Hydrogen polysulfides (H₂S_n, n > 1) have continuously been proved to act as important signal mediators in many physiological processes. However, the physiological role of H₂S_n and their signaling pathways in complex diseases, such as the most common liver disease, nonalcoholic fatty liver disease (NAFLD), have not been elucidated due to lack of suitable tools for selective detection of intracellular H₂S_n. Herein, we adopted a general and practical strategy including recognition site screening, construction of a ratiometric probe and self-assembly of nanoparticles, to significantly improve the probes' selectivity, photostability and biocompatibility. The ratiometric probe PPG-Np-RhPhCO selectively responds to H₂S_n, avoiding interaction with biothiol and persulfide. Moreover, this probe was applied to image H₂S_n in NAFLD for the first time and reveal the H₂S_n generation pathways in the cell model of drug-treated NAFLD. The pathway of H₂S_n revealed by PPG-Np-RhPhCO provides significant insights into the roles of H₂S_n in NAFLD and future drug development.

中文翻译：

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设计用于H2Sn比例成像的高选择性探针并揭示其在脂肪肝疾病中的信号传导途径

多硫化氢（H ₂ S _n，n > 1）已被连续证明是许多生理过程中重要的信号介体。然而，由于缺乏用于选择性检测细胞内H的合适工具，H ₂ S _n的生理学作用及其信号转导途径在复杂疾病（例如最常见的肝脏疾病，非酒精性脂肪肝疾病（NAFLD））中的作用尚未阐明₂小号_ñ。本文中，我们采用了一种通用且实用的策略，包括识别位点筛选，比例探针的构建和纳米粒子的自组装，以显着提高探针的选择性，光稳定性和生物相容性。比例探针PPG-Np-RhPhCO选择性响应H ₂ S _n，避免与生物硫醇和过硫化物相互作用。此外，该探针首次应用于NAFLD中的H ₂ S _n图像，并揭示了药物处理的NAFLD细胞模型中H ₂ S _n的生成途径。PPG-Np-RhPhCO揭示H ₂ S _n的途径H ₂ S _n在NAFLD和未来药物开发中的作用提供了重要的见解。