94 research outputs found

    Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate.

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    Pulmonary alveolar type I (AT1) cells cover more than 95% of alveolar surface and are essential for the air-blood barrier function of lungs. AT1 cells have been shown to retain developmental plasticity during alveolar regeneration. However, the development and heterogeneity of AT1 cells remain largely unknown. Here, we conducted a single-cell RNA-seq analysis to characterize postnatal AT1 cell development and identified insulin-like growth factor-binding protein 2 (Igfbp2) as a genetic marker specifically expressed in postnatal AT1 cells. The portion of AT1 cells expressing Igfbp2 increases during alveologenesis and in post pneumonectomy (PNX) newly formed alveoli. We found that the adult AT1 cell population contains both Hopx+Igfbp2+ and Hopx+Igfbp2- AT1 cells, which have distinct cell fates during alveolar regeneration. Using an Igfbp2-CreER mouse model, we demonstrate that Hopx+Igfbp2+ AT1 cells represent terminally differentiated AT1 cells that are not able to transdifferentiate into AT2 cells during post-PNX alveolar regeneration. Our study provides tools and insights that will guide future investigations into the molecular and cellular mechanism or mechanisms underlying AT1 cell fate during lung development and regeneration

    4H-SiC trench MOSFET with integrated fast recovery MPS diode

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    A 4H-SiC trench metal-oxide-semiconductor field-effect-transistor (MOSFET) design with an integrated merged PiN Schottky (MPS) diode is proposed. The Schottky contact is embedded on the bottom of the trench structure for the first time. The low electric field in the oxide and Schottky contact surface can be achieved simultaneously using the proposed integration design which enhances the oxide reliability and reduces leakage from the Schottky diode. The integration of the MPS diode reduces the total chip area and the required number of dies compared with the conventional method of using an external Schottky diode

    Experimental realization of a highly secure chaos communication under strong channel noise

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    A one-way coupled spatiotemporally chaotic map lattice is used to contruct cryptosystem. With the combinatorial applications of both chaotic computations and conventional algebraic operations, our system has optimal cryptographic properties much better than the separative applications of known chaotic and conventional methods. We have realized experiments to pratice duplex voice secure communications in realistic Wired Public Switched Telephone Network by applying our chaotic system and the system of Advanced Encryption Standard (AES), respectively, for cryptography. Our system can work stably against strong channel noise when AES fails to work.Comment: 15 pages, 5 figure

    Alterations to the Lung Microbiome in Idiopathic Pulmonary Fibrosis Patients

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    Lung microbiome ecosystem homeostasis in idiopathic pulmonary fibrosis (IPF) remains uncharacterized. The aims of this study were to identify unique microbial signatures of the lung microbiome and analyze microbial gene function in IPF patients. DNA isolated from BALF samples was obtained for high-throughput gene sequencing. Microbial metagenomic data were used for principal component analysis (PCA) and analyzed at different taxonomic levels. Shotgun metagenomic data were annotated using the KEGG database and were analyzed for functional and metabolic pathways. In this study, 17 IPF patients and 38 healthy subjects (smokers and non-smokers) were recruited. For the PCA, the first and the second principal component explained 16.3 and 13.4% of the overall variability, respectively. The β diversity of microbiome was reduced in the IPF group. Signature of IPF's microbes was enriched of Streptococcus, Pseudobutyrivibrio, and Anaerorhabdus. The translocation of lung microbiome was shown that 32.84% of them were from oral. After analysis of gene function, ABC transporter systems, biofilm formation, and two-component regulatory system were enriched in IPF patients' microbiome. Here we shown the microbiology characteristics in IPF patients. The microbiome may participate in altering internal conditions and involving in generating antibiotic resistance in IPF patients

    A Novel N-Arylpyridone Compound Alleviates the Inflammatory and Fibrotic Reaction of Silicosis by Inhibiting the ASK1-p38 Pathway and Regulating Macrophage Polarization

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    Silicosis is one of the potentially fatal occupational diseases characterized by respiratory dysfunction, chronic interstitial inflammation, and fibrosis, for which treatment options are limited. Previous studies showed that a novel N-arylpyridone compound named AKEX0011 exhibited anti-inflammatory and anti-fibrotic effects in bleomycin-induced pulmonary fibrosis; however, it is unknown whether it could also be effective against silicosis. Therefore, we sought to investigate the preventive and therapeutic roles of AKEX0011 in a silicosis rodent model and in a silica-stimulated macrophage cell line. In vivo, our results showed that AKEX0011 ameliorated silica-induced imaging lung damages, respiratory dysfunction, reduced the secretion of inflammatory and fibrotic factors (TNF-α, IL-1β, IL-6, TGF-β, IL-4, and IL-10), and the deposition of fibrosis-related proteins (collagen I, fibronectin, and α-SMA), regardless of early or advanced therapy. Specifically, we found that AKEX0011 attenuated silicosis by inhibiting apoptosis, blocking the ASK1-p38 MAPK signaling pathway, and regulating polarization of macrophages. In vitro, AKEX0011 inhibited macrophages from secreting inflammatory cytokines and inhibited apoptosis of macrophages in pre-treated and post-treated models, concurrent with blocking the ASK1-p38 pathway and inhibiting M1 polarization. Collectively, AKEX0011, as a novel N-arylpyridone compound, exerted protective effects for silica-induced pulmonary inflammation and fibrosis both in vivo and in vitro, and hence, it could be a strong drug candidate for the treatment of silicosis

    Unregulated miR-96 Induces Cell Proliferation in Human Breast Cancer by Downregulating Transcriptional Factor FOXO3a

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    FOXO transcription factors are key tumor suppressors in mammalian cells. Until now, suppression of FOXOs in cancer cells was thought to be mainly due to activation of multiple onco-kinases by a phosphorylation-ubiquitylation-mediated cascade. Therefore, it was speculated that inhibition of FOXO proteins would naturally occur through a multiple step post-translational process. However, whether cancer cells may downregulate FOXO protein via an alternative regulatory mechanism is unclear. In the current study, we report that expression of miR-96 was markedly upregulated in breast cancer cells and breast cancer tissues compared with normal breast epithelial cells (NBEC) and normal breast tissues. Ectopic expression of miR-96 induced the proliferation and anchorage-independent growth of breast cancer cells, while inhibition of miR-96 reduced this effect. Furthermore, upregulation of miR-96 in breast cancer cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-96 downregulated FOXO3a expression by directly targeting the FOXO3a 3′-untranslated region. Taken together, our results suggest that miR-96 may play an important role in promoting proliferation of human breast cancer cells and present a novel mechanism of miRNA-mediated direct suppression of FOXO3a expression in cancer cells

    A Dioid Linear Algebra Approach to Study a Class of Continuous Petri Nets

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    Abstract. Continuous Event Graphs (CEGs), a subclass of Continuous Petri Nets, are defined as the limiting cases of timed event graphs and Timed Event Multigraphs. A set of dioid algebraic linear equations will be inferred as a novel method of analyzing a special class of CEG, if treated the cumulated token consumed by transitions as state-variables, endowed the monotone nondecreasing functions pointwise minimum as addition, and endowed the lower-semicontinuous mappings, from the collection of monotone nondecreasing functions to itself, the pointwise minimum as addition and composition of mappings as multiplication. As a new modeling approach, it clearly illustrate characteristic of continuous events. Based on the algebraic model, an example of optimal Control is demonstrated
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