Ligand-mediated structural modulation and membrane stabilization of LPA1 receptor: Insights from molecular dynamics simulations.

Lysophosphatidic acid (LPA) is an important bioactive signaling molecule that activates six distinct G protein-coupled receptors (GPCRs), among which the LPA1 subtype possesses high therapeutic target potential due to its critical roles in malignant tumors, pulmonary fibrosis, inflammation, and neuropathic pain. Recent studies have shown that the small molecule ONO-0740556 can effectively disrupt the overall structure of LPA1 in solution; however, its effects in a native membrane environment remain unclear. According to the Traditional Chinese Medicine Systems Pharmacology Database (TCMS), Dan Shen(Salvia miltiorrhiza) exhibits anti-inflammatory and anti-pulmonary fibrosis properties, and its natural compound cryptoxanthin may serve as a novel LPA1 inhibitor.

Characterization of a Single-Molecule Sensitive Digital Flow Cytometer for Amplification-Free Digital Assays.

Digital assays such as digital PCR for nucleic acids and digital ELISA for proteins provide absolute quantitation and greater accuracy, sensitivity, and reproducibility than their analogue counterparts (real-time PCR and standard ELISA), but current digital assays involve amplification (e.g., DNA amplification in digital PCR and signal amplification in digital ELISA), which makes high multiplexing difficult, often requires complex and expensive sample compartmentalization, and adds reaction steps.

Comparison of EV characterization by commercial high-sensitivity flow cytometers and a custom single-molecule flow cytometer.

High-sensitivity flow cytometers have been developed for multi-parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high-sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single-molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di-8-ANEPPS and with PE-conjugated anti-EGFR or anti-tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers.

Hibiscus manihot L. flower extract induces anticancer activity through modulation of apoptosis and autophagy in A549 cells.

Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment.

ACSS3 regulates the metabolic homeostasis of epithelial cells and alleviates pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease of unknown etiology. The emerging evidence demonstrates that metabolic homeostatic imbalance caused by repetitive injuries of the alveolar epithelium is the potential pathogenesis of IPF. Proteomic analysis identified that Acetyl-CoA synthetase short chain family member 3 (ACSS3) expression was decreased in IPF patients and mice with bleomycin-induced fibrosis.

ADRB2 inhibition combined with antioxidant treatment alleviates lung fibrosis by attenuating TGFβ/SMAD signaling in lung fibroblasts.

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease with a poor prognosis and limited therapeutic options, which is characterized by aberrant myofibroblast activation and pathological remodeling of the extracellular matrix, while the mechanism remains elusive. In the present investigation, we observed a reduction in ADRB2 expression within both IPF and bleomycin-induced fibrotic lung samples, as well as in fibroblasts treated with TGF-β1. ADRB2 inhibition blunted bleomycin-induced lung fibrosis.

Anti-lung Cancer, Anti-microbial, Anti-α-glucosidase, Anti-sorbitol Dehydrogenase, and in silico Studies of Wogonoside and Isoliquiritigenin as Natural Compounds.

Natural substances have long been used in cancer treatment, particularly in Chinese or Indian traditional medicine. Natural compounds are defined as chemical molecules that are found in fungus, marine animals, plants, or bacteria and have significant biological and pharmacological effects. Wogonoside and isoliquiritigenin are two well-known examples of plant-derived chemicals.

Single-Cell RNA Sequencing Provides New Insights into Therapeutic Roles of Thyroid Hormone in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3'-triiodothyronine (T) administration on lung alveolar regeneration and fibrosis at the single-cell level. T supplementation significantly altered the gene expression in fibrotic lung tissues.

Injured Endothelial Cell: A Risk Factor for Pulmonary Fibrosis.

The pathological features of pulmonary fibrosis (PF) are the abnormal activation and proliferation of myofibroblasts and the extraordinary deposition of the extracellular matrix (ECM). However, the pathogenesis of PF is still indistinct. In recent years, many researchers have realized that endothelial cells had a crucial role in the development of PF.

Serum Proteomics Identifies Biomarkers Associated With the Pathogenesis of Idiopathic Pulmonary Fibrosis.

The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS.

Artificial neural network identified the significant genes to distinguish Idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that causes irreversible damage to lung tissue characterized by excessive deposition of extracellular matrix (ECM) and remodeling of lung parenchyma. The current diagnosis of IPF is complex and usually completed by a multidisciplinary team including clinicians, radiologists and pathologists they work together and make decision for an effective treatment, it is imperative to introduce novel practical methods for IPF diagnosis. This study provided a new diagnostic model of idiopathic pulmonary fibrosis based on machine learning.

Effectiveness assessment of reservoir projects for flash flood control, water supply and irrigation in Wangmo Basin, China.

Most flash floods in countries around the world occur in poor rural mountainous areas and typically cause more casualties and economic losses due to monitoring challenges and early warning difficulties. In mountainous regions, reservoir projects are a very effective measure for mitigating the risk of flash floods and can also be used for water supplies and irrigation, but there is a lack of research on the comprehensive benefit assessments of reservoirs. In this paper, we simulate the inundation extents of flash floods for the Wangmo Basin in China, where flash floods frequently occur, under different return periods using the HEC-HMS (HEC-Hydrologic Modelling System) model and FLO-2D model and compare the resulting housing losses with and without reservoirs.

Isolating Rare Cells and Circulating Tumor Cells with High Purity by Sequential eDAR.

Isolation and analysis of circulating tumor cells (CTCs) from the blood of patients at risk of metastatic cancers is a promising approach to improving cancer treatment. However, CTC isolation is difficult due to low CTC abundance and heterogeneity. Previously, we reported an ensemble-decision aliquot ranking (eDAR) platform for the rare cell and CTC isolation with high throughput, greater than 90% recovery, and high sensitivity, allowing detection of low surface antigen-expressing cells linked to metastasis.

Abietane-Type Diterpenoids Inhibit Protein Tyrosine Phosphatases by Stabilizing an Inactive Enzyme Conformation.

Protein tyrosine phosphatases (PTPs) contribute to a striking variety of human diseases, yet they remain vexingly difficult to inhibit with uncharged, cell-permeable molecules; no inhibitors of PTPs have been approved for clinical use. This study uses a broad set of biophysical analyses to evaluate the use of abietane-type diterpenoids, a biologically active class of phytometabolites with largely nonpolar structures, for the development of pharmaceutically relevant PTP inhibitors. Results of nuclear magnetic resonance analyses, mutational studies, and molecular dynamics simulations indicate that abietic acid can inhibit protein tyrosine phosphatase 1B, a negative regulator of insulin signaling and an elusive drug target, by binding to its active site in a non-substrate-like manner that stabilizes the catalytically essential WPD loop in an inactive conformation; detailed kinetic studies, in turn, show that minor changes in the structures of abietane-type diterpenoids (e.

Optimal control theory enables homonuclear decoupling without Bloch-Siegert shifts in NMR spectroscopy.

The Bloch-Siegert shift is a phenomenon in NMR spectroscopy and atomic physics in which the observed resonance frequency is changed by the presence of an off-resonance applied field. In NMR, it occurs especially in the context of homonuclear decoupling. Here we develop a practical method for homonuclear decoupling that avoids inducing Bloch-Siegert shifts.

The Molecular Origin of Enthalpy/Entropy Compensation in Biomolecular Recognition.

Biomolecular recognition can be stubborn; changes in the structures of associating molecules, or the environments in which they associate, often yield compensating changes in enthalpies and entropies of binding and no net change in affinities. This phenomenon-termed enthalpy/entropy (H/S) compensation-hinders efforts in biomolecular design, and its incidence-often a surprise to experimentalists-makes interactions between biomolecules difficult to predict. Although characterizing H/S compensation requires experimental care, it is unquestionably a real phenomenon that has, from an engineering perspective, useful physical origins.

Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions.

Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood.

A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate.

This paper describes the design and fabrication of a "pop-up" electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)-a biomarker for diabetic ketoacidosis-using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure.

Optical painting and fluorescence activated sorting of single adherent cells labelled with photoswitchable Pdots.

The efficient selection and isolation of individual cells of interest from a mixed population is desired in many biomedical and clinical applications. Here we show the concept of using photoswitchable semiconducting polymer dots (Pdots) as an optical 'painting' tool, which enables the selection of certain adherent cells based on their fluorescence, and their spatial and morphological features, under a microscope. We first develop a Pdot that can switch between the bright (ON) and dark (OFF) states reversibly with a 150-fold contrast ratio on irradiation with ultraviolet or red light.

Simultaneous and selective isolation of multiple subpopulations of rare cells from peripheral blood using ensemble-decision aliquot ranking (eDAR).

Rare cells, such as circulating tumor cells (CTCs), can be heterogeneous. The isolation and identification of rare cells with different phenotypes is desirable, for clinical and biological applications. However, CTCs exist in a complex biological environment, which complicates the isolation and identification of particular subtypes.

New generation of ensemble-decision aliquot ranking based on simplified microfluidic components for large-capacity trapping of circulating tumor cells.

Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we report the next generation of eDAR, where we designed and optimized a new hydrodynamic switching scheme for the active sorting step in eDAR, which provided fast cell sorting with an improved reproducibility and stability. The microfluidic chip was also simplified by incorporating a functional area for subsequent purification using microslits fabricated by standard lithography method.

Imaging multiple biomarkers in captured rare cells by sequential immunostaining and photobleaching.

Several technologies recently have been developed for separating and counting circulating tumor cells (CTCs) in the human blood. CTCs play an important role in the metastasis of cancer. Most of the current applications are focused on the enumeration of CTCs; however, analysis of the enumerated CTCs has been proven to be increasingly important.

An automated high-throughput counting method for screening circulating tumor cells in peripheral blood.

Enumeration of circulating tumor cells (CTCs) has proved valuable for early detection and prognosis in cancer treatment. This paper describes an automated high-throughput counting method for CTCs based on microfluidics and line-confocal microscopy. Peripheral blood was directly labeled with multiple antibodies, each conjugated with a different fluorophore, pneumatically pumped through a microfluidic channel, and interrogated by a line-confocal microscope.

[Analysis of infection-related mortality after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapse acute leukemia].

Objective: To investigate infection-related mortality (IRM) after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapse acute leukemia.

Methods: We conducted a retrospective analysis of 127 patients with refractory/relapse acute leukemia and investigated the incidence, causes and risk factors of IRM.

Results: Sixty-seven of the patients died after the transplantation.