Pharmacokinetics, mass balance, and metabolism of [C]PLB1004, a selective and irreversible EGFR-TKI in humans.

Purpose: PLB1004, developed by Beijing Avistone Biotechnology Co., Ltd., is a safe, highly selective, and efficient irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) employed in treating non-small-cell-lung-cancer (NSCLC).

Mechanotransduction pathways regulating YAP nuclear translocation under Yoda1 and vibration in osteocytes.

Yes-associated protein (YAP) is a mechanosensitive protein crucial for bone remodeling. Although research has identified pathways and components involved in YAP regulation, the precise mechanisms of its localization during Piezo1 activation or vibration remain unclear. Piezo1, a mechanosensitive ion channel, allows calcium ions to flow into cells upon activation.

Effect of macrophage-to-myofibroblast transition on silicosis.

Background: The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition (MMT) in silicosis.

Methods: Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system. Murine macrophage MH-S cells were randomly divided into a control group and an SiO group.

Label-free electrochemical detection of glycated hemoglobin (HbA1c) and C-reactive protein (CRP) to predict the maturation of coronary heart disease due to diabetes.

The pathophysiological link between diabetes and heightened propensity for the development of coronary heart disease (CHD) is well-established. Prevailing evidence confirms that small increases in low concentrations of high-sensitivity C reactive protein (hs-CRP) in the human body can determine the tendency of developing CHD. Additionally, glycated hemoglobin (HbA1c) is a well-recognized biomarker to evaluate diabetes progression.

Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics.

Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW junction), and the pons across human brain tissue from four distinct donors. We investigate the three-dimensional expression patterns of Piezo1, Piezo2, and TMEM150C, while also examining their associated histological features and mechanotransduction signaling networks, particularly focusing on the YAP/β-catenin axis.

LRP4-related signalling pathways and their regulatory role in neurological diseases.

The mechanism of action of low-density lipoprotein receptor related protein 4 (LRP4) is mediated largely via the Agrin-LRP4-MuSK signalling pathway in the nervous system. LRP4 contributes to the development of synapses in the peripheral nervous system (PNS). It interacts with signalling molecules such as the amyloid beta-protein precursor (APP) and the wingless type protein (Wnt).

Targeted deep learning classification and feature extraction for clinical diagnosis.

Protein biomarkers can be used to characterize symptom classes, which describe the metabolic or immunodeficient state of patients during the progression of a specific disease. Recent literature has shown that machine learning methods can complement traditional clinical methods in identifying biomarkers. However, many machine learning frameworks only apply narrowly to a specific archetype or subset of diseases.

Corticotropin-releasing factor signaling and its potential role in the prefrontal cortex-dependent regulation of anxiety.

A large body of literature has highlighted the significance of the corticotropin-releasing factor (CRF) system in the regulation of neuropsychiatric diseases. Anxiety disorders are among the most common neuropsychiatric disorders. An increasing number of studies have demonstrated that the CRF family mediates and regulates the development and maintenance of anxiety.

Advancing our understanding of bioreactors for industrial-sized cell culture: health care and cellular agriculture implications.

Bioreactors are advanced biomanufacturing tools that have been widely used to develop various applications in the fields of health care and cellular agriculture. In recent years, there has been a growing interest in the use of bioreactors to enhance the efficiency and scalability of these technologies. In cell therapy, bioreactors have been used to expand and differentiate cells into specialized cell types that can be used for transplantation or tissue regeneration.

Self-maintaining macrophages within the kidney contribute to salt and water balance by modulating kidney sympathetic nerve activity.

The kidney is critical in controlling salt and water balance, with the interstitium involved with a variety of components including immune cells in steady state. However, the roles of resident immune cells in kidney physiology are largely unknown. To help unravel some of these unknowns, we employed cell fate mapping, and identified a population of embryo-derived self-maintaining macrophages (SM-MØ) that were independent of the bone marrow in adult mouse kidneys.

Quercetin Alleviates Pulmonary Fibrosis in Silicotic Mice by Inhibiting Macrophage Transition and TGF-β-Smad2/3 Pathway.

Silicosis is a pulmonary disease caused by the inhalation of silica. There is a lack of early and effective prevention, diagnosis, and treatment methods, and addressing silicotic fibrosis is crucial. Quercetin, a flavonoid with anti-carcinogenic, anti-inflammatory, and antiviral properties, is known to have a suppressive effect on fibrosis.

The CaT stretcher: An open-source system for delivering uniaxial strain to cells and tissues (CaT).

Integration of mechanical cues in conventional 2D or 3D cell culture platforms is an important consideration for and models of lung health and disease. Available commercial and published custom-made devices are frequently limited in breadth of applications, scalability, and customization. Herein we present a technical report on an open-source, cell and tissue (CaT) stretcher, with modularity for different and systems, that includes the following features: 1) Programmability for modeling different breathing patterns, 2) scalability to support low to high-throughput experimentation, and 3) modularity for submerged cell culture, organ-on-chips, hydrogels, and live tissues.

Integrative Investigation Reveals the Host-Virus Interactions in Repurposed Drugs Against SARS-CoV-2.

The ongoing COVID-19 outbreak have posed a significant threat to public health worldwide. Recently Toll-like receptor (TLR) has been proposed to be the drug target of SARS-CoV-2 treatment, the specificity and efficacy of such treatments remain unknown. In the present study we performed the investigation of repurposed drugs via a framework comprising of Search Tool for Interacting Chemicals (STITCH), Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking, and virus-host-drug interactome mapping.

Comparison of Three Methods for Skeleton Age Estimation.

Objectives: To find the appropriate method for age estimation for different ages and sexes.

Methods: The costal cartilage, sternum and pubic symphysis of 91 unknowns from 2000 to 2020 from the Forensic Department of the Criminal Investigation Team of Shanghai Public Security Bureau were collected. Costal cartilage, sternal and pubic symphysis inferences were used to estimate the age, and the consistency between the estimated results and the actual physiological age of the unknowns was tested.

CAFs/tumor cells co-targeting DNA vaccine in combination with low-dose gemcitabine for the treatment of Panc02 murine pancreatic cancer.

In this study, we investigate the synergistic effect of gemcitabine (Gem) and a novel DNA vaccine in the treatment of pancreatic cancer in mice and explore the anti-tumor mechanism of this combination therapy. Fibroblast activation protein α-expressing cancer-associated fibroblasts (FAPα CAFs), a dominant component of the tumor microenvironment (TME), have been shown to modulate the extracellular matrix (ECM) to promote the growth, invasion, and metastasis of pancreatic cancer (PC). Therefore, FAPα CAFs may be an ideal target for the treatment of PC.

Reduced CircSMOC1 Level Promotes Metabolic Reprogramming via PTBP1 (Polypyrimidine Tract-Binding Protein) and miR-329-3p in Pulmonary Arterial Hypertension Rats.

Background: Pulmonary arterial hypertension maintains rapid cell proliferation and vascular remodeling through metabolic reprogramming. Recent studies suggested that circRNAs play important role in pulmonary vascular remodeling and pulmonary arterial smooth muscle cells proliferation. However, the relationship between circRNA, cell proliferation, and metabolic reprogramming in pulmonary arterial hypertension has not been investigated.

Quercetin Alleviates Pulmonary Fibrosis in Mice Exposed to Silica by Inhibiting Macrophage Senescence.

Quercetin exerts anti-inflammatory, anti-oxidant and other protective effects. Previous studies have shown that senescent cells, such as fibroblasts and type II airway epithelial cells, are strongly implicated in the development of pulmonary fibrosis pathology. However, the role of senescent macrophages during silicosis remains unclear.

The relationship between anal disease and quality of life: a bibliometric study.

Background: Anal disease has a significant impact on patients' quality of life (QoL), and surgical treatment may further diminish QoL. The purpose of this study was to conduct bibliometric analysis to investigate the profile of studies on anorectal disease-related QoL.

Methods: The database of Science Citation Index Expanded (SCI-E) in Web of Science Core Collection (WOSCC) was searched.

ER stress-related protein, CHOP, may serve as a biomarker of mechanical asphyxia: a primary study.

The precise authentication of death from mechanical asphyxia (DMA) has been a complex problem in forensic medicine. Besides the traditional methods that concern the superficial characterization of the body, researchers are now paying more attention to the biomarkers that may help the identification of DMA. It has been reported that the extremely hypoxic environment created by DMA can cause the specific expression of mitochondria-related protein, which may sever as the biomarkers of DMA authentication.

Fast DNA Vaccination Strategy Elicits a Stronger Immune Response Dependent on CD8CD11c Cell Accumulation.

Conventional DNA vaccine strategies usually employ a regimen of immunizations at 2-week or longer intervals to induce effective memory cell-dependent immune responses. Clinical cancer treatment requires a faster immunization strategy to contend with tumor progression. In this study, a novel fast immunization strategy was established, wherein a DNA vaccine was intramuscularly administered on days 0, 2, and 5 in a murine lung cancer model.

Model for the prediction of mechanical asphyxia as the cause of death based on four biological indexes in human cardiac tissue.

Determination of mechanical asphyxia as the cause of death has always been difficult for forensic pathologists, particularly when signs of asphyxia are not obvious on the body. Currently, depending on only physical examination of corpses, pathologists must be cautious when making cause-of-death appraisals. In a previous study, four biomarkers-dual-specificity phosphatase 1 (DUSP1), potassium voltage-gated channel subfamily J member 2 (KCNJ2), miR-122, and miR-3185-were screened in human cardiac tissue from cadavers that died from mechanical asphyxia compared with those that died from craniocerebral injury, hemorrhagic shock, or other causes.

Ac-SDKP Attenuates Activation of Lung Macrophages and Bone Osteoclasts in Rats Exposed to Silica by Inhibition of TLR4 and RANKL Signaling Pathways.

Background: Silica-induced inflammatory activation is associated with silicosis and various non-respiratory conditions. The present study was designed to examine the anti-inflammatory effects of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on lung macrophages and bone osteoclasts after silica inhalation in rats.

Methods: Wistar rats and NR8383 and RAW 264.

The migration of metastatic breast cancer cells is regulated by matrix stiffness via YAP signalling.

Matrix stiffness is a driver of breast cancer progression and mechanosensitive transcriptional activator YAP plays an important role in this process. However, the interplay between breast cancer and matrix stiffness, and the significance of this interplay remained largely unknown. Here, we showed an increase in YAP nuclear localization and a higher proliferation rate in both highly metastatic MDA-MB-231 cells and the non-metastatic counterpart MCF-7 cells when they were exposed to the stiff matrix.