Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording.

The patch clamp technique is a fundamental tool for investigating ion channel dynamics and electrophysiological properties. This study proposes the first artificial intelligence framework for characterizing multiple ion channel kinetics of whole-cell recordings. The framework integrates machine learning for anomaly detection and deep learning for multi-class classification.

Extracellular Silica Nanomatrices Promote In Vitro Maturation of Anti-tumor Dendritic Cells via Activation of Focal Adhesion Kinase.

The efficacy of dendritic cell (DC)-based cancer vaccines is critically determined by the functionalities of in vitro maturated DCs. The maturation of DCs typically relies on chemicals that are cytotoxic or hinder the ability of DCs to efficiently activate the antigen-specific cytotoxic T-lymphocytes (CTLs) against tumors. Herein, the maturation chemicals are replaced with extracellular silica nanomatrices, fabricated by glancing angle deposition, to promote in vitro maturation of murine bone marrow-derived DCs (mBMDCs).

Regulation of PM on mitochondrial damage in H9c2 cells through miR-421/SIRT3 pathway and protective effect of miR-421 inhibitor and resveratrol.

Fine particulate matter (PM) exposure is associated with cardiovascular disease (CVD) morbidity and mortality. Mitochondria are sensitive targets of PM, and mitochondrial dysfunction is closely related to the occurrence of CVD. The epigenetic mechanism of PM-triggered mitochondrial injury of cardiomyocytes is unclear.

The volume regulated anion channel VRAC regulates NLRP3 inflammasome by modulating itaconate efflux and mitochondria function.

The NLRP3 inflammasome is a supramolecular complex that is linked to sterile and pathogen-dependent inflammation, and its excessive activation underlies many diseases. Ion flux disturbance and cell volume regulation are both reported to mediate NLRP3 inflammasome activation, but the underlying orchestrating signaling remains not fully elucidated. The volume-regulated anion channel (VRAC), formed by LRRC8 proteins, is an important constituent that controls cell volume by permeating chloride and organic osmolytes in response to cell swelling.

Caveolin-1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.

Associations between fine particulate matter and colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) is the second deadliest cancer worldwide. The impact of fine particulate matter (PM) on many diseases is a global concern, yet its association with CRC is unclear. This study aimed to assess the effect of PM exposure on CRC.

The Antiangiogenic and Antitumor Effects of Scoparasin B in Non-Small-Cell Lung Cancer.

Angiogenesis and vasculogenic mimicry (VM) are crucial for the growth and metastasis of non-small-cell lung cancer (NSCLC). Most tumor angiogenesis inhibitors mainly target endothelial cell-mediated angiogenesis, ignoring tumor-cell-mediated VM and frequently leading to tumor recurrence and metastasis. Thus, development of bioactive molecules interfering with both tumor angiogenesis and VM is necessary.

Exploring the Effective Components and Mechanism of Action of Japanese in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Experimental Verification.

Japanese is widely used as a hepatoprotective and anti-inflammatory agent in China. However, the active ingredients in Japanese and their potential mechanisms of action in the treatment of autoimmune hepatitis (AIH) are unknown. The pharmacodynamic substance and mechanism of action of Japanese in the treatment of AIH were investigated using network pharmacology and molecular docking technology in this study.

Aberrant Transferrin and Ferritin Upregulation Elicits Iron Accumulation and Oxidative Inflammaging Causing Ferroptosis and Undermines Estradiol Biosynthesis in Aging Rat Ovaries by Upregulating NF-Κb-Activated Inducible Nitric Oxide Synthase: First Demonstration of an Intricate Mechanism.

We report herein a novel mechanism, unraveled by proteomics and validated by in vitro and in vivo studies, of the aberrant aging-associated upregulation of ovarian transferrin and ferritin in rat ovaries. The ovarian mass and serum estradiol titer plummeted while the ovarian labile ferrous iron and total iron levels escalated with age in rats. Oxidative stress markers, such as nitrite/nitrate, 3-nitrotyrosine, and 4-hydroxy-2-nonenal, accumulated in the aging ovaries due to an aberrant upregulation of the ovarian transferrin, ferritin light/heavy chains, and iron regulatory protein 2(IRP2)-mediated transferrin receptor 1 (TfR1).

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells.

Polyphyllin II (PPII) is a natural steroidal saponin occurring in . It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported.

Facet-Dependent Activity of CeO Nanozymes Regulate the Fate of Human Neural Progenitor Cell via Redox Homeostasis.

Neural progenitor cells (NPCs) therapy, a promising therapeutic strategy for neurodegenerative diseases, has a huge challenge to ensure high survival rate and neuronal differentiation rate. Cerium oxide (CeO) nanoparticles exhibit multienzyme mimetic activities and have shown the capability of regulating reactive oxygen species (ROS), which is a pivotal mediator for intracellular redox homeostasis in NPCs, regulating biological processes including differentiation, proliferation, and apoptosis. In the present study, the role of facet-dependent CeO-mediated redox homeostasis in regulating self-renewal and differentiation of NPCs is reported for the first time.

Associations between indoor environment and lifestyles and sick building syndrome symptoms among adults in Taiyuan and Urumqi of China.

The complex and uncertain causes of sick building syndrome (SBS) have become one of the most challenging and hot issues worldwide. Studies on the correlation between indoor environment and SBS based on local characteristics are relatively limited in China. We studied typical SBS risk factors related to the indoor environment and lifestyle in two northern Chinese cities.

An anti-inflammatory and anti-fibrotic proprietary Chinese medicine nasal spray designated as Allergic Rhinitis Nose Drops (ARND) with potential to prevent SARS-CoV-2 coronavirus infection by targeting RBD (Delta)- angiotensin converting enzyme 2 (ACE2) binding.

Background: Since the outbreak of COVID-19 has resulted in over 313,000,000 confirmed cases of infection and over 5,500,000 deaths, substantial research work has been conducted to discover agents/ vaccines against COVID-19. Undesired adverse effects were observed in clinical practice and common vaccines do not protect the nasal tissue. An increasing volume of direct evidence based on clinical studies of traditional Chinese medicines (TCM) in the treatment of COVID-19 has been reported.

An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM exposure.

Fine particulate matter (PM) is associated with increased risks of Alzheimer's disease (AD), yet the toxicological mechanisms of PM promoting AD remain unclear. In this study, wild-type and APP/PS1 transgenic mice (AD mice) were exposed to either filtered air (FA) or PM for eight weeks with a real-world exposure system in Taiyuan, China (mean PM concentration in the cage was 61 µg/m). We found that PM exposure could remarkably aggravate AD mice's ethological and brain ultrastructural damage, along with the elevation of the pro-inflammatory cytokines (IL-6 and TNF-α), Aβ-42 and AChE levels and the decline of ChAT levels in the brains.

Isoalantolactone Induces Cell Cycle Arrest, Apoptosis and Autophagy in Colorectal Cancer Cells.

Colorectal cancer (CRC) is an aggressive cancer. Isoalantolactone (IATL) has been reported to exert cytotoxicity against various cancer cells, but not CRC. In this study, we explored the anti-CRC effects and mechanism of action of IATL and .

Evaluating seasonal variations of fecal coliform colonization in Magallana hongkongensis and Crassostrea rhizophorae: A preliminary study of oyster quality grown in Hong Kong aquacultural farms.

The objective of this research is to investigate the spatial and temporal patterns of bacteriological quality in raw oysters sampled from different aquacultural farms located in Aberdeen Typhoon Shelter, Carp Gates, Lau Fau Shan, Ma Wan, and Mui Wo in Hong Kong. Magallana hongkongensis and Crassostrea rhizophorae were collected and analyzed for fecal coliforms. Throughout the 13-month monitoring period, all samples had generally high bacterial loads, ranging from 1.

Real-world PM exposure induces pathological injury and DNA damage associated with miRNAs and DNA methylation alteration in rat lungs.

Fine particulate matter (PM) has been demonstrated to threaten public health and increase lung cancer risk. DNA damage is involved in the pathogenesis of lung cancer. However, the mechanisms of epigenetic modification of lung DNA damage are still unclear.

Rhamnolipids from non-pathogenic Acinetobacter calcoaceticus: Bioreactor-scale production, characterization and wound healing potency.

Rhamnolipids are predominantly produced from the opportunistic pathogen Pseudomonas aeruginosa, which restricts their scaled-up production and biomedical applications. Moreover, the wound healing property of rhamnolipids is mainly focused on either mono- or di-rhamnolipid congeners, which are obtained after extensive and costly purification procedures. Here, crude rhamnolipids from non-pathogenic Acinetobacter calcoaceticus BU-03 have been prepared and characterized and their wound healing potency evaluated in vitro and in vivo.

Fine particulate matter induces endoplasmic reticulum stress-mediated apoptosis in human SH-SY5Y cells.

Exposure to ambient fine particulate matter (PM) may contribute to brain injury, however, the molecular mechanisms have not yet been fully described. In this study, the human SH-SY5Y cells were treated with PM with different concentrations (0, 25, 100, and 250 μg/mL) for 24 h to investigate the cell apoptosis mediated by endoplasmic reticulum (ER) stress. The ratio of apoptosis, Ca level, biomarkers of ER stress and apoptosis were determined.

ML365 inhibits TWIK2 channel to block ATP-induced NLRP3 inflammasome.

Dysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases.

Protective Effect of Pre-treatment Against Experimental Cerebral Ischemia Injury via Regulating GSK-3β/HO-1 Pathway.

() a famous formula in traditional Chinese medicine, has been clinically used for centuries for treating cerebral diseases, but the protective effects of pre-treatment with on cerebral ischemia have not yet been reported. The present study aimed to test such protective effects and elucidate the underlying mechanisms on cerebral ischemia in rats by phenotypic approaches (i.e.

MiR-30a-5p Regulates GLT-1 Function via a PKCα-Mediated Ubiquitin Degradation Pathway in a Mouse Model of Parkinson's Disease.

Glutamate excitotoxicity is caused by dysfunctional glutamate transporters and plays an important role in the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not fully elucidated. MicroRNAs(miRNA), which are abundant in astrocytes and neurons, have been reported to play key roles in regulating the translation of glutamate-transporter mRNA. In this study, we hypothesized that the miR-30a-5p contributes to the pathogenesis of PD by regulating the ubiquitin-mediated degradation of glutamate transporter 1 (GLT-1).

Ambient air PM exposure induces heart injury and cardiac hypertrophy in rats through regulation of miR-208a/b, α/β-MHC, and GATA4.

Ambient air fine particulate matter (PM) may increase cardiovascular disease risks. In this study, we investigated the miR-208/GATA4/myosin heavy chain (MHC) regulation mechanisms on cardiac injury in rats after PM exposure via an animal inhalation device. The results showed that PM exposure for 2 months caused pathological heart injury, reduced nucleus-cytoplasm ratio, and increased the levels of CK-MB and cTnI, showing cardiac hypertrophy.

Effects of α-Synuclein-Associated Post-Translational Modifications in Parkinson's Disease.

α-Synuclein (α-syn), a small highly conserved presynaptic protein containing 140 amino acids, is thought to be the main pathological hallmark in related neurodegenerative disorders. Although the normal function of α-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of α-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded α-syn has a critical role in PD pathogenesis.