Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype

Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions

Clinical Benefit from Lenvatinib and Pembrolizumab Observed in Mullerian Adenosarcoma: A Case Report

A 32-year-old woman with chemorefractory mullerian adenosarcoma showed clinical benefit in response to administration of lenvatinib plus pembrolizumab. In this case report, we describe the course of her illness and her response to this treatment

A Facile Methodology for the Production of In Situ Inorganic Nanowire Hydrogels/Aerogels

Creating inorganic nanowire hydrogels/aerogels using various materials and inexpensive means remains an outstanding challenge despite their importance for many applications. Here, we present a facile methodology to enable highly porous inorganic nanowire hydrogel/aerogel production on a large scale and at low cost. The hydrogels/aerogels are obtained from in situ hydrothermal synthesis of one-dimensional (1D) nanowires that directly form a cross-linking network during the synthesis process. Such a method not only offers great simplicity but also allows the interconnecting nanowires to have much longer length. The longer length offers aerogels with remarkable porosity and surface area extremely low densities (as low as 2.9 mg/cm3), are mechanically robust, and can have superelasticity by tuning the synthesis conditions. The nanowires in the hydrogels/aerogels serve both as structural support and active sites, for example, for catalysis or absorption. In this work, we have found that the as-grown hydrogels can be used directly as water filters to remove pollutants such as heavy metal ions and toxic organic contents. Our studies indicate that this method for nanowire hydrogels/aerogels production is not only economical but greatly augmented their applications in environmental, catalysis, sensing, absorption, energy storage, and beyond.National Science Foundation (U.S.) (Award DMR 0845358)National Science Foundation (U.S.) (Grant DMR-100414

Room-Temperature, Solution-Processed Polyimide Gate Dielectrics for Reliable Organic Field-Effect Transistors

Polyimide (PI) gate dielectrics are one of the most promising candidates for achieving fully solution-processed flexible organic field-effect transistors (OFETs) due to their remarkable chemical resistance, mechanical flexibility and solution processability. However, OFETs with PI dielectrics have been demonstrated only with expensive plastic or rigid substrates because of the high thermal annealing temperature for chemical imidization of the PI films. In this study, we successfully fabricated low-temperature, solution-processed OFETs by introducing the fully imidized soluble PI dielectrics. Through electrical and chemical investigations, soluble PIs are appropriate gate dielectrics for reliable, high-performance OFETs and can be processed at room temperature, namely thermal annealing-free. As a proof-of-concept,a low-temperature, solution-processed OFET with soluble PI dielectric is fabricated on ultrathin parylene C substrates and exhibits excellent mechanical durability without device performance degradation.1

Flexible and stable organic field-effect transistors using low-temperature solution-processed polyimide gate dielectrics

Polyimide (PI) has been widely used as a gate dielectric due to its remarkable thermal stability, chemical resistance, and mechanical flexibility. However, the high processing temperature and high surface energy of PI gate dielectrics hinder the realization of flexible and reliable electronic applications with low-cost manufacturing. Here, a low-temperature solution-processed organic field-effect transistor (OFET) is successfully demonstrated using a fully imidized soluble PI gate dielectric. The low temperature processability of soluble PI gate dielectrics is confirmed by investigating the effect of annealing temperature on the dielectric properties and electrical characteristics. By blending 6,13-Bis(triisopropylsilylethynyl)pentacene with polystyrene, the reliability of OFET is considerably enhanced while maintaining high device performance. As a result, OFETs exhibit excellent flexibility and can be integrated with ultrathin parylene substrates without degrading device performance. This work presents the steps to develop flexible and reliable electronic applications with low-cost manufacturing.11Nsciescopu