Predicting lung aging using scRNA-Seq data.

Age prediction based on single cell RNA-Sequencing data (scRNA-Seq) can provide information for patients' susceptibility to various diseases and conditions. In addition, such analysis can be used to identify aging related genes and pathways. To enable age prediction based on scRNA-Seq data, we developed PolyEN, a new regression model which learns continuous representation for expression over time.

Therapeutic potential of archaeal unfoldase PANet and the gateless T20S proteasome in P23H rhodopsin retinitis pigmentosa mice.

Neurodegenerative diseases are characterized by the presence of misfolded and aggregated proteins which are thought to contribute to the development of the disease. In one form of inherited blinding disease, retinitis pigmentosa, a P23H mutation in the light-sensing receptor, rhodopsin causes rhodopsin misfolding resulting in complete vision loss. We investigated whether a xenogeneic protein-unfolding ATPase (unfoldase) from thermophilic Archaea, termed PANet, could counteract the proteotoxicity of P23H rhodopsin.

Dual Centrifugation-Based Screening for pH-Responsive Liposomes.

In liposomal drug delivery development, the delicate balance of membrane stability is a major challenge to prevent leakage (during shelf-life and blood circulation), and to ensure efficient payload release at the therapeutic destination. Our composite screening approach uses the processing by dual centrifugation technique to speed up the identification of de novo formulations of intermediate membrane stability. By screening binary lipid combinations at systemically varied ratios we highlight liposomal formulations of intermediate stability, what we termed "the edge of stability", requiring moderate stimuli for destabilization.

Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis.

ProEnd: A Comprehensive Database for Identifying HbYX Motif-Containing Proteins Across the Tree of Life.

The proteasome plays a crucial role in cellular homeostasis by degrading misfolded, damaged, or unnecessary proteins. Understanding the regulatory mechanisms of proteasome activity is vital, particularly the interaction with activators containing the hydrophobic-tyrosine-any amino acid (HbYX) motif. Here, we present ProEnd, a comprehensive database designed to identify and catalog HbYX motif-containing proteins across the tree of life.

Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.

Changes in peripheral blood cell populations have been observed, but not detailed, at single-cell resolution in idiopathic pulmonary fibrosis (IPF). We sought to provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. Peripheral blood mononuclear cells (PBMCs) from patients with IPF and control subjects were profiled using 10× chromium 5' single-cell RNA sequencing.

[Therapeutic Pathways in Sarcoidosis. A Position Paper of the German Society of Respiratory Medicine (DGP)].

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.

Organ Boundary Circuits Regulate Sox9+ Alveolar Tuft Cells During Post-Pneumonectomy Lung Regeneration.

Tissue homeostasis is controlled by cellular circuits governing cell growth, organization, and differentation. In this study we identify previously undescribed cell-to-cell communication that mediates information flow from mechanosensitive pleural mesothelial cells to alveolar-resident stem-like tuft cells in the lung. We find mesothelial cells to express a combination of mechanotransduction genes and lineage-restricted ligands which makes them uniquely capable of responding to tissue tension and producing paracrine cues acting on parenchymal populations.

Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs models of mesothelioma.

The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies.

Unagi: Deep Generative Model for Deciphering Cellular Dynamics and In-Silico Drug Discovery in Complex Diseases.

Human diseases are characterized by intricate cellular dynamics. Single-cell sequencing provides critical insights, yet a persistent gap remains in computational tools for detailed disease progression analysis and targeted in-silico drug interventions. Here, we introduce UNAGI, a deep generative neural network tailored to analyze time-series single-cell transcriptomic data.

Peripheral Blood Single-Cell Sequencing Uncovers Common and Specific Immune Aberrations in Fibrotic Lung Diseases.

Rationale And Objectives: The extent and commonality of peripheral blood immune aberrations in fibrotic interstitial lung diseases are not well characterized. In this study, we aimed to identify common and distinct immune aberrations in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (FHP) using cutting-edge single-cell profiling technologies.

Methods: Single-cell RNA sequencing was performed on patients and healthy controls' peripheral blood and bronchoalveolar lavage samples using 10X Genomics 5' gene expression and V(D)J profiling.

iDESC: identifying differential expression in single-cell RNA sequencing data with multiple subjects.

Background: Single-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect contributes to the major source of variation in scRNA-seq data with multiple subjects, which severely confounds cell type specific differential expression (DE) analysis. Moreover, dropout events are prevalent in scRNA-seq data, leading to excessive number of zeroes in the data, which further aggravates the challenge in DE analysis.

Lung endothelium, tau, and amyloids in health and disease.

Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes.