Automated solvent system screening for the preparative countercurrent chromatography of pharmaceutical discovery compounds

A fully automated countercurrent chromatography system has been constructed to rapidly screen the commonly used heptane/ethyl acetate/methanol/water solvent system series and translate the results to preparative scale separations. The system utilizes “on‐demand” preparation of the heptane/ethyl acetate/methanol/water solvent system upper and lower phases. Elution‐extrusion countercurrent chromatography was combined with non‐dynamic equilibrium injection reducing the screening time for each heptane/ethyl acetate/methanol/water system to 17 min. The result enabled solvent system development to be reduced to under 2 h. The countercurrent chromatography system was interfaced with a mass spectrometer to allow selective detection of target components in crude medicinal chemistry reaction mixtures. Mass‐directed preparative countercurrent chromatography purification was demonstrated for the first time using a synthetic tetrazole epoxide derived from a routine medicinal chemistry support workflow.     

不同管径聚乙烯管的旋转挤出

通过口模旋转挤出制备3种管径聚乙烯(PE)管,系统研究其结构与性能。结果表明,相较于传统挤出PE管内串晶平行与轴向,旋转挤出过程中聚合物熔体的流动是轴向牵引流动和环向拖曳流动的叠加,其方向偏离轴向,可诱导串晶偏离轴向排列,从而提高PE管的环向取向度,实现PE管的环向增强,抑制裂纹在PE管内沿轴向扩展。随PE管管径的增加,在相同旋转角速度下环向流动线速度增大,串晶偏离轴向的夹角增加,环向取向度更高,因而旋转挤出制备的大口径PE管具有更优的性能。     

A Facile Method to Prepare Double‐Layer Isoporous Hollow Fiber Membrane by In Situ Hydrogen Bond Formation in the Spinning Line

A double‐layer hollow fiber is fabricated where an isoporous surface of polystyrene‐block‐poly(4‐vinylpyridine) is fixed on a support layer by co‐extrusion. Due to the sulfonation of the support layer material, delamination of the two layers is suppressed without increasing the number of subsequent processing steps for isoporous composite membrane formation. Electron microscope‐energy‐dispersive X‐ray spectroscopy images unveil the existence of a high sulfur concentration in the interfacial region by which in‐process H‐bond formation between the layers is evidenced. For the very first time, our study reports a facile method to fabricate a sturdy isoporous double‐layer hollow fiber.

     

IUPAC-LDPE的流变性测试实验之间的相对滑动

以IUPAC—LDPE熔体在150℃下详细的流变学表征实验和毛细管挤出实验为基础考察了该熔体在挤出实验中的滑动问题．根据相对滑动特性给出了判断相对滑动存在和计算相对滑动速度的方法．用Wagner模型，PSM模型和Osaki模型计算的表观剪切速率，在10s^-1时的毛细管壁面剪切应力比毛细管挤出实验给出的应力值高出约15％-17％，这个结果意味着IUPAC—LDPE熔体在挤出实验中存在滑动现象．在表观剪切速率为0．1，1．0和10s^-1时，挤出实验条件下的流动与根据在旋转流变仪上测定的流变特性用PSM模型计算的流动相比，它们之间存在的相对滑动速度分别为0．004，0．071和1．343mm／s．用Wagner模型和Osaki模型计算的相对滑动速度与PSM模型的结果相近．     

Validation of an in-line Raman spectroscopic method for continuous active pharmaceutical ingredient quantification during pharmaceutical hot-melt extrusion

A calibration model for in-line API determination was developed based on Raman spectra collected during hot-melt extrusion. This predictive model was validated by calculating the accuracy profile based on the analysis results of validation experiments. Furthermore, based on the data of the accuracy profile, the measurement uncertainty was determined. Finally, the robustness of the model was evaluated.     

Proteomic analysis of a spring wheat cultivar in response to prolonged cold stress

Cold represents one of the major abiotic factors influencing plant growth and development worldwide. We analysed the long-term responsiveness of an Iranian spring wheat (cv. Kohdasht) to cold from a proteomic point of view, in order to unravel the molecular mechanisms helping a cold-sensitive cultivar to survive exposure to suboptimal temperatures. Plants were grown at 20 or 4°C until entering the reproductive stage and a cross-comparison on the leaf proteomes was performed. Quantitative analyses on protein alterations occurring upon low-temperature exposure showed a reinforcement in ascorbate recycling (dehydroascorbate reductase, ascorbate peroxidase) and protein processing (proteasome subunit, cysteine proteinase), as well as the accumulation of the enzyme devoted to tetrapyrrole resynthesis (glutamate semialdehyde aminomutase). In contrast, among proteins down-regulated after cold stress, we could identify some key Krebs cycle enzymes (isocitrate dehydrogenase, malate dehydrogenase), together with many photosynthesis-related proteins (oxygen-evolving complex proteins, ATP synthase subunits, ferredoxin NADPH oxidoreductase and some Calvin cycle enzymes). Physiological and biochemical parameters (such as shoot apex dissection, chlorophyll, proline and sugar content determination) sustained proteomics findings allowing the present research to contribute to the current knowledge on these long-term responses, which may be crucial to stress adaptation under field conditions.     

Effect of sterilization on non-woven polyethylene terephthalate fiber structures for vascular grafts

Non-woven polyethylene terephthalate (PET) fibers produced via melt blowing and compounded into a 6 mm diameter 3D tubular scaffold were developed with artery matching mechanical properties. This work compares the effects of ethylene oxide (EtO) and low temperature plasma (LTP) sterilization on PET surface chemistry and biocompatibility. As seen through X-ray photoelectron spectroscopy (XPS) analysis, LTP sterilization led to an increase in overall oxygen content and the creation of new hydroxyl groups. EtO sterilization induced alkylation of the PET polymer. The in vitro cytotoxicity showed similar fibroblastic viability on LTP- and EtO-treated PET fibers. However, TNF-α release levels, indicative of macrophage activation, were significantly higher when macrophages were incubated on EtO-treated PET fibers. Subcutaneous mice implantation revealed an inflammatory response with foreign body reaction to PET grafts independent of the sterilization procedure.     

Poly(ester urethane) guides for peripheral nerve regeneration

A biocompatible and elastomeric PU was synthesized from low-molecular-weight PCL as macrodiol, CMD as chain extender and HDI as chain linker for applications in the field of peripheral nerve repair. PU cast films supported in vitro attachment and proliferation of NOBEC. The in vitro adhesion and proliferation of S5Y5 neuroblastoma cells on the inner surface of uncoated, gelatin- and PL-coated PU guides were compared. Due to their superior in vitro performance, PL-coated PU guides were tested in vivo for the repair of 1.8 cm-long defects in rat sciatic nerves. The progressive regeneration was confirmed by EMG and histological analysis showing the presence of regenerating fibers in the distal stumps.     

大气压冷等离子体射流灭活子宫颈癌Hela细胞

研究了大气压冷等离子体射流对子宫颈癌Hela细胞的灭活机制. 在倒置显微镜下观察不同等离子体处理条件下的细胞形态, 并通过中性红吸收测试定量测定各个条件下的细胞存活率. 将功率维持在18 W, 在900 mL/min 氩等离子体中添入氧气的百分含量分别为1%, 2%, 4% 和8%的条件下处理Hela细胞, 探讨活性气体氧气在惰性气体氩气中的百分含量对Hela癌细胞灭活效率的影响, 发现添加2%氧气时, 氩/氧等离子体灭活效果最佳, 处理180 s后细胞存活率可降至7%. 当继续添加氧超过2%时, 灭活效果逐渐减弱, 直至8%时, 其效果反而不如单纯氩等离子体. 通过测量等离子体发射光谱, 结果表明活性氧自由基在癌细胞灭活过程中可能起关键作用. 关键词： 大气压冷等离子体射流 Hela癌细胞 存活率 发射光谱