Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.     

Loliolide,a New Therapeutic Option for Neurological Diseases? In Vitro Neuroprotective and Anti-Inflammatory Activities of a Monoterpenoid Lactone Isolated from Codium tomentosum

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW 264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells’ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells’ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-kB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF-α and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.     

Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson’s Disease Model

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson’s disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP⁺)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP⁺-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.     

AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

马尔可夫跳变线性系统最优控制的研究现状与进展

马尔可夫跳变线性系统（MJLS）是一种具有多个模态的随机系统，系统在各个模态之间的跳变转移由一组马尔可夫链来决定。MJLS模型因其在表示过程中可以产生突变而更能精确的描述实际工程应用中的系统。近年来，MJLS的最优控制问题成为了研究的热点，动态规划、极大值原理以及线性矩阵不等式等成为了解决此类问题的主流方法。本文对MJLS最优控制领域的研究现状进行了综述。分别对一般情况下、带有噪声的情况下、带有时滞的情况下以及某些特定情况下的MLJS最优控制问题的国内外研究现状进行论述。最后进行了总结并提出MJLS最优控制领域未来值得关注的研究方向。     

基于多特征融合的电影推荐系统

协同过滤算法（CF）根据用户-物品的评分矩阵做推荐，未考虑物品自身属性。本文将MovieLens数据集上的电影属性，作为影响推荐结果的因素，融合电影的简介、评论、评分、导演和演员等多种因素，进行推荐。使用CNN（卷积神经网络）和Word2Vec（Word to Vector,词向量模型）处理电影简介；使用AFINN（Finn rup Nielsen情感词典）处理评论，并对结果进行映射；对导演和演员数据进行建模，得到该因素下的预测评分，最后将各因素下的结果进行加权融合，通过调整权重，得到最佳效果。经验证，该方法的推荐性能优于传统的CF算法。     

凝胶型99Mo-99mTc发生器研究现状

与裂变型⁹⁹Mo-^99mTc发生器相比，凝胶型⁹⁹Mo-^99mTc发生器制备^99mTc具有工艺简单、产生的放射性废物容易处理、对环境影响小等优点。本文主要论述了凝胶型⁹⁹Mo-^99mTc发生器与裂变型⁹⁹Mo-99mTc发生器的区别，堆照生产⁹⁹Mo原料和凝胶材料的研究进展，凝胶结构以及凝胶组分等多种条件因素对凝胶型⁹⁹Mo-^99mTc发生器性能的影响等，并对低比活度⁹⁹Mo生产^99mTc的研究进展进行综述。     

Evaluation of adult and offspring thiamine deficiency in salmonine species from Lake Ontario

Thiamine Deficiency Complex (TDC) is an ongoing problem impacting salmonine health in various waterbodies, including Lake Ontario. The prevalence of TDC has been variable and explanations for differences are limited. In the current study, thiamine concentrations were measured in eggs, liver tissue, and muscle tissue sampled from brown trout (Salmo trutta), Chinook salmon (Oncorhynchus tshawytscha), coho salmon (O. kisutch), lake trout (Salvelinus namaycush), and steelhead trout (O. mykiss) that were collected from Lake Ontario and its surrounding tributaries. The occurrence of TDC was measured for each species based on TDC-induced offspring mortality rates under laboratory conditions. TDC-induced offspring mortality was observed for all species except brown trout. For affected species, egg free thiamine (Th) was consistently low compared to lake trout collected from Lake Superior that are considered thiamine replete. In addition, species with the lowest percentages of Th in their eggs were the most susceptible to TDC, suggesting that limited thiamine reserves in the form of Th may cause TDC-induced offspring mortality. Lastly, our results show that egg thiamine concentrations have yearly variation and increased for all species throughout the study. Reasons for such variation are undetermined; but, if egg thiamine concentrations continue to increase, the impacts of TDC on these salmonine species may lessen. Future monitoring is needed for determining if thiamine concentrations are increasing and the potential impacts that may have on the entire Lake Ontario fishery.     

Flower‐shaped ultra‐wideband fractal antenna

A flower‐shaped ultra‐wideband fractal antenna is presented. It comprises a fourth iterative flower‐shaped radiator, asymmetrical stub‐loaded feeding line, and coplanar quarter elliptical ground planes. A wide operating band of 12.12 GHz (4.58‐16.7 GHz) for S ₁₁ ≤ ? 10 dB is achieved along with an overall antenna footprint of 15.7 × 11.4 mm². In addition, other desirable characteristics, that is, omnidirectional radiation patterns, peak gain upto 5 dB, and fidelity factor more than 75% are achieved. A good agreement exists between the simulation and measured results. The obtained results illustrate that this antenna has wide operating range and compact dimensions than available structures.     

基于改进耦合增强随机共振的滚动轴承故障诊断

针对强背景噪声下经典随机共振方法对滚动轴承故障特征提取效果差的问题,提出了一种基于改进耦合增强随机共振的滚动轴承故障诊断方法。首先,利用一个定参双稳系统和一个变参双稳系统构成耦合随机共振系统,外部输入直接作用于定参双稳系统;然后,通过调节变参双稳系统参数和耦合系数实现耦合系统的随机共振控制,并借助遗传算法实现控制参数的自适应选取。实验和工程应用验证了所提方法的有效性和优越性。