The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.     

超宽带多注速调管的模拟研究

本文介绍了多注速调管的发展历史和现状,以及速调管模拟软件的发展情况。用1．5维软件KIystron-MSU和2．5维软件Arsenal-MSU对超宽带多注速调管进行了设计计算,并对计算结果进行分析,得到了比较好的输出特性。计算结果表明可以实现该超宽带多注速调管,其带宽10-14％,增益40～50dB,效率40～50％。     

Analysis of Residual Stresses and Dislocation Density of AA6082 Butt Welds Produced by Friction Sir Welding

Metallurgical and Materials Transactions A - The Friction Stir Welding (FSW) method was employed to join AA6082 sheets. The welds were produced with different tool traverse speed (200 and...     

Acridine/Acridone–Carborane Conjugates as Strong DNA-Binding Agents with Anticancer Potential

Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine ( 30 ) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propanamido]acridine ( 29 ) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα.     

Magical Transubstantiations: A Voyage to Italy

Visiting Italy in 1978 as part of his own Grand Tour, Lebbeus Woods was able to see some of the treasures of the Renaissance and the Baroque. The ensuing mix of reality and imagination prompted the Editors of this 2, Aleksandra Wagner and Neil Spiller , to consider the visual travelogue –Cityscapes – in a similar manner, combining speculation and truth.     

Search for Alternative Two-Step-Absorption Photoinitiators for 3D Laser Nanoprinting

Recent studies have opened the door to a new generation of photoinitiators for 3D laser nanoprinting. Therein, the simultaneous absorption of two photons, commonly referred to as two-photon absorption, is replaced by the sequential absorption of two photons in two consecutive one-photon absorption processes. This process has been termed two-step absorption. Importantly, two-step absorption can be accomplished by inexpensive compact low-power continuous-wave blue laser diodes instead of femtosecond laser systems in the red spectral region. Red-shifting the second absorption step with respect to the first one results in an and-type optical nonlinearity based on two-color two-step absorption. Herein, alternatives are systematically explored to the few already reported one- and two-color two-step-absorption photoinitiators, including the search for photoinitiators that can be excited by one-color two-step absorption and be de-excited by a disparate laser color.     

Repurposing of 8-Hydroxyquinoline-Based Butyrylcholinesterase and Cathepsin B Ligands as Potent Nonpeptidic Deoxyribonuclease I Inhibitors

A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors was screened in vitro for inhibition of deoxyribonuclease I (DNase I). Compounds 22 , 8 and 7 are among the most potent synthetic non-peptide DNase I inhibitors reported to date. Three 8-hydroxyquinoline analogues inhibited both DNase I and BChE with IC₅₀ values below 35 μM and 50 nM, respectively, while two nitroxoline derivatives inhibited DNase I and Cat B endopeptidase activity with IC₅₀ values below 60 and 20 μM. Selected derivatives were screened for various co-target binding affinities at dopamine D₂ and D₃, histamine H₃ and H₄ receptors and inhibition of 5-lipoxygenase. Compound 8 bound to the H₃ receptor and is highlighted as the most promising multifunctional ligand with a favorable pharmacokinetic profile and one of the most potent non-peptide DNase I inhibitors. The present study demonstrates that 8-hydroxyquinoline is a structural fragment critical for DNase I inhibition in the presented series of compounds.