Development and validation of LC–MS/MS method for amlexanox in rat plasma and its application in preclinical pharmacokinetics

Amlexanox, an anti-inflammatory and anti-allergic agent, has been widely used clinically for the treatment of canker sores, asthma, and allergic rhinitis. Recently, amlexanox has received considerable attention in curing nonalcoholic fatty liver diseases and hepatitis virus infection. Herein, we first established a sensitive high-performance liquid chromatography-tandem mass spectrum (LC–MS/MS) method for the determination of amlexanox in rat plasma. Propranolol was used as the internal standard (IS). Using a simple protein precipitation method, the amlexanox and IS were separated with Capcell Pak C18 column (2.0 × 50 mm, 5 μm) and eluted with water and acetonitrile each containing 0.1% formic acid using gradient elution condition at a flow rate of 0.4 mL·min⁻¹. Amlexanox and IS were detected by a triple quadrupole mass in multiple reactive monitoring (MRM) under the transitions of m/z 299.2 → 281.2 and m/z 259.9 → 116.1 with positive electrospray ionization, respectively. The calibration curves of amlexanox were established with the range of 50 to 2000 ng·mL⁻¹ (r² > 0.99). The validation method consisted of selectivity, accuracy, precision, carryover effect, matrix effect, recovery, dilution effect, and stability. The fully validated method was successfully applied to the pharmacokinetic study of amlexanox in Wistar rats.     

Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.     

基于深度学习的ELM实时识别研究

基于深度学习的方法，在HL-2A装置上开发出了一套边缘局域模(ELM)实时识别算法。算法使用5200次放电数据(约24.19万数据切片)进行学习，得到一个深度为22层的卷积神经网络。为衡量算法的识别能力，识别了HL-2A装置自2009年实现稳定ELMy H模放电以来所有历史数据(约26000次放电数据)，共识别出1665次H模放电，其中误识别35次，误报率为2.10%。在实际的1634次H模放电中，漏识别4次，漏识别率为0.24%。该误报率和漏报率可以满足ELM实时识别的精度要求。识别算法在实时控制环境下，对单个时间点的平均计算时间为0.46ms，可以满足实时控制的计算速度要求。     

一种PD雷达动目标模拟与微波测控系统

介绍了一种基于PC／104总线，具有GPIB程控功能，采用无内部微波源体制，通过在雷达载频上调制多普勒频率模型目标速度信息，延迟雷达发射机触发脉冲模拟目标距离信息并具有微波功率精确定标与衰减功能的PD雷达动目标模拟与微波测控系统。     

微流控分析芯片制作中的低温键合技术

微流控分析芯片制作方法的研究是微流控分析的基础。制作性能良好的微流控分析芯片时,基片与盖片的键合技术十分重要。本文针对近年来发展迅速的低温键合技术,对各种方法进行了评价,并对其发展前景进行了展望。     

草酸钙在硫酸软骨素自组装膜上周期沉淀的研究

利用硫酸软骨素(chondroitin sulfate，CS)在云母基底上通过浇铸法制备的自组装膜为基底，诱导草酸钙在其上的凝集生长。发现当硫酸软骨素的浓度为1．Omg／ml时在该膜体系中可形成规整的周期性草酸钙环状沉淀。这种有序的环状结构可能是耗散结构的一种具体表现形式。利用原子力显微镜(atomic forcemicroscope，AFM)和傅立叶红外光谱仪对这种结构进行了表征，实验结果显示合适浓度下形成的CS膜在一定程度上可以抑制草酸钙的凝集结晶，表明高分子基质与无机离子间强烈的相互作用对无机盐的成核结晶有显著影响，为探讨结石的形成与抑制提供了一定的实验依据。     

21~28GHz波段平衡式放大器

采用OMM IC的0.2μm PHEM T工艺设计了工作在21~28 GH z的平衡式放大器。正交耦合电桥采用兰格电桥。兰格电桥和平衡式放大器的在片测试结果和仿真结果基本吻合,平衡式放大器在21~28 GH z的增益为18~20 dB,输入和输出回波损耗小于-20 dB,在26 GH z处的输出1 dB压缩点功率为21 dBm。     

一阶最优性条件研究

本对由Botsko的关于多变量函数取极值的一阶导数检验条件定理^[1]进行了分析研究，给出了更实用而简捷的差别条件。最后，举出若干例子予以说明。     

时间分辨光子计数系统的研究和应用

对由SPCM-AQR-14和MCS组成的时间分辨光子计数系统进行了研究,分析了SPCM和MCS的工作原理及主要特性.利用该系统对磷光物质和洋葱的延迟发光进行了测量,对它们的光子计数率曲线进行拟合,发现其光强衰减符合双曲线规律.     

最速下降规则不失为一可用规则

本从统计意义上平均迭代次数的观点出发，指出求解线性规划的最速下降规则是可取的，好用的。