Sediment storage and shallow groundwater response to beaver dam analogues in the Colorado Front Range,USA

Enthusiasm for using beaver dam analogues (BDAs) to restore incised channels and riparian corridors has been increasing. BDAs are expected to create a similar channel response to natural beaver dams by causing channel bed aggradation and overbank flow, which subsequently raise water tables and support vegetation growth. However, lack of funding for monitoring projects post‐restoration has limited research on whether BDAs actually cause expected channel change in the Front Range and elsewhere. Geomorphic and hydrologic response to BDAs was monitored in two watersheds 1 year post‐restoration. BDAs were studied at Fish Creek, a steep mountainous catchment, and Campbell Creek, a lower gradient piedmont catchment from May to October 2018. At each restoration site, the upstream‐ and downstream‐most BDAs were chosen for intensive study in comparison with unrestored reference reaches. Monitoring focused on quantifying sediment volumes in BDA ponds and recording changes to stream stage and riparian groundwater. Despite differences in physical basin characteristics, BDA pools at both sites stored similar volumes of sediment and stored more sediment than reference pools. Sediment storage is positively correlated to BDA height and pool surface area. However, BDAs did not have a significant influence on shallow groundwater. The lack of groundwater response proximal to BDAs could indicate that local watershed factors have a stronger influence on groundwater response than restoration design 1 year post‐restoration. Systematic, long‐term studies of channel and floodplain response to BDAs are needed to better understand how BDAs will influence geomorphology and hydrology.     

贝特类调血脂前药与类似物的研究进展

对非诺贝特酸、苯扎贝特、吉非罗齐等贝特类调血脂前药及其类似物的研究进展做一综述,并对今后贝特类前药的开发做一展望.为新型调血脂药物的开发提供线索.     

Sphaeropsidin A: A Pimarane Diterpene with Interesting Biological Activities and Promising Practical Applications

Sphaeropsidin A (SphA) is a tetracyclic pimarane diterpene, first isolated as the main phytotoxin produced by Diplodia cupressi the causal agent of a severe canker disease of Italian cypress (Cupressus sempervirens L.). It was also produced, together with several analogues, by different pathogenic Diplodia species and other fungi and showed a broad array of biological activities suggesting its promising application in agriculture and medicine. The anticancer activity of SphA is very potent and cell specific. Recent studies have revealed its unique mode of action. This minireview reports the structures of SphA and its family of natural analogues, their biosynthetic origins, their fungal sources, and biological activities. The preparation of various SphA derivatives is also described as well as the results of structure-activity relationship (SAR) studies and on their potential practical applications.     

Detailed Insight into the Interaction of Bicyclic Somatostatin Analogue with Cu(II) Ions

Somatostatin analogues are useful pharmaceuticals in peptide receptor radionuclide therapy. In previous studies, we analyzed a new bicyclic somatostatin analogue (BCS) in connection with Cu(II) ions. Two characteristic sites were present in the peptide chain: the receptor- and the metal-binding site. We have already shown that this ligand can form very stable imidazole complexes with the metal ion. In this work, our aim was to characterize the intramolecular interaction that occurs in the peptide molecule. Therefore, we analyzed the coordination abilities of two cyclic ligands, i.e., P1 only with the metal binding site and P2 with both sites, but without the disulfide bond. Furthermore, we used magnetic circular dichroism (MCD) spectroscopy to better understand the coordination process. We applied this method to analyze spectra of P1, P2, and BCS, which we have described previously. Additionally, we analyzed the MCD spectra of P3 ligand, which has only the receptor binding site in its structure. We have unequivocally shown that the presence of the Phe-Trp-Lys-Thr motif and the disulfide bond significantly increases the metal binding efficiency.     

The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well‐known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6′, 9′, 1 and 7‐positions, is described. In a previous study, replacement of the naturally occurring N‐methyl group in the 6′‐position with an N‐ethylaminocarbonyl was shown to promote cell‐cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9′‐position, regioselective O‐demethylation to reveal a free phenol in the 7‐position, and reduction of the lactone to the corresponding cyclic ether in the 1‐position. The incorporation of new aryl substituents in the 9′‐position was also investigated. The study identified interesting new compounds able to induce G2/M cell‐cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF‐7, and the human pancreatic epithelioid carcinoma cell line PANC‐1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6′‐ethylaminocarbonyl along with 9′‐chloro, 7‐hydroxy and lactone moieties exhibited the most promising biological activities, with EC₅₀ values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.     

Preparation of rice analogues using extrusion technology

Rice is considered as staple food in many parts of the world. An issue of concern is the breakage of rice kernels in milling processes, and these broken kernels are not generally accepted by consumers. These broken kernels can be mixed with some desired additives to improve their quality and extruded for the preparation of reconstituted rice kernels or rice analogues. Various studies have been conducted for the preparation of the rice analogues in the past few decades, and recently attempts have been made to fortify these analogues with protein, certain vitamins and minerals. The main features such as colour, shape, size, texture, and cooking characteristics and cooking time of these rice‐like grains can be tailored to the requirements of specific applications by modification of the extrusion parameters. Various organisations, such as Wuxi NutriRice Co. (DSM/Buhler) and China National Cereals, Oils and Foodstuffs Corporate (COFCO), Superlative Snacks Inc., Vigui and PATH, have utilised this technique to prepare fortified and reconstituted rice. Studies have shown that it is possible to improve the nutritional quality of rice by fortified rice analogues. This article reviews research results of the many approaches to the formation of fortified rice analogues by extrusion‐based technologies.     

Synthesis and Biopharmaceutical Evaluation of Imatinib Analogues Featuring Unusual Structural Motifs

A convenient synthesis of imatinib, a potent inhibitor of ABL1 kinase and widely prescribed drug for the treatment of a variety of leukemias, was devised and applied to the construction of a series of novel imatinib analogues featuring a number of non‐aromatic structural motifs in place of the parent molecule's phenyl moiety. These analogues were subsequently evaluated for their biopharmaceutical properties (e.g., ABL1 kinase inhibitory activity, cytotoxicity). The bicyclo[1.1.1]pentane‐ and cubane‐containing analogues were found to possess higher themodynamic solubility, whereas cubane‐ and cyclohexyl‐containing analogues exhibited the highest inhibitory activity against ABL1 kinase and the most potent cytotoxicity values against cancer cell lines K562 and SUP‐B15. Molecular modeling was employed to rationalize the weak activity of the compounds against ABL1 kinase, and it is likely that the observed cytotoxicity of these agents arises through off‐target effects.     

Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors

Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.     

一种吲哚基姜黄素类似物的合成及其抗氧化活性研究

吲哚-3-甲醛与2-羟基-5-甲氧基苯乙酮进行羟醛缩合反应,生成一种吲哚基姜黄素类似物1-(2-羟基-5-甲氧基苯基)-3-(3-吲哚基)-2-烯-1-酮,在不同的催化剂、温度、溶剂等条件下,探索研究合成反应所需的最优工艺条件,采用合适的方法分离提纯得到纯净产品。通过熔点测定、氢核磁共振分析法、质谱分析法等对合成产物进行分析,并研究其抗氧化生物活性。结果表明,该化合物均具有清除DPPH自由基、羟基自由基的能力,表现出明显的抗氧化活性。     

Ⅰ型聚酮类天然产物中利用点突变产生类似物的研究

点突变是指通过聚合酶链式反应（PCR）等方法向目的DNA片段中引入所需变化（通常是表征有利方向的变化）,包括碱基的添加、删除、改变等。通过构建发生突变的质粒利用遗传转移的方法同源重组到野生型基因组中,使得氨基酸改变从而引起蛋白功能发生变化,获得鉴定正确的突变株后发酵筛选结构类似物。聚酮类天然产物在生物合成过程中,其聚酮链会发生若干步氧化还原反应,通过点突变的方法失活该蛋白,从而跳过该步氧化还原反应的作用,产生PKS骨架上的改变,从而得到结构类似物。