Humanβ-galactosidase(β-gal)is recognized as a crucial biomarker for evaluating senescence at the cellular and tissue levels in humans.However,tools to precisely track the endogenousβ-gal are still limited.Herein,we...Humanβ-galactosidase(β-gal)is recognized as a crucial biomarker for evaluating senescence at the cellular and tissue levels in humans.However,tools to precisely track the endogenousβ-gal are still limited.Herein,we present two novel self-calibratingβ-gal probes 7a and 7b which were constructed on a unique green/red dual-emissive fluorescence platform.The two probes inherently exhibited a stable green fluorescence signal impervious toβ-gal activity,serving as a reliable internal reference.They also displayed a progressively diminishing red fluorescence signal with the increasing ofβ-gal expression levels.The dual behavior endows them with self-calibration capacity and then renders excellently selective and sensitive for precisely monitoringβ-gal activity.Notably,compared with E.coliβ-gal,the two probes are more effectively response to A.oryzaeβ-gal homologous to humanβ-gal,indicating their unique species-selectivity.Furthermore,7a was validated for its effectiveness in determining senescenceassociatedβ-galactosidase(SA-β-gal)expression in senescent NRK-52E and HepG2 cells,underscoring its practical applicability in senescence research.展开更多
慢性神经炎症现已确定为阿尔茨海默病(Alzheimer disease,AD)的核心病理特征之一,但其在AD病理机制中的作用尚未完全阐明。作为胶质细胞来源的炎症因子,几丁质酶3样蛋白1(Chitinase-3-like protein 1,CHI3L1,又称YKL-40)参与调控神经炎...慢性神经炎症现已确定为阿尔茨海默病(Alzheimer disease,AD)的核心病理特征之一,但其在AD病理机制中的作用尚未完全阐明。作为胶质细胞来源的炎症因子,几丁质酶3样蛋白1(Chitinase-3-like protein 1,CHI3L1,又称YKL-40)参与调控神经炎症、神经元变性及死亡等关键病理过程。研究表明,YKL-40通过抑制脑内淀粉样斑块清除和增强神经元毒性,促进AD核心病理的进展。其表达水平与AD的早期识别、疾病严重程度及预后显著相关。深入了解YKL-40与AD的关系,不仅对阐明神经炎症驱动AD发生发展的途径至关重要,更凸显了其作为新型AD生物标志物及潜在治疗靶点的重大价值,为开发更有效的AD诊疗策略提供重要方向。展开更多
Polarity,as a crucial environmental characteristic,plays a significant role in numerous cellular physiological processes.Abnormal changes in polarity are closely associated with various diseases.However,existing tools...Polarity,as a crucial environmental characteristic,plays a significant role in numerous cellular physiological processes.Abnormal changes in polarity are closely associated with various diseases.However,existing tools still have certain limitations that hinder accurate detection of polarity.Therefore,there is a pressing need to develop powerful tools for precisely monitoring changes in polarity.In this study,we developed two dual-emissive fluorogenic dyes by innovatively introducing 1,3-dithio-2-heteroarsenic cyclopentane and 1,2-diselenocyclopentane respectively into the near-infrared(NIR)coumarin-benzopyranium skeleton to enhance their cellular uptake capability.Additionally,we synthesized the polarity-sensitive dual-emissive fluorogenic probe CSFNS,which exhibits high cellular uptake rate,by modifying the spironolactone(Aldactone)structure of CBA into spirolactam.CSFNS not only demonstrates excellent polarity sensitivity in vitro but is also successfully applied to visually monitor the polarity changes in various types of living cells,including healthy cells,cancer cells and drug-induced senescent cells.展开更多
基金the financial support from the National Natural Science Foundation of China(Nos.21977082,22037002and 21472148)the Natural Science Basic Research Program of Shaanxi(No.2020JC-38)。
文摘Humanβ-galactosidase(β-gal)is recognized as a crucial biomarker for evaluating senescence at the cellular and tissue levels in humans.However,tools to precisely track the endogenousβ-gal are still limited.Herein,we present two novel self-calibratingβ-gal probes 7a and 7b which were constructed on a unique green/red dual-emissive fluorescence platform.The two probes inherently exhibited a stable green fluorescence signal impervious toβ-gal activity,serving as a reliable internal reference.They also displayed a progressively diminishing red fluorescence signal with the increasing ofβ-gal expression levels.The dual behavior endows them with self-calibration capacity and then renders excellently selective and sensitive for precisely monitoringβ-gal activity.Notably,compared with E.coliβ-gal,the two probes are more effectively response to A.oryzaeβ-gal homologous to humanβ-gal,indicating their unique species-selectivity.Furthermore,7a was validated for its effectiveness in determining senescenceassociatedβ-galactosidase(SA-β-gal)expression in senescent NRK-52E and HepG2 cells,underscoring its practical applicability in senescence research.
文摘慢性神经炎症现已确定为阿尔茨海默病(Alzheimer disease,AD)的核心病理特征之一,但其在AD病理机制中的作用尚未完全阐明。作为胶质细胞来源的炎症因子,几丁质酶3样蛋白1(Chitinase-3-like protein 1,CHI3L1,又称YKL-40)参与调控神经炎症、神经元变性及死亡等关键病理过程。研究表明,YKL-40通过抑制脑内淀粉样斑块清除和增强神经元毒性,促进AD核心病理的进展。其表达水平与AD的早期识别、疾病严重程度及预后显著相关。深入了解YKL-40与AD的关系,不仅对阐明神经炎症驱动AD发生发展的途径至关重要,更凸显了其作为新型AD生物标志物及潜在治疗靶点的重大价值,为开发更有效的AD诊疗策略提供重要方向。
基金the financial support from the National Natural Science Foundation of China(Nos.22477101,22277098 and 22037002)the Natural Science Basic Research Plan for Distinguished Young Scholars in Shaanxi Province of China(No.2020JC-38)the Shaanxi Fundamental Science Research Project for Chemistry and Biology(No.22JHQ070)。
文摘Polarity,as a crucial environmental characteristic,plays a significant role in numerous cellular physiological processes.Abnormal changes in polarity are closely associated with various diseases.However,existing tools still have certain limitations that hinder accurate detection of polarity.Therefore,there is a pressing need to develop powerful tools for precisely monitoring changes in polarity.In this study,we developed two dual-emissive fluorogenic dyes by innovatively introducing 1,3-dithio-2-heteroarsenic cyclopentane and 1,2-diselenocyclopentane respectively into the near-infrared(NIR)coumarin-benzopyranium skeleton to enhance their cellular uptake capability.Additionally,we synthesized the polarity-sensitive dual-emissive fluorogenic probe CSFNS,which exhibits high cellular uptake rate,by modifying the spironolactone(Aldactone)structure of CBA into spirolactam.CSFNS not only demonstrates excellent polarity sensitivity in vitro but is also successfully applied to visually monitor the polarity changes in various types of living cells,including healthy cells,cancer cells and drug-induced senescent cells.
