A20 deficiency in myeloid cells protects mice from diet-induced obesity and insulin resistance due to increased fatty acid metabolism

Obesity-induced inflammation is a major driving force in the development of insulin resistance, type 2 diabetes (T2D), and related metabolic disorders. During obesity, macrophages accumulate in the visceral adipose tissue, creating a low-grade inflammatory environment. Nuclear factor kappa B (NF-kappa B) signaling is a central coordinator of inflammatory responses and is tightly regulated by the anti-inflammatory protein A20. Here, we find that myeloid-specific A20-deficient mice are protected from diet-induced obesity and insulin resistance despite an inflammatory environment in their metabolic tissues. Macrophages lacking A20 show impaired mitochondrial respiratory function and metabolize more palmitate both in vitro and in vivo. We hypothesize that A20-deficient macrophages rely more on palmitate oxidation and metabolize the fat present in the diet, resulting in a lean phenotype and protection from metabolic disease. These findings reveal a role for A20 in regulating macrophage immunometabolism

Flexible and Transparent All-Graphene Circuits for Quaternary Digital Modulations

In modern communication system, modulation is a key function that embeds the baseband signal (information) into a carrier wave so that it can be successfully broadcasted through a medium such as air or cables. A flexible signal modulation scheme is hence essential to wide range of applications based on flexible electronics. Here we report a fully bendable all-graphene modulator circuit with the capability to encode a carrier signal with quaternary digital information for the first time. By exploiting the ambipolarity and the nonlinearity in a graphene transistor, we demonstrated two types of quaternary modulation schemes: 4-ary amplitude-shift keying (4-ASK) and quadrature phase-shift keying (QPSK). Remarkably, 4-ASK and QPSK can be realized with just 1 and 2 all-graphene transistors, respectively, representing a drastic reduction in circuit complexity when compared with conventional digital modulators. In addition, the circuit is not only flexible but also highly transparent (~95% transmittance) owing to their all-graphene design with every component (channel, interconnects, load resistor, and source/drain/gate electrodes) fabricated from graphene films. Taken together, these results represent a significant step toward achieving a high speed communication system that can be monolithically integrated on a flexible and transparent platform.Comment: 29 pages, 8 figures, 1 tabl

Studies on the mechanical stretchability of transparent conductive film based on graphene-metal nanowire structures

Transparent electrodes with superior flexibility and stretchability as well as good electrical and optical properties are required for applications in wearable electronics with comfort designs and high performances. Here, we present hybrid nanostructures as stretchable and transparent electrodes based on graphene and networks of metal nanowires, and investigate their optical, electrical, and mechanical properties. High electrical and optical characteristics, superb bendability (folded in half), excellent stretchability (10,000 times in stretching cycles with 100% in tensile strain toward a uniaxial direction and 30% in tensile strain toward a multi-axial direction), strong robustness against electrical breakdown and thermal oxidation were obtained through comprehensive study. We believe that these results suggest a substantial promise application in future electronicsopen1

A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death

An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-κB (NF-κB) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF-κB-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor