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.     

Improved quantum efficiency of Sr(Al,Si)5(O,N)7:Ce3+ by selection of Ce raw material

The luminescence properties of yellow-emitting Ce³⁺-doped Sr-containing sialon phosphor Sr(Al,Si)₅(O,N)₇:Ce³⁺ were notably improved by the Ce raw material selection. By changing the Ce raw material from oxides to nitrides or chlorides, the emission wavelength shifted to above 560 nm, which is beneficial for higher color rendering index white light-emitting diodes. This result from an increase in the covalency of the host crystal being associated with a decrease in the oxygen content. When Ce chloride was used, both the absorption and internal quantum efficiency increased, resulting in an increase in the external quantum efficiency up to 65%–72%. Inductively coupled plasma mass spectrometry, X-ray diffraction, and electron spin resonance measurements showed that the reason for the absorption increase is an increase in Ce³⁺ content and suppression of the generation of the second phase, and the reason for the increase in the internal quantum efficiency is a decrease in the host crystal absorption via suppression of anion vacancy generation. It was found that Ce chloride not only suppresses oxygen impurities but also acts as a flux that results in improved crystallinity.     

Adjunctive Application of Antimicrobial Photodynamic Therapy in Nonsurgical Periodontal Treatment: A Review of Literature

Periodontal disease is caused by dental plaque biofilms, and the removal of these biofilms from the root surface of teeth plays a central part in its treatment. The conventional treatment for periodontal disease fails to remove periodontal infection in a subset of cases, such as those with complicated root morphology. Adjunctive antimicrobial photodynamic therapy (aPDT) has been proposed as an additional treatment for this infectious disease. Many periodontal pathogenic bacteria are susceptible to low-power lasers in the presence of dyes, such as methylene blue, toluidine blue O, malachite green, and indocyanine green. aPDT uses these light-activated photosensitizer that is incorporated selectively by bacteria and absorbs a low-power laser/light with an appropriate wavelength to induce singlet oxygen and free radicals, which are toxic to bacteria. While this technique has been evaluated by many clinical studies, some systematic reviews and meta-analyses have reported controversial results about the benefits of aPDT for periodontal treatment. In the light of these previous reports, the aim of this review is to provide comprehensive information about aPDT and help extend knowledge of advanced laser therapy.     

Processing of nanolitre liquid plugs for microfluidic cell-based assays

Plugs, i.e. droplets formed in a microchannel, may revolutionize microfluidic cell-based assays. This study describes a microdevice that handles nanolitre-scale liquid plugs for the preparation of various culture setups and subsequent cellular assays. An important feature of this mode of liquid operation is that the recirculation flow generated inside the plug promotes the rapid mixing of different solutions after plugs are merged, and it keeps cell suspensions homogeneous. Thus, serial dilutions of reagents and cell suspensions with different cell densities and cell types were rapidly performed using nanolitres of solution. Cells seeded through the plug processing grew well in the microdevice, and subsequent plug processing was used to detect the glucose consumption of cells and cellular responses to anticancer agents. The plug-based microdevice may provide a useful platform for cell-based assay systems in various fields, including fundamental cell biology and drug screening applications.     

A robust implicit state observer for multiple-input multiple-output uncertain systems

A new mathematical method of estimating the state for uncertain continuous-time multiple-input multiple-output minimum-phase (with respect to the relation between the disturbance and the output) dynamical systems with arbitrarily relative degrees is presented. For the systems with relative degree one, the state observer which is perfectly robust to disturbances is constructed by using only the input and output information. The estimating error of the state decays to zero exponentially. For the systems with higher relative degrees, the state observer is formulated for the first time, where the input and output information, and the a priori information of the upper and lower bounds of the disturbances are employed. In this case, the estimating error of the state can be controlled to be as small as is needed by the design parameters. The attraction of the proposed observers lies in their robustness to disturbances and insensitivity to the high-frequency noises accompanying the inputs. A design example and its simulation results are presented to illustrate the proposed algorithm.     

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.     

Effects of phosphorus content on generation and growth of cracks in nickel–phosphorus platings owing to thermal cycling

We observed crack generation and structural changes in electroless nickel–phosphorus (Ni–P) plating layers formed on copper-metalized silicon nitride substrates both during thermal cycling from ? 40 to 250 °C and during storage (not cycling) at 250 °C in order to investigate the effect of the phosphorus contents on crack generation and growth in the Ni–P platings. The used platings contained phosphorus at three different contents: 2.1 wt% [Ni–P(low)], 6.5 wt% [Ni–P(med)], and 10.9 wt% [Ni–P(high)]. The generation time and the amount of cracks were strongly dependent on their phosphorus contents. More cracks appeared after thermal cycling than after storage at 250 °C. In Ni–P(low), cracks were generated after 200 thermal cycles, whereas no cracks were observed even after 250 h of storage at 250 °C. In Ni–P(med) and Ni–P(high), both during thermal cycling and storage at 250 °C, cracks formed during or after crystallization of the amorphous layers. These results suggest that the primary factors affecting the generation of cracks in electroless Ni–P platings are crystallization of the Ni–P platings and repeated changes in thermal stress.     

Fabrication of magnesium based composites reinforced with carbon nanotubes having superior mechanical properties

Magnesium (Mg) composite reinforced with carbon nanotubes (CNTs) having superior mechanical properties was fabricated using both pure Mg and AZ61 Mg alloy matrix in this study. The composites were produced via powder metallurgy route containing wet process using isopropyl alcohol (IPA) based zwitterionic surfactant solution with unbundled CNTs. The produced composites were evaluated with tensile test and Vickers hardness test and analyzed by X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM) equipped with energy dispersive spectroscopy (EDS) and electron back scattered diffraction (EBSD). As a result, only with AZ61 Mg alloy matrix, tensile strength of the composite was improved. In situ formed Al₂MgC₂ compounds at the interface between Mg matrix and CNTs effectively reinforced the interfacial bonding and enabled tensile loading transfer from the Mg matrix to nanotubes. Furthermore, it was clarified that the microstructures and grain orientations of the composite matrix were not significantly influenced by CNT addition.