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.     

Direct Observation of Pure Cu and Cu-Ag Anode Passivation in H2SO4-CuSO4 Aqueous Solution by Channel Flow Double Electrode and Optical Microscopy

Metallurgical and Materials Transactions B - The dissolution and passivation of pure Cu and Cu-5 wt pct Ag anodes in H2SO4-CuSO4 electrolyte were investigated by a direct...     

Stability,cure properties,and applicability as one part adhesives of systems of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisepoxide

Heterogeneous curable compositions of divalent metal salts of mono(hydroxyethyl) phthalate–anhydride–bisphenol A diglycidyl ether (BADG) systems were prepared by merely mixing these components at room temperature. Stability at room temperature and cure properties at high temperature of the compositions were investigated for evaluating their applicability as one part adhesive. It was found that the systems containing Mg were generally more stable than those containing Ca. Similarly, at 150°C the Ca-containing systems showed generally shorter gelation time than the Mg-containing ones, due to the fact that the Ca salt dissolves more rapidly and enters into the addition reaction with the anhydride, leading to the faster appearance of the catalytic activities of the Ca carboxylate group. Among the various combinations of components, the metal salt–succinic anhydride (SA)–BADG systems were stable at room temperature for more than 6 months and rapidly cured at high temperature, showing excellent adhesive properties. This result indicates that the SA-containing systems should be of interest in applications to one part adhesives.     

Galvanic cell measurements on supersaturated activities of oxygen in Fe-Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) melts

Using a mullite (3Al₂O₃ · 2SiO₂)-tube and ZrO₂-9 mol pct MgO-plug type solid electrolyte galvanic cells, the activities of supersaturated oxygen in Fe-0.0017 to 0.41 mass pct Al-M (M=C, Te, Mn, Cr, Si, Ti, Zr, and Ce) alloys were measured as a function of total Al or M contents at 1873 K in an alumina crucible. Based on these results, the effects of alloying elements on the supersaturated oxygen activity with respect to alumina precipitation were studied. In the Fe-Al-M (M=C, Te, Mn, Cr, and Si) alloys, the supersaturated oxygen activities for a given Al level approach the equilibrium values with increasing contents of alloying elements. However, the oxygen activities for a given Al level are still supersaturated in the Fe-Al-M (M=Ti, Zr, and Ce) alloys even in the presence of considerable amounts of the alloying elements.     

Bacteremia caused by the Bacteroides fragilis group in patients with hematologic diseases

During a 22-year period, 13 patients with hematologic diseases developed bacteremia caused by the Bacteroides fragilis group, with a frequency which remained almost unchanged. Nine patients (69%) had polymicrobial infections. Acute leukemia was the most common underlying disease. The lower intestinal tract (necrotizing enterocolitis and anorectal abscesses) was the most common source of infection. Prior antibiotic therapy was the most frequent host condition before bacteremia, followed by cancer chemotherapy, neutropenia, thrombocytopenia and hypoproteinemia. Septic shock occurred only in seven patients with polymicrobial infections. Six patients, including five with shock, died within a week of onset, while the other seven survived for at least three weeks. Despite its clinical similarity to aerobic gram-negative infection, bacteremia due to the B. fragilis group may well, therefore, be suspected particularly when neutropenic patients who present with lower intestinal symptomatology develop a persistent fever unresponsive to the initial empiric antibiotic therapy.     

P-MOSFET's with ultra-shallow solid-phase-diffused drain structureproduced by diffusion from BSG gate-sidewall

A p-MOSFET structure with solid-phase diffused drain (SPDD) is proposed for future 0.1-μm and sub-0.1-μm devices. Highly doped ultrashallow p⁺ source and drain junctions have been obtained by solid-phase diffusion from a highly doped borosilicate glass (BSG) sidewall. The resulting shallow, high-concentration drain profile significantly improves short channel effects without increasing parasitic resistance. At the same time, an in situ highly-boron-doped LPCVD polysilicon gate is introduced to prevent the transconductance degradation which arises in ultrasmall p-MOSFETs with lower process temperature as a result of depletion formation in the p⁺-polysilicon gate. Excellent electrical characteristics and good hot-carrier reliability are achieved     

Color registration error reduction method compensating the influence of belt thickness variation in electrophotographic process

This paper proposes a new belt drive control method for reducing a belt velocity-fluctuation that is caused by a belt thickness-variation in the circumferential direction. A belt driving system performs feedback control with a rotary encoder-output mounted on a driven roller. This proposed method correct the reference value of the feedback control for the purpose of the belt velocity regulation. The correction includes two steps. The first step acquires the encoder-output of the driven roller and calculates the rotational angular velocity-fluctuation with one cycle of the belt rotation. The second step converts from the velocity-fluctuation to the correction value of the feedback reference. The correction value cancels a detection error of the driven roller caused by the belt thickness-variation. After these steps, the belt driving system controls the belt velocity as compensating the belt velocity-fluctuation. Experimental result showed the significant fluctuation reduction on a typical tandem-engine printer.