Phosphatase of Regenerating Liver-3 （PRL-3） is a newly identified colorectal cancer metastasis-related protein, which is a 22 kDa non-classical protein tyrosine phosphatase with a C-terminal prenylation motif. In th...Phosphatase of Regenerating Liver-3 （PRL-3） is a newly identified colorectal cancer metastasis-related protein, which is a 22 kDa non-classical protein tyrosine phosphatase with a C-terminal prenylation motif. In this study, the inhibition kinetics of protein tyrosine phosphatases（PTPs） by a fluorescent substrate, 6,8-difluoro-4-methylumbelliferyl phosphate（DiFMUP） was evaluated. PRL-3 exhibits classical Michaelis-Menten kinetics with a Vmax value of 11.3 μmol · L^-l · min^-1 Analysis of PRL-3 by a Michaelis-Menten plot and a double-reciprocal plot indicated that the inhibitor magnolol can cause Km to increase, but does not alter the Vmax value, which suggests the competitive inhibition of PRL-3. At the same time, it was found that DiFMUP is a more sensitive substrate for PRL-3 than para-nitrophenyl phosphate（pNPP） that is more frequently used at present. Furthermore, the method of screening for PTPs by the use of DiFMUP was developed, which studied the acceptance of DiFMUP by other PTPs.展开更多
A series of new flavanone derivatives of farrerol was designed and synthesized as a potent inhibitor of vascular smooth muscle cells（VSMCs） vegetation according to a convenient method. The structures of all the synt...A series of new flavanone derivatives of farrerol was designed and synthesized as a potent inhibitor of vascular smooth muscle cells（VSMCs） vegetation according to a convenient method. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR and EIHR-MS. The biological activities of these compounds against VSMCs in vitro were evaluated. The assay results indicate that two compounds, 5,7-dihydroxy-6,8-dimethyl- 2-（2-nitrophenyl）chroman-4-one（7f） and 2,3-dibromo-4,5-dihydroxydiphenylmethanone（7j） exhibited high activity against VSMCs in vitro with IC50 values of 9.9 and 6.7 μmol/L, respectively, and the preliminary structure-activity relationship（SAR） was described.展开更多
Recent studies suggest that PRL-3 is involved in the metastasis of colorectal cancer, but the mechanism concerning that has not been well defined. This article expresses PRL-1, PRL-2, and PRL-3 and the catalytically i...Recent studies suggest that PRL-3 is involved in the metastasis of colorectal cancer, but the mechanism concerning that has not been well defined. This article expresses PRL-1, PRL-2, and PRL-3 and the catalytically inactive mutant forms of those enzymes in SW620 and SW480 cells, two human cell lines derived from non-metastatic cancer and metastatic colorectal cancer, respectively. While the expression of the native forms of PRLs promotes the spreading, adhesion, and proliferation of these cells, the expression of their mutant forms inhibits the earlier-mentioned processes. These data thus provide a cellular mechanism for the role of PRL-3 in tumor metastasis and suggest that all the three PRLs have similar functions.展开更多
目前自适应软件正在为众多领域系统提供着对运行环境的适应能力.如何建立一种能够保障识别质量的自适应分析方法,使之可从运行环境中快速且准确地识别出异常事件,是确保自适应软件长期稳定运行所必须考虑的研究问题之一.当前运行环境的...目前自适应软件正在为众多领域系统提供着对运行环境的适应能力.如何建立一种能够保障识别质量的自适应分析方法,使之可从运行环境中快速且准确地识别出异常事件,是确保自适应软件长期稳定运行所必须考虑的研究问题之一.当前运行环境的不确定性给该问题的攻关带来两方面的挑战:其一,现有分析方法一般通过预先建立环境状态与事件之间的映射关系来识别事件.但在系统运行之前,已无法仅凭经验确定环境状态并建立全面且正确的映射关系.仅依赖映射关系建立分析方法的设计思路已无法保障识别的准确性.其二,不确定环境何时会发生何种事件已变得不可预期.如果采用现有设计思路,定期地获取环境状态再进行事件识别,则无法保障识别效率.然而,目前却缺乏应对这些紧迫挑战的相关工作,因此提出了一种基于事件关系保障识别质量的自适应分析方法(self-adaptation analysis method for recognition quality assurance using event relationships,简称SAFER).SAFER采用序列模式挖掘算法、模糊故障树与贝叶斯网络等技术抽取并建模事件因果关系,并基于该类关系与映射关系通过贝叶斯网络的正向推理能力共同识别事件,与传统的仅依赖映射关系的识别方法相比可保证识别的准确性;基于贝叶斯网络的反向推理能力,确定易引发事件的精英感知对象,并动态调整获取精英感知对象状态数据的采样周期,以便于在事件发生后尽快获得相关环境状态,从而保障识别效率.实验结果表明,在自适应软件实际运行过程中,SAFER可实现对事件的识别并保障识别准确性与识别效率,为自适应软件稳定运行提供了有效支持.展开更多
文摘Phosphatase of Regenerating Liver-3 （PRL-3） is a newly identified colorectal cancer metastasis-related protein, which is a 22 kDa non-classical protein tyrosine phosphatase with a C-terminal prenylation motif. In this study, the inhibition kinetics of protein tyrosine phosphatases（PTPs） by a fluorescent substrate, 6,8-difluoro-4-methylumbelliferyl phosphate（DiFMUP） was evaluated. PRL-3 exhibits classical Michaelis-Menten kinetics with a Vmax value of 11.3 μmol · L^-l · min^-1 Analysis of PRL-3 by a Michaelis-Menten plot and a double-reciprocal plot indicated that the inhibitor magnolol can cause Km to increase, but does not alter the Vmax value, which suggests the competitive inhibition of PRL-3. At the same time, it was found that DiFMUP is a more sensitive substrate for PRL-3 than para-nitrophenyl phosphate（pNPP） that is more frequently used at present. Furthermore, the method of screening for PTPs by the use of DiFMUP was developed, which studied the acceptance of DiFMUP by other PTPs.
基金Supported by the National High-Tech Research and Development Program of China(No.2006AA09Z446)the Fund of State Key Laboratory of Natural and Biomimetic Drags+7 种基金 Peking UniversityChina(No.20080210)the Shanxi Provincial Foundation for Overseas Returned China(No.2009021005)the Program for the Top Young and Middle-aged Innovative Talents of Higher Learning Institutions of Shanxi Province China(No.20091041-1)the Innovative Program of Shanxi Medical University China (No.38)
文摘A series of new flavanone derivatives of farrerol was designed and synthesized as a potent inhibitor of vascular smooth muscle cells（VSMCs） vegetation according to a convenient method. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR and EIHR-MS. The biological activities of these compounds against VSMCs in vitro were evaluated. The assay results indicate that two compounds, 5,7-dihydroxy-6,8-dimethyl- 2-（2-nitrophenyl）chroman-4-one（7f） and 2,3-dibromo-4,5-dihydroxydiphenylmethanone（7j） exhibited high activity against VSMCs in vitro with IC50 values of 9.9 and 6.7 μmol/L, respectively, and the preliminary structure-activity relationship（SAR） was described.
文摘Recent studies suggest that PRL-3 is involved in the metastasis of colorectal cancer, but the mechanism concerning that has not been well defined. This article expresses PRL-1, PRL-2, and PRL-3 and the catalytically inactive mutant forms of those enzymes in SW620 and SW480 cells, two human cell lines derived from non-metastatic cancer and metastatic colorectal cancer, respectively. While the expression of the native forms of PRLs promotes the spreading, adhesion, and proliferation of these cells, the expression of their mutant forms inhibits the earlier-mentioned processes. These data thus provide a cellular mechanism for the role of PRL-3 in tumor metastasis and suggest that all the three PRLs have similar functions.
文摘目前自适应软件正在为众多领域系统提供着对运行环境的适应能力.如何建立一种能够保障识别质量的自适应分析方法,使之可从运行环境中快速且准确地识别出异常事件,是确保自适应软件长期稳定运行所必须考虑的研究问题之一.当前运行环境的不确定性给该问题的攻关带来两方面的挑战:其一,现有分析方法一般通过预先建立环境状态与事件之间的映射关系来识别事件.但在系统运行之前,已无法仅凭经验确定环境状态并建立全面且正确的映射关系.仅依赖映射关系建立分析方法的设计思路已无法保障识别的准确性.其二,不确定环境何时会发生何种事件已变得不可预期.如果采用现有设计思路,定期地获取环境状态再进行事件识别,则无法保障识别效率.然而,目前却缺乏应对这些紧迫挑战的相关工作,因此提出了一种基于事件关系保障识别质量的自适应分析方法(self-adaptation analysis method for recognition quality assurance using event relationships,简称SAFER).SAFER采用序列模式挖掘算法、模糊故障树与贝叶斯网络等技术抽取并建模事件因果关系,并基于该类关系与映射关系通过贝叶斯网络的正向推理能力共同识别事件,与传统的仅依赖映射关系的识别方法相比可保证识别的准确性;基于贝叶斯网络的反向推理能力,确定易引发事件的精英感知对象,并动态调整获取精英感知对象状态数据的采样周期,以便于在事件发生后尽快获得相关环境状态,从而保障识别效率.实验结果表明,在自适应软件实际运行过程中,SAFER可实现对事件的识别并保障识别准确性与识别效率,为自适应软件稳定运行提供了有效支持.
