Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it...Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.展开更多
The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer sc...The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale.However,many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging,owing to their unmatched absorption and emission wavelengths,small Stokes'shift,easy photo-bleaching,etc.Herein,we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor(D)-7c-acceptor(A)compound.The electron-rich carbazole group and the electron-poor pyridinium bromide group,linked by 7i-conjugated thiophen-bridge,ensure strong near infrared(NIR)emission with a Stokes'shift larger than 200 nm.The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer(CT)state(Φ<0.04)to highly emissive locally-excited(LE)state(Φ=0.57),giving rise to a fluorescence Turn-On probe.Together with large Stokes'shift,good photostability and high depletion efficiency,the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power.Moreover,the ex-vivo super-resolution imaging of(E)-1-butyl-4(2-(5-(9-ethyl-9Hcarbazol-3-yl)thiophen-2-yl)vinyl)pyridinium bromide(CTPB)probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated.This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism,providing a new approach to the development of future amyloid probes.展开更多
基金This work was supported by the National Natural Science Foundation of China(81970425)by the National High Technology Research and Development Program of China(2020YFA0803700),and by Hangzhou Qianjiang Distinguished Expert Project(Prof.Lemin Zheng).
文摘Aortic aneurysm is a chronic aortic disease affected by many factors.Although it is generally asymptomatic,it poses a significant threat to human life due to a high risk of rupture.Because of its strong concealment,it is difficult to diagnose the disease in the early stage.At present,there are no effective drugs for the treatment of aneurysms.Surgical intervention and endovascular treatment are the only therapies.Although current studies have discovered that inflammatory responses as well as the production and activation of various proteases promote aortic aneurysm,the specific mechanisms remain unclear.Researchers are further exploring the pathogenesis of aneurysms to find new targets for diagnosis and treatment.To better understand aortic aneurysm,this review elaborates on the discovery history of aortic aneurysm,main classification and clinical manifestations,related molecular mechanisms,clinical cohort studies and animal models,with the ultimate goal of providing insights into the treatment of this devastating disease.The underlying problem with aneurysm disease is weakening of the aortic wall,leading to progressive dilation.If not treated in time,the aortic aneurysm eventually ruptures.An aortic aneurysm is a local enlargement of an artery caused by a weakening of the aortic wall.The disease is usually asymptomatic but leads to high mortality due to the risk of artery rupture.
基金the Top Talent Support Program for Medical Experts Team and for Young and Middle-Aged People of Wuxi Health Committee(202109 and 202014)the National Key R&D Program of China(2021YFC2501100 and 2020YFA0803700)the National Natural Science Foundation of China(82071296,81801158,and 81970425)。
基金This work was supported by the Ministry of Science and Technology of China(Nos.2017YFA0204503 and 2018YFA0704805)the National Natural Science Foundation of China(Nos.21503139,21573251,21673144,21873065,21833005,81970425 and 21790364)+5 种基金the Beijing Natural Science Foundation of China(No.2192011)the High-level Teachers in Bejing Municipal Universities in the Period of 13^th Five-year Plan(Nos.IDHT20180517 and CIT&TCD20180331)the Open Fund of the State Key Laboratory of Integrated Optoelectronics(No.IOSKL2019KF01)Capacity Building for Sci-Tech Innovation-Fundamental Scientific Research Funds(Nos.025185305000/210,009/19530050162 and 19530012018)Youth Innovative Research Team of Capital Normal University(No,009/19530050148)Beijing Advanced Innovation Center for Imaging Theory and Technology(No.009/19530011009).
文摘The formation of amyloid plaques usually occurs in the early-stage of Alzheimer’s disease(AD).Stimulated emission depletion(STED)imaging provided a powerful tool for visualizing amyloid structures on the nanometer scale.However,many commercial probes adopted in detecting amyloid fibrils are inapplicable to STED imaging,owing to their unmatched absorption and emission wavelengths,small Stokes'shift,easy photo-bleaching,etc.Herein,we demonstrated a polarity-activated STED probe based on an intramolecular charge transfer donor(D)-7c-acceptor(A)compound.The electron-rich carbazole group and the electron-poor pyridinium bromide group,linked by 7i-conjugated thiophen-bridge,ensure strong near infrared(NIR)emission with a Stokes'shift larger than 200 nm.The tiny change in polarity before and after binding with amyloid plaques leads to a transition from weakly emission charge-transfer(CT)state(Φ<0.04)to highly emissive locally-excited(LE)state(Φ=0.57),giving rise to a fluorescence Turn-On probe.Together with large Stokes'shift,good photostability and high depletion efficiency,the super-resolution imaging of the formation and morphology of amyloid fibrils in vitro based on this probe was realized with a lateral spatial resolution better than 33 nm at an extremely low depletion power.Moreover,the ex-vivo super-resolution imaging of(E)-1-butyl-4(2-(5-(9-ethyl-9Hcarbazol-3-yl)thiophen-2-yl)vinyl)pyridinium bromide(CTPB)probe in Aβ plaques in the brain slices of a Tg mouse was demonstrated.This research provides a demonstration of the super resolution imaging probe of amyloid fibrils based on polarity-response mechanism,providing a new approach to the development of future amyloid probes.
