Viral envelope fusion with the host plasma membrane(PM)for genome release is a hallmark step in the life cycle of many enveloped viruses.This process is regulated by a complex network of biomolecules on the PM,but rob...Viral envelope fusion with the host plasma membrane(PM)for genome release is a hallmark step in the life cycle of many enveloped viruses.This process is regulated by a complex network of biomolecules on the PM,but robust tools to precisely elucidate the dynamic mechanisms of virus-PM fusion events are still lacking.Here,we developed a quantitative single-virus tracking approach based on highly efficient dual-color labelling of viruses and batch trajectory analysis to achieve the spatiotemporal quantification of fusion events.This approach allows us to comprehensively analyze the membrane fusion mechanism utilized by pseudotyped severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the singlevirus level and precisely elucidate how the relevant biomolecules synergistically regulate the fusion process.Our results revealed that SARS-CoV-2 may promote the formation of supersaturated clusters of cholesterol to facilitate the initiation of the membrane fusion process and accelerate the viral genome release.展开更多
BACKGROUND While primary liver cancer(PLC)is one of the most common cancers around the world,few large-scale population-based studies have been reported that evaluated the clinical survival outcomes among peripartum a...BACKGROUND While primary liver cancer(PLC)is one of the most common cancers around the world,few large-scale population-based studies have been reported that evaluated the clinical survival outcomes among peripartum and postmenopausal women with PLC.AIM To investigate whether peripartum and postmenopausal women with PLC have lower overall survival rates compared with women who were not peripartum and postmenopausal.METHODS The Taiwan National Health Insurance claims data from 2000 to 2012 was used for this propensity-score-matched study.A cohort of 40 peripartum women with PLC and a reference cohort of 160 women without peripartum were enrolled.In the women with PLC with/without menopause study,a study cohort of 10752 menopausal females with PLC and a comparison cohort of 2688 women without menopause were enrolled.RESULTS Patients with peripartum PLC had a non-significant risk of death compared with the non-peripartum cohort[adjusted hazard ratios(aHR)=1.40,95%confidence intervals(CI):0.89-2.20,P=0.149].The survival rate at different follow-up durations between peripartum PLC patients and those in the non-peripartum cohort showed a non-significant difference.Patients who were diagnosed with PLC younger than 50 years old(without menopause)had a significant lower risk of death compared with patients diagnosed with PLC at or older than 50 years(postmenopausal)(aHR=0.64,95%CI:0.61-0.68,P<0.001).The survival rate of women<50 years with PLC was significantly higher than older women with PLC when followed for 0.5(72.44%vs 64.16%),1(60.57%vs 51.66%),3(42.92%vs 31.28%),and 5 year(s)(37.02%vs 21.83%),respectively(P<0.001).CONCLUSION Peripartum females with PLC have no difference in survival rates compared with those patients without peripartum.Menopausal females with PLC have worse survival rates compared with those patients without menopause.展开更多
基金supported by the National Natural Science Foundation of China(22293032,22293030,and 91859123)the National Key Research and Development Program of China(2019YFA0210500)+1 种基金the Fundamental Research Funds for the Central Universities of China(63211023)the financial support from Haihe Laboratory of Sustainable Chemical Transformations.
文摘Viral envelope fusion with the host plasma membrane(PM)for genome release is a hallmark step in the life cycle of many enveloped viruses.This process is regulated by a complex network of biomolecules on the PM,but robust tools to precisely elucidate the dynamic mechanisms of virus-PM fusion events are still lacking.Here,we developed a quantitative single-virus tracking approach based on highly efficient dual-color labelling of viruses and batch trajectory analysis to achieve the spatiotemporal quantification of fusion events.This approach allows us to comprehensively analyze the membrane fusion mechanism utilized by pseudotyped severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the singlevirus level and precisely elucidate how the relevant biomolecules synergistically regulate the fusion process.Our results revealed that SARS-CoV-2 may promote the formation of supersaturated clusters of cholesterol to facilitate the initiation of the membrane fusion process and accelerate the viral genome release.
文摘BACKGROUND While primary liver cancer(PLC)is one of the most common cancers around the world,few large-scale population-based studies have been reported that evaluated the clinical survival outcomes among peripartum and postmenopausal women with PLC.AIM To investigate whether peripartum and postmenopausal women with PLC have lower overall survival rates compared with women who were not peripartum and postmenopausal.METHODS The Taiwan National Health Insurance claims data from 2000 to 2012 was used for this propensity-score-matched study.A cohort of 40 peripartum women with PLC and a reference cohort of 160 women without peripartum were enrolled.In the women with PLC with/without menopause study,a study cohort of 10752 menopausal females with PLC and a comparison cohort of 2688 women without menopause were enrolled.RESULTS Patients with peripartum PLC had a non-significant risk of death compared with the non-peripartum cohort[adjusted hazard ratios(aHR)=1.40,95%confidence intervals(CI):0.89-2.20,P=0.149].The survival rate at different follow-up durations between peripartum PLC patients and those in the non-peripartum cohort showed a non-significant difference.Patients who were diagnosed with PLC younger than 50 years old(without menopause)had a significant lower risk of death compared with patients diagnosed with PLC at or older than 50 years(postmenopausal)(aHR=0.64,95%CI:0.61-0.68,P<0.001).The survival rate of women<50 years with PLC was significantly higher than older women with PLC when followed for 0.5(72.44%vs 64.16%),1(60.57%vs 51.66%),3(42.92%vs 31.28%),and 5 year(s)(37.02%vs 21.83%),respectively(P<0.001).CONCLUSION Peripartum females with PLC have no difference in survival rates compared with those patients without peripartum.Menopausal females with PLC have worse survival rates compared with those patients without menopause.