As a highly important fish virus,nervous necrosis virus(NNV)has caused severe economic losses to the aquaculture industry worldwide.Autophagy,an evolutionarily conserved intracellular degradation process,is involved i...As a highly important fish virus,nervous necrosis virus(NNV)has caused severe economic losses to the aquaculture industry worldwide.Autophagy,an evolutionarily conserved intracellular degradation process,is involved in the pathogenesis of several viruses.Although NNV can induce autophagy to facilitate infection in grouper fish spleen cells,how it initiates and mediates autophagy pathways during the initial stage of infection is still unclear.Here,we found that red-spotted grouper NNV(RGNNV)induced autophagosome formation in two fish cell lines at 1.5 and 3 h post infection,indicating that autophagy is activated upon entry of RGNNV.Moreover,autophagic detection showed that RGNNV entry induced incomplete autophagy by impairing the fusion of autophagosomes with lysosomes.Further investigation revealed that binding of the RGNNV capsid protein(CP)to the Lateolabrax japonicus heat shock protein HSP90ab1(LjHSP90ab1),a cell surface receptor of RGNNV,contributed to RGNNV invasion-induced autophagy.Finally,we found that CP blocked the interaction of L.japonicus protein kinase B(AKT)with LjHSP90ab1 by competitively binding the NM domain of LjHSP90ab1 to inhibit the AKT-mechanistic target of the rapamycin(MTOR)pathway.This study provides novel insight into the relationship between NNV receptors and autophagy,which may help clarify the pathogenesis of NNV.展开更多
As a highly efficient production method, the technique of multi-branch horizontal well is widely used in low permeability reservoirs, heavy oil reservoirs, shallow layer reservoirs and multi-layer reservoirs, because ...As a highly efficient production method, the technique of multi-branch horizontal well is widely used in low permeability reservoirs, heavy oil reservoirs, shallow layer reservoirs and multi-layer reservoirs, because it can significantly improve the productivity of a single well, inhibit coning and enhance oil recovery. Study on sweep efficiency and parameters optimization of multi-branch horizontal well is at the leading edge of research. Therefore, the study is important for enhancing oil recovery and integral exploitation benefit of oil fields. In many applications, streamline simulation shows particular advantages over finite-difference simulation. With the advantages of streamline simulation such as its ability to display paths of fluid flow and acceleration factor in simulation, the flooding process is more visual. The communication between wells and flooding area has been represented appropriately. This method has been applied to the XS9 reservoir in Daqing Oilfield. The production history of this reservoir is about 10 years. The reservoir is maintained above bubble point so that the simulation meets the slight compressibility assumption. New horizontal wells are drilled following this rule.展开更多
Objective: To analyze the potential active components and molecular mechanism of Ganlu Xiaodu MicroPill in the treatment of COVID-19 by network pharmacology and molecular docking. Methods: the active chemical constitu...Objective: To analyze the potential active components and molecular mechanism of Ganlu Xiaodu MicroPill in the treatment of COVID-19 by network pharmacology and molecular docking. Methods: the active chemical constituents and action targets of Ganlu Xiaodu MicroPill were searched by TCMSP and BATMAN-TCM platform, and the key targets were matched with the COVID-19 targets searched by CTD database. The core targets were selected and analyzed by GO and KEGG enrichment analysis by R software to predict the action mechanism of traditional Chinese medicine compound. The key component sets were docked with 3CLpro and ACE2. Results: 138 active components and 53 key targets were obtained. There are 1298 items in GO biological process, 59 items in cell composition, 62 items in molecular function, and 120 items enriched in KEGG pathway. Results: molecular docking showed that the affinity of 20 chemical components such as quercetin, luteolin and kaempferol with ACE2 and 3CLpro was higher than that of ribavirin and chloroquine. Conclusion: Ganlu Xiaodu MicroPill may regulate and interfere with SARS-CoV-2 infection through antivirus, inhibition of inflammatory factors and regulation of immunity, which fully reflects the therapeutic advantages of multi-components, multi-targets and multi-pathways of traditional Chinese medicine.展开更多
基金supported by the Pearl River S&T Nova Program of Guangzhou(201806010047)National Natural Science Foundation of China(32173001,3210284,31771587)+1 种基金China Postdoctoral Science Foundation Funded Project(2021M693678)Natural Science Foundation of Guangxi Province(2021GXNSFDA075015)。
文摘As a highly important fish virus,nervous necrosis virus(NNV)has caused severe economic losses to the aquaculture industry worldwide.Autophagy,an evolutionarily conserved intracellular degradation process,is involved in the pathogenesis of several viruses.Although NNV can induce autophagy to facilitate infection in grouper fish spleen cells,how it initiates and mediates autophagy pathways during the initial stage of infection is still unclear.Here,we found that red-spotted grouper NNV(RGNNV)induced autophagosome formation in two fish cell lines at 1.5 and 3 h post infection,indicating that autophagy is activated upon entry of RGNNV.Moreover,autophagic detection showed that RGNNV entry induced incomplete autophagy by impairing the fusion of autophagosomes with lysosomes.Further investigation revealed that binding of the RGNNV capsid protein(CP)to the Lateolabrax japonicus heat shock protein HSP90ab1(LjHSP90ab1),a cell surface receptor of RGNNV,contributed to RGNNV invasion-induced autophagy.Finally,we found that CP blocked the interaction of L.japonicus protein kinase B(AKT)with LjHSP90ab1 by competitively binding the NM domain of LjHSP90ab1 to inhibit the AKT-mechanistic target of the rapamycin(MTOR)pathway.This study provides novel insight into the relationship between NNV receptors and autophagy,which may help clarify the pathogenesis of NNV.
文摘As a highly efficient production method, the technique of multi-branch horizontal well is widely used in low permeability reservoirs, heavy oil reservoirs, shallow layer reservoirs and multi-layer reservoirs, because it can significantly improve the productivity of a single well, inhibit coning and enhance oil recovery. Study on sweep efficiency and parameters optimization of multi-branch horizontal well is at the leading edge of research. Therefore, the study is important for enhancing oil recovery and integral exploitation benefit of oil fields. In many applications, streamline simulation shows particular advantages over finite-difference simulation. With the advantages of streamline simulation such as its ability to display paths of fluid flow and acceleration factor in simulation, the flooding process is more visual. The communication between wells and flooding area has been represented appropriately. This method has been applied to the XS9 reservoir in Daqing Oilfield. The production history of this reservoir is about 10 years. The reservoir is maintained above bubble point so that the simulation meets the slight compressibility assumption. New horizontal wells are drilled following this rule.
基金Major national science and technology projects-prevention and treatment of major infectious diseases such as AIDS and viral hepatitis(No.2018ZX10303502)National Nature Fund Youth Fund(No.81804063)+2 种基金China postdoctoral Science Foundation Program(No.2019M662500)China postdoctoral Science Foundation Program(No.2019M662500)Key Scientific Research Project of National Clinical Research Base of traditional Chinese Medicine of Henan Provincial Administration of traditional Chinese Medicine(No.2018JDZX1100)
文摘Objective: To analyze the potential active components and molecular mechanism of Ganlu Xiaodu MicroPill in the treatment of COVID-19 by network pharmacology and molecular docking. Methods: the active chemical constituents and action targets of Ganlu Xiaodu MicroPill were searched by TCMSP and BATMAN-TCM platform, and the key targets were matched with the COVID-19 targets searched by CTD database. The core targets were selected and analyzed by GO and KEGG enrichment analysis by R software to predict the action mechanism of traditional Chinese medicine compound. The key component sets were docked with 3CLpro and ACE2. Results: 138 active components and 53 key targets were obtained. There are 1298 items in GO biological process, 59 items in cell composition, 62 items in molecular function, and 120 items enriched in KEGG pathway. Results: molecular docking showed that the affinity of 20 chemical components such as quercetin, luteolin and kaempferol with ACE2 and 3CLpro was higher than that of ribavirin and chloroquine. Conclusion: Ganlu Xiaodu MicroPill may regulate and interfere with SARS-CoV-2 infection through antivirus, inhibition of inflammatory factors and regulation of immunity, which fully reflects the therapeutic advantages of multi-components, multi-targets and multi-pathways of traditional Chinese medicine.
