As present NO donor drugs cannot localize to release NO at the hypoxic site, along with the short half-life and bidirectional regulation of NO, they are unable to overcome low...

Purpose Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia induced drug resistance.Methods In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown and overexpression assay certi cated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.Results Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance, and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.Conclusion Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.

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Purpose Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia induced drug resistance.Methods In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.Results Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance, and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.Conclusion Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.

Low pylon cable-stayed bridge is a new type of composite bridge between girder bridge and traditional cable-stayed bridge. Because of its good mechanical properties, economic benefits and beautiful shape, low pylon cable-stayed bridge is widely used in highway and urban landscape bridges. In this paper, a wide and low pylon cable-stayed bridge under construction is taken as the research background, and the numerical simulation model is established by using the finite element analysis software MIDAS CIVIL. The influence of the length of the cable-free zone is studied. By changing the length of cable-free zone at the tower root and the length of cable-free zone in the middle of span, the influence of the length of non-cable zone on the deformation, bending moment, internal force and cable force of low pylon cable-stayed bridge at the completion stage is studied. The reasonable value range of non-cable zone length is obtained. The research results will provide theoretical guidance for the design and construction of similar projects.