Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previou...Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.展开更多
On the basis of introducing the nutrient composition and biogas fertilizer,the effects of biogas fertilizer on soil,crops and environment are summarized. Biogas fertilizer can improve soil structure,increase soil orga...On the basis of introducing the nutrient composition and biogas fertilizer,the effects of biogas fertilizer on soil,crops and environment are summarized. Biogas fertilizer can improve soil structure,increase soil organic matter,available nutrient contents and enzyme activity,increase crop yield,quality and resistance,and relieve the non-point source pollution effectively. The harmlessness,application technology and risk are analyzed. Some suggestions are put forward to control the source pollution,strengthen the research of fermentation technology,define the standard of biogas fertilizer,and carry out large and medium-sized biogas engineering.展开更多
文摘Significant progress was achieved in the search of a thrombin receptor antagonist as a novel antithrombotic treatment since the thrombin receptor (protease-activated receptor-1, PAR-1) was cloned 20 years ago. Previous works have shown that it is possible to develop potent thrombin receptor antagonists to compete effectively with the receptor’s internal “tethered” ligand to block platelet activation. Vorapaxar (SCH 530348) from Schering-Plough (now Merck) and atopaxar (E5555) from Eisai have been advanced to human clinical trials. Recently, the pivotal phase III clinical trial results for vorapaxar were published. In this article we review these results plus the phase II results from atopaxar. Several newly described thrombin receptor antagonists from the literature will also be discussed. The phase III results from vorapaxar demonstrated that a thrombin receptor antagonist can achieve efficacy in addition to current standard- of-care in treating atherothrombotic patients, especially those with previous myocardial infarction (MI). However, the increased moderate and severe bleeding, especially intracranial bleeding, point to the limitations of current thrombin receptor antagonists. Future thrombin receptor antagonists that can improve on the efficacy and bleeding profile of current ones should have a promising place in meeting the unmet medical need in treating atherothrombotic patients using current standard therapy.
基金Supported by National Key Research and Development Program of China(2016YFD0200401)Hebei Science and Technology Project(16227005D)
文摘On the basis of introducing the nutrient composition and biogas fertilizer,the effects of biogas fertilizer on soil,crops and environment are summarized. Biogas fertilizer can improve soil structure,increase soil organic matter,available nutrient contents and enzyme activity,increase crop yield,quality and resistance,and relieve the non-point source pollution effectively. The harmlessness,application technology and risk are analyzed. Some suggestions are put forward to control the source pollution,strengthen the research of fermentation technology,define the standard of biogas fertilizer,and carry out large and medium-sized biogas engineering.
