Nanocatalytic Inhibition of ROS-Dependent GSDMD Palmitoylation Mitigates Sepsis Progression.

Authors

Chenglong Zhu, Renqi Yao, Wuyang Wei, Jiaojiao Feng, Lindong Cheng, Tian Zhou, Ruoyu Jiang, Wangzheqi Zhang, Yaohua Yu, Meiqi Chang, Yu Chen, Zui Zou

Published in

Advanced materials (Deerfield Beach, Fla.). Oct 27, 2026. Epub Oct 27, 2026.

Abstract

Sepsis is a life-threatening condition characterized by multiple organ dysfunction, high morbidity, and mortality. Gasdermin D (GSDMD)-mediated pyroptosis constitutes a key pathogenic mechanism. Here, we discovered that GSDMD in peripheral blood mononuclear cells (PBMCs) from septic patients undergoes enhanced palmitoylation, driven by reactive oxygen species (ROS) and mediated by ZDHHC5/ZDHHC9 transferases. Targeting this new mechanism, we designed and screened vanadium oxide hydroxide nanosheets (VOOH NSs) as catalytic ROS scavengers and GSDMD palmitoylation inhibitor. Crucially, we investigated and optimized the exposure patterns of specific lattice planes to maximize their ROS-eliminating capability. This intervention measure prevents GSDMD palmitoylation, inhibits both canonical and non-canonical pyroptosis, alleviates inflammatory damage, and demonstrates potent therapeutic effects in two sepsis animal models. Validation in GSDMD-knockout mice further confirms this palmitoylation pathway as the key therapeutic target. These results demonstrate that targeting ROS-mediated GSDMD palmitoylation is a key therapeutic strategy for treating sepsis.

PMID:
42935374
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.