SummaryThe integrated stress response (ISR) is a homeostatic mechanism by which eukaryotic cells sense and respond to stress-inducing signals, such as amino acid starvation. General controlled nonrepressed (GCN2) kinase is a key orchestrator of the ISR, and modulates cellular metabolism in response to amino acid starvation. Here we demonstrate that GCN2 controls intestinal inflammation by suppressing inflammasome activation. Enhanced activation of ISR was observed in intestinal antigen presenting cells (APCs) and epithelial cells during amino acid starvation, or intestinal inflammation. Genetic deletion of GCN2 in CD11c+ APCs or intestinal epithelial cells resulted in enhanced intestinal inflammation and Th17 responses, due to enhanced inflammasome activation and IL-1β production. This was caused by reduced autophagy in GCN2−/− intestinal APCs and epithelial cells, leading to increased reactive oxygen species (ROS), a potent activator of inflammasomes1. Thus, conditional ablation of Atg5 and Atg7 in intestinal APCs resulted in enhanced ROS and Th17 responses. Furthermore, in vivo blockade of ROS and IL-1β resulted in inhibition of Th17 responses and reduced inflammation in GCN2−/− mice. Importantly, acute amino acid starvation suppressed intestinal inflammation via a mechanism dependent on GCN2. These results reveal a mechanism that couples amino acid sensing with control of intestinal inflammation via GCN2.
Commercial corundum powder and a liquid‐shaping approach are used for manufacturing complex hollow components and large flat windows of sintered and hot isostatically pressed Al2O3 ceramics having grain sizes of 0.4–0.6 μm at relative densities of >99.9%. High macrohardness (HV10 = 20–21 GPa) and four‐point bending strength (600–700 MPa; 750–900 MPa in three‐point bending) are associated with a real in‐line transmission of 55%–65% through polished plates. The submicrometer microstructure and the optical properties can be retained for use at >1100°C using dopants that shift the sintering temperature to high values without additional grain growth.
Sintered corundum components with submicrometer grain sizes exhibit properties which enable numerous new applications. Wet powder processing is developed to associate minimum grain sizes at highest densities with the lowest population of macrodefects. A closest ratio of powder particle size and sintered grain size is important for obtaining most fine‐grained microstructures. This target was approached best by using powders with particle sizes in the range of 100–200 nm rather than with smaller nanoparticles.
Phosphoric
acid-doped polybenzimidazole (PA-PBI) used in high-temperature
proton exchange membranes (HT-PEMs) frequently suffers from a serious
loss of mechanical strength because of the “plasticizing effect”
of the dopant acid. Conventional cross-linking approaches generally
enhance membrane stability. However, acid doping levels (ADLs) and
consequently proton conductivity inevitably decrease. This is due
to the formation of more compact molecular structures and a reduced
amount of functional imidazole units, caused by their consumption
in introducing the cross-linker. To resolve the common problems of
current PA-PBI-based HT-PEMs, herein, a highly acidophilic imidazole-rich
cross-linked network with superior “antiplasticizing”
ability is constructed based on a novel multifunctional cross-linker.
This unique bischloro/bibenzimidazole (“A2B2-type”)
molecular structure has extremely high reactivity, including “self-reaction”
among the cross-linkers and “inter-reaction” between
the cross-linker and PBI molecules. The resulting imidazole-rich cross-linked
membranes exhibit the desired combination of high ADLs, high conductivity,
outstanding dimensional–mechanical stability, and excellent
fuel cell performance. In comparison to a corresponding linear PBI
membrane, one membrane with a high content of the cross-linker of
30% has a 100 wt % increased acid uptake, a doubling in proton conductivity
at 200 °C, and a maximum power density of 533 mW·cm–2 at 160 °C without humidification.
Two D-A-type molecules, 4-N-[4-(9-phenylcarbazole)]-3,5-bis(4-diphenylamine)phenyl-4H-1,2,4-triazole and 4,4'-(9-(4-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)-9H-carbazole-3,6-diyl) bis-(N,N-diphenylaniline), are designed and synthesized. Organic lightemitting diodes based on them exhibit deep-blue emission and the singlet formation ratios are higher than the simple spin-statistics of 25%. A triplet-polaroninteraction-induced upconversion from triplet to singlet through a one-electron transfer mechanism is proposed, and is proven by magnetocurrent measurement and quantum-chemistry computation.
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