An imbalance in the lineages of immunosuppressive regulatory T cells (T cells) and the inflammatory T17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under T17 cell-inducing conditions and was required for T17 differentiation and T17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the T17-defining transcription factor RORγt. In addition, TAZ attenuated T cell development by decreasing acetylation of the T cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under T cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted T cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced T cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed T17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of T cells and T17 cells.

Reactive oxygen species (ROS) production in phagocytes is a major defense mechanism against pathogens. However, the cellular self-protective mechanism against such potential damage from oxidative stress remains unclear. Here we show that the kinases Mst1 and Mst2 (Mst1/2) sense ROS and maintain cellular redox balance by modulating the stability of antioxidant transcription factor Nrf2. Site-specific ROS release recruits Mst1/2 from the cytosol to the phagosomal or mitochondrial membrane, with ROS subsequently activating Mst1/2 to phosphorylate kelch like ECH associated protein 1 (Keap1) and prevent Keap1 polymerization, thereby blocking Nrf2 ubiquitination and degradation to protect cells against oxidative damage. Treatment with the antioxidant N-acetylcysteine disrupts ROS-induced interaction of Mst1/2 with phagosomes or mitochondria, and thereby diminishes the Mst-Nrf2 signal. Consistently, loss of Mst1/2 results in increased oxidative injury, phagocyte ageing and death. Thus, our results identify the Mst-Nrf2 axis as an important ROS-sensing and antioxidant mechanism during an antimicrobial response.

It is a major challenge to develop the low-temperature catalysts (LTC, <250 • C) with excellent efficiency and stability for selective catalytic reduction (SCR) of NO x by NH 3 from stationary sources. Mn-based LTC have been widely investigated due to its various valence states and excellent redox performance, while the poisoning by H 2 O or/and SO 2 is one of the severe weaknesses. This paper reviews the latest research progress on Mn-based catalysts that are expected to break through the resistance, such as modified MnO x -CeO 2 , multi-metal oxides with special crystal or/and shape structures, modified TiO 2 supporter, and novel carbon supporter (ACF, CNTs, GE), etc. The SCR mechanisms and promoting effects of redox cycle are described in detail. The reaction kinetics will be a benefit for the quantitative study of Eley-Rideal (ER) and Langmuir-Hinshelwood (LH) mechanisms. This paper also introduces the applications of quantum-chemical calculation using density functional theory to analyze the physic-chemical properties, explicates the reaction and poisoning mechanisms, and directs the design of functional catalysts on molecule levels. The intensive study of H 2 O/SO 2 inhibition effects is by means of the combination analysis of in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT), and the amplification of tolerance mechanisms will be helpful to design an excellent SCR catalyst.

Glucose oxidase (GOx)-mediated starvation therapy has demonstrated good application prospect in cancer treatment. However, the glucose- and oxygen-depletion starvation therapy still suffers from some limitations like low therapeutic efficiency and potential side effects to normal tissues. To overcome these disadvantages, herein a novel enzymatic cascade nanoreactor (Pd@Pt-GOx/hyaluronic acid (HA)) with controllable enzymatic activities was developed for high-efficiency starving-enhanced chemodynamic cancer therapy. The Pd@Pt-GOx/HA was fabricated by covalent conjugation of GOx onto Pd@Pt nanosheets (NSs), followed by linkage with hyaluronic acid (HA). The modification of HA on Pd@Pt-GOx could block the GOx activity, catalase (CAT)-like and peroxidase (POD)-like activities of Pd@Pt, reduce the cytotoxicity to normal cells and organs, and effectively target CD44-overexpressed tumors by active targeting and passive enhanced permeability and retention (EPR) effect. After endocytosis by tumor cells, the intracellular hyaluronidase (Hyase) could decompose the outer HA and expose Pd@Pt-GOx for the enzymatic cascade reaction. The GOx on the Pd@Pt-GOx could catalyze the oxidation of intratumoral glucose by O2 for cancer starvation therapy, while the O2 produced from the decomposition of endogenous H2O2 by the Pd@Pt with the CAT-like activity could accelerate the O2-dependent depletion of glucose by GOx. Meanwhile, the upregulated acidity and H2O2 content in the tumor region generated by GOx catalytic oxidation of glucose dramatically facilitated the pH-responsive POD-like activity of the Pd@Pt nanozyme, which then catalyzed degradation of the H2O2 to generate abundant highly toxic •OH, thereby realizing nanozyme-mediated starving-enhanced chemodynamic cancer therapy. In vitro and in vivo results indicated that the controllable, self-activated enzymatic cascade nanoreactors exerted highly efficient anticancer effects with negligible biotoxicity.

TLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response.

Ultra-small palladium nanosheets are employed as the safe carriers of immunoadjuvant CpG for highly efficient cancer photothermal combined immunotherapy.

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efficiency (PCE) of rigid-substrate-based devices has exceeded 25%. [2] Meanwhile, flexible devices have also reached the highest PCE of 21.05%. [3] The merits of PSCs, such as low cost, suitable bandgaps for indoor light sources such as lightemitting diodes (LEDs), and simply fabricating flexible devices, [4][5][6][7] also enhance the indoor commercialization possibility. [8] In the past several years, research on indoor photovoltaics has also accelerated, which promotes the realization of the idea of the indoor Internet of Things (IoT) in the future. [9] The surfaces of indoor small electronic devices are usually irregularly curved. Compared to devices with rigid substrates, flexible devices can better fit the surface of small electrical appliances, which can increase the effective functional area and widen the application field range. [10] As the demand for adaptation to various indoor application scenarios, the mechanical stability of flexible devices is a very important concern. [11][12][13][14] Herein, we get inspiration from the balloon glue. The reason that balloon glue can deform so sharply but not break contributes to the cross-linking agent borax (Na 2 B 4 O 7 ). Borax is a common crosslinking agent that has excellent flexibility. The oxygen ion groups at both sides of the molecule can form stronger coordination bonds with lead than the lead-iodine bond, thereby acting as a stretch bridge at grain boundaries of perovskite films. We conducted physical tensile tests and extreme temperature variation tests (−180 to 150 °C) on the optimized films and found that the treated films exhibited better mechanical stability and phase stability. To prove the indoor application prospects of flexible devices, we first systematically reported the trap density of states of flexible devices under different light intensities. It is found that the trap density of formamidinium-lead-iodide (FAPbI 3 )-based perovskite is reduced after optimization, which is more suitable for indoor applications. [15,16] Meanwhile, since the improved film formation quality of perovskite contributed to passivation treatment of borax, the champion PCE of optimized rigid and flexible PSCs reached 23.05% and 21.63%, respectively, under AM 1.5G illumination. Moreover, the flexible device presents an a superior indoor PCE of 31.85% under 1062 lux (LED, 2956 K), which is currently the best flexible perovskite indoor photovoltaic device.Perovskite photovoltaics are strong potential candidates to drive low-power off-grid electronics for indoor applications. Compared with rigid devices, flexible perovskite devices can provide a more suitable surface for indoor small electronic devices, enabling them have a broader indoor application prospect. However, the mechanical stability of flexible perovskite photovoltaics is an urgent issue solved. Herein, a kind of 3D crosslinking agent named borax is selected to carry out grain boundary penetration treatment on perovskite film to realize full-dimensional stress release. This strategy improves the mechanical a...