Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

Resource management in UAV-assisted MEC: state-of-the-art and open challenges

Wireless Networks - Unmanned aerial vehicles (UAV) have been widely used in various fields because of their high mobility and portability. At the same time, due to the rapid development of...     

Changes in the content and antioxidative activity of β-carotene and its metabolite vitamin A during gastrointestinal digestion and absorption and optimisation of HPLC-based detection

The β-Carotene (BC), an important precursor of vitamin A (VA), possesses antioxidant activity but is fat-soluble and has low bioavailability. In previous in-vitro assays evaluating antioxidant and 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) free radical scavenging, both BC and VA showed a strong ability to scavenge radicals and protected cells from oxidative stress. Here, we used artificially simulated gastrointestinal digestion and Caco-2 cell absorption models to evaluate the bioavailability of the BC during gastrointestinal digestion and absorption using high-performance liquid chromatography (HPLC) analysis. We observed high absorptive and transfer rates of BC and detected retinol metabolites (Vitamin A). Therefore, BC can be detected in the acidic gastrointestinal environment using HPLC. Optimised method provided better separation of BC and VA in the column, improving the accuracy of the test results.     

Optical design of the Lyman alpha based beam emission spectroscopy(LAB)diagnostic on the HL-2A tokamak

In this article, we present the optical design of a novel diagnostic on the HL-2 A tokamak, i.e. the20-channel edge Lyman-alpha beam emission spectroscopy, which is a promising solution for edge density turbulence research on tokamaks, as it offers the possibility of density fluctuation measurement with a 3.3 mm spatial resolution while maintains a high temporal resolution of1 μs. The optical path, including the reflective collection optics, the high-dispersion spectrometer, and the linear detector array, is carefully optimized to obtain a good image quality and a high throughput. The maximum root mean square radius of the collection optics is 64 μm.The detected photon flux is estimated to be about 10~(11) photons/s/channel.     

Porous Co3O4 column as a high-performance Lithium anode material

Journal of Porous Materials - Co3O4 has been widely investigated as a promising candidate anode material for lithium-ion batteries. We report on the porous Co3O4 column synthesized via a simple...     

The effect of alkali metal oxide on the properties of borosilicate fireproof glass: Structure,thermal properties,viscosity, chemical stability

The purpose of the current work was to research the effect of alkali metal oxide on the structure, thermal properties, viscosity and chemical stability in the glass system (R₂O–CaO–B₂O₃–SiO₂) systematically. Because the glass would emulsify when Li₂O was added to the glass batch, this article did not discuss Li₂O. The results showed that when the amount of Na₂O was less than 4 mol.%, there was a higher interconnectivity of borate and silicate sub-networks in glass, as more mixed Si–O–B bonds were present in glass. The glass samples exhibited excellent thermal properties and chemical stabilities. As the amount of Na₂O exceeded 4 mol.%, the interconnectivity of borate and silicate sub-networks was weakened. The thermal properties and chemical stabilities of the glass samples were reduced. The connectivity of the silicate sub-network was weakened slightly as the Na/K ratio varied, and the coefficient of thermal expansion (CTE) of the glass samples gradually increased, and the resistance to thermal shock (RTS) value gradually decreased. Moreover, the viscosity of the glass samples decreased with the ratio of Na/Si and Na/K increased.     

AQP3 Increases Intercellular Cohesion in NSCLC A549 Cell Spheroids through Exploratory Cell Protrusions

Tumor cell aggregation is critical for cell survival following the loss of extracellular matrix attachment and dissemination. However, the underlying mechanotransduction of clustering solitary tumor cells is poorly understood, especially in non-small cell lung cancers (NSCLC). Here, we examined whether cell surface protrusions played an important role in facilitating the physical contact between floating cells detached from a substrate. We employed poly-2-hydroxyethyl methacrylate-based 3D culture methods to mimic in vivo tumor cell cluster formation. The suprastructural analysis of human NSCLC A549 cell spheroids showed that finger-like protrusions clung together via the actin cytoskeleton. Time-lapse holotomography demonstrated that the finger-like protrusions of free-floating cells in 3D culture displayed exploratory coalescence. Global gene expression analysis demonstrated that the genes in the organic hydroxyl transport were particularly enriched in the A549 cell spheroids. Particularly, the knockdown of the water channel aquaporin 3 gene (AQP3) impaired multicellular aggregate formation in 3D culture through the rearrangement of the actomyosin cytoskeleton. Moreover, the cells with reduced levels of AQP3 decreased their transmigration. Overall, these data indicate that cell detachment-upregulated AQP3 contributes to cell surface protrusions through actomyosin cytoskeleton remodeling, causing the aggressive aggregation of free-floating cells dependent on the property of the substratum and collective metastasis.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.