Immuno-Transcriptomic Profiling of Blood and Tumor Tissue Identifies Gene Signatures Associated with Immunotherapy Response in Metastatic Bladder Cancer.

Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response

Functional Interactions between KCNE1 C-Terminus and the KCNQ1 Channel

The KCNE1 gene product (minK protein) associates with the cardiac KvLQT1 potassium channel (encoded by KCNQ1) to create the cardiac slowly activating delayed rectifier, IKs. Mutations throughout both genes are linked to the hereditary cardiac arrhythmias in the Long QT Syndrome (LQTS). KCNE1 exerts its specific regulation of KCNQ1 activation via interactions between membrane-spanning segments of the two proteins. Less detailed attention has been focused on the role of the KCNE1 C-terminus in regulating channel behavior. We analyzed the effects of an LQT5 point mutation (D76N) and the truncation of the entire C-terminus (Δ70) on channel regulation, assembly and interaction. Both mutations significantly shifted voltage dependence of activation in the depolarizing direction and decreased IKs current density. They also accelerated rates of channel deactivation but notably, did not affect activation kinetics. Truncation of the C-terminus reduced the apparent affinity of KCNE1 for KCNQ1, resulting in impaired channel formation and presentation of KCNQ1/KCNE1 complexes to the surface. Complete saturation of KCNQ1 channels with KCNE1-Δ70 could be achieved by relative over-expression of the KCNE subunit. Rate-dependent facilitation of K+ conductance, a key property of IKs that enables action potential shortening at higher heart rates, was defective for both KCNE1 C-terminal mutations, and may contribute to the clinical phenotype of arrhythmias triggered by heart rate elevations during exercise in LQTS mutations. These results support several roles for KCNE1 C-terminus interaction with KCNQ1: regulation of channel assembly, open-state destabilization, and kinetics of channel deactivation

Biocompatibility of four common orthopedic biomaterials following neuroelectromyostimulation: An in‐vivo

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The Solar-Driven Coal/Fe3O4 Redox System

The solar-driven endothermic reaction of coal and magnetite was studied for mixing solar and fossil energies. The overall reaction can be represented by CHx + Fe3O4 = CO + 3FeO + 1/2xH2 where x depends on the coal(x= 0.2 in our study). Laboratory experimental studies with an equimolar mixture of anthracite coal and Fe3O4 powder using an infrared furnace showed rapid gas evolution above about 1200°C and 1bar, producing FeO(s) and a gas mixture containing a CO/CO2 molar ratio of 4.5. Solar-driven experiments were conducted using a high-flux solar furnace. Samples were directly exposed for short time intervals to a solar flux irradiation of 300 W/cm2. The carbon content decreased rapidly after only 1 second exposure, suggesting efficient heat transfer and chemical conversion by direct absorption of concentrated solar energy at the reaction site. The proposed solar thermochemical process offers the possibility of performing simultaneously the gasification of coal and reduction of iron oxide, and for producing a fuel with an upgraded calorific value

Solar Energy Conversion into H2 Energy Using Ferrites

A cation-excess (Ni,Mn) ferrite Ni0.52Mn0.51Fe2.05O4.0 with a single phase was synthesized by heating the mixture of corresponding metal salts and oxide in 5% O2/75% CO2/20% N2 gas mixture for 18h at 1100C. It could be thermochemically activated to form a cation-excess ferrite Ni0.52(1+δ)Fe2.05(1+δ)O4.0 in N2 gas at elevated temperature : The (value was 0.031 at 1100C. The activated (Ni,Mn) ferrite was reacted with water to form H2 gas at 700C. The process was reversible and could be carried out repeatedly