Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment o...Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.展开更多
The in-cylinder gas exchange process is crucial to the power performance of two-stroke aircraft piston engines,which is easily influenced by complex factors such as high-altitude performance variation and in-cylinder ...The in-cylinder gas exchange process is crucial to the power performance of two-stroke aircraft piston engines,which is easily influenced by complex factors such as high-altitude performance variation and in-cylinder flow characteristics.This paper reviews the development history and characteristics of gas exchange types,as well as the current state of theory and the validation methods of gas exchange technology,while also discusses the trends of cutting-edge technologies in the field.This paper provides a theoretical foundation for the optimization and engineering design of gas exchange systems and,more importantly,points out that the innovation of gas exchange types,the modification of theoretical models,and the technology of variable airflow organization are the key future research directions in this field.展开更多
Unlike adult mammalian heart,zebrafish heart has a remarkable capacity to regenerate after injury.Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium ...Unlike adult mammalian heart,zebrafish heart has a remarkable capacity to regenerate after injury.Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury,however,the molecular mechanism has not been fully explored.In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium.First we showed that both homologues of human gene KLF2 in zebrafish,klf2a and klf2b,could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration.Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia.Overall,our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.展开更多
As a highly conserved signaling pathway in metazoans,the Notch pathway plays important roles in embryonic development and tissue regeneration.Recently,cardiac injury and regeneration have become an increasingly popula...As a highly conserved signaling pathway in metazoans,the Notch pathway plays important roles in embryonic development and tissue regeneration.Recently,cardiac injury and regeneration have become an increasingly popular topic for biomedical research,and Notch signaling has been shown to exert crucial functions during heart regeneration as well.In this review,we briefly summarize the molecular functions of the endocardial Notch pathway in several cardiac injury and stress models.Although there is an increase in appreciating the importance of endocardial Notch signaling in heart regeneration,the mechanism of its activation is not fully understood.This review highlights recent findings on the activation of the endocardial Notch pathway by hemodynamic blood flow change in larval zebrafish ventricle after partial ablation,a process involving primary cilia,mechanosensitive ion channel Trpv4 and mechanosensitive transcription factor Klf2.展开更多
基金the National Natural Science Foundation of China(No.32272575)National College Student Innovation and Entrepreneurship Training Program(No.202210459164)for financial support.
文摘Methicillin-resistant Staphylococcus aureus (MRSA), the most common pathogen in hospital and community environments, can cause serious and even fatal infections. The antibiotics currently used for clinical treatment of MRSA have developed resistance, and there is an urgent need to develop new antimicrobials to treat infections caused by MRSA strains. Quinoline analogues play an important role in the development of antimicrobials. Herein, we discussed the current development of antibacterial activities of quinoline analogues, mainly for anti-MRSA activity, and their structure-activity relationships (SARs) from the perspective of using the quinoline nucleus to search for novel potential anti-MRSA candidates. Additionally, the mechanisms of some representative quinoline analogues against MRSA were clarified. Altogether, this review could provide further insights for the rational development of quinoline-based antibacterial drugs, especially against MRSA.
基金funded by the National Natural Science Foundation of China(Nos.52206131,U2233213and 51775025)the National Key R&D Program of China(2022YFB2602002,2018YFB0104100)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(LQ22E060004)the Science Center of Gas Turbine Project,China(No.P2022-A-I-001-001)。
文摘The in-cylinder gas exchange process is crucial to the power performance of two-stroke aircraft piston engines,which is easily influenced by complex factors such as high-altitude performance variation and in-cylinder flow characteristics.This paper reviews the development history and characteristics of gas exchange types,as well as the current state of theory and the validation methods of gas exchange technology,while also discusses the trends of cutting-edge technologies in the field.This paper provides a theoretical foundation for the optimization and engineering design of gas exchange systems and,more importantly,points out that the innovation of gas exchange types,the modification of theoretical models,and the technology of variable airflow organization are the key future research directions in this field.
基金We thank Haitao Zhou and Lifeng Li for fish care,Kaa Seng Lai,Yabo Fang and Wenyan Li for technical support and other lab members for in depth discussion.We thank Dr Tao Zhong for providing reagents.This study was supported by National Key R&D Program of China grant 2018YFA0801004 and NSFC grant 31571492 to R.Z.
文摘Unlike adult mammalian heart,zebrafish heart has a remarkable capacity to regenerate after injury.Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury,however,the molecular mechanism has not been fully explored.In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium.First we showed that both homologues of human gene KLF2 in zebrafish,klf2a and klf2b,could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration.Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia.Overall,our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.
基金This study was supported by National Key R&D Program of China grant 2018YFA0801000 and NSFC grant 31571492 to R.
文摘As a highly conserved signaling pathway in metazoans,the Notch pathway plays important roles in embryonic development and tissue regeneration.Recently,cardiac injury and regeneration have become an increasingly popular topic for biomedical research,and Notch signaling has been shown to exert crucial functions during heart regeneration as well.In this review,we briefly summarize the molecular functions of the endocardial Notch pathway in several cardiac injury and stress models.Although there is an increase in appreciating the importance of endocardial Notch signaling in heart regeneration,the mechanism of its activation is not fully understood.This review highlights recent findings on the activation of the endocardial Notch pathway by hemodynamic blood flow change in larval zebrafish ventricle after partial ablation,a process involving primary cilia,mechanosensitive ion channel Trpv4 and mechanosensitive transcription factor Klf2.
