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However, conventional molecular design strategies face significant challenges. Both integrated molecules and multicomponent physical hybrid systems suffer from inherent drawbacks, such as irreversible substrate consumption, emission blue-shift and inefficient energy transfer, which ultimately limit their performance and applications. To address these issues, we report an independent and efficient pyridone scaffold for constructing afterglow molecules. 2-pyridone was employed as a stable, nonconsumable substrate to prevent depletion and blue-shift, while covalent linkage with the relay unit ensured efficient intramolecular energy transfer. Based on this scaffold, a series of afterglow chemiluminescent molecules (RB-Py, BDP-Py, HC-Py, CS-Py, Cy-Py) were constructed. Upon encapsulation with Pluronic F127 to form nanoparticles, these molecules demonstrated excellent afterglow performance in PBS. An activatable afterglow chemiluminescence probe (HFO-NPs) was developed, which can simultaneously activate fluorescence and afterglow signals in the presence of peroxynitrite (ONOO\u2013). Furthermore, we successfully applied it for the precise diagnosis of APAP-induced early liver injury and the visualization of ONOO\u2013 levels. Together, these findings establish a new paradigm for organic afterglow molecules and provide a powerful new platform for precise molecular sensing and disease diagnosis.<\/jats:p>","DOI":"10.1021\/jacs.6c09236","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:01:41Z","timestamp":1786028501000},"page":"34626-34638","source":"Crossref","is-referenced-by-count":0,"title":["Independent and Efficient\nPyridone Scaffold: Universal\nAfterglow Chemiluminescence Platform for High-Contrast Bioimaging"],"prefix":"10.1021","volume":"148","author":[{"given":"Xingwei","family":"Li","sequence":"first","affiliation":[{"name":"Shanxi University , , ,","place":["Taiyuan, China, 030006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi University , , ,","place":["Taiyuan, China, 030006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Ai","sequence":"additional","affiliation":[{"name":"Shanxi University , , ,","place":["Taiyuan, China, 030006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangjun","family":"Huo","sequence":"additional","affiliation":[{"name":"Shanxi University , , ,","place":["Taiyuan, China, 030006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-6333","authenticated-orcid":true,"given":"Caixia","family":"Yin","sequence":"additional","affiliation":[{"name":"Shanxi University , , ,","place":["Taiyuan, China, 030006"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026081910234275200_cit1","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1152\/physrev.00049.2010","article-title":"A molecular imaging primer: modalities, imaging agents,\nand applications","volume":"92","author":"James","year":"2012","journal-title":"Physiol. 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