An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent

Recently, we characterized neoamphimedine (neo) as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%). In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC₅₀ values) in all, with significant potency against colorectal cancer (lowest IC₅₀ = 6 nM). We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis.     

2021 年 9 期目录

近年来,随着气候变化和人类活动的加剧,全球森林面积持续减少、质量下降,生态环境事件频发,森林健康的问题受到前所未有的关注,已经成为生态文明战略的重要组成部分。我国森林资源持续增长,但同时也面临一些问题,如:造林结构单一、林分质量不高、生态稳定性弱等,如何系统准确评价其森林健康状况仍然是当前难点。相对于传统地面调查方法,遥感技术具有实时获取、重复监测以及多时空尺度等优势,并且随着高分遥感和人工智能等技术的飞速发展,大幅提高了解决森林健康评价难题的能力。为系统评估新型遥感技术应用于评价森林健康的潜力,本文在文献分析基础上,指出了现有路径和方法,具体包括:（1）通过文献计量学方法分析并明确了森林健康评价的4大核心内容（活力、组织结构、抵抗力和恢复力）和4大关键问题（树种分类、林木活力、林业有害生物、干旱胁迫）。（2）从不同尺度（单木?林分?生态系统?景观）、不同平台（近地面遥感?航空遥感?卫星遥感）和不同传感器（包括RGB相机、多/高光谱相机、激光雷达、热红外相机、微波雷达和叶绿素荧光扫描仪）3个角度,系统梳理现有遥感技术的优缺点。（3）围绕4个关键问题,阐述近年来应用遥感技术评价森林健康的路径和方法。进一步,本文指出了包括多数据源融合分析、森林健康监测网络与近地面遥感、森林健康大数据应用在内的挑战与机遇,以期为我国森林资源智慧管理提供参考。      

"实践性德育"初探

“实践性德育”的提出,是对国内外与“实践性德育”相关研究成果的借鉴和发挥,也是对当代“灌输式德育”的反思与矫正。“实践性德育”是一种以实践课程体系为主导的新的德育范型,它将实践性视为德育的本质,视为未来学校德育的起点、过程与终点的基本特征。     

太湖流域典型地区农村水环境氮、磷污染状况的研究

一年中分6次采样测定分析太湖流域典型地区（宜兴、常熟的王庄和辛庄）的农村各水体中总磷（TP）、硝态氮（NO3^-N）和铵态氮（NH4^＋-N）含量。结果表明,一年中的丰水期（5至9月）,农田各个水体中氮、磷含量明显高于其他时期;地表水中NH4^＋-N含量较高,地下水中NO3^--N含量也偏高。地下水中的NH4^＋-N污染程度高于NO3^--N,其中宜兴和王庄地下水中的NH4^＋-N污染比辛庄严重,年均值分别为1.596和2.103mg·L^-1,最高值分别为5.782和5.441mg·L^-1,都超过了V类地下水限值的10倍以上。辛庄5至9月地下水中NO3^--N含量超过了世界卫生组织（WHO）规定的生活饮用水硝态氮浓度10mg·L^-1的上限,已不适合作饮用水。研究区域内太湖水TP年均含量为0.492mg·L^-1,污染程度比农村灌溉水和城市河水严重,表现为TP在太湖中有累积的趋势;NO3^-N和NH4^＋-N年均为2.152和2.885mg·L^-1,太湖长期处于富营养化状态。     

Properties and Structures of Flours and Starches from Whole,Broken, and Yellowed Rice Kernels in a Model Study

The objective of this study was to compare the structure and properties of flours and starches from whole, broken, and yellowed rice kernels that were broken or discolored in the laboratory. Physicochemical properties including pasting, gelling, thermal properties, and X‐ray diffraction patterns were determined. Structure was elucidated using high‐performance size‐exclusion chromatography (HPSEC) and high‐performance anion‐exchange chromatography with pulsed amperometric detection (HPAEC‐PAD). The yellowed rice kernels contained a slightly higher protein content and produced a significantly lower starch yield than did the whole or broken rice kernels. Flour from the yellowed rice kernels had a significantly higher pasting temperature, higher Brabender viscosities, increased damaged starch content, reduced amylose content, and increased gelatinization temperature and enthalpy compared with flours from the whole or the broken rice kernels. However, all starches showed similar pasting, gelling, thermal properties, and X‐ray diffraction patterns, and no structural differences could be detected among different starches by HPSEC and HPAEC‐PAD. α‐Amylase may be responsible for the decreased amylopectin fraction, decreased apparent amylose content, and increased amounts of low molecular weight saccharides in the yellowed rice flour. The increased amount of reducing sugars from starch hydrolysis promoted the interaction between starch and protein. The alkaline‐soluble fraction during starch isolation is presumed to contribute to the difference in pasting, gelling, and thermal properties among whole, broken, and yellowed rice flours.     

Effects of Wheat Starch and Gluten on Tortilla Texture

Wheat starches were isolated from three wheat flours. Two vital wheat glutens, one from a commercial source and another one isolated from straight-grade flour, were combined with wheat starches to form reconstituted flours with a protein level of 10%. Several characteristics of tortillas made with the hot-press method were measured. No significant difference (P < 0.05) occurred in texture of tortillas made with hard wheat gluten and soft wheat gluten. Wheat starches did not have any significant (P < 0.05) effect on tortilla stretchability or foldability. Analysis of variance confirmed that wheat starch and gluten had limited effects on tortilla texture. The possible reasons were that the solubles of wheat flour were not included, and the shortening in the tortilla formula interfered with the interaction of gluten and starch.     

临安区山核桃林地土壤水解酶活性空间分布特征及土壤肥力评价

  目的  探索山核桃Carya cathayensis产区土壤水解酶活性空间分布特征和土壤肥力状况。  方法  在浙江省杭州市临安区山核桃主产区选取了259个样地，测定了土壤α-葡萄糖苷酶(AG)、β-葡萄糖苷酶(BG)、纤维二糖水解酶(CBH)、木糖苷酶(XYL)、亮氨酸氨基肽酶(LAP)、N-乙酰-β-氨基葡萄糖苷酶(NAG)、酸性磷酸酶(PHOS)等7种水解酶活性和主要的肥力指标，并运用主成分分析、地统计分析、相关性分析、冗余分析等方法，分析了临安区山核桃林地土壤中7种水解酶活性的空间异质性、影响因素以及土壤肥力状况。  结果  AG、BG、CBH、LAP、NAG、XYL、PHOS活性的块基比C₀/(C+C₀)分别为55%、42%、56%、49%、66%、47%、78%，全局莫兰指数(I_g)均大于0。土壤中碱解氮、有效磷、速效钾、有机质位于丰富等级的样地数分别占64%、56%、23%、45%，平均pH为5.76。58.7%的样地土壤肥力低于平均水平，仅32.7%的土壤肥力为Ⅰ、Ⅱ等级，大部分土壤肥力处于Ⅲ、Ⅳ等级 。  结论  7种土壤水解酶中，AG、BG、CBH、LAP、NAG、XYL具有中等空间自相关性，它们的变异情况受人为扰动和地形结构因素的共同影响。PHOS具有较弱的空间自相关，其活性空间分布主要受人为干扰的影响。7种水解酶活性均存在空间相关性，高低聚类情况相似。在岛石镇附近出现高值聚集，在清凉峰以及河桥、龙岗、昌化交界处附近出现低值聚集的情况，有机质、pH、碱解氮是影响水解酶活性高低值聚类的关键因素。土壤肥力指标分级和综合肥力得分结果表明:大部分林地土壤养分足以支撑山核桃林正常生长，但综合肥力还有待提高。图3表5参32