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. 相似文献
Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B4 (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types. 相似文献
Radiophotoluminescence phenomena have been widely investigated on various types of materials for dosimetry applications. We report that an aluminoborosilicate glass containing 0.005 mol% copper exhibits intense photoluminescence in the visible region induced by X-ray and γ-ray irradiation. The luminescence is assigned to the 3d94s1 → 3d10 transition of Cu+. The proportionality of the intensity of the induced photoluminescence to the irradiation dose was confirmed up to 0.5 kGy using 60Co γ-ray irradiation. Based on the spectroscopic results, a potential mechanism was proposed for the enhancement of the photoluminescence. The exposure to the ionizing radiation generates electron-hole pairs in the glass, and the electrons are subsequently captured by the Cu2+ ions, which are converted to Cu+ and emit the luminescence. For the glass containing 0.01 mol% copper, the pronounced enhancement of the photoluminescence was not observed because the reverse reaction, ie, the capture of the holes by the Cu+ ions, becomes prominent. The photoluminescence induced by the irradiation was stably observed for the glasses kept at room temperature and even for the glasses heat-treated at 150°C. However, the induced photoluminescence could be eliminated by the heat treatment at a temperature at 500°C, and the glass returned to the initial pre-irradiation state. The Cu-doped aluminoborosilicate glass is a potential candidate for use in dosimetry applications. 相似文献
Liquid marble (LM) is a droplet that is wrapped by hydrophobic solid particles, which behave as a non-wetting soft solid. Based on these properties, LM can be applied in fluidics and soft device applications. A wide variety of functional particles have been synthesized to form functional LMs. However, the formation of multifunctional LMs by integrating several types of functional particles is challenging. Here, a general strategy for the flexible patterning of functional particles on droplet surfaces in a patchwork-like design is reported. It is shown that LMs can switch their macroscopic behavior between a stable and active state on super-repellent surfaces in situ by jamming/unjamming the surface particles. Active LMs hydrostatically coalesce to form a self-sorted particle pattern on the droplet surface. With the support of LM handling robotics, on-demand cyclic activation–manipulation–coalescence–stabilization protocols by LMs with different sizes and particle types result in the reliable design of multi-faced LMs. Based on this concept, a single bi-functional LM is designed from two mono-functional LMs as an advanced droplet carrier. 相似文献
Summary
The potato phosphorylase-catalyzed polymerization of α-D-glucose-1-phosphate (G-1-P) onto poly[styrene-block-(4-vinylbenzyl maltohexaoside)] (1) was performed at the molar ratios of [G-l-P]0 and [maltohexaose]0 of 35, 80, and 250. The product was found to be soluble in dimethyl sulfoxide, which was a good solvent for amylose, and
showed the complex-formation with iodine, indicating that the product was assignable to poly[styrene-block-(styrene-graft-amylose)] (2). The quantitative analysis of the liberated phosphoric acid gave the average degree of polymerization o f the glucose unit
(n) as 27, 5 1, and 180 for 2-I, 2-II, and 2-III, respectively.
Received: 29 November 2002/Accepted: 22 December 2002
Correspondence to Toyoji Kakuchi 相似文献
This paper describes the high performance of T-shaped-gate CMOS devices with effective channel lengths in the sub-0.1-μm region. These devices were fabricated by using selective W growth, which allows low-resistance gates smaller than 0.1 μm to be made without requiring fine lithography alignment. We used counter-doping to scale down the threshold voltage while still maintaining acceptable short-channel effects. This approach allowed us to make ring oscillators with a gate-delay time as short as 21 ps at 2 V with a gate length of 0.15 μm. Furthermore, we experimentally show that the high circuit speed of a sub-0.1-μm gate length CMOS device is mainly due to the PMOS device performance, especially in terms of its drivability 相似文献
The catalytic decomposition of acrylonitrile (AN) over Cu-ZSM-5 prepared with various Cu loadings was investigated. AN conversion, during which the nitrogen atoms in AN were mainly converted to N2, increased as Cu loading increased. N2 selectivities as high as 90–95% were attained. X-ray diffraction measurements (XRD) and temperature-programmed reduction by H2 (H2-TPR) showed the existence of bulk CuO in Cu-ZSM-5 with a Cu loading of 6.4 wt% and the existence of highly dispersed CuO in Cu-ZSM-5 with a Cu loading of 3.3 wt%. Electron spin resonance measurements revealed that Cu-ZSM-5 contains three forms of isolated Cu2+ ions (square-planar, square-pyramidal, and distorted square-pyramidal). The H2-TPR results suggested that in Cu-ZSM-5 with a Cu loading of 2.9 wt% and below, Cu+ existed even after oxidizing pretreatment. The activity of AN decomposition over Cu/SiO2 suggested that CuO could form N2, but, independent of the CuO dispersion, nitrogen oxides (NOx) were formed above 350 °C. Cu+ and the square-pyramidal and distorted square-pyramidal forms of Cu2+ showed low activity for AN decomposition. Temperature-programmed desorption of NH3 suggested that N2 formation from NH3 proceeded on Cu2+, resulting in the formation of Cu+. The Cu+ ions were oxidized to Cu2+ at around 300 °C. Thus, high N2 selectivity over Cu-ZSM-5 with a wide range of temperature was probably attained by the reaction over the square-planar Cu2+, which can be reversibly reduced and oxidized. 相似文献
By using structural equations, we investigated the effect of chronic stress on salivary cortisol rhythm and proposed a causal model of chronic stress by using psychosocial and physiological data. First, 111 healthy workers (48 males, 63 females) completed questionnaires on chronic stress and lifestyle habits. Then, they provided saliva samples and answered questionnaires that were prepared to assess their psychological states 5 times (on waking up and at 10:00, 11:40, 14:00, and 16:00) on workdays. Structural equation modeling (SEM) revealed that chronic stress and longer commuting time resulted in sleep irregularities and this disrupted the cortisol circadian rhythm. This suggests that chronic stress disrupts the cortisol circadian rhythm even in healthy individuals, and sleep regularity mediates the effect of chronic stress on the cortisol rhythm.