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We further investigated the potential tissue damage induced by the short laser pulses. We found that fresh liver tissue can only tolerate a laser power at \u223c 20\u2005mW, without showing obvious accumulated photothermal damage, while at least 40\u2005mW is needed to generate decent THG signals of negative-contrast nuclei of hepatocytes. To avoid this issue, we then developed a deep learning framework that maps THG imaging data acquired with 20\u2005mW laser power to the 40\u2005mW equivalents, allowing visualization of hepatocyte nuclei having negative THG contrast, without optical-induced tissue damage. Collectively, our findings reveal a contrast mechanism of THG in liver tissue that has not been reported previously, which will open new applications for THG and HHG imaging in liver tumor diagnosis.<\/jats:p>","DOI":"10.1364\/boe.605242","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:00:06Z","timestamp":1786518006000},"page":"4617","update-policy":"https:\/\/doi.org\/10.1364\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-pulsed AI-augmented third harmonic generation imaging visualizes negative-contrast cell nuclei in fresh mouse liver tissue without optical-induced damage"],"prefix":"10.1364","volume":"17","author":[{"given":"Qiyu","family":"Bo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Nankai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyue","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiang","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelai","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Tianjin Key Laboratory of Micro-scale Optical Information Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjiang","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Tianjin Key Laboratory of Micro-scale Optical Information Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangwu","family":"Li","sequence":"additional","affiliation":[{"name":"Nankai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Qiu","sequence":"additional","affiliation":[{"name":"Shantou Central Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-0340","authenticated-orcid":true,"given":"Zhiqing","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Tianjin Key Laboratory of Micro-scale Optical Information Science and Technology"},{"name":"Nankai International Advanced Research Institute (Shenzhen Futian)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"285","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"boe-17-9-4617-R1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1038\/s41566-021-00881-0","type":"journal-article","volume":"15","author":"Wu","year":"2021","journal-title":"Nat. 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