Identification and quantitative analysis of physalin D and its metabolites in rat urine and feces by liquid chromatography with triple quadrupole time‐of‐flight mass spectrometry

Physalin D is known to show extensive bioactivities. However, no excretion study has elucidated the excretion of physalin D and its metabolites. This study investigates the excretion of physalin D and its metabolites in rats. Metabolites in rat urine and feces were separated and identified by liquid chromatography with triple quadrupole time‐of‐flight mass spectrometry. Furthermore, a validated high‐performance liquid chromatography with tandem mass spectrometry method was developed to quantify physalin D, physalin D glucuronide, and physalin D sulfate in rat feces and urine after the intragastric administration of physalin D. The analyte showed good linearity over a wide concentration range (r  > 0.995), and the lower limit of quantification was 0.0532 μg/mL and 0.226 μg/g for urine and feces, respectively. Nine metabolites, including five phase I and four phase II metabolites, were identified and clarified after dosing in vivo. Only 4.0% of the gavaged dose, including physalin D and its phase II metabolites, was excreted in urine, whereas 10.8% was found in feces in the unchanged form. The results indicate that the extensive and rapid metabolism may be the main factors leading to the short half‐life of physalin D. These results can provide a basis for further studies on the structural modification and pharmacology of physalin D.     

An Organoruthenium Anticancer Agent Shows Unexpected Target Selectivity For Plectin

Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics-based target-response profiling approach as a potent hypothesis-generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock-out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin-1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.     

基于多特征算法选择的太赫兹时域光谱用于水稻种子掺假研究

该文提出了一种基于太赫兹时域光谱的水稻种子模式识别方法。实验以10种不同品牌混合掺假的水稻种子为样本,基于采集的样本太赫兹时域光谱数据,通过建立Relief、随机森林（RF）、支持向量机递归特征消除（SVM-RFE）和最大相关最小冗余（mRMR）模型分别对样本光谱波长进行特征选择,最后设计分类器对4种特征选择方法处理后的样本进行分类识别。结果表明,基于布谷鸟算法（CS）优化的极限学习机模型对经RF特征选择算法提取后的样本光谱数据具有最佳识别效果,其准确率可达100%,实验对于法庭科学领域内种子的掺假鉴定具有一定的借鉴意义。     

Large scale synthesis of red emissive carbon dots powder by solid state reaction for fingerprint identification

Red emissive carbon dots(CDs) powder was synthesized on a large scale from phloroglucinol and boric acid by a novel solid state reaction with yield up to 75%. This method is safe and convenient, for it needs neither high pressure reactors nor complicated post-treatment procedures. The as-prepared carbon dots powder exhibited strong red fluorescence with excitation-independent behavior. XPS measurement and PL spectra suggest that such red fluorescence arise from boron-doped structures in CDs, which increases along with the boron concentration on CDs surface but decreases when the concentration quenching effect takes place. To overcome the aggregation induced fluorescence quenching of the solid CDs powder,the conventional methods are dispersing CDs into a large amount of inert substrates. But our present work provides a new strategy to realize strong red fluorescence of CDs in solid state. As a result, such carbon dots powder works well for latent fingerprint identification on various material surfaces.     

毒品与化学*

毒品与化学的种种纠葛在2018年中国毒品形势报告中得到了淋漓尽致的体现,因此为做好禁毒工作,必须厘清化学与毒品的关系。从为什么毒品是化学品(毒品的本质),毒品检验和识别,毒品成瘾的本质,由传统毒品到新型毒品的转变等4个方面系统阐述毒品与化学的关系。     

基于宏微辨析核心素养分析高中《化学1(必修)》教材*

教材分析是连接教材和课程的桥梁,基于宏观辨识和微观探析核心素养,比较分析了2004年版和2019年版高中《化学1(必修)》教材的特点。通过运用“三序结合”原则,从静态视角对比教材栏目设置、内容组织形式、核心素养呈现方式、学生认知水平以及作业布置形式等5个维度要素在宏微辨析核心素养领域的建构。分析结果显示,2019年版《化学1(必修)》教材在以上要素方面均围绕宏微辨析核心素养,呈现不同水平阶梯型设置。建议在“宏微符”概念形成的过程中增设更为细致的过渡内容,以及更为详尽的与教材配套的辅助内容,便于教材的二次开发。     

Metabolite Profiling and Characterization of LW6, a Novel HIF-1α Inhibitor,as an Antitumor Drug Candidate in Mice

A novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6.     

色谱在药物-机体复杂巨系统研究中的应用进展

色谱是一门以分离分析为主,旨在追求复杂事物纯而净的分析化学的重要分支学科。其经过百余年的发展,理论与技术日臻完善,集科学、技术与艺术于一体。近年来,色谱及其与质谱、核磁共振波谱、原子发射光谱等联用技术极大推动了环境、食品、石油化工、生物医药等领域中所涉及复杂体系的研究进展。作为我国传统文化的核心代表,中医药为中国乃至世界人民的健康服务逾千年,从古至今历经上千年临床考验,疗效经久不衰。近年来,中国政府强调继承与创新,加大推进中医药的现代化与国际化。然而中药自身的多成分协同起效复杂性及其与机体时刻新陈代谢变化的复杂性往往相互作用,由此形成了药物-机体复杂巨系统。该复杂巨系统的分析研究是中医药现代化进程的关键瓶颈。色谱的优势在于复杂成分的分离与分析,此恰能为上述复杂巨系统提供技术支撑,色谱及其联用技术已成为推动中医药分子化、数字化、信息化乃至现代化的主流技术。该文综述了色谱及其联用技术在中药复杂体系、复杂生命过程及药物-机体复杂巨系统中的应用进展,介绍了笔者研究团队对中医药现代化的认识、研究思路和研究工作,最后笔者结合对于百年色谱与千年中医药文化之现代化交织的感悟,对色谱技术在此领域的前景做出了展望。     

Rapid and label-free classification of pathogens based on light scattering,reduced power spectral features and support vector machine

The rapid identification of pathogens is crucial in controlling the food quality and safety. The proposed system for the rapid and label-free identification of pathogens is based on the principle of laser scattering from the bacterial microbes. The clinical prototype consists of three parts: the laser beam, photodetectors, and the data acquisition system. The bacterial testing sample was mixed with 10 mL distilled water and placed inside the machine chamber. When the bacterial microbes pass by the laser beam, the scattering of light occurs due to variation in size, shape, and morphology. Due to this reason, different types of pathogens show their unique light scattering patterns. The photo-detectors were arranged at the surroundings of the sample at different angles to collect the scattered light. The photodetectors convert the scattered light intensity into a voltage waveform. The waveform features were acquired by using the power spectral characteristics, and the dimensionality of extracted features was reduced by applying minimal-redundancy-maximal-relevance criterion (mRMR). A support vector machine (SVM) classifier was developed by training the selected power spectral features for the classification of three different bacterial microbes. The resulting average identification accuracies of E. faecalis,E. coli and S. aureus were 99%, 87%, and 94%, respectively. The overall experimental results yield a higher accuracy of 93.6%, indicating that the proposed device has the potential for label-free identification of pathogens with simplicity, rapidity, and cost-effectiveness.     

外泌体分离与纯化技术研究进展

外泌体是所有真核细胞分泌到细胞外的直径介于30～150 nm的一种膜性纳米囊泡,参与细胞间生物信号的传递。大量实验证据表明,外泌体参与多种生物功能并发挥重要作用,包括蛋白质、RNA和脂质等生物分子的转移及多种疾病生理和病理过程的调节,被认为是疾病诊断、治疗和预后的重要的生物标志物和药物载体,因此发展简单、高效、经济的外泌体分离与纯化技术将有助于疾病的早期诊断和精准治疗。目前,利用外泌体的物理化学和生物化学特性已开发出多种分离外泌体的技术,但仍缺乏标准化和规模化临床级外泌体的分离方法,从而限制了其临床应用。另外,对分离出的外泌体的特征、纯度和数量的鉴定是判断外泌体分离纯化方法优劣的重要指标。本文综述了外泌体分离与纯化技术以及鉴定方法的研究进展,主要讨论分离技术的机制、性能、挑战和前景以及外泌体的鉴定方法,以期为外泌体的分离纯化提供新的思路和解决策略。