Kynurenic Acid and Its Analog SZR104 Exhibit Strong Antiinflammatory Effects and Alter the Intracellular Distribution and Methylation Patterns of H3 Histones in Immunochallenged Microglia-Enriched Cultures of Newborn Rat Brains

Kynurenic acid (KYNA) is implicated in antiinflammatory processes in the brain through several cellular and molecular targets, among which microglia-related mechanisms are of paramount importance. In this study, we describe the effects of KYNA and one of its analogs, the brain-penetrable SZR104 (N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-hydroxyquinoline-2-carboxamide), on the intracellular distribution and methylation patterns of histone H3 in immunochallenged microglia cultures. Microglia-enriched secondary cultures made from newborn rat forebrains were immunochallenged with lipopolysaccharide (LPS). The protein levels of selected inflammatory markers C–X–C motif chemokine ligand 10 (CXCL10) and C–C motif chemokine receptor 1 (CCR1), histone H3, and posttranslational modifications of histone H3 lys methylation sites (H3K9me3 and H3K36me2, marks typically associated with opposite effects on gene expression) were analyzed using quantitative fluorescent immunocytochemistry and western blots in control or LPS-treated cultures with or without KYNA or SZR104. KYNA and SZR104 reduced levels of the inflammatory marker proteins CXCL10 and CCR1 after LPS-treatment. Moreover, KYNA and SZR104 favorably affected histone methylation patterns as H3K9me3 and H3K36me2 immunoreactivities, and histone H3 protein levels returned toward control values after LPS treatment. The cytoplasmic translocation of H3K9me3 from the nucleus indicated inflammatory distress, a process that could be inhibited by KYNA and SZR104. Thus, KYNA signaling and metabolism, and especially brain-penetrable KYNA analogs such as SZR104, could be key targets in the pathway that connects chromatin structure and epigenetic mechanisms with functional consequences that affect neuroinflammation and perhaps neurodegeneration.     

Fatty Acids,CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.     

Synthesis of Invar 36 type alloys from elemental and prealloyed powders by mechanical alloying

Invar 36 (Fe₆₄Ni₃₆) nanocrystalline powders were successfully obtained by the mechanical alloying process. The mechanically alloyed Invar 36 powders were obtained from both, Fe–Ni elemental and Fe–Ni₃Fe prealloyed powders. XRD, DSC and magnetic measurements were used to characterise the Invar 36 powders. The lattice parameter evolution versus temperature of Invar 36 powders was investigated by in-situ high-temperature X-ray diffraction (HT-XRD). For both, Invar 36 (Fe, Ni) and Invar 36 (Fe, Ni₃Fe) powders, the lattice parameter values are constant up to about 350°C. The magnetic measurement also indicated that the Invar 36-type alloys are formed after 16?h of milling.     

船舶及海洋工程用耐蚀E36钢板的性能分析

采用耐蚀微合金化、冶金质量控制、夹杂物改性及组织控制的耐蚀性改进技术思路,对E36钢进行了耐蚀性改进研究,并结合控轧控冷工艺对耐蚀E36钢板进行试制。结果表明,微合金化有助于提高钢的自腐蚀电位,高洁净度控制和夹杂物改性可降低点蚀敏感性,组织控制可减小复相组织选择性腐蚀倾向;试制钢板耐海水腐蚀性能较传统E36钢板有了大幅提升,其在酸性氯离子环境中的腐蚀速率降至0.59mm/a,耐蚀性较传统E36钢提高约4.6倍。     

利用组成型表达载体pMG36e电转化德式乳杆菌保加利亚亚种的研究

以典型的乳酸菌组成型表达质粒pMG36e为载体,德式乳杆菌保加利亚亚种为受体.采用电转化方法研究受体菌株的生长状态与细胞壁处理方式、质粒浓度、电转化参数、复苏培养基组成与复苏培养时间、受体菌株的限制修饰作用对电转化效率的影响,探讨电转化的最适条件,以提高电转化效率.结果表明:选择含2.5%甘氨酸的SMRS培养基培养受体细胞至对数中期,收获制成感受态细胞,在电场强度12 kV/cm、电阻200Ω、电容25μF条件下电击转化,以含20 mmol/L MgCl2、CaCl2的SMRS培养基复苏培养2 h,涂板筛选得到较高的电转化效率.特别是采用受体菌株修饰的质粒进行电转化,转化效率提高30倍以上,达到6.3×104cfu/μg DNA.本研究结果为进一步构建乳酸菌组成型高效表达系统和食品级基因工程乳酸菌株提供试验依据.     

In vivo effect of oat cereal β‐glucan on metabolic indexes and satiety‐related hormones in diet‐induced obesity C57‐Bl mice

This study explored the dose‐dependent effect of oat cereal β‐glucan on improving metabolic indexes of obesity mice. C57‐Bl mice were randomized to chow diet (N) group and high fat diet group and other three doses of oat β‐glucan groups (low β‐glucan, medium β‐glucan, and high β‐glucan). Energy intake, glucose, lipids, and appetite related hormones were tested. Dose‐dependent relation was observed on oat β‐glucan doses and body weight change, average energy intake, total cholesterol, HDL cholesterol, plasma neural peptide Y, arcuate neural peptide Y mRNA, and arcuate neural peptide Y receptor 2 mRNA level. Oat β‐glucan helped to increase plasma peptide Y‐Y and intestine peptide Y‐Y expression in obesity mice.     

Studies on kinetics and preparation of C36 dimer acid esters

C₃₆ Dimer acids were esterified with various short-chain alcohols, namely 2-propanol, n-butanol, n-hexanol, n-octanol, 2-octanol and 2-ethyl-1-hexanol by using sulfuric acid as catalyst and benzene as an azeotropic solvent. Various reaction parameters were standardized. In case of isopropyl esters, acid-to-alcohol mole ratio of 1:5 and sulfuric acid concentration of 2% based on the weight of dimer acids were found to be optimum. In case of straight-chain primary alcohols, namely n-butanol, n-hexanol and n-octanol, 1:2.5 mole ratio of acid to alcohol and 1% by weight of sulfuric acid were found satisfactory. Esterification reaction rates were determined from the fall in acid value of the product. The reaction followed pseudo first order kinetics. The reaction rates increased with the increase in chainlength of straight-chain primary alcohols from n-butanol to n-octanol. The rate of reaction decreased from n-octanol to 2-ethyl-1-hexanol to 2-octanol due to the branching of the chain in 2-ethyl-1-hexanol and secondary nature of the −OH group in 2-octanol.     

Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3–36)

Vitamin B₁₂–peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B₁₂ (B₁₂). There remains a lack of structural studies investigating the effects of B₁₂ conjugation on peptide secondary structure. Determining the solution structure of a B₁₂–peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B₁₂ conjugates of the anorectic peptide PYY(3–36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3–36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B₁₂ conjugates and validates the fact that B₁₂ can be conjugated to a peptide without markedly affecting peptide secondary structure.     

全钢载重子午线轮胎0°带束层胶配方及混炼工艺优化

试验研究全钢载重子午线轮胎0°带束层胶配方及混炼工艺的优化效果。结果表明,在全钢载重子午线轮胎0°带束层胶配方中并用炭黑N660,增粘树脂选用TKM-M-11,并减小炭黑N375、白炭黑和不溶性硫黄用量,同时在混炼工艺中采取分段加氧化锌、多段加炭黑等优化措施,降低了胶料的门尼粘度,提高了炭黑分散性、胶料自粘性及硫化胶物理性能,改善了0°带束层的表面粘性,提高了成品轮胎的强度和耐久性能,有效地解决了0°带束层散线的质量问题。     

玻璃布增强环氧复合材料拉伸疲劳失效判据

以试样断裂为失效判据,测试得到了±45°玻璃布增强环氧复合材料（EW 250F/3238A）的拉伸疲劳S-N曲线。发现了该类复合材料具有明显的拉伸疲劳大变形、刚度衰减特征。对于该类复合材料,单纯以试样断裂作为失效判据确定其疲劳寿命是不合理的,必须考虑材料的刚度变化,根据工程经验制定刚度失效判据,合理地确定其疲劳寿命。提出以位移峰/谷值增长率或动刚度保持率来表征该类复合材料的刚度失效判据,并验证了其可操作性。