SUMMARY Regulatory T (Treg) cells suppress inflammatory immune responses and autoimmunity caused by self-reactive T cells. The key Treg cell transcription factor Foxp3 is downregulated during inflammation to allow for the acquisition of effector T cell-like functions. Here, we demonstrate that stress signals elicited by proinflammatory cytokines and lipopolysaccharide lead to the degradation of Foxp3 through the action of the E3 ubiquitin ligase Stub1. Stub1 interacted with Foxp3 to promote its K48-linked polyubiquitination in an Hsp70-dependent manner. Knockdown of endogenous Stub1 or Hsp70 prevented Foxp3 degradation. Furthermore, the overexpression of Stub1 in Treg cells abrogated their ability to suppress inflammatory immune responses in vitro and in vivo, and conferred a T helper 1 (Th1) cell-like phenotype. Our results demonstrate the critical role of the stress-activated Stub1-Hsp70 complex in promoting Treg cell inactivation, thus providing a potential therapeutic target for the intervention against autoimmune disease, infection and cancer.

Emerging moisture sensitive devices require robust encapsulation strategies to inhibit water ingress and prevent premature failure. A scalable, open-air plasma process has been developed to deposit alternating layers of conformal organosilicate and dense SiO2 thin-film barriers to prevent moisture ingress. The in situ low-temperature process is suitable for direct deposition on thermally sensitive devices and is compatible with flexible polymeric substrates. Using optical calcium testing, low water vapor transmission rates on the order of 10–3 g/m2/day at an accelerated aging condition of 38 °C and 90% relative humidity (RH) are achieved. Using moisture-sensitive perovskite devices as a representative moisture-susceptible device, devices retain over 80% of their initial performance for over 660 h in a 50 °C 50% RH accelerated aging environment. The ability of the multilayer barrier to enable device resistance to humid environments is crucial toward realizing longer operating lifetimes.

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Pathological mineralization (PTM) often occurs under inflammation and affects the prognosis of diseases, such as atherosclerosis and cancers. However, how the PTM impacts inflammation has not been well explored. Herein, poly lactic-co-glycolic acid (PLGA)/gelatin/hydroxyapatite (HA) electrospun nanofibers are rationally designed as an ideal PTM microenvironment biomimetic system for unraveling the role of PTM on inflammation. The results demonstrate that the inflammatory response decreases continuously during the process of mineralization. When mature macromineralization forms, the inflammation almost completely disappears. Mechanistically, the PTM formation is mediated by matrix proteins, local high calcium, and cell debris (nuclei), or actively regulated by the lysosomal/plasma membrane components secreted by macrophages. These inflammatory inducible factors (calcium, cell debris, etc.) can be "buried" through PTM process, resulting in reduced immune responses. Overall, the present study demonstrates that PTM is an innate mechanism of inflammation subsidence, providing valuable insight into understanding the action of mineralization on inflammation.