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Female Kunming mice with melasma\u2010like conditions were treated using four different picosecond laser modes. Concurrently, in\u00a0vitro experiments were conducted to assess changes in melanin and autophagy in mouse melanoma B16\u2010F10 cells treated with these laser modes. Changes in melanin in mouse skin were detected via Fontana\u2013Masson staining, and melanin particles were evaluated in B16\u2010F10 cells. Real\u2010time polymerase chain reaction and western blotting were used to analyse the expression levels of melanosome and autophagy\u2010related messenger ribonucleic acid (mRNA) and proteins. A combination of large\u2010spot low\u2010fluence 1064\u2010nm and fractional 1064\u2010nm picosecond lasers resulted insignificant decreases in melanin as well as in mRNA and protein expression of melanin\u2010synthesizing enzymes (TYR, TRP\u20101 and MITF). This combination also led to increased expression of the autophagy\u2010related proteins, Beclin1 and ATG5, with a marked decrease in p62 expression. Intervention with the PI3K activator, 740 Y\u2010P, increased TYR, TRP\u20101, MITF, p\u2010PI3K, p\u2010AKT, p\u2010mTOR and p62 expression but decreased the expression of LC3, ATG5 and Beclin1. A combination of large\u2010spot low\u2010fluence 1064\u2010nm and fractional 1064\u2010nm picosecond lasers proved more effective and safer. It inhibits melanin production, downregulates the PI3K\/AKT\/mTOR pathway, enhances melanocyte autophagy and accelerates melanin metabolism, thereby reducing melanin content.<\/jats:p>","DOI":"10.1111\/exd.15094","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T12:20:05Z","timestamp":1715689205000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Combining large\u2010spot low\u2010fluence 1064\u2010nm and fractional 1064\u2010nm picosecond lasers for promoting protective melanosome autophagy via the PI3K\/Akt\/mTOR signalling pathway for the treatment of melasma"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-0820","authenticated-orcid":false,"given":"Jie","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Dermatology First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"},{"name":"Department of 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