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The compensatory pathways between ROS and inflammation limited the efficacy of modulating the above single treatment regimen after SCI. Here, novel \u201cnanoflower\u201d Mn\n                    <jats:sub>3<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    integrated with \u201cpollen\u201d\n                    <jats:italic>\n                      <jats:sup>IRF\u20105<\/jats:sup>\n                      SiRNA\n                    <\/jats:italic>\n                    was designed as a combination antioxidant and anti\u2010inflammatory treatment after SCI. The \u201cnanoflower\u201d and \u201cpollen\u201d structure was encapsulated with a neutrophil membrane for protective and targeted delivery. Furthermore, valence\u2010engineered nanozyme Mn\n                    <jats:sub>3<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    imitated the cascade response of antioxidant enzymes with a higher substrate affinity compared to natural antioxidant enzymes. Nanozymes effectively catalyzed ROS to generate O\n                    <jats:sub>2<\/jats:sub>\n                    , which is advantageous for reducing oxidative stress and promoting angiogenesis. The screened \u201cpollen\u201d\n                    <jats:italic>\n                      <jats:sup>IRF\u20105<\/jats:sup>\n                      SiRNA\n                    <\/jats:italic>\n                    could reverse the inflammatory phenotype by reducing interferon regulatory factors\u20105 (IRF\u20105) expression (protein level: 73.08% and mRNA level: 63.10%). The decreased expression of pro\u2010inflammatory factors reduced the infiltration of inflammatory cells, resulting in less neural scarring. In SCI rats, multifunctional nanozymes enhanced the proliferation of various neuronal subtypes (motor neurons, interneurons, and sensory neurons) and the recovery of locomotor function, demonstrating that the remodeling of the extrinsic neural environment is a promising strategy to facilitate nerve regeneration.\n                  <\/jats:p>","DOI":"10.1002\/advs.202205997","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T21:42:01Z","timestamp":1673905321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Multifunctional Integrated Nanozymes Facilitate Spinal Cord Regeneration by Remodeling the Extrinsic Neural Environment"],"prefix":"10.1002","volume":"10","author":[{"given":"Tiandi","family":"Xiong","sequence":"first","affiliation":[{"name":"School of Nano Technology and Nano Bionics University of Science and Technology of China  Hefei 230026 China"},{"name":"Key Laboratory 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