Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation.Mitochondria-specific photosensitizers have been reported to be critica...Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation.Mitochondria-specific photosensitizers have been reported to be critical for inducing cell apoptosis.Two-photon fluorescence imaging provides a new technique for delineating biological structures and activities in deep tissues.Herein,we developed a new aggregation-induced emission(AIE)active photosensitizer by attaching a pyridinium group for mitochondrial target-ing.The rationally designed photosensitizer(TTTP)exhibited excellent photophysical properties,good biocompatibility,reactive oxygen species(ROS)stimulation ability,anticancer efficacy,and two-photon imaging properties.TTTP was highly taken up by cells and accumulated specifically in mitochondria but was selectively cytotoxic to cancer cells.Under light irradiation,the generation of ROS was significantly boosted,leading to actively induced apoptosis.The in vivo tumor photodynamic therapeutic efficacy of TTTP showed significant inhibition of tumor growth.Furthermore,the underlying mechanism of TTTP tu-mor suppression revealed that the apoptosis agonist Bax was markedly up-regulated while the antagonist Bcl-xL was down-regulated.This research provides a potential mitochondrial-targeted phototherapeutic agent for effective therapy and two-photon fluorescence imaging.展开更多
Based on dynamic rupture simulations on a planar fault in a homogeneous half-space, we investigated the nucleation processes using the time-weakening friction law. Both the characteristic time and the rupture speed in...Based on dynamic rupture simulations on a planar fault in a homogeneous half-space, we investigated the nucleation processes using the time-weakening friction law. Both the characteristic time and the rupture speed in the nucleation asperity play an important role in determining rupture behaviors on a fault plane following the time-weakening friction law, with which rupture starts from a single point in the nucleation asperity and propagates at a given speed toward the boundary of the nucleation area. Rupture with a small characteristic time or a large rupture speed in the nucleation asperity propagates earlier from the hypocenter. Rupture following the slipweakening friction law requires a smaller radius of nucleation patch to have similar rupture front contours of the time-weakening friction law. Even if the rupture velocity in the nucleation patch of the time-weakening friction law increases to infinity, the peak slip rate in the nucleation asperity is smaller than that of the slip-weakening law. The peak ground velocity distributions of ruptures following the two friction laws are also compared.展开更多
Erythropoietic protoporphyria(EPP)is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase(FECH),resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissue...Erythropoietic protoporphyria(EPP)is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase(FECH),resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissues.Here,we report a patient with photosensitive dermatitis and acute icteric hepatitis caused by EPP,whose clinical and biochemical results successfully improved following 2-month treatment with glucose load,ursodeoxycholic acid capsules,and cholestyramine powder.This case provides a reference for a combination therapy strategy for patients with liver and skin injury caused by EPP.展开更多
文摘肿瘤实性成分占比(consolidation tumor ratio,CTR)是近年来肺癌影像学研究的热点,是指在高分辨计算机断层扫描(high resolution computed tomography,HRCT)扫描肺窗中肿瘤最大实性直径与肿瘤最大直径的比值。目前诸多研究也证实其可作为早期肺癌良恶性判断指标及亚肺叶切除的主要参考指标,是早期肺癌复发及预后的独立相关因素。尤其在日本JCOG0804和JCOG0802两个基于肿瘤大小和实性成分占比的研究结果相继公布后,早期肺癌的传统外科手术方式被彻底打破,为早期肺癌患者带来了良好获益。但目前对CTR值的研究数据仍有限,CTR值的测定尚缺少客观的评价系统。本文就CTR值在肺结节良恶性预测、外科手术方式选择、淋巴结清扫、气腔播散(spread through air spaces,STAS)等热点研究方面的进展进行综述,同时进一步探讨CTR值可能存在的疗效预测指标,并对早期周围型肺癌外科治疗的发展趋势以及存在的问题进行总结和分析,为临床工作提供新思路。
基金supported by the Natural Sci-ence Foundation of Fujian Province(No.2021J011374)the Science and Technology Program of Guangzhou(No.202002030486)the Science and Technology Project of Guangdong Province(No.2018B090944002).
文摘Mitochondria are well-acknowledged as ideal targets for tumor therapy due to their important role in energy supply and cellular signal regulation.Mitochondria-specific photosensitizers have been reported to be critical for inducing cell apoptosis.Two-photon fluorescence imaging provides a new technique for delineating biological structures and activities in deep tissues.Herein,we developed a new aggregation-induced emission(AIE)active photosensitizer by attaching a pyridinium group for mitochondrial target-ing.The rationally designed photosensitizer(TTTP)exhibited excellent photophysical properties,good biocompatibility,reactive oxygen species(ROS)stimulation ability,anticancer efficacy,and two-photon imaging properties.TTTP was highly taken up by cells and accumulated specifically in mitochondria but was selectively cytotoxic to cancer cells.Under light irradiation,the generation of ROS was significantly boosted,leading to actively induced apoptosis.The in vivo tumor photodynamic therapeutic efficacy of TTTP showed significant inhibition of tumor growth.Furthermore,the underlying mechanism of TTTP tu-mor suppression revealed that the apoptosis agonist Bax was markedly up-regulated while the antagonist Bcl-xL was down-regulated.This research provides a potential mitochondrial-targeted phototherapeutic agent for effective therapy and two-photon fluorescence imaging.
基金supported by the National Natural Science Foundation of China (Nos. 41504039, 41474037 and 41274053)
文摘Based on dynamic rupture simulations on a planar fault in a homogeneous half-space, we investigated the nucleation processes using the time-weakening friction law. Both the characteristic time and the rupture speed in the nucleation asperity play an important role in determining rupture behaviors on a fault plane following the time-weakening friction law, with which rupture starts from a single point in the nucleation asperity and propagates at a given speed toward the boundary of the nucleation area. Rupture with a small characteristic time or a large rupture speed in the nucleation asperity propagates earlier from the hypocenter. Rupture following the slipweakening friction law requires a smaller radius of nucleation patch to have similar rupture front contours of the time-weakening friction law. Even if the rupture velocity in the nucleation patch of the time-weakening friction law increases to infinity, the peak slip rate in the nucleation asperity is smaller than that of the slip-weakening law. The peak ground velocity distributions of ruptures following the two friction laws are also compared.
基金the Guangdong Key Field R&D Plan of China(2019B020228001)the 5010 Project of Clinical Research in Sun Yat-sen University,China(No.2018024).
文摘Erythropoietic protoporphyria(EPP)is a rare inherited disease caused by partial deficiency activity of the enzyme ferrochelatase(FECH),resulting in excessive accumulation of protoporphyrin IX in erythrocyte and tissues.Here,we report a patient with photosensitive dermatitis and acute icteric hepatitis caused by EPP,whose clinical and biochemical results successfully improved following 2-month treatment with glucose load,ursodeoxycholic acid capsules,and cholestyramine powder.This case provides a reference for a combination therapy strategy for patients with liver and skin injury caused by EPP.
