QuestionCystic fibrosis (CF) is characterised by the accumulation of viscous, adherent mucus in the lungs. While several hypotheses invoke a direct relationship with CFTR dysfunction (i.e., acidic airway surface liquid (ASL) pH, low [HCO3−], airway dehydration), the dominant biochemical alteration of CF mucus remains unknown.Materials/MethodsWe characterised a novel cell line (CFTR-KO Calu3 cells) and the responses of human bronchial epithelial (HBE) cells from subjects with G551D or F508del mutations to Ivacaftor and Elexacaftor-Tezacaftor-Ivacaftor (ETI). A spectrum of assays such as short-circuit currents (Isc), qPCR, ASL pH, western blotting (WB), light scattering/refractometry (SEC-MALS), scanning electron microscopy (SEM), % solids, and particle tracking were performed to determine the impact of CFTR function on mucus properties.ResultsLoss of CFTR function in Calu3 cells resulted in ASL pH acidification and mucus hyperconcentration (dehydration). Modulation of CFTR in CF HBE cells did not affect ASL pH or mucin mRNA expression, but decreased mucus concentration, relaxed mucus network ultrastructure, and improved mucus transport. In contrast with modulator-treated cells, a large fraction of airway mucins remained attached to naïve CF cells following short apical washes, as revealed by the use of reducing agents to remove residual mucus from the cell surfaces. Extended hydration, but not buffers alkalised with NaOH or HCO3−, normalised mucus recovery to modulator-treated cell levels.ConclusionThese results indicate that airway dehydration, not acidic pH and/or low [HCO3−], is responsible for abnormal mucus properties in CF airways and CFTR modulation predominantly restores normal mucin entanglement.
A rapid thermal oxynitridation process using mixtures of nitrous oxide and oxygen for the fabrication of metal-oxide-semiconductor (MOS) capacitors is presented herein. This approach provides excellent control of Si/SiO2 interfacial nitrogen concentration from 0–1 at. % by varying growth temperature and N2O mol %. The dielectric quality of oxynitrides with interfacial nitrogen concentrations of 0.10, 0.22, 0.39 at. % was studied. As-processed oxynitride capacitors have Dit and fixed charge density as low as oxide capacitors. However, a small nitrogen incorporation at the interface improves Qbd and suppresses interface state generation caused by Fowler–Nordheim (FN) injection.
We prepared oxynitrides with different interracial nitrogen concentration ([N~nt]) using RTP. Reoxidation kinetics of these oxynitrides was studied. It was found that reoxidation thickness strongly depends on the [N~nt]. The reoxidation kinetics can be used for the evaluation of [N~n,].
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