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Introduction and background: Idiopathic pulmonary fibrosis (IPF) is a fatal form of interstitial lung disease that mainly affects the elderly population. One of the hallmarks of IPF pathogenesis is dysfunction of Type 2 alveolar epithelial progenitor cells (AEC2s). We reported that there is a significant loss of AEC2s from IPF lungs. Aims and objective: To determine the metabolic mechanism of AEC2 dysfunction during aging in persistent lung fibrosis. Methods: Single cell RNA-seq of IPF AEC2s as well as murine AEC2s from old and bleomycin-injured mouse lungs. 3D organoid culture of AEC2 was used for assessing AEC2 renewal capacity. Mouse line with AEC2 cell type specific gene deletion was generated to determine the role of Zip8 in lung fibrosis in vivo. Results: Similar to that in IPF lungs, there is a reduction in AEC2 cell number as well as renewal capacity of AEC2s in old mouse lungs. Single cell RNA-seq analysis identified reduction in gene expression of SLC39A8 (ZIP8), the gene encoding a specific zinc transporter for AEC2s, in IPF AEC2s, as well as AEC2s from old and bleomycin injured mouse lungs. Replenishment with exogenous zinc promotes self-renewal and differentiation of AEC2s, and the response to zinc treatment was diminished in aged AEC2s. Zip8 Deletion in murine AEC2s leads to downregulation of Sirt1 expression, reduced number of AEC2s recovered from the lungs, and reduced renewal capacity of AEC2s. Conclusion: We have identified novel metabolic defects of AEC2s during aging and in IPF. Therapeutic strategies to restore critical components of these metabolic programs could improve AEC2 progenitor activity and mitigate ongoing fibrogenesis.

The spontaneous emission properties of a single layer organic film in plane optical microcavities were studied. Optical microcavity was formed by a Tris(8-quinolinolato) aluminium (Alq) film sandwiched between a distributed Bragg reflector (DBR) and a Ag metallic reflector. Two kinds of microcavities were devised by using a different DBR structure. Compared with a Alq film, significantly spectral narrowing and intensity enhancement was observed in the two microcavities, which is attributed to the microcavity effect. The spectra characteristics of the two microcavities showed that the structure of DBR has much influence on the emission properties of a microcavity. (C) 2000 Elsevier Science S.A. All rights reserved.