were used to detect the expression of the fusion protein in the supernatants of these cells. Meanwhile, the fusion protein expressed was then purified with affinity chromatography, and its biological activity was demonstrated by flow cytometry, MTT colorimetry and ELISA assay. The experimental results showed that these two inserts were successfully cloned into plasmid pcDNA3.0, and the highly purified fusion protein was obtained. This fusion protein was proved to be able to upregulate the density of CD80 on leukemic cells, deliberately promote the proliferative reactions of mouse allogenic lymphocytes and increase the killing activity against WEHI-3 cells from 49.7% up to 84.6%. In addition, this fusion protein could also enhance the IL-2 secretion from allogenic lymphocytes activated by tumor-specific antigens. It is concluded that the recombinant vector constructed can be functionally expressed in the mammalian cells, thus providing a solid foundation for the further investigation on the mechanism to eliminate the immune escape of leukemic cells in vivo.展开更多
Open and dynamic environments lead to inher- ent uncertainty of Web service QoS (Quality of Service), and the QoS-aware service selection problem can be looked upon as a decision problem under uncertainty. We use an...Open and dynamic environments lead to inher- ent uncertainty of Web service QoS (Quality of Service), and the QoS-aware service selection problem can be looked upon as a decision problem under uncertainty. We use an empiri- cal distribution function to describe the uncertainty of scores obtained from historical transactions. We then propose an approach to discovering the admissible set of services in- cluding alternative services that are not dominated by any other alternatives according to the expected utility criterion. Stochastic dominance (SD) rules are used to compare two services with uncertain scores regardless of the distribution form of their uncertain scores. By using the properties of SD rules, an algorithm is developed to reduce the number of SD tests, by which the admissible services can be reported pro- gressively. We prove that the proposed algorithm can be run on partitioned or incremental alternative services. Moreover, we achieve some useful theoretical conclusions for correct pruning of unnecessary calculations and comparisons in each SD test, by which the efficiency of the SD tests can be im- proved. We make a comprehensive experimental study using real datasets to evaluate the effectiveness, efficiency, and scal- ability of the proposed algorithm.展开更多
This study explored the effects of nuclear factor-kappa B(NF-κB)inhibitor Bay 11-7082 on Fas/FasL system and Fas-mediated apoptosis in cell line HL-60 cells.The mRNA and protein levels of Fas,FasL,and X-linked inhibi...This study explored the effects of nuclear factor-kappa B(NF-κB)inhibitor Bay 11-7082 on Fas/FasL system and Fas-mediated apoptosis in cell line HL-60 cells.The mRNA and protein levels of Fas,FasL,and X-linked inhibitor of apoptosis protein(XIAP)were detected by reverse transcription-polymerase chain reaction(RT-PCR)and flow cytometry(FCM);the level of sFasL was evaluated by enzyme-linked immunosorbent assay(ELISA);and apoptosis was determined by FCM.After treatment with Bay 11-7082,the mRNA and protein levels of FasL and XIAP in HL-60 cells were significantly lower than in the controls(P<0.05),but the mRNA and protein levels of Fas and sFasL did not change significantly(P>0.05).Apoptotic rate of HL-60 cells treated with Bay 11-7082 was significantly higher than in the controls(P<0.05).Therefore,we conclude that Bay 11-7082 can enhance Fas-mediated apoptosis in HL-60 cells by downregulating FasL and XIAP levels.展开更多
Proteinase-activated receptors(PARs)are a novel subclass of seven transmembrane-spanning,G protein-coupled receptors.PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many phys...Proteinase-activated receptors(PARs)are a novel subclass of seven transmembrane-spanning,G protein-coupled receptors.PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes includ-ing inflammation and immune response.However,little is known about the function of PAR-1,2 in acute graft vs host disease(GVHD).In the present study,wefirst detected the expression of PAR-1,2 protein and mRNA in a murine model of acute GVHD using the methods of immunohis-tochemistry,Western blot and quantitative real-time polymerase chain reaction(PCR).Syngeneic hematopoie-tic stem cell transplantation(HSCT)mice served as controls.The relative gene expression level of PAR-1 was significantly increased in the skin,liver,small intestine of allogeneic HSCT mice(in skin:0.039�0.013 vs 0.008�0.002 of controls,P=0.009;in liver:0.165�0.006 vs 0.017�0.006 of controls,P=0.004;in small intestine:0.215�0.009 vs 0.016�0.002 of con-trols,P=0.003),but not in the stomach,lung and kidney of allogeneic HSCT mice(P>0.05).PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice(in liver:0.010�0.002 vs 0.003�0.001 of controls,P=0.008;in small intestine:0.006�0.001 vs 0.003�0.001 of controls,P=0.024)was increased significantly,but PAR-2 mRNA expression in the other organs(P>0.05)was not found to be significantly elevated.PAR-1,2 protein expression was in accordance with the mRNA expression,as shown by Western blot.Using immunohistochemistry the present study demon-strated that there was strong PAR-1,2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD.Ourfindings of markedly increased expression of PAR-1,2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.展开更多
基金Project supported by the National Natural Science Foundation of China (Grant Nos. 61974144, 62004127, and 12074263)Key-Area Research and Development Program of Guangdong Province (Grant Nos. 2020B010174003 and 2020B010169001)+2 种基金Guangdong Science Foundation for Distinguished Young Scholars (Grant No. 2022B1515020073)the Science and Technology Foundation of Shenzhen (Grant No. JSGG20191129114216474)the Open Project of State Key Laboratory of Functional Materials for Informatics。
文摘Al_(1-x)In_(x)N, a Ⅲ-nitride semiconductor material, is currently of great research interest due to its remarkable physical properties and chemical stability. When the Al and In compositions are tuned, its band-gap energy varies from 0.7 eV to 6.2 eV, which shows great potential for application in photodetectors. Here, we report the fabrication and performance evaluation of integrated Al_(1-x)In_(x)N on a free-standing GaN substrate through direct radio-frequency magnetron sputtering.The optical properties of Al_(1-x)In_(x)N will be enhanced by the polarization effect of a heterostructure composed of Al_(1-x)In_(x)N and other Ⅲ-nitride materials. An Al_(1-x)In_(x)N/Ga N visible-light photodetector was prepared by semiconductor fabrication technologies such as lithography and metal deposition. The highest photoresponsivity achieved was 1.52 A·W^(-1)under 365 nm wavelength illumination and the photodetector was determined to have the composition Al0.75In0.25N/GaN.A rise time of 0.55 s was observed after transient analysis of the device. The prepared Al_(1-x)In_(x)N visible-light photodetector had a low dark current, high photoresponsivity and fast response speed. By promoting a low-cost, simple fabrication method,this study expands the application of ternary alloy Al_(1-x)In_(x)N visible-light photodetectors in optical communication.
文摘Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.
文摘BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.
基金the National Natural Science Foundation of China(No.81500136 and No.81670145).
文摘Discontinuation of tyrosine kinase inhibitor(TKI)therapy after achieving a persistent deep molecular response(DMR)is an urgently needed treatment goal for chronic myeloid leukemia(CML)patients and has been included in the National Comprehensive Cancer Network(NCCN)guidelines(version 2.2017)for CML.Indeed,various studies have confirmed the feasibility of discontinuing TKI therapy.In this study,we analyzed data from 45 CML patients who had discontinued TKI therapy.Univariate analysis was performed to predict factors that were potentially related to treatment-free remission(TFR)and identify the differences between early relapse and late relapse.Out of the 45 patients,20 exhibited molecular relapse after a median follow-up of 18 months(range,1-54 months),and the estimated TFR at 24 months was 40%.The univariate analysis revealed that a high Sokal score and interruptions or dose reductions during TKI treatment were the only baseline factors associated with poor outcomes.Our results indicate that TKI discontinuation could be successfully put into practice in China.
文摘OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.
文摘Although the advent of tyrosine kinase inhibitors(TKIs)has dramatically improved the survival of patients with chronic myeloid leukaemia(CML),acquired drug resistance and TKI-insensitive leukaemic stem cells(LSCs)remain major obstacles to a CML cure.In recent years,the reprogramming of mitochondrial metabolism has emerged as a hallmark of cancers,including CML,and in turn may be exploited for therapeutic purposes.Here,we investigated the effects of several drugs on the mitochondrial function of the CML cell line K562 and found that 5-aminoimidazole-4-carboxamide ribotide(AICAR)and decitabine could effectively increase the ATP content and mitochondrial biogenesis.In addition,these two drugs induced cell cycle arrest and a decrease in colony-forming capacity and promoted K562 cell differentiation.Moreover,we demonstrated that treatment with AICAR or decitabine enhanced the sensitivity o f K562 cells to imatinib,as evidenced by a combination treatment assay.Altogether,our findings indicate that TKIs combined with mitochondrial regulation may provide a therapeutic strategy for the treatment of CML.
文摘The nuclear transcription factors κB (NF-κB) is widely existing in various kinds of cell types in the nervous system and plays an important role in neuron apoptosis and neurodegenerative diseases. Estrogen receptor alpha 36 (ER-α36), is a novel variant of ERα (as known ER-α66) which can transduce both estrogenand antiestrogen-dependent activation of MAPK signal pathway and stimulate cell growth. Here, we aimed to detect the effect of ER-α36 gene silencing on the expression of NF-κB in normal cultured PC12 cells and to provide an experimental foundation for understanding the function of ER-α36 innerve cells. PC12 cells with ER-α36 expression knocked down by the shRNA method. Then Western blot and immunocytochemical staining were performed to detect the expression and translocation of NF-κB after transfection. The results showed that NF-κB expression was significantly higher comparing with the control group after transfection (P 0.01). Also, NF-κB subunit entered nuclear after transfection;Immunofluorescence staining and immunocytochemical staining of PC12 cells demonstrated that ER-α36 was expressed mainly on the plasma membrane and on the cell nucleus membrane. These data indicate that ER-α36 gene silencing can increase the expression of NF-κB and promote its nuclear translocation in PC12 cells.
文摘To construct the recombinant expression vector for CD80-IgG fusion gene and to express it functionally in Chinese hamster ovary cells in order to be used as an effective method to eliminate the immune escape of leukemic cells, the cDNA encoding the signal and extracellular domains of murine CD80 was generated by PCR amplification from plasmid pcDNA/B7 containing the full length cDNA of murine CD80 and those of murine IgG1, in which the Fc fragment was obtained through RT-PCR amplification from murine spleen cells. These two cDNAs were then cloned in tandem into eukaryotic expression vector pcDNA3.0 and the resultant recombinant plasmid pcDNA/CD80-IgG was then transfected to Chinese hamster ovary cells with liposome transfection reagent. The cell clones constitutively expressing CD80-IgG fusion protein were obtained by G418 screening. Western blotting and dot ELISA assay were used to detect the expression of the fusion protein in the supernatants of these cells. Meanwhile, the fusion protein expressed was then purified with affinity chromatography, and its biological activity was demonstrated by flow cytometry, MTT colorimetry and ELISA assay. The experimental results showed that these two inserts were successfully cloned into plasmid pcDNA3.0, and the highly purified fusion protein was obtained. This fusion protein was proved to be able to upregulate the density of CD80 on leukemic cells, deliberately promote the proliferative reactions of mouse allogenic lymphocytes and increase the killing activity against WEHI-3 cells from 49.7% up to 84.6%. In addition, this fusion protein could also enhance the IL-2 secretion from allogenic lymphocytes activated by tumor-specific antigens. It is concluded that the recombinant vector constructed can be functionally expressed in the mammalian cells, thus providing a solid foundation for the further investigation on the mechanism to eliminate the immune escape of leukemic cells in vivo.
基金This work was partially supported by the National Natural Science Foundation of China (Grand No. 71161015, 61462056, 61163003, 61472345 and 61462051), the Applied Fundamental Re- search Project of Yunnan Province (2014FA028, 2014FA023, 2014FB133, 2013FA013 and 2013FA032), and the Yunnan Provincial Foundation for Leaders of Disciplines in Science and Technology (2012HB01M). The au- thors appreciate the reviewers for their extensive and informative comments for the improvement of this paper.
文摘Open and dynamic environments lead to inher- ent uncertainty of Web service QoS (Quality of Service), and the QoS-aware service selection problem can be looked upon as a decision problem under uncertainty. We use an empiri- cal distribution function to describe the uncertainty of scores obtained from historical transactions. We then propose an approach to discovering the admissible set of services in- cluding alternative services that are not dominated by any other alternatives according to the expected utility criterion. Stochastic dominance (SD) rules are used to compare two services with uncertain scores regardless of the distribution form of their uncertain scores. By using the properties of SD rules, an algorithm is developed to reduce the number of SD tests, by which the admissible services can be reported pro- gressively. We prove that the proposed algorithm can be run on partitioned or incremental alternative services. Moreover, we achieve some useful theoretical conclusions for correct pruning of unnecessary calculations and comparisons in each SD test, by which the efficiency of the SD tests can be im- proved. We make a comprehensive experimental study using real datasets to evaluate the effectiveness, efficiency, and scal- ability of the proposed algorithm.
文摘This study explored the effects of nuclear factor-kappa B(NF-κB)inhibitor Bay 11-7082 on Fas/FasL system and Fas-mediated apoptosis in cell line HL-60 cells.The mRNA and protein levels of Fas,FasL,and X-linked inhibitor of apoptosis protein(XIAP)were detected by reverse transcription-polymerase chain reaction(RT-PCR)and flow cytometry(FCM);the level of sFasL was evaluated by enzyme-linked immunosorbent assay(ELISA);and apoptosis was determined by FCM.After treatment with Bay 11-7082,the mRNA and protein levels of FasL and XIAP in HL-60 cells were significantly lower than in the controls(P<0.05),but the mRNA and protein levels of Fas and sFasL did not change significantly(P>0.05).Apoptotic rate of HL-60 cells treated with Bay 11-7082 was significantly higher than in the controls(P<0.05).Therefore,we conclude that Bay 11-7082 can enhance Fas-mediated apoptosis in HL-60 cells by downregulating FasL and XIAP levels.
基金supported by the National Natural Science Foundation of China(Grant No.30600570).
文摘Proteinase-activated receptors(PARs)are a novel subclass of seven transmembrane-spanning,G protein-coupled receptors.PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes includ-ing inflammation and immune response.However,little is known about the function of PAR-1,2 in acute graft vs host disease(GVHD).In the present study,wefirst detected the expression of PAR-1,2 protein and mRNA in a murine model of acute GVHD using the methods of immunohis-tochemistry,Western blot and quantitative real-time polymerase chain reaction(PCR).Syngeneic hematopoie-tic stem cell transplantation(HSCT)mice served as controls.The relative gene expression level of PAR-1 was significantly increased in the skin,liver,small intestine of allogeneic HSCT mice(in skin:0.039�0.013 vs 0.008�0.002 of controls,P=0.009;in liver:0.165�0.006 vs 0.017�0.006 of controls,P=0.004;in small intestine:0.215�0.009 vs 0.016�0.002 of con-trols,P=0.003),but not in the stomach,lung and kidney of allogeneic HSCT mice(P>0.05).PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice(in liver:0.010�0.002 vs 0.003�0.001 of controls,P=0.008;in small intestine:0.006�0.001 vs 0.003�0.001 of controls,P=0.024)was increased significantly,but PAR-2 mRNA expression in the other organs(P>0.05)was not found to be significantly elevated.PAR-1,2 protein expression was in accordance with the mRNA expression,as shown by Western blot.Using immunohistochemistry the present study demon-strated that there was strong PAR-1,2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD.Ourfindings of markedly increased expression of PAR-1,2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.