具有保护肠上皮细胞HT-29免受大肠杆菌和H2O2损伤潜力的植物乳杆菌的筛选

益生菌可在肠道定植从而发挥抗炎或抗氧化活性，有利于宿主肠道健康。本实验研究了从新疆传统发酵乳制品中分离得到的8?株植物乳杆菌对大肠杆菌侵袭和过氧化氢刺激肠上皮细胞HT-29的保护作用。结果表明：在8?株植物乳杆菌中，植物乳杆菌35具有最高的黏附能力。植物乳杆菌35可通过取代、竞争、排阻的方式抑制大肠杆菌对HT-29细胞的黏附，抑制率分别为42.60%、59.17%、60.19%。植物乳杆菌35及其多糖可抑制大肠杆菌刺激HT-29细胞产生白细胞介素-8；同时保护HT-29细胞免受过氧化氢的损伤，增加超氧化物歧化酶、谷胱甘肽过氧化物酶活力水平并降低丙二醛含量。结论：植物乳杆菌35及其粗胞外多糖具有抑制大肠杆菌O157诱导的炎症性肠病的潜力。     

四氢姜黄素经PI3K/Akt信号通路对人血小板活化和聚集的调控作用

目的：探讨姜黄素的主要肠道代谢物四氢姜黄素（tetrahydrocurcumin，THC）对血小板活化和聚集的影响及其可能的分子机制。方法：在体外实验中，用不同浓度的THC（0、0.5、1、10 μmol/L）提前与健康人纯化血小板共同孵育40 min，然后加入凝血酶激活血小板2 min，用流式细胞术测定血小板表面CD62P和CD63的表达量，用酶联免疫吸附法测定血小板释放血小板因子-4（platelet factor-4，PF4）和趋化因子配体-5（chemokine ligand 5，CCL5）水平，用血小板聚集仪检测血小板释放ATP水平和血小板最大聚集率，用Western blot蛋白免疫印迹法检测血小板磷酸肌醇-3-激酶（phosphoinositide 3-kinase，PI3K）和Akt蛋白的磷酸化水平。结果：与模型组（血小板悬液中加入0.05%二甲基亚砜）相比，THC能抑制凝血酶诱导的血小板表面CD62P和CD63的表达，抑制PF4、CCL5和ATP的释放，降低血小板最大聚集率，下调PI3K和Akt蛋白的磷酸化水平，且呈浓度依赖效应，其中10 μmol/L的浓度下作用效果显著（P＜0.01、P＜0.001）。PI3K的特异性激动剂740 Y-P可部分逆转THC对PF4和CCL5释放和血小板聚集的抑制作用（P＜0.05、P＜0.01）。结论：THC具有显著抑制血小板活化和聚集的作用，其机制可能是THC可下调PI3K/Akt介导的信号通路。     

Thermal properties of hierarchical YSZ and LZO ceramic microspheres with multi-scaled voids investigated by using theoretical,experimental and simulation methods

Heat transfer within ceramic feedstock powders is still unclear, which impedes optimization of the thermal and mechanical properties of the thermal sprayed coatings. The microspheres (yttria-stabilized zirconia YSZ and lanthanum zirconate LZO) were prepared via the electro-spraying assisted phase inversion method (ESP). The thermal properties of the two ESP microspheres and a commercial hollow spherical powder (HOSP) were investigated by using theoretical, experimental, and simulation methods. Thermal conductivity of the single microsphere was estimated via a novel nest model that was derived from the Maxwell-Eucken 1 and the EMT model. Thermal conductivity of a single YSZ/LZO-ESP microsphere prepared at 1100–1200 °C was within 0.36–0.75 W/m K, which was ～ 20 % lower than that of a single YSZ-HOSP microsphere with a similar porosity. Heat flux simulation showed that high tortuosity around the multi-scaled voids of the ESP microsphere led to a more efficient decrease in thermal conductivity compared with total porosity.     

No-Reference Video Quality Assessment using novel hybrid features and two-stage hybrid regression for score level fusion

This paper presents a novel No-Reference Video Quality Assessment (NR-VQA) model that utilizes proposed 3D steerable wavelet transform-based Natural Video Statistics (NVS) features as well as human perceptual features. Additionally, we proposed a novel two-stage regression scheme that significantly improves the overall performance of quality estimation. In the first stage, transform-based NVS and human perceptual features are separately passed through the proposed hybrid regression scheme: Support Vector Regression (SVR) followed by Polynomial curve fitting. The two visual quality scores predicted from the first stage are then used as features for the similar second stage. This predicts the final quality scores of distorted videos by achieving score level fusion. Extensive experiments were conducted using five authentic and four synthetic distortion databases. Experimental results demonstrate that the proposed method outperforms other published state-of-the-art benchmark methods on synthetic distortion databases and is among the top performers on authentic distortion databases. The source code is available at https://github.com/anishVNIT/two-stage-vqa.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Radiation- and Photo-Induced Oxidation Pathways of Methionine in Model Peptide Backbone under Anoxic Conditions

Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO^•) play an important role, being the most aggressive towards biomolecules. The reactions of HO^• with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO^• generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HO^•, and by CB triplets allowed for assigning transient species to the pathways of products formation.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.