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.     

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.     

Photoluminescence and doping mechanism of theranostic Eu3+/Fe3+ dual-doped hydroxyapatite nanoparticles

Theranostic nanoparticles currently have been regarded as an emerging concept of ‘personalized medicine’ with diagnostic and therapeutic dual-functions. Eu³⁺ doped hydroxyapatite (HAp) has been regarded as a promising fluorescent probe for in vivo imaging applications. Additionally, substitution of Ca²⁺ with Fe³⁺ in HAp crystal may endow the capability of producing heat upon exposure to a magnetic field. Here we report a preliminary study of doping mechanism and photoluminescence of Eu³⁺ and Fe³⁺ doped HAp nanoparticles (Eu/Fe:HAp). HAp with varied concentration of Eu³⁺ and Fe³⁺ doping are presented as Eu(10 mol%):HAp, Eu(7 mol%)-Fe(3 mol%):HAp, Eu(5 mol%)-Fe(5 mol%):HAp, Eu(3 mol%)-Fe(7 mol%):HAp, and Fe(10 mol%):HAp in the study. The results showed that the HAp particles, in nano-size with rod-like morphology, were successfully doped with Eu³⁺ and Fe³⁺, and the particles can be well suspended in cell culture medium. Photoluminescence analysis revealed that particles have prominent emissions at 536 nm, 590 nm, 615 nm, 650 nm and 695 nm upon excitation at a wavelength of 397 nm. Moreover, these Eu/Fe:HAp nanoparticles belonged to B-type carbonated HAp, which has been considered an effective biodegradable and biocompatible drug/gene carrier in biological applications.     

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.     

Competitive adsorption of fibronectin and albumin on hydroxyapatite nanocrystals

Competitive adsorption of two-component solutions containing fibronectin (Fn) and albumin (Ab) on hydroxyapatite (HAp) nanocrystals was analyzed in situ using the quartz crystal microbalance with dissipation (QCM-D) technique. Adsorption of the one-component protein (Fn or Ab) and the two-component proteins adjusted to different molar ratios of Fn to Ab at a fixed Fn concentration was investigated. The frequency shift (Δf; Hz) and the dissipation energy shift (ΔD) were measured with the QCM-D technique, and the viscoelastic changes of adlayers were evaluated by the saturated ΔD/Δf value and the Voigt-based viscoelastic model. For the adsorption of the one-component protein, the Fn adlayer showed a larger mass and higher viscoelasticity than the Ab adlayer, indicating the higher affinity of Fn on HAp. For the adsorption of the two-component proteins, the viscoelastic properties of the adlayers became elastic with increase in Ab concentration, whereas the adsorption mass was similar to that of Fn in the one-component solution regardless of the Ab concentration. The specific binding mass of the Ab antibody to the adlayers increased with increase in Ab concentration, whereas that of the Fn antibody decreased. Therefore, Fn preferentially adsorbs on HAp and Ab subsequently interacts with the adlayers, indicating that the interfacial viscoelasticity of the adlayers was dominated by the interaction between Fn and Ab.     

Hydrothermal Synthesis of Oriented Anatase Films Consisting of Columnar Aggregates and Their Wetting Properties

We hydrothermally synthesized anatase films on Ti substrates from transparent aqueous solutions of layered titanate colloids. The morphology and wetting properties of the films were examined. The films consisted of columnar aggregates grown on the Ti substrates, which resulted in high orientation. Randomly oriented films were obtained when alumina was used as a substrate, whereas the sol–gel precoating of a titanium oxide (TiO₂) layer on alumina substrates resulted in similar orientation as that of the films on Ti substrates. Thus, the presence of TiO₂ on the substrate surface plays an important role in the orientation of columnar aggregates. The columnar aggregates were similar in microstructure to the arms of a type of six-pointed star-like anatase aggregate synthesized hydrothermally from the same reaction solutions. They were composed of twins of tapered anatase nanocrystals, which provided a rough film surface. The film surface was highly hydrophilic and oleophilic due to the nanoscale roughness even when the film was not irradiated with UV light.     

Classification of particles by centrifugal separator and analysis of the fluid behavior

This study gives fundamental knowledge on the particle classification performance by centrifugal separator.It is found that the cut size of a centrifugal separator decreases as the rotational speed increases and the liquid flow rate decreases. Fitting our experimental results with the theory, they agree with each other at high flow rate. However, the difference between them generates at low flow rate. This is because dead spaces are generated in the centrifugal separator at the low flow rate. Also, the computer simulation of the fluid behavior in the centrifugal separator can find the decrease of the velocity near the wall under the low flow rate, which suggests the possibility of the formation of dead spaces in the separator.     

Preferential mineralization of CaCO3 layers on polymer surfaces from CaCl2 and water‐soluble carbonate salt solutions supersaturated by poly(acrylic acid)

CaCO₃ was mineralized from solutions supersaturated only by poly(acrylic acid) (PAA), without bubbling any CO₂ gas in the solution. For example, a layer of CaCO₃ was built up on the surface of a chitosan membrane from a supersaturated aqueous solution containing CaCl₂, Na₂CO₃, and PAA. In this newly developed method, the PAA alone suppresses the precipitation of CaCO₃ from the bulk solution, and therefore, increases the supersaturated concentration. This concentration is estimated to be the same order as that attained in the method in which both CO₂ gas and PAA were used. At the same time, PAA supplies nucleation fields by forming a polymer complex with chitosan. The crystal system obtained was different from those obtained when using CO₂ gas. Self‐organization of aragonite crystallites led to the formation of uniform, concentric, or branching patterns in the surface‐domain structure. These patterns had morphologies similar to those discovered by other researchers, typically in the crystallization of ascorbic acid. Thicker layers of CaCO₃ could be formed on chitosan membranes, the surfaces of which had been converted to a polyelectrolyte complex (PEC) by exposure to PAA solution before the onset of mineralization. Under certain conditions, the CaCO₃ layer had a small spherical curvature, similar to a half‐lens, and generated Newton's ring pattern from the interference fringes of visible light. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91:3627–3634, 2004