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.     

Emergency egress for the elderly in care home fire situations

Practitioners are continuing to develop egress modelling software for the design of the built environment. These models require data about human behaviour and factors for calibration, validation and verification. This study aims to address the specific data and knowledge gap: emergency egress of the elderly. Such data are difficult to collect given privacy and consent concerns, with strong relationships generally being required between residences and researchers. Through the observation of nine fire drills at six Canadian long-term care (LTC) and retirement homes, specific evacuation actions and behaviour were observed for 37 staff members and information about the evacuation of 56 residents was collected. These drills demonstrated that emergency egress in LTC and retirement homes is highly staff dependent with 72% of residents recorded requiring full assistance at all stages of movement in evacuation, and that the type of announced/unannounced drill and level of resident care will affect the type of data collected. The development of travel speed and pre-movement is discussed subject to limitation with qualitative behavioural insights of residents that were observed. This study provides valuable methodological discussion on how to conduct behavioural studies in similar highly restricted research environments. Specific attention is given to understanding the considerations that must be made when using fire drills as data sources, and the impact that these can have on using such data for modelling. This study may inform the initial setup and programming of evacuation models from an actions and behavioural perspectives of staff members and residents.     

Industry 4.0: a supply chain innovation perspective

The Fourth Industrial Revolution – also known as Industry 4.0 (i4.0) – comprises the digitalisation of the industrial sector. This paper uses the theoretical lens of supply chain innovation (SCI) to investigate the implications of i4.0 on supply chain management. For these purposes, the method of structured content analysis is applied to more than 200 use cases of i4.0-enabled SCI introduced by both established and startup companies. i4.0-enabled SCI manifests along three dimensions: process, technology, and business architecture. The key findings of this study can be summarised as follows: first, i4.0-enabled SCI extends the initial focus on productivity improvements in SC processes towards scalability and flexibility. Second, extant i4.0 solutions rely mostly on analytics and smart things while omitting smart people technology and the human-centric approach associated with the i4.0 paradigm. Third, established companies adopt i4.0 merely to sustain their existing business architectures while startup companies radically change their operating models, relying heavily on data analytics and the platform economy. Consequently, established companies pursue a problem-driven, engineering-based approach to SCI while startup companies follow an ‘asset-light’, business-driven approach. Lastly, there are two distinct approaches to digitalising operational SC processes: platform-based crowdsourcing of standard processes and on-demand provision of customised services.     

Multiply Charged Conjugated Polyelectrolytes as a Multifunctional Interlayer for Efficient and Scalable Perovskite Solar Cells

A series of anionic conjugated polyelectrolytes (CPEs) is synthesized based on poly(fluorene-co-phenylene) by varying the side-chain ionic density from two to six per repeat units (MPS2-TMA, MPS4-TMA, and MPS6-TMA). The effect of MPS2, 4, 6-TMA as interlayers on top of a hole-extraction layer of poly(bis(4-phenyl)-2,4,6-trimethylphenylamine (PTAA) is investigated in inverted perovskite solar cells (PeSCs). Owing to the improved wettability of perovskites on hydrophobic PTAA with the CPEs, the PeSCs with CPE interlayers demonstrate a significantly enhanced device performance, with negligible device-to-device dependence relative to the reference PeSC without CPEs. By increasing the ionic density in the MPS-TMA interlayers, the wetting, interfacial defect passivation, and crystal growth of the perovskites are significantly improved without increasing the series resistance of the PeSCs. In particular, the open-circuit voltage increases from 1.06 V for the PeSC with MPS2-TMA to 1.11 V for the PeSC with MPS6-TMA. The trap densities of the PeSCs with MPS2,4,6-TMA are further analyzed using frequency-dependent capacitance measurements. Finally, a large-area (1 cm²) PeSC is successfully fabricated with MPS6-TMA, showing a power conversion efficiency of 18.38% with negligible hysteresis and a stable power output under light soaking for 60 s.     

Precise Extraction of Charge Carrier Mobility for Organic Transistors

Unreliable mobility values, and particularly greatly overestimated values and severely distorted temperature dependences, have recently hampered the development of the organic transistor field. Given that organic field‐effect transistors (OFETs) have been routinely used to evaluate mobility, precise parameter extraction using the electrical properties of OFETs is thus of primary importance. This review examines the origins of the various mobilities that must be determined for OFET applications, the relevant extraction methods, and the data selection limitations, which help in avoiding conceptual errors during mobility extraction. For increased precision, the review also discusses device fabrication considerations, calibration of both the specific gate‐dielectric capacitance and the threshold voltage, the contact effects, and the bias and temperature dependences, which must actually be handled with great care but have mostly been overlooked to date. This review serves as a systematic overview of the OFET mobility extraction process to ensure high precision and will also aid in improving future research.     

Isolation of antimicrobial agent from the marine algae Cystoseira hakodatensis

Cystoseira hakodatensis is an unutilised brown algae belonging to family Sargassaceae. A crude methanol extract from the algae showed inhibitory effects on the growths of Bacillus cereus and Bacillus licheniformis. To isolate the major antimicrobial agent, a sequential active‐guided isolation procedure was applied: liquid–liquid extraction, column chromatography and bio‐autography. A marked antimicrobial agent (active α) was isolated in hydrophobic fraction and was determined to phenolics without carbohydrates and proteins by phytochemical test. Regarding the antimicrobial potential, the isolated active α showed better inhibitory effects against B. cereus and B. licheniformis at 2 and 4 times of lower concentrations (62.5 and 31.3 μg mL^?1) in comparison with epigallocatechin gallate. These results showed that C. hakodatensis is a potential source of antimicrobial agent capable of preventing the growth of the two bacteria.