Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Effect of malondialdehyde oxidation on structure and physicochemical properties of amandin

Oil, accounting for 45% of almonds, is easily oxidised and can further induce the protein oxidation to reduce their quality. Structure and physicochemical properties of amandin, the main water-soluble protein in almonds, inducing oxidation by malondialdehyde (MDA) were investigated. The results showed that the content of carbonyl group increased from 5.23 to 33.25 nmol mg⁻¹ of protein with the increase in MDA concentration (P < 0.05). However, the sulphydryl content, surface hydrophobicity, particle size and the absolute value of ζ-potential first increased and then decreased. Fourier-transformed infrared spectroscopy (FT-IR) confirmed that the structure of amandin changed from order to disorder. Fluorescence spectroscopic analysis revealed that mild oxidation (0–0.1 mmol L⁻¹ MDA) exposed hydrophobic groups of the protein. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) suggested that protein oxidation promoted crosslinking between protein molecules. Furthermore, protein oxidation markedly declined the total amino acid content of amandin (P < 0.05). In conclusion, MDA oxidation changed the structure and amino acid content of amandin, and caused the protein aggregate and crosslink through hydrophobic interaction and electrostatic interaction.     

Synthesis and photoluminescent properties of high-efficient color-tunable Ba3Y2B6O15: Ce3+, Tb3+ phosphors

High-efficient Ce³⁺/Tb³⁺ co-doped Ba₃Y₂B₆O₁₅ phosphors with multi color-emitting were firstly prepared, and their structural and luminescent properties were studied by XRD Rietveld refinement, emission/excitation spectra, fluorescence lifetimes as well as temperature-variable emission spectra. Upon 365?nm excitation, the characteristic blue Ce³⁺ band along with green Tb³⁺ peaks were simultaneously found in the emission spectra. Moreover, by increasing concentration of Tb³⁺, a blue-to-green tunable emitting color could be realized by effective Ce³⁺→Tb³⁺ energy transfer. Furthermore, all Ba₃Y₂B₆O₁₅: Ce³⁺, Tb³⁺ phosphors exhibit high internal quantum efficiency of ~?90%, while the temperature-variable emission spectra reveal that the phosphors possess impressive color stability as well as good thermal stability (T₅₀ =?~?120?°C). The results indicate that these efficient color-tuning Ba₃Y₂B₆O₁₅: Ce³⁺, Tb³⁺ might be candidate as converted phosphor for UV-excited light-emitting diodes.     

Structural,optical and temperature dependent photoluminescence properties of Cr3+-activated LaGaO3 persistent phosphor for optical thermometry

Cr³⁺ doped LaGaO₃ phosphor was prepared by hydrothermal reaction method with post-annealing treatment. XRD pattern showed the pure orthorhombic phase of LaGaO₃ at an annealing temperature of 1000 °C. TEM image showed the particles in the range 40-120 nm. The bandgap energy and Urbach tail increased in the doped sample as compared to the undoped sample as estimated from UV–visible diffuse reflectance spectra. PL excitation spectra showed peaks in UV, blue and orange regions. The emission spectra showed broadband with peaks in the NIR region due to emission from ⁴T₂ and ²E states. The intermediate strength of the crystal field has been calculated from the estimated spectroscopic parameter. The average lifetime was found to be in the ms range. Afterglow decay was also recorded. From the low-temperature PL, the zero phonon line, stokes shift energy, vibrational energy and Huang-Rhys parameter were calculated. With rising the temperature, PL emission peak intensity and lifetime values decreased and FWHM increased because of increased numbers of electrons in ⁴T₂ state and increasing non-radiative transition. Temperature-dependent peak intensity ratios and lifetime values were utilized for temperature sensing applications in below room temperature and above room temperature. The results indicate the possibility of present phosphor to be used as optical nanothermometer.     

Using provenance to efficiently improve metadata searching performance in storage systems

In cloud storage systems, more than 50% of requests are metadata operations, and thus the file system metadata search performance has become increasingly important to different users. With the rapid growth of storage system scales in volume, traditional full-size index trees cannot offer high-performance metadata search due to hierarchical indexing bottleneck. In order to alleviate the long latency and improve the quality-of-service (QoS) in cloud storage service, we proposed a novel provenance based metadata-search system, called PROMES. The metadata search in PROMES is split into three phases: (i) leveraging correlation-aware metadata index tree to identify several files as seeds, most of which can satisfy the query requests, (ii) using the seeds to find the remaining query results via relationship graph search, (iii) continuing to refine and rerank the whole search results, and sending the final results to users. PROMES has the salient features of high query accuracy and low latency, due to files’ tight and lightweight indexing in relationship graph coming from provenance’s analysis. Compared with state-of-the-art metadata searching schemes, PROMES demonstrates its efficiency and efficacy in terms of query accuracy and response latency.     

Promoting Bone Mesenchymal Stem Cells and Inhibiting Bacterial Adhesion of Acid-Etched Nanostructured Titanium by Ultraviolet Functionalization

Titanium(Ti) and its alloys are used extensively in orthopedic implants because of their excellent biocompatibility,mechanical properties and corrosion resistance. However,titanium-based implant materials face many severe complications,such as implant loosening due to poor osseointegration and bacterial infections,which may lead to implant failure. Hence,preparing a biomaterial surface,which enhances the interactions with host cells and inhibits bacterial adhesion,may be an optimal strategy to reduce the incidence of implant failure. This study aims to improve osseointegration and confer antibacterial properties on Ti through a combination of two surface modifications including nanostructuring generated by acid etching and ultraviolet(UV) light treatment.Our results showed that without UV treatment,the acid etching treatment of Ti surface was effective at both improving the adhesion of bone mesenchymal stem cells(BMSCs) and increasing bacterial adhesion. A further UV treatment of the acid-etched surface however,not only significantly improved the cell adhesion but also inhibited bacterial adhesion. The acid-etched nanostructured titanium with UV treatment also showed a significant enhancement on cell proliferation,alkaline phosphatase(ALP) activity and mineralization. These results suggest that such nanostructured materials with UV treatment can be expected to have a good potential in orthopedic applications.     

Key Role of Microtubule and Its Acetylation in a Zinc Oxide Nanoparticle–Mediated Lysosome–Autophagy System

Autophagy is a biological process that has attracted considerable attention as a target for novel therapeutics. Recently, nanomaterials (NMs) have been reported to modulate autophagy, which makes them potential agents for the treatment of autophagy‐related diseases. In this study, zinc oxide nanoparticles (ZNPs) are utilized to evaluate NM‐induced autophagy and debate the mechanisms involved. It is found that ZNPs undergo pH‐dependent ion shedding and that intracellular zinc ions (Zn²⁺) play a crucial role in autophagy. Autophagy is activated with ZNPs treatment, which is inhibited after Zn²⁺ sequestration via ethylenediamine tetra‐acetic acid. Lysosome‐based autophagic degradation is halted after ZNPs treatment for more than 3 h and is accompanied by blockage of lysophagy, which renews impaired lysosomes. Furthermore, the microtubule (MT) system participates in ZNP‐induced lysosome–autophagy system changes, especially in the fusion between autophagosomes and lysosomes. MT acetylation is helpful for protecting from ZNP‐induced MT disruption, and it promotes the autophagic degradation process. In conclusion, this study provides valuable information on NM‐induced lysosome–autophagy system changes, particularly with respect to the role of lysophagy and the MT system, which point to some attractive targets for the design of engineered nanoparticles.     

基于自适应融合的手掌静脉增强方法

针对掌脉轮廓不清晰，图像对比度低、亮度低，进而导致识别性能降低的现象，提出一种自适应融合的手掌静脉增强方法。首先，基于暗原色先验（DCP）去雾算法，根据掌脉图像变异系数自适应选择去雾系数，得到DCP增强图像，并且基于部分子块重叠直方图均衡（POSHE）算法得到POSHE增强图像；然后，将图像分为16个子块，依据图像灰度均值与标准差确定各子块权重；最后，根据各子块权重对DCP和POSHE增强图像进行自适应融合，得到最终增强图像。该方法既保留了DCP算法在增强图像对比度和亮度的同时不引入明显噪声的优点，又保留了POSHE算法在增强图像对比度和亮度的同时不损失局部细节的特点；同时，两者的自适应融合既解决了DCP图像阴影部分掌脉缺失现象，又削弱了POSHE产生的块效应。在对两个公开库和自建库分别进行的实验中，三个数据库的等错误率分别为0.0004、0.0472、0.0579，识别率分别为99.98%、94.27%、92.05%。实验结果表明，与现有的图像增强方法相比，该方法降低了等错误率，提高了识别精度。