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This can be attributed to the activation of facial nerves in a state of hysteria due to an abnormally elevated interaction between SNAP25 and RAB3A proteins involved in the synaptic vesicle cycle (SVC). Facilitated by AI\u2010assisted structural design, a refined peptide called <jats:italic>RSI<\/jats:italic><jats:sub>pep<\/jats:sub> is developed to modulate this interaction and normalize SVC. Drawing inspiration from prions, which possess the ability to protect themselves against proteolysis and invade neighboring nerve cells through macropinocytosis, <jats:italic>RSI<\/jats:italic><jats:sub>pep<\/jats:sub> is engineered to demonstrate a GSH\u2010responsive reversible self\u2010assembly into a prion\u2010like supermolecule (<jats:italic>RSI<\/jats:italic><jats:sub>prion<\/jats:sub>). <jats:italic>RSI<\/jats:italic><jats:sub>prion<\/jats:sub> showcases protease resistance, micropinocytosis\u2010dependent cellular internalization, and low adhesion with constituent molecules in the cuticle, thereby endowing it with the transdermic absorption and subsequent biofunction in redressing the frenzied SVC. As a facial mud mask, it effectively reduces periorbital and perinasal wrinkles in the human face. Collectively, <jats:italic>RSI<\/jats:italic><jats:sub>prion<\/jats:sub> not only presents a clinical potential as an anti\u2010wrinkle prion\u2010like supermolecule, but also exemplifies a reproducible instance of bionic strategy\u2010guided drug development that bestows transdermal ability upon the pharmaceutical molecule.<\/jats:p>","DOI":"10.1002\/advs.202308764","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T14:16:07Z","timestamp":1718720167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Transdermal Prion\u2010Bionics Supermolecule as a RAB3A Antagonist for Enhancing Facial Youthfulness"],"prefix":"10.1002","volume":"11","author":[{"given":"Wenjia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Head and Neck Surgery The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710004 China"},{"name":"Institute for Stem Cell &amp; Regenerative Medicine The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710004 China"},{"name":"Ministry of Education Key Laboratory of Surgical Critical Care and Life Support (Xi'an Jiaotong University)  Xi'an 710004 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell &amp; Regenerative Medicine The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710004 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenguang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710061 P. 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