The gasdermin family:emerging therapeutic targets in diseases

The gasdermin(GSDM)family has garnered significant attention for its pivotal role in immunity and disease as a key player in pyroptosis.This recently characterized class of pore-forming effector proteins is pivotal in orchestrating processes such as membrane permeabilization,pyroptosis,and the follow-up inflammatory response,which are crucial self-defense mechanisms against irritants and infections.GSDMs have been implicated in a range of diseases including,but not limited to,sepsis,viral infections,and cancer,either through involvement in pyroptosis or independently of this process.The regulation of GSDM-mediated pyroptosis is gaining recognition as a promising therapeutic strategy for the treatment of various diseases.Current strategies for inhibiting GSDMD primarily involve binding to GSDMD,blocking GSDMD cleavage or inhibiting GSDMD-N-terminal(NT)oligomerization,albeit with some off-target effects.In this review,we delve into the cutting-edge understanding of the interplay between GSDMs and pyroptosis,elucidate the activation mechanisms of GSDMs,explore their associations with a range of diseases,and discuss recent advancements and potential strategies for developing GSDMD inhibitors.

Bioinspired cellulose-integrated MXene-based hydrogels for multifunctional sensing and electromagnetic interference shielding

Bioinspired hydrogels are complex materials with distinctive properties comparable to biological tissues.Their exceptional sensitivity to various external stimuli leads to substantial application potential in wearable smart devices.However,these multifaceted hydrogels are often challenging to be combined with pattern customization,stimulus responsiveness,self-healing,and biocompatibility.Herein,inspired by mussel secretions,a printable,self-healing,and biocompatible MXene-based composite hydrogel was designed and prepared by incorporating Ti3C2Tx MXene nanosheets into the hydrogel framework through the chelation of calcium ions(Ca2+)with polyacrylic acid and cellulose nanofibers at alkaline conditions.The biocompatible conductive hydrogel exhibited sensitivity(gauge factor of 2.16),self-healing(within 1 s),recognition,and adhesion,distinguishing it as an ideal candidate for wearable multifunctional sensors toward strain sensing,vocal sensing,signature detection,and Morse code transmission.Additionally,the multifunctional hydrogel manifested efficient electromagnetic interference shielding properties(reaching more than 30 dB at a thickness of 2.0 mm),protecting electronics and humans from electromagnetic radiation and pollution.Therefore,the presented work represents a versatile strategy for developing environmentally friendly conductive hydrogels,demonstrating the perspectives of intelligent hydrogels for multifunctional applications.

Distinct and shared endothermic strategies in the heat producing tissues of tuna and other teleosts

Although most fishes are ectothermic,some,including tuna and billfish,achieve endothermy through specialized heat producing tissues that are modified muscles.How these heat producing tissues evolved,and whether they share convergent molecular mechanisms,remain unresolved.Here,we generated a high-quality genome from the mackerel tuna(Euthynnus affinis)and investigated the heat producing tissues of this fish by single-nucleus and bulk RNA sequencing.Compared with other teleosts,tuna-specific genetic variation is strongly associated with muscle differentiation.Single-nucleus RNA-seq revealed a high proportion of specific slow skeletal muscle cell subtypes in the heat producing tissues of tuna.Marker genes of this cell subtype are associated with the relative sliding of actin and myosin,suggesting that tuna endothermy is mainly based on shivering thermogenesis.In contrast,cross-species transcriptome analysis indicated that endothermy in billfish relies mainly on nonshivering thermogenesis.Nevertheless,the heat producing tissues of the different species do share some tissue-specific genes,including vascular-related and mitochondrial genes.Overall,although tunas and billfishes differ in their thermogenic strategies,they share similar expression patterns in some respects,highlighting the complexity of convergent evolution.