Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO–NP and PbO–NP. These results correlate with a shift in the expression of myosin heavy chain (MHC) isoforms towards slowly cycling β–MHC. The type of CdO–NP + PbO–NP combined cardiotoxicity depends on the effect of the toxic impact, the extent of this effect, the ratio of toxicant doses, and the degree of stretching of cardiomyocytes and muscle type studied. Some indices of combined Pb–NP and CdO–NP cardiotoxicity and general toxicity (genotoxicity included) became fully or partly normalized if intoxication developed against background administration of a bioprotective complex.     

The miR-106b/NR2F2-AS1/PLEKHO2 Axis Regulates Migration and Invasion of Colorectal Cancer through the MAPK Pathway

Increasing numbers of miRNAs have been observed as oncogenes or tumor suppressors in colorectal cancer (CRC). It was recently reported that hsa-miR-106b-5p (miR-106b) promoted CRC cell migration and invasion. However, there were also studies showing contradictory results. Therefore, in the present study, we further explore the role of miR-106b and its downstream networks in the carcinogenesis of CRC. We observed that the expression of miR-106b is significantly increased in Pan-Cancer and CRC tissues compared with normal tissues from The Cancer Genome Atlas (TCGA) database. Furthermore, we used Transwell, Cell Counting Kit-8, and colony formation assays to clarify that miR-106b promotes the migratory, invasive, and proliferative abilities of CRC cells. For the first time, we systematically screened the target mRNAs and lncRNAs of miR-106b using TCGA database and the bioinformatics algorithms. Dual-luciferase reporter assay confirmed that NR2F2-AS1 and PLEKHO2 are the direct targets of miR-106b. Furthermore, NR2F2-AS1 acts as a competing endogenous RNA (ceRNA) to regulate PLEKHO2 expression by sponging miR-106b. The results of Gene set enrichment analysis (GSEA) and Western blot indicated that they play important roles in CRC progression by regulating MAPK pathway. Thus, miR-106b/NR2F2-AS1/PLEKHO2/MAPK signaling axis may suggest the potential usage in CRC treatment.     

Embryonic Trophectoderm Secretomics Reveals Chemotactic Migration and Intercellular Communication of Endometrial and Circulating MSCs in Embryonic Implantation

Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial–mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-τ); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period.     

球团链箅机回转窑工艺中氯和硫元素迁移规律

摘要：对链箅机回转窑工艺中各段球团样品进行实验分析,研究了氯元素和硫元素在链箅机回转窑工艺中的迁移规律,明晰了烟气中HCl的生成机制。结果表明,球团原料中的氯元素主要是以NaCl的形式存在,氯元素有一部分在链箅机抽风干燥段会转变成HCl气体并进入烟气,一部分在链箅机预热Ⅱ段之后以NaCl的形式汽化进入烟气,剩余的氯元素仍以NaCl的形式存在于成品球团矿中。烟气中的HCl气体是在抽风干燥段,由富含SO2的烟气与含水球团料层中的NaCl发生反应生成的,烟气中SO2转变成Na2SO4重新固定于料层中。在预热Ⅰ段和预热Ⅱ段,烟气中的SO2与原料中碳酸钙分解生成的游离CaO反应生成CaSO4,也会重新固定烟气中的SO2。     

鱼类下行过坝的导鱼栅系统设计及试验研究

以龙开口水利枢纽为例,提出一种辅助鱼类下行过坝的导鱼栅系统方案。该方案首先结合大坝泄流建筑物的特点确定导鱼栅系统的布置位置,然后以鳙鱼为试验对象,用控制变量法并选择四种导鱼栅叶片角（15°、30°、45°、90°）和三种导鱼栅布置角（15°、30°、45°）在室内开展模型试验,以确定最优运行工况。研究结果表明,导鱼栅系统布置在该枢纽的灌溉引水口最佳。试验中,当布置角控制为30°时,四种叶片角下的鱼类通过率分别为53%、95%、59%和72%;当叶片角控制为30°时,三种布置角下的鱼类通过率分别为53%、95%和41%。因此,在导鱼栅叶片角和布置角同为30°时,导鱼栅系统辅助鱼类下行的效率最高,通过率为95%。研究成果可为我国类似导鱼栅系统设计提供参考。     

PKA国家参考品的制备

本文应用 PKA 微量滴定板方法,用 WHO1984年建立的 PKA 国际标准品进行标定,制备了我国第一批 PKA 国家参考品。     

Comparison of the Effect of a Hydrocarbon Oil and a Terpene Tackifier on the Autohesion of Styrene-Butadiene Rubber

Blends of uncrosslinked styrene-butadiene rubber (SBR) with a terpene tackifier resin or a naphthenic oil have been characterized, and their autohesion and cohesion determined using a T-peel geometry. SBR/oil blends are homogeneous at all proportions, while SBR/resin blends, based on DSC and DMA analysis, undergo bulk phase separation at about 50% resin. However, migration of tackifier to the surface region is proposed at much lower resin contents. Compositions diluted with oil have autohesion similar to the neat SBR. This is attributed to compensating effects; although oil hastens self-bond formation by increasing chain mobility, this is nearly equally balanced by more facile chain separation during bond rupture. In short, oil-diluted compositions are soft and weak. On the other hand, SBR compositions containing small amounts of resin have high autohesion. Resin-diluted specimens deform easily at low strain, just as those containing oil, but intertwined chains of the former have greater resistance to separation, due at least in part to higher glass transition temperatures. It is proposed that autohesion is further enhanced by migration of tackifier to the surface. This causes SBR/resin compositions to be both soft and strong-a necessary condition for high autohesion.     

Performance of a Vertical‐Slot Fish Pass for the Sea Lamprey Petromyzon marinus L. and Habitat Recolonization

In 2011, a vertical‐slot fish pass was built at the Coimbra Açude‐Ponte dam (Mondego River, Portugal), approximately 45 km upstream from the river mouth. The performance of this infrastructure for sea lamprey passage was evaluated between 2011 and 2015 using several complementary methodologies, namely radio telemetry [conventional and electromyogram (EMG)], passive integrated transponder (PIT) telemetry and electrofishing surveys. During the study period, the electrofishing revealed a 29‐fold increase in the abundance of larval sea lamprey upstream of the fish pass. Of the 20 radio‐tagged individuals released downstream from the dam, 33% managed to find and successfully surpass the obstacle in less than 2 weeks, reaching the spawning areas located in the upstream stretch of the main river and in one important tributary. Fish pass efficiency was assessed with a PIT antenna installed in the last upstream pool and revealed a 31% efficiency, with differences between and within migratory seasons. Time of day and river flow significantly influenced the attraction efficiency of the fish pass, with lampreys negotiating it mainly during the night period and when discharge was below 50 m³ s^?1. Sea lampreys tagged with EMG transmitters took 3 h to negotiate the fish pass, during which high muscular effort was only registered during passage, or passage attempts, of the vertical slots. The use of complementary methodologies provided a comprehensive passage evaluation for sea lamprey, a species for which there is a considerable paucity of valuable data concerning behavioural, physiological and environmental influences on obstacle negotiation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.     

Fat-simulating and accelerating solvents for polyolefins and MWD of solvent extracts of polyethylenes

Migration kinetics of straight-chain oligomers and antioxidants from several polyolefins at different temperatures into various solvents have been studied by radioactive tracer techniques. Anhydrous ethanol appears to be a well suited food-oil or liquid-fat simulant for extracting different types of migrants from polyolefins. Pure and mixed triglycerides are also good oil or fat simulants, but the triglycerides offer no simpler analytical procedures than the use of oil or fat themselves. n-Octanol may also be considered as a reasonable oil or fat simulant; however, its action depends somewhat on the choice of migrants. The accelerating action of n-heptane over that of oil or simulants is quantitatively demonstrated. The accelerating effects are greater for migration systems with lower diffusion coefficients. The diffusion coefficients for migration into n-heptane are about 20 times greater than the diffusion coefficients into ethanol or oil for otherwise identical migration systems yielding diffusion coefficients of about 10^?7 cm²s^?1 into oil or ethanol. For systems yielding diffusion coefficients into oil or ethanol of about 10^?12 cm²s^?1, the corresponding diffusion coefficients into n-heptane are about 1000 times greater. The molecular weight distributions (MWDs) of the n-heptane and ethanol extracts of polyolefins have been analysed. n-Heptane can not only accelerate the migration of the individual migrant but also remove oligomer species that are slightly soluble or present at low levels in the oil or simulant extracts.