Drug metabolite cluster centers-based strategy for comprehensive profiling of Neomangiferin metabolites in vivo and in vitro and network pharmacology study on anti-inflammatory mechanism

Neomangiferin (NMF) is an extremely special xanthone that could be simultaneously attributed to C-glycoside and O-glycoside with a variety of biological activities, such as anti-inflammatory, antitumor, antipyretic, and so on. So far as we know, the metabolism profiling has been insufficient until now. Herein, Drug Metabolite Cluster Centers (DMCCs)-based Strategy has been developed to profile the NMF metabolites in vivo and in vitro. Firstly, the DMCCs was proposed depending on literature-related and preliminary analysis results. Secondly, the specific metabolic rule was implemented to screen the metabolites of candidate DMCCs from the acquired Ultra High Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS) data by extracted ion chromatography (EIC) method. Thirdly, candidate metabolites were accurately and tentatively identified according to the pyrolysis law of mass spectrometry, literature reports, comparison of reference substances, and especially the diagnostic product ions (DPIs) deduced preliminarily. Finally, network pharmacology was adopted to elucidate the anti-inflammatory action mechanism of NMF on the basis of DMCCs. As a result, 3 critical metabolites including NMF, Mangiferin (MF) and Norathyriol (NA) were proposed as DMCCs, and a total of 61 NMF metabolites (NMF included) were finally screened and characterized coupled with 3 different biological sample preparation methods including solid phase extraction (SPE), acetonitrile precipitation and methanol precipitation. Among them, 32 metabolites were discovered in rat urine, 30 in rat plasma, 12 in rat liver, 9 metabolites in liver microsomes and 8 in rat faeces, respectively. Our results also illustrated that NMF primarily underwent deglucosylation, glucuronidation, methylation, sulfation, dihydroxylation and their composite reactions in vivo and in vitro. Additionally, network pharmacology analysis based on DMCCs revealed 85 common targets of disease-metabolites, and the key targets were TNF, EGFR, ESR1, PTGS2, HIF1A, IL-2, PRKCA and PRKCB. They exerted anti-inflammatory effects mainly through the pathways of inflammatory response, calcium-dependent protein kinase C activity, nitrogen metabolism, pathways in cancer and so on. In general, our study constructed a novel strategy to comprehensive elucidate the biotransformation pathways of NMF in vivo and in vitro, and provided vital reference for further understanding its anti-inflammatory action mechanism. Moreover, the established strategy could be generalized to the metabolism and action mechanism study of other natural products.     

Development and prevalidation of a method for phenol determination by solid-phase spectrophotometry

A simple, sensitive and rapid solid-phase spectrophotometric procedure was developed for the determination of traces of phenol with 4-aminoantipyrine as a reagent (AAP-SPS), and the optimal experimental conditions were established. This method was performed by sorption and direct absorbance measurements of the product phenol-AAP sorbed on the anion-exchanger Dowex 1-X4 (0.2 g) at 495 nm (absorption maximum) and 700 nm (non-absorption wavelength). The sensitivity offered by the AAP-SPS procedure was higher by a factor of 40 compared with the respective conventional spectrophotometric method. Metrological characteristics were established using a prevalidation strategy. The AAP-SPS procedure is characterized by a linear calibration function in the working range of 0.05–0.50 μmol, low standard deviation of procedure (±0.012), low limit of determination (0.021 μmol), and favorable random (±0.85 to ±11.27%) and systematic deviations (−4.55 to +11.50%). Moreover, the accuracy of the system investigated by the recovery test is acceptable (99–102%). Favorable working and performance characteristics make the new SPS method ideal for phenol monitoring in pharmaceutical preparations as well as other matrices.     

利用早停可微架构搜索的三维点云模型分类

针对现有三维点云分类网络采用人工设计费时费力的问题,提出早停可微架构搜索(early-stopping differentiable architecture search,ES-DARTS)算法。利用从人工设计网络架构中提取到的先验知识,预定义一个包含高效候选操作的搜索空间,可快速搜索出适用于三维模型分类任务的高性能网络模型;通过追踪网络搜索阶段各候选操作的权重变化,找出跳跃连接操作在双重优化过程中发挥不公平竞争作用的临界点并在此处停止搜索,以保证各候选操作之间的稳定性,解决DARTS算法搜索过程中易出现性能崩溃的问题。提出的算法在ModelNet40数据集上达到了93.2%的识别准确率,比当前人工设计的主流网络具有更高的识别准确率。     

Lamination Design Optimization for Continuous Fiber Reinforced Composites of Variable Thicknesses北大核心CSCD

由于具备高的比强度、比刚度,利用连续纤维增强复合材料代替传统金属材料以实现结构轻量化正受到设计者们的广泛关注。然而,结构的复杂性给复合材料的铺层设计与优化带来了很大的挑战。针对航空用复合材料铺层设计约束多的问题,通过逐步构建设计变量准确表达结构的铺层信息。基于经典遗传算法框架,结合各设计变量特点,定义了铺层优化算法中的遗传算子,通过引入“修复”策略保证了每一代解都能满足设计约束,分布在可行域区间内。最后利用精英保留策略提高了算法的局部寻优能力,可以降低复杂复合材料结构铺层设计的计算成本。通过解决经典benchmark问题并与已有优化结果的比较,验证了前述铺层优化算法的全局、局部寻优能力,为工程实际中的复合材料铺层设计优化提供了理论支撑。     

棉纺厂管理信息系统的研制

本文根据开发CTU-JMS管理信息系统已取得的成功经验,介绍CTU—JMS管理信息系统的运行环境;总体规划中运用的两种设计策略——“由顶向下”分析法和“由下至上”分析法;MIS中建立大型基础数据库采用的主要技术;MIS决策管理层的形成以及生产经营决策子系统的技术特点。为推进我国的纺织企业管理信息系统的开发和实现现代化管理作了探索。     

汽车制造商分时租赁模式采用及产品线策略研究

考虑自有平台和第三方平台两种分时租赁方式,将汽车质量划分为性能质量和环境质量,构建销售模式、纯分时租赁模式和混合模式下的产品线策略模型,研究制造商产品线策略与商业模式之间的相互作用。研究发现,同品牌产品间竞争和合并效应是分时租赁模式影响产品线策略的两个关键因素。同品牌产品间竞争的加剧和合并效应的增大都会激励企业选择性能更好的车型而忽略其环境表现。分时租赁模式能同时改进利润与产品环境表现,但存在条件:当消费者价格敏感性较低时,使用成本高且合并效应小是实现同时改进的条件;当消费者价格敏感较高时,使用成本低且合并效应小则是同时改进的条件。     

A-P-S组合策略的多重绩效及其“褪色”效应分析

为了降低城市交通拥堵及空气污染程度,本文在现有研究的基础上引入罚款政策,利用系统动力学方法原理构建了机动车污染物减排管控模型。通过仿真和比较分析来探索空气污染收费(Air pollution charging fee,简称APCF)、罚款(penalty)和补贴(subsidy)政策(简称A-P-S策略)的作用效果。研究结果表明:一方面,组合策略具有多重绩效,不但能够降低污染损失(经济-环境效益)、死亡人口的生命价值(社会-经济效益)、交通拥堵程度(社会效益)和机动车污染物总量(环境效益),而且能大大改善环境生态承载力(环境效益)和机动车非法出行增长量(社会安全绩效);另一方面,政策在实施过程中也会遇到一定的局限性,如初期的滞后性,后期的“褪色”效应和“反弹”效应,因此,从长期来看,需要及时调整组合方案。最后,根据仿真结果提出了相应的政策建议,进而为城市交通和环保等相关部门提供决策参考。     

对“铁路运输走向市场”若干问题的认识

“铁路运输走向市场”的第一层含义是铁路运输企业经营市场化,第二层含义是铁路运输作为市场经济的基础条件,必须起到保证整个社会主义市场经济运行的基础作用,在我国当前条件下,必须把提高运输能力作为铁路运输走向市场的出发点和归宿。在提高运输能力过程中,必须科学处理运输能力与运输效率的关系．以市场经济和社会基础性的眼光看,我国铁路运输高效率并不一定是一件好事。铁路运输走向市场可以采取“重点突破,整体推进”的战略。     

Parameter choice by discrepancy principles for ill-posed problems leading to optimal convergence rates

Schock (Ref. 1) considered a general a posteriori parameter choice strategy for the Tikhonov regularization of the ill-posed operator equationTx=y which provides nearly the optimal rate of convergence if the minimal-norm least-squares solution belongs to the range of the operator (T ^* T) ^v , o<v1. Recently, Nair (Ref. 2) improved the result of Schock and also provided the optimal rate ifv=1. In this note, we further improve the result and show in particular that the optimal rate can be achieved for 1/2v1.The final version of this work was written while M. T. Nair was a Visiting Fellow at the Centre for Mathematics and Its Applications, Australian National University, Canberra, Australia. The work of S. George was supported by a Senior Research Fellowship from CSIR, India.     

无源传感器引导AESA雷达目标搜索

无源传感器引导有源电扫阵列(AESA)雷达完成目标搜索是机载多传感器协同探测的重要应用形式。综合了引导传感器的测角误差以及目标运动产生的偏差2种因素,建立目标指示成功概率模型。提出了一种满足时效性、指示成功率和误交接概率要求的最优搜索策略。采用分步优化的方法在多种场景下对搜索策略和性能指标进行了计算。仿真结果表明:提出的搜索策略与传统搜索策略相比在满足指示成功率要求的前提下,通过增加较少的搜索波位,较大幅度地降低了误交接概率,保证了引导条件下目标搜索的准确性。