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.     

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.     

Progressive NO2 Sensors with Rapid Alarm and Persistent Memory-Type Responses for Wide-Range Sensing Using Antimony Triselenide Nanoflakes

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.     

Molecular structure and granule morphology of native and heat‐moisture‐treated pinhão starch

Pinhão seed is an unconventional source of starch and the pines grow up in native forests of southern Latin America. In this study, pinhão starch was adjusted at 15, 20 and 25% moisture content and heated to 100, 110 and 120 °C for 1 h. A decrease in λ max (starch/iodine complex) was observed as a result of increase in temperature and moisture content of HMT. The ratio of crystalline to amorphous phase in pinhão starch was determined via Fourier transform infra red by taking 1045/1022 band ratio. A decrease in crystallinity occurred as a result of HMT. Polarised light microscopy indicated a loss of birefringence of starch granules under 120 °C at 25% moisture content. Granule size distribution was further confirmed via scanning electron microscopy which showed the HMT effects. These results increased the understanding on molecular and structural properties of HMT pinhão starch and broadened its food and nonfood industrial applications.     

Distributed De La Garza algorithm for load-balancing routing in wireless sensor networks

Large scale wireless sensor networks raise many challenges in the design of efficient and effective routing algorithm due to their complexity and hardware constraints. However, the scalability challenge may be mitigated from a macroscopic perspective. One example is the distributed De la Garza iteration (DDLGI) algorithm for global routing load-balancing, based on a set of partial differential equations iteratively solved by the De la Garza method. We theoretically analyze the parallelism of DDLGI and illustrate that the region of interest may impact the degree of parallelism and error. Furthermore, though DDLGI always converges, the slow convergence and long-range information exchange problems may lead to excess energy consumption in communication. Thus, we propose various enhanced De la Garza routing (E-DLGR) algorithms to alleviate the energy consumption problem by which nodes may exchange less information and only need to exchange information with closer nodes to complete each iteration. Our theoretical analysis and simulation results show that the proposed E-DLGR algorithms may have less transmission overhead, thus further reducing energy consumption, and converge faster while still maintaining adequate accuracy.