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.     

Biotransformation of three aromadendrane‐type sesquiterpenoids by Aspergillus wentii

BACKGROUND: The biotransformation of sesquiterpenoids, which are a large class of naturally occurring compounds, using microorganisms as a biocatalyst to produce useful novel organic compounds was investigated. The biotransformation of sesquiterpenoids, (+)‐aromadendrene ( 1 ), (−)‐alloaromadendrene ( 2 ) and (+)‐ledene ( 3 ) has been investigated using Aspergillus wentii as a biocatalyst. Results: Compound 1 was converted to (−)‐(10S,11S)‐10,13,14‐trihydroxyaromadendrane ( 4 ). Compound 2 was converted to (+)‐(1S,11S)‐1,13‐dihydroxyaromadendrene ( 5 ) and (−)‐5,11‐epoxycadin‐1(10)‐en‐14‐ol ( 6 ). Compound 3 was converted to compound 6 , (+)‐(10R,11S)‐10,13‐dihydroxyaromadendr‐1‐ene ( 7 ) and (+)‐(10S,11S)‐10,13‐dihydroxyaromadendr‐1‐ene ( 8 ). The structure of the metabolic products has been elucidated on the basis of their spectral data. CONCLUSION: Compound 1 gave only one product that was hydroxylated at C‐10, C‐13 and C‐14. By contrast, compounds 2 and 3 gave a number of products, one of which was common. The differences in oxidation of 1–3 are due to the configuration of the C‐1 position. Compounds 4–8 were new compounds. Copyright © 2008 Society of Chemical Industry     

Pressureless sintering and characterization of cordierite/ZrO2 composites

Cordierite/ZrO₂ composites with 5 to 25 wt% ZrO₂ were fabricated by conventional powder mixing and pressureless sintering method. Their densification behavior, microstructure, mechanical and thermal properties were studied. By dispersing 25 wt% (9.57 vol%) ZrO₂, densified cordierite/ZrO₂ composite with a relative density of 98.5% was obtained at an optimum sintering condition of 1440 °C and 2 h. ZrO₂ particles were homogenously dispersed within matrix grains and at the grain boundaries. The intragranular particles were finer than 100 nm and the intergranular particles were coarser. Both fracture strength and toughness could be enhanced more than two times higher, compare to those of monolithic cordierite, by dispersing 25 wt% ZrO₂ into the cordierite matrix. The toughening mechanism in the present composites was mainly attributed to martensitic transformation due to ZrO₂ dispersion. Electronic Publication     

Preparation and characterization of porous and electrically conducting carbon-clay composites

Porous and electrically conducting carbon-clay composites were prepared by firing mixtures of carbon powder (0 to 20 wt%) and clay minerals. They showed porosity of 50 to 65% and had high mechanical strength (compressive strength = 130 to 400 kg cm^–2) as well as high resistance against thermal oxidation in air. Their electrical conductivity, , increased with increasing carbon content levelling off at about 20 wt% of carbon content to give a value of about 2 S cm^–1. Formation of carbon chains is considered to be responsible for the electrical conduction in the composite, and a model to correlate the electrical conductivity with the carbon content has been proposed by modifying a model previously proposed by Scarisbrick.     

Magnetic probe array with high sensitivity for fluctuating field

A magnetic probe array is constructed to measure precisely the spatial structure of a small fluctuating field included in a strong confinement field that varies with time. To exclude the effect of the confinement field, the magnetic probes consisting of figure-eight-wound coils are prepared. The spatial structure of the fluctuating field is obtained from a Fourier analysis of the probe signal. It is found that the probe array is more sensitive to the fluctuating field with a high mode number than that with a low mode number. An experimental demonstration of the present method is attempted using a field-reversed configuration plasma, where the fluctuating field with 0.1% of the confinement field is successfully detected.     

Critical assessment 29: TRIP-aided bainitic ferrite steels

Transformation-induced plasticity (TRIP)-aided bainitic ferrite steels developed for automotive applications have attractive mechanical properties such as ductility, formability, toughness, fatigue strength and delayed fracture strength. These mechanical properties are principally associated with a ductile lath-structure matrix and the strain-induced transformation of the metastable-retained austenite films of 3–20 vol.%. In this paper, data on the microstructural and mechanical properties of the low-carbon TRIP-aided bainitic ferrite steels are critically assessed, as well as their deformation mechanism.     

A chemo-thermo-mechanically coupled analysis of ground deformation induced by gas hydrate dissociation

We present a numerical analysis of gas hydrate dissociation in hydrate-bearing sediments in the seabed ground. Behavior of multiphase materials has been described within the framework of a macroscopic continuum approach through the use of the theory of porous media. The proposed simulation method has been developed based on chemo-thermo-mechanically coupled analysis, taking into account phase changes from solids to fluids, that is, water and gas, flow of water and gas, heat transfer, and ground deformation. From the numerical results, it has been found that ground deformation is induced by generation and dissipation of water and gas, and by reduction of soil strength due to the loss of hydrates.     

Aroma Characteristic and Volatile Profiling of Carrot Varieties and Quantitative Role of Terpenoid Compounds for Carrot Sensory Attributes

The aroma characteristics and volatile profiles of 14 carrot varieties were investigated by sensory evaluations and gas chromatography–mass spectrometry volatile analyses. The sensory map obtained by principal components analysis showed that the sensory attributes comprised 3 categories: sour/green, overall carrot/harsh/ink‐like, and fruity/fresh/sweet. The Kuroda type is characterized by lower intensities of overall carrot/harsh/ink‐like and fruity/fresh/sweet notes. Furthermore, volatile profiling indicated that this type did not have significantly higher amounts of volatiles. Partial least squares regression analysis determined the quantitative contributions to ink‐like, harsh, and fruity carrot aromas; monoterpenes had significant positive correlations with these attributes, while bisabolene isomers had negative correlations. The aroma attribute intensity and contents of volatiles and nutritional compounds are relatively low in the Kuroda type than in other carrot types. This type may be useful for reducing carrot harshness during the development of new carrots with good eating qualities.     

A novel gene delivery system in plants with calcium alginate micro-beads

We have produced micrometer-sized calcium alginate beads referred to as "bio-beads" that encapsulate plasmid DNA molecules carrying a reporter gene. In order to evaluate the efficiency of the bio-beads in mediating genetic transfection, protoplasts isolated from cultured tobacco cells (BY-2) were transfected with bio-beads containing a plasmid that carries the modified green fluorescent protein gene CaMV35S-sGFP. With the bio-beads treatment, approximately ten-fold higher GFP expression was observed after 24 h incubation compared to that with the conventional method using a naked plasmid solution. Transfection was up to 0.22% efficient. These results indicate that bio-beads have a possibility for efficient transformation in plants.     

Formation of high-purity organic thin films by gas flow deposition and the effect of impurities on device characteristics

A gas flow deposition (GFD) system was developed to manufacture large-scale organic light-emitting diodes (OLEDs). A N,N′-di(1-naphthyl)-N,N′-diphenylbenzidine (α-NPD) thin film with a high purity of 99.97% was obtained using the GFD system. The film properties such as morphology, and electrical and optical characteristics were almost the same as those of films made by conventional vacuum thermal evaporation.