TRP Channels in Excitotoxicity.

Glutamate excitotoxicity is a central mechanism contributing to cellular dysfunction and death in various neurological disorders and diseases, such as stroke, traumatic brain injury, epilepsy, schizophrenia, addiction, mood disorders, Huntington's disease, Alzheimer's disease, Parkinson's disease, multiple sclerosis, pathologic pain, and even normal aging-related changes. This detrimental effect emerges from glutamate binding to glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, -methyl-d-aspartate receptors, kainate receptors, and GluD receptors. Thus, excitotoxicity could be prevented by targeting glutamate receptors and their downstream signaling pathways.

TRP Channels in Stroke.

Ischemic stroke is a devastating disease that affects millions of patients worldwide. Unfortunately, there are no effective medications for mitigating brain injury after ischemic stroke. TRP channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular injury.

Activation of endothelial TRPM2 exacerbates blood-brain barrier degradation in ischemic stroke.

Aims: Damage of the blood-brain barrier (BBB) is a hallmark of brain injury during the early stages of ischemic stroke. The subsequent endothelial hyperpermeability drives the initial pathological changes and aggravates neuronal death. Transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable nonselective cation channel activated by oxidative stress.

Cardiac ultrastructure inspired matrix induces advanced metabolic and functional maturation of differentiated human cardiomyocytes.

The vast potential of human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) in preclinical models of cardiac pathologies, precision medicine, and drug screening remains to be fully realized because hiPSC-CMs are immature without adult-like characteristics. Here, we present a method to accelerate hiPSC-CM maturation on a substrate, cardiac mimetic matrix (CMM), mimicking adult human heart matrix ligand chemistry, rigidity, and submicron ultrastructure, which synergistically mature hiPSC-CMs rapidly within 30 days. hiPSC-CMs matured on CMM exhibit systemic transcriptomic maturation toward an adult heart state, are aligned with high strain energy, metabolically rely on oxidative phosphorylation and fatty acid oxidation, and display enhanced redox handling capability, efficient calcium handling, and electrophysiological features of ventricular myocytes.

Research on Design and Performance of Self-Compacting Cement Emulsified Bitumen Mixture (CEBM).

To meet the needs of the road industry for maintenance operations, a new cement emulsified bitumen mixture (CEBM) with early-strength, self-compacting, and room-temperature construction characteristics was designed. The strength formation mechanism of CEBM was revealed with a scanning electron microscope (SEM) and the surface free energy (SFE) theory. The mechanical properties and road performance of the CEBM were investigated extensively.

TRPM2 deficiency in mice protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages.

Atherosclerosis is the major cause of ischemic heart disease and stroke, the leading causes of mortality worldwide. The central pathological features of atherosclerosis include macrophage infiltration and foam cell formation. However, the detailed mechanisms regulating these two processes remain unclear.

Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury.

Excitotoxicity induced by NMDA receptor (NMDAR) activation is a major cause of neuronal death in ischemic stroke. However, past efforts of directly targeting NMDARs have unfortunately failed in clinical trials. Here, we reveal an unexpected mechanism underlying NMDAR-mediated neurotoxicity, which leads to the identification of a novel target and development of an effective therapeutic peptide for ischemic stroke.

Mechanism and Performance of Bituminous Mixture Using 100% Content RAP with Bio-Rejuvenated Additive (BRA).

The low RAP content, hot mixing conditions, and the addition of a high ratio of new bitumen and aggregates result in low economic and environmental benefits for current regeneration technologies. A bio-rejuvenated additive (BRA) that can fully (100%) regenerate the RAP without heating is proposed in this paper. To reveal the mechanisms of BRA-rejuvenated RAP, the effects of BRA on the chemical structure and molecular weight of the RAP were investigated using Fourier-transform infrared spectroscopy and gel permeation chromatography.

A Systemic Review of the Integral Role of TRPM2 in Ischemic Stroke: From Upstream Risk Factors to Ultimate Neuronal Death.

Ischemic stroke causes a heavy health burden worldwide, with over 10 million new cases every year. Despite the high prevalence and mortality rate of ischemic stroke, the underlying molecular mechanisms for the common etiological factors of ischemic stroke and ischemic stroke itself remain unclear, which results in insufficient preventive strategies and ineffective treatments for this devastating disease. In this review, we demonstrate that transient receptor potential cation channel, subfamily M, member 2 (TRPM2), a non-selective ion channel activated by oxidative stress, is actively involved in all the important steps in the etiology and pathology of ischemic stroke.

Effects of Low-Temperature Construction Additives (LCAs) on the Performance of Asphalt Mixtures.

Green production of asphalt materials is very important to promote energy savings and emission reduction during the construction and maintenance of asphalt pavement. A low-temperature construction additive (LCA) made from the waste plastic and waste rubber is proposed, which belongs to a class of environmentally friendly additives for asphalt mixtures. Marshall stability was tested to evaluate the mechanical performance of LCA-modified asphalt mixtures (LCA-AMs).

CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells.

Magnesium is essential for cellular life, but how it is homeostatically controlled still remains poorly understood. Here, we report that members of CNNM family, which have been controversially implicated in both cellular Mg2+ influx and efflux, selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. Coexpression of CNNMs with the channel markedly increased uptake of divalent cations, which is prevented by an inactivating mutation to the channel's pore.

Establishing reference intervals for islet autoantibodies in Han Chinese type 1 diabetes.

Currently, islet autoantibodies (IAbs) constitute the most reliable marker for detecting the autoimmune process of type 1 diabetes (T1D). However, there are no appropriate reference intervals (RIs) to interpret the results of IAbs in China. In this study, we aimed to establish the RIs of four common IAbs based on the Han Chinese population and evaluate their clinical diagnostic values in patients with T1D.

Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension.

Ophiocordyceps sinensis (OCS), an entomopathogenic fungus, is known to exert antiproliferative and antitissue remodeling effects. Vascular remodeling and vasoconstriction play critical roles in the development of pulmonary hypertension (PH). The therapeutic potential of OCS for PH was investigated using rodent PH models, and cultured pulmonary artery endothelial and smooth muscle cells (PAECs and PASMCs), with a focus on the involvement of TRPM7.

Upregulation of transient receptor potential melastatin 4 (TRPM4) in ventricular fibroblasts from heart failure patients.

The transient receptor potential melastatin 4 (TRPM4) is a Ca-activated nonselective monovalent cation channel belonging to the TRP channel superfamily. TRPM4 is widely expressed in various tissues and most abundantly expressed in the heart. TRPM4 plays a critical role in cardiac conduction.

Effect of sample delivery conditions on Renin-Angiotensin-Aldosterone System (RAAS) assay.

Renin-Angiotensin-Aldosterone System (RAAS) measurements are influenced by several factors. We investigated the effect of sample delivery conditions on RAAS measurements including sample storage temperature and time. Blood samples were collected from thirty participants using enzyme inhibitor tubes and serum separation gel evacuated tubes.

An Effective Biclustering-Based Framework for Identifying Cell Subpopulations From scRNA-seq Data.

The advent of single-cell RNA sequencing (scRNA-seq) techniques opens up new opportunities for studying the cell-specific changes in the transcriptomic data. An important research problem related with scRNA-seq data analysis is to identify cell subpopulations with distinct functions. However, the expression profiles of individual cells are usually measured over tens of thousands of genes, and it remains a difficult problem to effectively cluster the cells based on the high-dimensional profiles.

Biodegradable nanofiber-based piezoelectric transducer.

Piezoelectric materials, a type of "smart" material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs.

Ca Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases.

Cardiac fibrosis is the excessive deposition of extracellular matrix proteins by cardiac fibroblasts and myofibroblasts, and is a hallmark feature of most heart diseases, including arrhythmia, hypertrophy, and heart failure. This maladaptive process occurs in response to a variety of stimuli, including myocardial injury, inflammation, and mechanical overload. There are multiple signaling pathways and various cell types that influence the fibrogenesis cascade.

miR-497 inhibited proliferation, migration and invasion of thyroid papillary carcinoma cells by negatively regulating YAP1 expression.

Purpose: This article aimed to investigate the effect of miR-497 on thyroid papillary carcinoma.

Materials And Methods: miR-497 expression was analyzed using The Cancer Genome Atlas. A total of 56 papillary thyroid carcinoma patients' tumor tissues and normal tissues were collected.