Resistance to malaria parasites has quickly developed to almost all used antimalarial drugs. Cysteine protease falcipain-2(FP-2) and Plasmodium falciparum dihydrofolate reductase(PfDHFR) have crucial roles, which are ...Resistance to malaria parasites has quickly developed to almost all used antimalarial drugs. Cysteine protease falcipain-2(FP-2) and Plasmodium falciparum dihydrofolate reductase(PfDHFR) have crucial roles, which are absolutely necessary, in the parasite life cycle. In this study, based on the uniform pharmacophores of reported PfDHFR inhibitors and the first-generation dual inhibitors against FP-2 and PfDHFR, we identified a novel series of dual inhibitors through fragments assembly. Lead optimization led to the identification of 14, which showed potent inhibition against FP-2 and PfDHFR enzyme(IC_(50)= 6.8 + 1.8 mmol/L and IC_(50)= 8.8 + 0.3 mmol/L) and P. falciparum 3D7 strain(IC50= 2.9mmol/L).Additionally, 14 exhibited more potent inhibition to the proliferation of chloroquine-resistant P.falciparum Dd2 strain(IC_(50)= 1.1 mmol/L) than pyrimethamine(IC_(50)>10 mmol/L), and 14 displayed micromolar inhibitory activities against two clinical isolated strains Fab9(IC_(50)= 2.6 mmol/L) and GB4(IC_(50)= 1.0 mmol/L). Collectively, these data demonstrated that 14 might be a good lead compound for the treatment of malaria.展开更多
In recent years, Hyper Text Transfer Protocol （HTTP） spreads quickly and steadily in the usage of mobile applications as a common web protocol, so that the mobile applications can also benefit from HTTP/2, which is ...In recent years, Hyper Text Transfer Protocol （HTTP） spreads quickly and steadily in the usage of mobile applications as a common web protocol, so that the mobile applications can also benefit from HTTP/2, which is the new version of HTTP based on SPDY developed by Google to speed up the Internet transmission speed. HTTP/2 enables a more efficient use of network resources and a reduced perception of latency by in- troducing header field compression and allowing multiple concurrent exchanges on the same connection. However, what H3TP/2 focuses on is visiting websites through a browser, and mobile applications are not considered much. In this paper, firstly, mobile applications are classified based on the da- ta flow characteristics. Based on the classification, we propose an optimization of HTTP/2 for mobile applications, called HTTP/2-Advance, which uses multiple Transmission Control Protocol （TCP） connections to multiplex HTYP requests and responses. Then we build a tiny system which simulates actu- al requests and responses between mobile applications and servers. We figure out the best choice of the number of multiple TCP connections for mobile applications, and compare the performance of HTTP, HTTP/2 and HTrP/2-Advance in both simulated and in-situ experiments in our system.展开更多
Plant mechanical strength is an important agronomic trait of rice. An ethyl methane sulfonate （EMS）-induced rice mutant, fragile plant 2 （fp2）, showed morphological changes and reduced mechanical strength. Genetic...Plant mechanical strength is an important agronomic trait of rice. An ethyl methane sulfonate （EMS）-induced rice mutant, fragile plant 2 （fp2）, showed morphological changes and reduced mechanical strength. Genetic analysis indicated that the brittle of fp2 was controlled by a recessive gene. The fp2 gene was mapped on chromosome 10. Anatomical analyses showed that the fp2 mutation caused the reduction of cell length and cell wall thickness, increasing of cell width, and the alteration of cell wall structure as well as the vessel elements. The consequence was a global alteration in plant morphology. Chemical analyses indicated that the contents of cellulose and lignin decreased, and hemicelluloses and silicon increased in fp2. These results were different from the other mutants reported in rice. Thus, fp2 might affect the deposition and patterning of microflbrils, the biosynthesis and deposition of cell wall components, which influences the formation of primary and secondary cell walls, the thickness of cell walls, cell elongation and expansion, plant morphology and plant strength in rice.展开更多
基金Financial support for this research provided by the National Natural Science Foundation of China (Nos. 21372001 and 21672064)the "Shu Guang" Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 14SG28)
文摘Resistance to malaria parasites has quickly developed to almost all used antimalarial drugs. Cysteine protease falcipain-2(FP-2) and Plasmodium falciparum dihydrofolate reductase(PfDHFR) have crucial roles, which are absolutely necessary, in the parasite life cycle. In this study, based on the uniform pharmacophores of reported PfDHFR inhibitors and the first-generation dual inhibitors against FP-2 and PfDHFR, we identified a novel series of dual inhibitors through fragments assembly. Lead optimization led to the identification of 14, which showed potent inhibition against FP-2 and PfDHFR enzyme(IC_(50)= 6.8 + 1.8 mmol/L and IC_(50)= 8.8 + 0.3 mmol/L) and P. falciparum 3D7 strain(IC50= 2.9mmol/L).Additionally, 14 exhibited more potent inhibition to the proliferation of chloroquine-resistant P.falciparum Dd2 strain(IC_(50)= 1.1 mmol/L) than pyrimethamine(IC_(50)>10 mmol/L), and 14 displayed micromolar inhibitory activities against two clinical isolated strains Fab9(IC_(50)= 2.6 mmol/L) and GB4(IC_(50)= 1.0 mmol/L). Collectively, these data demonstrated that 14 might be a good lead compound for the treatment of malaria.
文摘In recent years, Hyper Text Transfer Protocol （HTTP） spreads quickly and steadily in the usage of mobile applications as a common web protocol, so that the mobile applications can also benefit from HTTP/2, which is the new version of HTTP based on SPDY developed by Google to speed up the Internet transmission speed. HTTP/2 enables a more efficient use of network resources and a reduced perception of latency by in- troducing header field compression and allowing multiple concurrent exchanges on the same connection. However, what H3TP/2 focuses on is visiting websites through a browser, and mobile applications are not considered much. In this paper, firstly, mobile applications are classified based on the da- ta flow characteristics. Based on the classification, we propose an optimization of HTTP/2 for mobile applications, called HTTP/2-Advance, which uses multiple Transmission Control Protocol （TCP） connections to multiplex HTYP requests and responses. Then we build a tiny system which simulates actu- al requests and responses between mobile applications and servers. We figure out the best choice of the number of multiple TCP connections for mobile applications, and compare the performance of HTTP, HTTP/2 and HTrP/2-Advance in both simulated and in-situ experiments in our system.
基金the Program for Changjiang Scholars and Innovative ResearchTeam in University (IRT0453).
文摘Plant mechanical strength is an important agronomic trait of rice. An ethyl methane sulfonate （EMS）-induced rice mutant, fragile plant 2 （fp2）, showed morphological changes and reduced mechanical strength. Genetic analysis indicated that the brittle of fp2 was controlled by a recessive gene. The fp2 gene was mapped on chromosome 10. Anatomical analyses showed that the fp2 mutation caused the reduction of cell length and cell wall thickness, increasing of cell width, and the alteration of cell wall structure as well as the vessel elements. The consequence was a global alteration in plant morphology. Chemical analyses indicated that the contents of cellulose and lignin decreased, and hemicelluloses and silicon increased in fp2. These results were different from the other mutants reported in rice. Thus, fp2 might affect the deposition and patterning of microflbrils, the biosynthesis and deposition of cell wall components, which influences the formation of primary and secondary cell walls, the thickness of cell walls, cell elongation and expansion, plant morphology and plant strength in rice.
