Abstract：
Autophagy is an essential degradative process that governs the renewal of organelle and maintains the homeostasis of cellular microenvironment. Its dysregulation has been demonstrated to be an indicator for neuroinflammation. To elucidate the interrelationship between neuroinflammation and autophagy, optical probes are ideal tools as they offer a number of advantages such as high spatiotemporal resolution and non-invasive sensing, which help to visualize the physiological and pathological functions of interested analytes. However, single autophagy parameter-response probes may generate false-positive results since they cannot distinguish between neuroinflammation and other autophagic stimuli. In contrast, chemosensors that respond to two (or more) targets can improve selectivity by qualifying response conditions. Herein, a \"dual-key-and-lock\" strategy was applied to construct probe (Vis-NO) to selectively recognize autophagy under inflammation out of other stimuli. The red fluorescence of Vis-NO was lit up only in the simultaneously presence of high viscosity and nitric oxide (NO) in lysosome. Due to the characteristics of high viscosity and overexpressed NO within lysosomes, Vis-NO could be used to selectively identify autophagy during neuroinflammation, providing expanding insights into the interrelationship between autophagy, neuroinflammation and stroke in pathology, and informing about the mechanisms through which autophagy regulates inflammation.
摘要：
自噬是调节细胞器更新和维持细胞微环境稳态的重要降解过程。已证明其失调是神经炎症的指标。阐明神经炎症和自噬之间的相互关系,光学探针是理想的工具，因为它们提供了许多优点，如高时空分辨率和非侵入式传感，这有助于可视化感兴趣的分析物的生理和病理功能。然而,单个自噬参数反应探针可能产生假阳性结果,因为它们不能区分神经炎症和其他自噬刺激.相比之下,响应两个（或更多）目标的化学传感器可以通过限定响应条件来提高选择性。在这里，将“双键和锁”策略应用于构建探针（Vis-NO），以在其他刺激下选择性识别炎症下的自噬。只有在溶酶体中同时存在高粘度和一氧化氮（NO）时，Vis-NO的红色荧光才被点亮。由于高粘度和溶酶体内NO过表达的特点，Vis-NO可用于选择性识别神经炎症过程中的自噬，提供对自噬之间相互关系的扩展见解，病理学中的神经炎症和中风，并告知自噬调节炎症的机制。
