The incomplete degradation of tumour cells by macrophages(Mϕ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mϕis mediated through phagosomes and lysosomes.In our prelimin...The incomplete degradation of tumour cells by macrophages(Mϕ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mϕis mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mϕto degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mϕto degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mϕphagosomes,causing Mϕto produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mϕby liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subsequently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mϕcannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mϕto degrade tumour cells by suppressing NOX2.展开更多
Background and Originality Content The catalytic hydrosilylation of unsaturated hydrocarbons,facilitated by transition metal(TM),is widely recognized as a proficient technique for the synthesis of high-value organosil...Background and Originality Content The catalytic hydrosilylation of unsaturated hydrocarbons,facilitated by transition metal(TM),is widely recognized as a proficient technique for the synthesis of high-value organosilicon compounds'ti-4l over the past few decades,the most dominant cata.lysts in hydrosilylation processes have been constituted by pre-Ccious metar complexesroceinerecent vears omore sustainabile earth-abundant metal catalysts have received increased attentionj2-14l The classcal mechanism of transition metal-catalyzed hydrosilylation is generally accomplished through a series of fundamental processes(Scheme 1a),including(i)coordination and oxidative addition of Si-H bond to a low-valent metal center to form e.g.,o-complex or silyl metal hydride;(ii)insertion of.C-C multipe bonds intometal-hdridelsior metal-silicon bond;jiol and(ii)reductive elimination that forwards the hydrosilylated product with Markovnikov or anti-Markovnikov selectivity.展开更多
Background:The outbreak of coronavirus disease 2019(COVID-19)has posed a huge threat to human health.However,little is known regarding the risk factors associated with COVID-19 severity.We aimed to explore early-stage...Background:The outbreak of coronavirus disease 2019(COVID-19)has posed a huge threat to human health.However,little is known regarding the risk factors associated with COVID-19 severity.We aimed to explore early-stage disease risk factors associated with eventual disease severity.Methods:This study enrolled 486 hospitalized,non-intensive care unit(ICU)-admitted adult patients with COVID-19(age≥18 years)treated at Wuhan Jinyintan Hospital,who were divided into three groups according to disease severity.The demographic,clinical,and laboratory data at admission and clinical outcomes were compared among severity groups,and the risk factors for disease severity were identified by multiple regression analysis.Results:Of 486 patients with COVID-19,405(83.33%)were discharged,33(6.71%)died outside of the ICU,and 48(7.20%)were still being treated in the ICU by the time the study period ended.Significant differences in age,lymphocyte counts,and the levels of procalcitonin,aspartate aminotransferase,and D-dimer(P<0.001 for all)among the three groups.Further analysis showed that older age,decreased lymphocyte counts,and increased procalcitonin,aspartate aminotransferase,and D-dimer levels were significantly associated with disease progression.Conclusion:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)may impair the immune system,the blood coagulation system,and hepatic and cardiac function.Some clinical characteristics and laboratory findings can help identify patients with a high risk of disease severity,which can be significant for appropriate resource allocation during the COVID-19 pandemic.展开更多
基金supported by National Natural Science Foundation of China(Grant No.:82074092)Natural Science Foundation of Guangdong Province,China(Grant No.:2023A1515011141)+1 种基金Research projects in Key Fields of Universities in Guangdong Province,China(Grant No.:2023ZDZX2020)Guangzhou Municipal Bureau of Science and Technology,China(Grant No.:202201011631).
文摘The incomplete degradation of tumour cells by macrophages(Mϕ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mϕis mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mϕto degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mϕto degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mϕphagosomes,causing Mϕto produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mϕby liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subsequently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mϕcannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mϕto degrade tumour cells by suppressing NOX2.
基金supported by the National Natural Science Foundation of China(22371198)the Postdoctoral Fellowship Programof CPSF(GZC20231885).
文摘Background and Originality Content The catalytic hydrosilylation of unsaturated hydrocarbons,facilitated by transition metal(TM),is widely recognized as a proficient technique for the synthesis of high-value organosilicon compounds'ti-4l over the past few decades,the most dominant cata.lysts in hydrosilylation processes have been constituted by pre-Ccious metar complexesroceinerecent vears omore sustainabile earth-abundant metal catalysts have received increased attentionj2-14l The classcal mechanism of transition metal-catalyzed hydrosilylation is generally accomplished through a series of fundamental processes(Scheme 1a),including(i)coordination and oxidative addition of Si-H bond to a low-valent metal center to form e.g.,o-complex or silyl metal hydride;(ii)insertion of.C-C multipe bonds intometal-hdridelsior metal-silicon bond;jiol and(ii)reductive elimination that forwards the hydrosilylated product with Markovnikov or anti-Markovnikov selectivity.
基金supported by the Fujian Provincial Intensive Medical Center Construction Project[2017-510].
文摘Background:The outbreak of coronavirus disease 2019(COVID-19)has posed a huge threat to human health.However,little is known regarding the risk factors associated with COVID-19 severity.We aimed to explore early-stage disease risk factors associated with eventual disease severity.Methods:This study enrolled 486 hospitalized,non-intensive care unit(ICU)-admitted adult patients with COVID-19(age≥18 years)treated at Wuhan Jinyintan Hospital,who were divided into three groups according to disease severity.The demographic,clinical,and laboratory data at admission and clinical outcomes were compared among severity groups,and the risk factors for disease severity were identified by multiple regression analysis.Results:Of 486 patients with COVID-19,405(83.33%)were discharged,33(6.71%)died outside of the ICU,and 48(7.20%)were still being treated in the ICU by the time the study period ended.Significant differences in age,lymphocyte counts,and the levels of procalcitonin,aspartate aminotransferase,and D-dimer(P<0.001 for all)among the three groups.Further analysis showed that older age,decreased lymphocyte counts,and increased procalcitonin,aspartate aminotransferase,and D-dimer levels were significantly associated with disease progression.Conclusion:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)may impair the immune system,the blood coagulation system,and hepatic and cardiac function.Some clinical characteristics and laboratory findings can help identify patients with a high risk of disease severity,which can be significant for appropriate resource allocation during the COVID-19 pandemic.
