Cholangiocarcinoma(CCA)is a particularly aggressive and challenging type of cancer,known for its poor prognosis,which is worsened by the complex interplay of various biological and environmental factors that contribut...Cholangiocarcinoma(CCA)is a particularly aggressive and challenging type of cancer,known for its poor prognosis,which is worsened by the complex interplay of various biological and environmental factors that contribute to its development.Recently,researchers have increasingly focused on the significant role of the biliary-enteric communication of liver-gut axis in the pathogenesis of CCA,highlighting a complex relationship that has not been thoroughly explored before.This review aims to summarize the key concepts related to the biliary-enteric communication of liver-gut axis and investigate its potential mechanisms that may lead to the onset and progression of CCA,a disease that presents substantial treatment challenges.Important areas of focus will include the microbiome's profound influence,which interacts with host physiology in ways that may worsen cancer development;changes in bile acid metabolism that can create toxic environments favorable for tumor growth;the regulation of inflammatory processes that may either promote or inhibit tumor progression;the immune system's involvement,which is crucial in the body's response to cancer;and the complex interactions within metabolic pathways that can affect cellular behavior and tumor dynamics.By integrating recent research findings from various studies,we aim to explore the multifaceted roles of the biliary-enteric communication of liver-gut axis in CCA,providing new insights and perspectives for future research while identifying promising therapeutic targets that could lead to innovative treatment strategies aimed at improving patient outcomes in this challenging disease.展开更多
The experimental research on zero-net-mass-flux jet closed-loop active control was conducted in the wind tunnel.The mu-level method successfully detected burst events of the coherent structures. The streamwise velocit...The experimental research on zero-net-mass-flux jet closed-loop active control was conducted in the wind tunnel.The mu-level method successfully detected burst events of the coherent structures. The streamwise velocity signals in the turbulent boundary layer were measured by HWA. The drag reduction rate of 16.7% is obtained comparable to that of the open-loop control and saves 75% of the input energy at the asynchronous 100 V/160 Hz control case, which reflects the advantages of the closed-loop control. The experimental findings indicate that the intensity increases in the near-wall region.The perturbation of the PZT vibrators on the skewness factor is concentrated in the region y+< 60. The generation of highspeed fluids is depressed and the downward effect of high-speed fluids weakens. The alteration of energy distribution and the discernible impact of modulation between structures of varying scales are observed. The correlation coefficient exhibits a strong positive correlation, which indicates that the large-scale structures produce modulation effect on small-scale ones.The occurrence of burst events is effectively suppressed. The disturbance has the characteristics of stable periodicity,positive and negative symmetry, low intermittency, and high pulsation strength. The conditional phase waveform shows that the fluctuation amplitude increases, indicating amplitude modulation effects on coherent structures.展开更多
Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular p...Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular patterns(MAMPs)trigger a very fast and transient ROS burst in plants.However,recently,we found that lipopolysaccharides(LPS),a typical bacterial MAMP,triggered a biphasic ROS burst.In this study,we isolated mutants defective in LPS-triggered biphasic ROS burst(delt)in Arabidopsis,and cloned the DELT1 gene that was shown to encode RBOHD.In the delt1-2 allele,the antepenultimate residue,glutamic acid(E919),at the C-terminus of RBOHD was mutated to lysine(K).E919 is a highly conserved residue in NADPH oxidases,and a mutation of the corresponding residue E568 in human NOX2 has been reported to be one of the causes of chronic granulomatous disease.Consistently,we found that residue E919 was indispensable for RBOHD function in the MAMP-induced ROS burst and stomatal closure.It has been suggested that the mutation of this residue in other NADPH oxidases impairs the protein’s stability and complex assembly.However,we found that the E919K mutation did not affect RBOHD protein abundance or the ability of protein association,suggesting that the residue E919 in RBOHD might have a regulatory mechanism different from that of other NOXs.Taken together,our results confirm that the antepenultimate residue E is critical for NADPH oxidases and provide a new insight into the regulatory mechanisms of RBOHD.展开更多
This article mainly focuses on the role of antepenultimate residue at the C-terminus of NADPH oxidase respiratory burst oxidase homolog D(RBOHD). E919 of RBOHD is critical for lipopolysaccharides(LPS)-induced reactive...This article mainly focuses on the role of antepenultimate residue at the C-terminus of NADPH oxidase respiratory burst oxidase homolog D(RBOHD). E919 of RBOHD is critical for lipopolysaccharides(LPS)-induced reactive oxygen species(ROS) production and stomatal closure in Arabidopsis.展开更多
文摘Cholangiocarcinoma(CCA)is a particularly aggressive and challenging type of cancer,known for its poor prognosis,which is worsened by the complex interplay of various biological and environmental factors that contribute to its development.Recently,researchers have increasingly focused on the significant role of the biliary-enteric communication of liver-gut axis in the pathogenesis of CCA,highlighting a complex relationship that has not been thoroughly explored before.This review aims to summarize the key concepts related to the biliary-enteric communication of liver-gut axis and investigate its potential mechanisms that may lead to the onset and progression of CCA,a disease that presents substantial treatment challenges.Important areas of focus will include the microbiome's profound influence,which interacts with host physiology in ways that may worsen cancer development;changes in bile acid metabolism that can create toxic environments favorable for tumor growth;the regulation of inflammatory processes that may either promote or inhibit tumor progression;the immune system's involvement,which is crucial in the body's response to cancer;and the complex interactions within metabolic pathways that can affect cellular behavior and tumor dynamics.By integrating recent research findings from various studies,we aim to explore the multifaceted roles of the biliary-enteric communication of liver-gut axis in CCA,providing new insights and perspectives for future research while identifying promising therapeutic targets that could lead to innovative treatment strategies aimed at improving patient outcomes in this challenging disease.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.12202309,1233000165,12172242,and 12272265)Science and Technology Program of Gansu Province of China(Grant No.22JR5RA304)Tianjin Research Innovation for Postgraduate Students(Grant No.22KJ049)。
文摘The experimental research on zero-net-mass-flux jet closed-loop active control was conducted in the wind tunnel.The mu-level method successfully detected burst events of the coherent structures. The streamwise velocity signals in the turbulent boundary layer were measured by HWA. The drag reduction rate of 16.7% is obtained comparable to that of the open-loop control and saves 75% of the input energy at the asynchronous 100 V/160 Hz control case, which reflects the advantages of the closed-loop control. The experimental findings indicate that the intensity increases in the near-wall region.The perturbation of the PZT vibrators on the skewness factor is concentrated in the region y+< 60. The generation of highspeed fluids is depressed and the downward effect of high-speed fluids weakens. The alteration of energy distribution and the discernible impact of modulation between structures of varying scales are observed. The correlation coefficient exhibits a strong positive correlation, which indicates that the large-scale structures produce modulation effect on small-scale ones.The occurrence of burst events is effectively suppressed. The disturbance has the characteristics of stable periodicity,positive and negative symmetry, low intermittency, and high pulsation strength. The conditional phase waveform shows that the fluctuation amplitude increases, indicating amplitude modulation effects on coherent structures.
基金the National Natural Science Foundation of China(No.31622006)the Postdoctoral Science Foundation of China(Nos.2018M630683 and 2018T110601)
文摘Production of reactive oxygen species(ROS)is a conserved immune response primarily mediated by NADPH oxidases(NOXs),also known in plants as respiratory burst oxidase homologs(RBOHs).Most microbe-associated molecular patterns(MAMPs)trigger a very fast and transient ROS burst in plants.However,recently,we found that lipopolysaccharides(LPS),a typical bacterial MAMP,triggered a biphasic ROS burst.In this study,we isolated mutants defective in LPS-triggered biphasic ROS burst(delt)in Arabidopsis,and cloned the DELT1 gene that was shown to encode RBOHD.In the delt1-2 allele,the antepenultimate residue,glutamic acid(E919),at the C-terminus of RBOHD was mutated to lysine(K).E919 is a highly conserved residue in NADPH oxidases,and a mutation of the corresponding residue E568 in human NOX2 has been reported to be one of the causes of chronic granulomatous disease.Consistently,we found that residue E919 was indispensable for RBOHD function in the MAMP-induced ROS burst and stomatal closure.It has been suggested that the mutation of this residue in other NADPH oxidases impairs the protein’s stability and complex assembly.However,we found that the E919K mutation did not affect RBOHD protein abundance or the ability of protein association,suggesting that the residue E919 in RBOHD might have a regulatory mechanism different from that of other NOXs.Taken together,our results confirm that the antepenultimate residue E is critical for NADPH oxidases and provide a new insight into the regulatory mechanisms of RBOHD.
文摘This article mainly focuses on the role of antepenultimate residue at the C-terminus of NADPH oxidase respiratory burst oxidase homolog D(RBOHD). E919 of RBOHD is critical for lipopolysaccharides(LPS)-induced reactive oxygen species(ROS) production and stomatal closure in Arabidopsis.
