Microenvironment-Sensitive Fluorescent Ligand Binds Ascaris Telomere Antiparallel G-Quadruplex DNA with Blue-Shift and Enhanced Emission

The development of small molecules that can selectively target G-quadruplex (G4) DNAs has drawn considerable attention due to their unique physiological and pathological functions. However, only a few molecules have been found to selectively bind a particular G4 DNA structure. We have developed a fluorescence ligand Q1 , a molecular scaffold with a carbazole–pyridine core bridged by a phenylboronic acid side chain, that acts as a selective ascaris telomere antiparallel G4 DNA ASC20 ligand with about 18 nm blue-shifted and enhanced fluorescence intensity. Photophysical properties revealed that Q1 was sensitive to the microenvironment and gave the best selectivity to ASC20 with an equilibrium binding constant K_a=6.04×10⁵ M⁻¹. Time-resolved fluorescence studies also demonstrated that Q1 showed a longer fluorescence lifetime in the presence of ASC20. The binding characteristics of Q1 with ASC20 were shown in detail in a fluorescent intercalator displacement (FID) assay, a 2-Ap titration experiment and by molecular docking. Ligand Q1 could adopt an appropriate pose at terminal G-quartets of ASC20 through multiple interactions including π–π stacking between aromatic rings; this led to strong fluorescence enhancement. In addition, a co-staining image showed that Q1 is mainly distributed in the cytoplasm. Accordingly, this work provides insights for the development of ligands that selectively targeting a specific G4 DNA structure.     

E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

Microstructural development during crystallization firing of a dental-grade nanostructured lithia-zirconia glass-ceramic

The microstructural development during crystallization firing of a commercially-available dental-grade nanostructured lithia-zirconia glass-ceramic (Vita Suprinity® PC) was unraveled using a wide battery of ex-situ and in-situ characterization techniques. It was found that the milling blocks are slightly crystallized glass-ceramics, with a complex chemical composition and consisting of partially de-polymerized glass plus lithium silicate (Li₂SiO₃) nanocrystals. It was also found that during crystallization firing the glassy matrix first reacts with part of the Li₂SiO₃ to form lithium disilicate (Li₂Si₂O₅) at ～810?820 °C, and then lithium orthophosphate (Li₃PO₄) precipitates from the glass. This results in glass-ceramics with abundant nanocrystals embedded in a sparse zirconosilicate glass matrix (containing many other cations subsumed) that, due to its high viscosity, inhibited crystal growth. Therefore, these dental glass-ceramics are not reinforced with zirconia (ZrO₂) crystals unless over-fired above ～890 °C and at the expense of its singular nanostructure. Finally, this study opens doors for optimizing the clinical performance of these dental glass-ceramics via microstructural tailoring.     

Dismantling of Active Drains in the Technological Enclosures of the MR Reactor

Atomic Energy - The results of the dismantling of the active drain system and the decontamination of technological enclosures of the loop installations of the MR reactor, which is being...     

Dynamic hierarchical collaborative caching scheme in ultra-dense networks

Pushing popular contents to the edge of the network can meet the growing demand for data traffic, reduce latency and relieve the pressure of the backhaul. However, considering the limited storage space of the base stations, it is impossible to cache all the contents, especially in ultra-dense network ( UDN). Furthermore, the uneven distribution of mobile users results in load imbalance among small base stations (SBSs) in both time and space, which also affects the caching strategy. To overcome these shortcoming, the impact of the changing load imbalance in UDN was investigated, and then a dynamic hierarchical collaborative caching (DHCC) scheme was proposed to optimize latency and caching hit rate. The storage of the SBS is logically divided into the independent caching layer and the collaborative caching layer. The independent caching layer caches the most popular contents for local users爷interest, and the collaborative caching layer caches contents as much as possible for the benefit of content diversity in the region. Different SBSs have respective storage space layer division ratios, according to their real-time traffic load. For SBSs with heavy load, the independent caching layers are allocated with more space. Otherwise, the collaborative caching layers could store more contents with larger space. The simulation results show that, DHCC improved both transmission latency and hit rate compared with existing caching schemes.     

聚合物对旋流器内油滴聚结与分离效率的影响

为了研究聚合物对水力旋流器内油滴聚结与分离效率的影响规律,以螺旋导流内锥式旋流器为研究对象,利用群体平衡模型(PBM)方法对不合聚与含聚0.5‰工况下油水两相在旋流器内的速度场、黏度场、油滴聚结、运移特性及分离效率进行数值分析,并通过实验验证.结果 表明:聚合物的加入增大了水相黏度,使油滴在旋流器内最大停留时间与轴向运动距离增加,增加了油滴碰撞聚结的机会,但降低轴心处油滴向上运动的轴向速度,使油滴无法快速从溢流口流出,最终从底流口流出,增加油水分离的难度.与不合聚时相比,含聚0.5‰工况下,轴心处的油滴粒径与含油体积分数较高,但简化分离效率由99.79％降低至94.72％.通过马尔文粒度仪对两种工况下入口与出口的油滴粒径进行测试,含聚0.5‰时溢流与底流口油滴粒径高于不合聚时,验证了模拟的准确性.     

Advanced Understanding of the Electron Transfer Pathway of Cytochrome P450s

Cytochrome P450s are heme-thiolate enzymes that participate in carbon source assimilation, natural compound biosynthesis and xenobiotic metabolism in all kingdoms of life. P450s can catalyze various reactions by using a wide range of organic compounds, thus exhibiting great potential in biotechnological applications. The catalytic reactions of P450s are driven by electron equivalents that are sourced from pyridine nucleotides and delivered by cognate or matching redox partners (RPs). The electron transfer (ET) route from RPs to P450s involves one or more redox center-containing domains. As the rate of ET is one of the main determinants of P450 efficacy, an in-depth understanding of the P450 ET pathway should increase our knowledge of these important enzymes and benefit their further applications. Here, the various P450 RP systems along with current understanding of their ET routes will be reviewed. Notably, state-of-the-art structural studies of the two main types of self-sufficient P450 will also be summarized.     

Lipids and Fatty Acids of the Gonads of Sea Urchin Diadema setosum (Echinodermata) From the Coastal Area of the Nha Trang Bay,Central Vietnam

The sea urchin Diadema setosum is edible and desirable as food by locals in central Vietnam and a promising target for potential fishing. The lipid profiles of the gonads of the sea urchin inhabiting the coastal area in Nha Trang Bay are studied for the first time. The determination of the content of the total lipids (TL), total phospholipids (PL), monoacylglycerols (MAG), diacylglycerols (DAG), triacylglycerols (TAG), cholesterol (Chol), sterol esters, and free fatty acids (FFA) is analyzed by high-performance thin layer chromatography (HPTLC); the phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) are determined by high-pressure liquid chromatography (HPLC); and the fatty acid levels of TLs are identified using gas chromatography (GC). Non-polar TAG, FFA, Chol, and DAG dominated. The content of total PL is significant. PC is abundant among PL fractions, followed by PE, PI, and PS. The TLs contain a high proportion of PUFA, mainly due to arachidonic fatty acid and eicosapentanoic fatty acid. The (n−6)/(n−3) ratio is 1.68, and the atherogenic and thrombogenic indexes of D. setosum are 1.13 and 0.73. The results can be used in the development of marine bioprospecting and methodological approaches for the creation of functional substances.     

Technological Aspects of Synthesizing Ceramic Coatings by Flow-Through Micro-Arc Oxidation

Refractories and Industrial Ceramics - The paper introduces a promising technology for utilizing a traditional scheme for implementing a flow-through micro-arc oxidation method to restore localized...