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.     

Covalent triazine framework with efficient photocatalytic activity in aqueous and solid media

Covalent triazine frameworks (CTFs) have been recently employed for visible light-driven photocatalysis due to their unique optical and electronic properties. However, the usually highly hydrophobic nature of CTFs, which originates from their overall aromatic backbone, leads to limitations of CTFs for applications in aqueous media. In this study, we aim to extend the range of the application media of CTFs and design hybrid material of a CTF and mesoporous silica (SBA-15) for efficient photocatalysis in aqueous medium. A thiophene-containing CTF was directly synthesized in mesopores of SBA-15. Due to the high surface area and the added hydrophilic properties by silica, the hybrid material demonstrated excellent adsorption of organic molecules in water. This leads not only to high photocatalytic performance of the hybrid material for the degradation of organic dyes in water, but also for efficient photocatalysis in solvent-free and solid state. Furthermore, the reusability, stability and easy recovery of the hybrid material offers promising metal-free heterogeneous photocatalyst for broader applications in different reaction media.     

强化研磨加工中喷射角度对GCr15轴承钢板塑性变形的影响

利用ABAQUS有限元仿真软件研究不同喷射角度强化研磨加工GCr15轴承钢板过程的塑性变形,得到不同喷射角度与等效塑性应变沿真实路径距离的关系,并通过拉伸试验进行验证。喷射角度为90°的强化研磨加工伸长率为1.4%,相比未经过强化研磨加工的伸长率数值缩减了2.0%。断口收缩率由空白组的4.9%降低到喷射角为90°的2.2%。结合仿真和试验可知,强化研磨加工中喷射角度越大,塑性变形能力越低,材料加工越难。     

KMI15系列集成转速传感器的原理与应用

集成转速传感器具有灵敏度高、测量范围宽、抗干扰能力强、外围电路简单等优点 ,是传统的分立式转速传感器的升级换代产品。文中介绍了KMI15系列磁阻式集成转速传感器的工作原理与典型应用     

Non-deterministic exponential time has two-prover interactive protocols

We determine the exact power of two-prover interactive proof systems introduced by Ben-Or, Goldwasser, Kilian, and Wigderson (1988). In this system, two all-powerful noncommunicating provers convince a randomizing polynomial time verifier in polynomial time that the inputx belongs to the languageL. We show that the class of languages having tow-prover interactive proof systems is nondeterministic exponential time.We also show that to prove membership in languages inEXP, the honest provers need the power ofEXP only.The first part of the proof of the main result extends recent techniques of polynomial extrapolation used in the single prover case by Lund, Fortnow, Karloff, Nisan, and Shamir.The second part is averification scheme for multilinearity of a function in several variables held by an oracle and can be viewed as an independent result onprogram verification. Its proof rests on combinatorial techniques employing a simple isoperimetric inequality for certain graphs:     

Amtshaftung bei Bauführung im Hochwassergebiet; fehlerhafter Flächenwidmungsplan; Nachforschungspflichten der Gemeinde

Bestehen ausreichende Anhaltspunkte für die Hochwassergef?hrdung, ist die Gemeinde verpflichtet, sich durch Nachforschungen Gewissheit über das Vorliegen oder Nichtvorliegen eines Hochwasserabflussgebietes gem § 38 Abs 3 WRG zu verschaffen. Liegt ein solches vor, hat sie gem § 12 Abs 1 Z 2 krnt GplG dieses im Fl?chenwidmungsplan ersichtlich zu machen. Erteilt die Gemeinde eine Baubewilligung ohne diese von der Erteilung einer wasserrechtlichen Bewilligung abh?ngig zu machen, haftet sie für die Kosten der Bauführung, die bei gesetzes-konformer Vorgangsweise unterlassen worden w?re.     

热处理对Ti-25V-15Cr-2Al-2Mo-0.2C合金组织稳定性的影响

研究了热处理对Ti-25V-15Cr-2A1-2Mo-0.2C阻燃β钛合金组织稳定性的影响。结果表明，高温固溶并直接时效处理导致合金β基体上析出较多的α相沉淀，尤其在随后的热暴露组织中形成了恶化合金塑性的连续晶界α膜。然而，若在时效前再进行一次低温固溶处理则可明显减少α相的析出数量，合金的热稳定性因此而得到显著改善。     

Photocatalytic degradation of methyl orange using heteropolytungstic acid-encapsulated TiSBA-15

Heteropolyphosphotungstic acid (H₃PW₁₂O₄₀) (HPA)-encapsulated titanium-supported SBA15 nanoporous materials (HPA-TiSBA-15) were synthesized as a new photocatalyst, and they were characterized by FT-IR and ³¹P NMR MAS spectroscopic methods. Their photocatalytic effects on degradation of methyl orange in water were investigated under natural conditions, and it was found that a 4-fold increase in the photodegradation rate is observed in the presence of HPA-TiSBA-15 as compared to the rate observed in the presence of titanium-supported SBA15 nanoporous materials (TiSBA-15) without HPA.