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1.
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.  相似文献   
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Silicon - Quadruple gate FinFET is a promising candidate among other multi-gate MOS devices due to it’s better scalability and higher short channel effect suppression capability in advanced...  相似文献   
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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.  相似文献   
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Antimony triselenide (Sb2Se3) nanoflake-based nitrogen dioxide (NO2) sensors exhibit a progressive bifunctional gas-sensing performance, with a rapid alarm for hazardous highly concentrated gases, and an advanced memory-type function for low-concentration (<1 ppm) monitoring repeated under potentially fatal exposure. Rectangular and cuboid shaped Sb2Se3 nanoflakes, comprising van der Waals planes with large surface areas and covalent bond planes with small areas, can rapidly detect a wide range of NO2 gas concentrations from 0.1 to 100 ppm. These Sb2Se3 nanoflakes are found to be suitable for physisorption-based gas sensing owing to their anisotropic quasi-2D crystal structure with extremely enlarged van der Waals planes, where they are humidity-insensitive and consequently exhibit an extremely stable baseline current. The Sb2Se3 nanoflake sensor exhibits a room-temperature/low-voltage operation, which is noticeable owing to its low energy consumption and rapid response even under a NO2 gas flow of only 1 ppm. As a result, the Sb2Se3 nanoflake sensor is suitable for the development of a rapid alarm system. Furthermore, the persistent gas-sensing conductivity of the sensor with a slow decaying current can enable the development of a progressive memory-type sensor that retains the previous signal under irregular gas injection at low concentrations.  相似文献   
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A recent development in tactile technology enables an improvement in the appreciation of the visual arts for people with visual impairment (PVI). The tactile sense, in conjunction with, or a possibly as an alternative to, the auditory sense, would allow PVIs to approach artwork in a more self‐driven and engaging way that would be difficult to achieve with just an auditory stimulus. Tactile colour pictograms (TCPs), which are raised geometric patterns, are ideographic characters that are designed to enable PVIs to identify colours and interpret information by touch. In this article, three TCPs are introduced to code colours in the Munsell colour system. Each colour pattern consists of a basic cell size of 10 mm × 10 mm to represent the patterns consistently in terms of regular shape. Each TCP consists of basic geometric patterns that are combined to create primary, secondary, and tertiary colour pictograms of shapes indicating colour hue, intensity and lightness. Each TCP represents 29 colours including six hues; they were then further expanded to represent 53 colours. Two of them did not increase the cell size, the other increased the cell size 1.5 times for some colours, such as yellow‐orange, yellow, blue, and blue‐purple. Our proposed TCPs use a slightly larger cell size compared to most tactile patterns currently used to indicate colour, but code for more colours. With user experience and identification tests, conducted with 23 visually impaired adults, the effectiveness of the TCPs suggests that they were helpful for the participants.  相似文献   
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The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.  相似文献   
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