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Herein, a colorimetric\u2010Surface\u2010enhanced Raman scattering (SERS) dual\u2010modal sensing platform is constructed to introduce 4f electron configurations of single\u2010atom ytterbium active site decorated on a nitrogen\u2010doped porous carbon (Yb\u2010N\/C) by a facile hierarchical cascade\u2010anchoring protocol. Specifically, this unique coordination environment can promote substrate molecule adsorption and activation energy barriers, possessing excellent peroxidase (POD)\u2010mimicking activity and SERS enhancement performance in TMB\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    system. In the presence of glutathione (GSH), Yb\u2010N\/C catalyst is inhibited to result in reducing oxTMB for returning its colorless state, consequently diminishing both the colorimetric readout and the SERS intensity. Interestingly, this reaction mechanism from Yb\u2010N\/C is systematically illustrated through the steady\u2010state kinetic, electron paramagnetic resonance (EPR), and density functional theory (DFT) calculations. Notably, the limited of detection (LOD) of GSH with colorimetric and SERS dual\u2010mode was as low as 0.30 and 0.11 \u00b5M, respectively. Our established dual\u2010modal analysis for intracellular GSH exhibits the favorable consistent with the standard kit in HepG2, KYSE150, and MCF\u20107 cells, respectively. This work will offer an in\u2010depth understanding of RESAzymes\u2010mimicking activity of colorimetric\u2010SERS biosensors by adjusting electronic structures in carbon\u2010based carrier.\n                  <\/jats:p>","DOI":"10.1002\/smll.75188","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:58:58Z","timestamp":1788512338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulating Rare\u2010Earth Single\u2010Atom Nanozyme for Colorimetric\u2010SERS Dual\u2010Modal Sensing of Intracellular Glutathione"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8168-5862","authenticated-orcid":false,"given":"Huifang","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Research Institute of Circadian Rhythm and Disease, Academy of Medical Sciences Shanxi Medical University  Taiyuan China"},{"name":"The 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