Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.     

Trypsiligase-Catalyzed Labeling of Proteins on Living Cells

Fluorescent fusion proteins are powerful tools for studying biological processes in living cells, but universal application is limited due to the voluminous size of those tags, which might have an impact on the folding, localization or even the biological function of the target protein. The designed biocatalyst trypsiligase enables site-directed linkage of small-sized fluorescence dyes on the N terminus of integral target proteins located in the outer membrane of living cells through a stable native peptide bond. The function of the approach was tested by using the examples of covalent derivatization of the transmembrane proteins CD147 as well as the EGF receptor, both presented on human HeLa cells. Specific trypsiligase recognition of the site of linkage was mediated by the dipeptide sequence Arg-His added to the proteins’ native N termini, pointing outside the cell membrane. The labeling procedure takes only about 5 minutes, as demonstrated for couplings of the fluorescence dye tetramethyl rhodamine and the affinity label biotin as well.     

Fabrication and joining mechanism of Nano-Cu/Si3N4 ceramic substrates

A novel method for fabricating a nano-Cu/Si₃N₄ ceramic substrate is proposed. The nano-Cu/Si₃N₄ ceramic substrate is first fabricated using spark plasma sintering (SPS) with the addition of nanoscale multilayer films (Ti/TiN/Ti/TiN/Ti) as transition layers. The microstructures of the nano-Cu metal layer and the interface between Cu and Si₃N₄ are investigated. The results show that a higher SPS temperature increases the grain size of the nano-Cu metal layer and affects the hardness. The microstructure of the transition layer evolves significantly after SPS. Ti in the transition layer can react with Si₃N₄ and with nano-Cu to form interfacial reaction layers of TiN and Ti–Cu, respectively; these ensure stronger bonding between nano-Cu and Si₃N₄. Higher SPS temperatures improve the diffusion ability of Ti and Cu, inducing the formation of Ti₃Cu₃O compounds in the nano-Cu metal layer and Ti₂Cu in the transition layer. This study provides an important strategy for designing and constructing a new type of ceramic substrate.     

Investigation of fabrication of gas diffusion substrate for proton exchange membrane fuel cells

The gas diffusion substrate (GDS) is essential in the proton exchange membrane fuel cells. Its fabrication techniques affect the performance significantly and are worthy of investigation. In this study, a manufacturing process of the GDS is proposed to understand the formation process of GDS and promote its structure and performance more pertinently. Different states during the preparation process, raw carbon paper, pre-curing, curing, carbonation, and graphitization, are characterized and measured. Experimental and numerical methods are employed to determine the relationships between microstructure, transport, and mechanical performance variation with the fabricating processes. The results show that its porosity, average pore size, and effective diffusivity decrease first and increase after curing. These parameters after graphitization are lower than that of the carbon paper (CP). The electrical resistivity increases dramatically while pre-curing and decreases gradually after curing, carbonation, and graphitization, and it is much reduced after graphitization. Moreover, mechanical measurement results show that both the picks of tensile strength and flexural modulus occur after curing. Its tensile strength shows little change after graphitization compared to the initial paper's. In contrast, the flexural modulus is improved significantly.     

Chromaticity-tunable remote LuYAG: Ce phosphor-in-glass film on regular textured glass substrate for white light emitting diodes

All inorganic remote phosphor-in-glass film exhibits excellent properties in high power white light-emitting-diodes (WLEDs) thanks to their easy fabrication and thermal stability. Herein, fabrication of (Lu, Y)₃Al₅O₁₂: Ce³⁺ (LuYAG: Ce)phosphors embedded in borosilicate glass film by the conventional solid state reaction and spin coating technology has been reported. The introduction of Y³⁺ ions reduces the difference of relative growth rate along some directions in growth of LuYAG microparticles, yielding a finer grain with smooth edges. By adjusting the molar concentration of Y³⁺ ions in LuAG phosphor, a series of tunable broadband emission from green to yellow region is observed and maintains excellent thermal stability. Meanwhile, the decay curves of samples with different Y³⁺ are almost same. SEM images show that phosphor particles are homogenously distributed within the glass matrix and keep their original morphology, suggesting the phosphor-in-glass films were synthesized as expected. Finally, a simple WLEDs based on the films was constructed using the commercial blue chip. The correlated color temperature ranging from 4853K to 4627K and high color rendering index from 81.4–79.7 were obtained. Upon the different driving current, the chromaticity coordinates of as-fabricated film exhibit good light color stability. These results bring an inspiring insight to tune the luminescent performance for remote WLEDs.     

Methane bi-reforming over boron-doped Ni/SBA-15 catalyst: Longevity evaluation

A highly active and stable boron-promoted catalyst was successfully prepared by using the sequential incipient wetness impregnation technique and examined for methane bi-reforming reaction. The initial investigation found that the NiO and B₂O₃ particles were dispersed on the outer surface of the high surface area SBA-15 support. In addition, the catalytic activity was increased linearly with the tested reaction temperature due to the endothermic nature of the reaction. In fact, the catalyst achieved the CH₄ conversion and H₂/CO molar ratio of approximately 67.3% and 2.7, respectively at 1073 K. The resulting product ratio is highly suitable for downstream Fischer-Tropsch (FT) synthesis. The B-promoted catalyst showed the lowest degree of catalyst deactivation (4%) at 1023 K. Additionally, the XPS measurements unveiled that the boron facilitates the adsorption of CO₂ by donating electrons to the neighbouring Ni cluster and thus improved its catalytic performance. Furthermore, Raman and XRD analysis revealed that the boron promotion on 10%Ni/SBA-15 could prevent the reoxidation and deposition of carbonaceous species.     

Failure mechanism of MCrAlY coating at the coating‐substrate interface under type I hot corrosion

MCrAlY coatings are widely used to provide protection of hot component in modern gas turbine engines against high‐temperature oxidation and hot corrosion. Coating‐substrate interface, where the substrate is only partially covered by the ?coatings, is vulnerable to the hot corrosion attack. The accelerated degradation at the coating‐substrate interface can cause fast spallation of the coating, leading to the early failure of the gas turbine components. In this paper, MCrAlY powder was deposited on IN792 disks by high‐velocity oxygen‐fuel spraying. The hot corrosion behavior of the coated sample was investigated using (0.8Na, 0.2K)₂SO ₄ salt deposition at 900°C in lab air. Results showed a minor attack in the coating center, however, an accelerated corrosion attack at the coating‐substrate interface. The fast growth of corrosion products from substrate caused large local volume expansions at the coating‐substrate interface, resulting in an early coating spallation.     

Covalent triazine framework with efficient photocatalytic activity in aqueous and solid media

Covalent triazine frameworks (CTFs) have been recently employed for visible light-driven photocatalysis due to their unique optical and electronic properties. However, the usually highly hydrophobic nature of CTFs, which originates from their overall aromatic backbone, leads to limitations of CTFs for applications in aqueous media. In this study, we aim to extend the range of the application media of CTFs and design hybrid material of a CTF and mesoporous silica (SBA-15) for efficient photocatalysis in aqueous medium. A thiophene-containing CTF was directly synthesized in mesopores of SBA-15. Due to the high surface area and the added hydrophilic properties by silica, the hybrid material demonstrated excellent adsorption of organic molecules in water. This leads not only to high photocatalytic performance of the hybrid material for the degradation of organic dyes in water, but also for efficient photocatalysis in solvent-free and solid state. Furthermore, the reusability, stability and easy recovery of the hybrid material offers promising metal-free heterogeneous photocatalyst for broader applications in different reaction media.