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.     

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.     

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.     

磁盘阵列环境下的取证目标系统重构

封存原始硬盘与业务系统服务的连续性是计算机取证中面临的一对矛盾。在独立硬盘环境中,问题的解决并不困难,但在磁盘阵列(RAID)环境下,目前还缺乏有效的解决办法。为此,为RAID环境下的取证目标系统的重构提出一套解决方案,并设计实现其中关键任务的处理软件。实验表明,该方法可适用于不同RAID等级、不同操作系统下的系统重构,使得用户感受不到重构得到的系统与原系统有任何差异。与数据同步方法相比,该方法可以有效地减少重构的时间开销,且不会破坏原始证据硬盘上的数据。     

应用免疫印迹法分析丙型肝炎相关性抗体

应用两种免疫印迹法对二代ELISA测试的69份血清进行了追加试验。结果表明:8份ELISA阴性血清免疫印迹均阴性,61份ELISA阳性血清有1份免疫印迹阴性。ELISA假阳性率为1.67％。在60份免疫印迹阳性血清中,抗结构区(capsid),非结构区NS_3和NS_4抗体的阳性率分别为83％、93.3％和70％。其中丙型肝炎相关性抗体的分布,以抗capsid、NS_3、NS_4抗体都阳性为主(58.7％)。在输血后急性肝炎和肝细胞癌患者中。丙型肝炎相关性抗体的分布没有统计学上的差异。     

在文明寨地区的高精度地震资料处理实践

文明寨地区构造复杂，断块多，岩性变化大，一些地质问题不明，需要高精度三维资料处理来提高资料的纵、横向分辨率^[1][2]及为储层、油藏研究提供精确的依据。针对东濮文明寨地区高精度处理过程中的关键技术进行了大量分析试验，形成了一套适合东濮地区的较为完整的3D高精度地震资料处理流程。实际资料处理表明效果较好。     

Study of siloxane additives migration to the surface of polyester-(melamine)-polyurethane coatings: Aging effects after ethanol cleaning

This study determines the influences of siloxane flow agents’ migration on the outermost surface composition of clearcoats, before and after ethanol cleaning. This evaluation is undertaken to improve adhesion of pressure-sensitive adhesives (PSAs) on automotive paint systems. Most of the siloxane flow agents segregate from the bulk to the clearcoat outermost surface during curing. These additives can cover until 50% of the surface area but X-ray photoelectron spectroscopy (XPS) and time of flight-secondary ion mass spectrometry (ToF-SIMS) analyses indicate that they can be removed by ethanol cleaning. Composition of the cleaned clearcoats surfaces are similar as the composition of clearcoat formulated without siloxane additives: the polyester-(melamine)-polyurethane network is more detected than before cleaning. However, outermost surface analyses show that several aging weeks increase the siloxane additives segregation. This post-cleaning migration modifies the clearcoat surface composition and cancels the chemical modifications due to the ethanol cleaning. XPS analyses show that silicon concentrations after cleaning and aging are inversely proportional to the initial silicon concentrations measured after curing. It highlights that aging has to be controlled to improve adhesion of PSAs on clearcoats. A second ethanol cleaning on aged clearcoats is not effective to remove these new siloxane additives. Their formulation should be different from the flow agents and it could modify their solubility in ethanol. This result could also indicate that these new siloxane additives are not located on the last molecular layer of surface and they would not be soluble in ethanol.     

Charge reduction and regeneration in K+, Na+, Mg2+, Ni2+ and Co2+-exchanged Wyoming Bentonite

Controlled calcination of ion-exchanged Wyoming Bentonite in the presence and absence of ammonia leads to layer charge reductions. Detailed chemical analyses of both unexchangeable and exchangeable species lead to the conclusion that in no case is there migration of the original interlamellar cations into the octahedral region of the layers although, in terms of ionic radius alone, Mg²⁺, Ni²⁺ and, possibly Co²⁺, might be expected to do so. The production of unexchangeable Mg, Ni or Co, is identified as resulting from high temperature hydrolysis leading to hydroxide or oxide formation.     

内部连接的球形多孔羟基磷灰石支架的制备

采用高分子模板,通过注浆成型制备了球形孔结构的羟基磷灰石(hroxyapatite,HA)支架,研究了支架的微观结构、压缩强度和相容性.结果表明:改变工艺参数可以控制高分子模板中球体间胶黏面的大小,控制所制备的HA多孔体孔内连接的尺寸.制备的支架具有开口、均匀而内部连通的多孔结构,当孔径为200μm、孔隙率为65%时,压缩强度可达8MPa左右.体外生物模拟实验表明:多孔结构HA支架有很好的相容性.随多孔球体孔隙率和尺寸的增加,支架的细胞吸收率逐步增加.