万古霉素手性固定相分离曼尼希碱类化合物对映体

采用大环抗生素类万古霉素手性固定相高效液相色谱法研究了一系列曼尼希碱类化合物的手性分离情况,并讨论了流动相中有机相的种类和比例、缓冲盐的种类和浓度、pH和柱温对该类化合物手性分离的影响。最佳实验条件为:乙腈:硝酸铵(35mmol/L,pH3.8)=15∶85(V/V),柱温15℃,流速0.6mL/min,检测波长300nm;四氢呋喃:硝酸铵(20mmol/L,pH4)=15∶85(V/V),柱温15℃,流速0.6mL/min,检测波长350nm。通过对比研究8种曼尼希碱类化合物的色谱行为,从结构上讨论了化合物中各种官能团对手性分离的影响,并探讨了手性分离的内在机制。     

Identification of Pharmacophoric Fragments of DYRK1A Inhibitors Using Machine Learning Classification Models

Dual-specific tyrosine phosphorylation regulated kinase 1 (DYRK1A) has been regarded as a potential therapeutic target of neurodegenerative diseases, and considerable progress has been made in the discovery of DYRK1A inhibitors. Identification of pharmacophoric fragments provides valuable information for structure- and fragment-based design of potent and selective DYRK1A inhibitors. In this study, seven machine learning methods along with five molecular fingerprints were employed to develop qualitative classification models of DYRK1A inhibitors, which were evaluated by cross-validation, test set, and external validation set with four performance indicators of predictive classification accuracy (CA), the area under receiver operating characteristic (AUC), Matthews correlation coefficient (MCC), and balanced accuracy (BA). The PubChem fingerprint-support vector machine model (CA = 0.909, AUC = 0.933, MCC = 0.717, BA = 0.855) and PubChem fingerprint along with the artificial neural model (CA = 0.862, AUC = 0.911, MCC = 0.705, BA = 0.870) were considered as the optimal modes for training set and test set, respectively. A hybrid data balancing method SMOTETL, a combination of synthetic minority over-sampling technique (SMOTE) and Tomek link (TL) algorithms, was applied to explore the impact of balanced learning on the performance of models. Based on the frequency analysis and information gain, pharmacophoric fragments related to DYRK1A inhibition were also identified. All the results will provide theoretical supports and clues for the screening and design of novel DYRK1A inhibitors.     

Organic Nanocrystals Based on a Solid-emission-tunable AIEgen for Cell Imaging

The development of fluorescent nanocrystals based on organic small molecules is of great importance in bioimaging due to the merits of easy modification,high brightness and excellent photostability,however suffering from the emission-detrimental aggregation-caused quenching(ACQ)effect.Herein,we successfully designed and synthesized an AIE-active di(N,N-dimethylaniline)-dibenzofulvene(named as NFTPE),which exhibits the crystallization-induced emission enhancement(CIEE)effect.Interestingly,two types of yellow-and orange-emissive crystals for NFTPE were obtained,exhibiting aggregation microenvironment-dependent emission tuning in the solid state.Single-crystal analysis and density functional theory(DFT)calculations reveal that different aggregation microenvironments result in the distinct molecular conformation for various emission.Excitingly,the crystallization of NFTPE in an aqueous solution under the assistance of amphiphilic PEG polymer matrices could be monitored in situ by the fluorescence changes,facilitating the preparation of NFTPE nanocrystals(NFTPE-NCs)by adjusting the aggregation microenvironment.The obtained NFTPE-NCs exhibit the superior performance in cell imaging in respect to high brightness,photostability,and biocompatibility,thus demonstrating the potential in bioimaging applications.     

Bruch’s-Mimetic Nanofibrous Membranes Functionalized with the Integrin-Binding Peptides as a Promising Approach for Human Retinal Pigment Epithelium Cell Transplantation

Background: This study aimed to develop an ultrathin nanofibrous membrane able to, firstly, mimic the natural fibrous architecture of human Bruch’s membrane (BM) and, secondly, promote survival of retinal pigment epithelial (RPE) cells after surface functionalization of fibrous membranes. Methods: Integrin-binding peptides (IBPs) that specifically interact with appropriate adhesion receptors on RPEs were immobilized on Bruch’s-mimetic membranes to promote coverage of RPEs. Surface morphologies, Fourier-transform infrared spectroscopy spectra, contact angle analysis, Alamar Blue assay, live/dead assay, immunofluorescence staining, and scanning electron microscopy were used to evaluate the outcome. Results: Results showed that coated membranes maintained the original morphology of nanofibers. After coating with IBPs, the water contact angle of the membrane surfaces varied from 92.38 ± 0.67 degrees to 20.16 ± 0.81 degrees. RPE cells seeded on IBP-coated membranes showed the highest viability at all time points (Day 1, p < 0.05; Day 3, p < 0.01; Days 7 and 14, p < 0.001). The proliferation rate of RPE cells on uncoated poly(ε-caprolactone) (PCL) membranes was significantly lower than that of IBP-coated membranes (p < 0.001). SEM images showed a well-organized hexa/polygonal monolayer of RPE cells on IBP-coated membranes. RPE cells proliferated rapidly, contacted, and became confluent. RPE cells formed a tight adhesion with nanofibers under high-magnification SEM. Our findings confirmed that the IBP-coated PCL membrane improved the attachment, proliferation, and viability of RPE cells. In addition, in this study, we used serum-free culture for RPE cells and short IBPs without immunogenicity to prevent graft rejection and immunogenicity during transplantation. Conclusions: These results indicated that the biomimic BM-IBP-RPE nanofibrous graft might be a new, practicable approach to increase the success rate of RPE cell transplantation.     

Designed fabrication of mesoporous silica-templated self-assembled theranostic nanomedicines

Theranostic nanosystems that integrate diagnosis and therapy have garnered increasing attention for personalized medicine.The integration of the versatile nanoparticles to fabricate self-assembled theranostic nanomedicines becomes increasingly important in current medical research.Mesoporous silica nanoparticles(MSN)with their highly attractive physicochemical properties and favorable morphological attributes represent ideal templates for the controlled assembly and integration of functional nanomaterials to fabricate self-assembled theranostic nanomedicines.The rationally designed combination strategy and heterostructure will improve the overall bioavailability and preserve the unique property of each nanocomponent.In this review,the cutting-edge strategies for the designed fabrication of MSN-templated self-assembled nanomedicines are summarized.We categorize MSN-based nanomedicines by their unique heterostructures,including core-shell,yolk-shell,core-satellite,heterodimer and core-shell-satellite structures,and discuss the controlled assembly approaches as well as the intriguing applications for disease theranostics.Finally,a perspective on the challenges in the clinical translation of self-assembled theranostic nanomedicines is highlighted.     

大学无机化学实验中碱式碳酸铜制备方法探讨

探讨大学无机化学实验中有关碱式碳酸铜制备的实验方法,并以Cu(NO3)2为原料、NaOH和Na2CO3的混合液为沉淀剂制备碱式碳酸铜。讨论反应物最佳配比、pH、温度等因素对产品的影响,并对所制产品进行XRD分析,提出一种制备碱式碳酸铜的大学无机化学实验方法。     

六维近凯勒流形的Kodaira维数

本文主要研究了六维近凯勒流形的典范丛和Kodaira维数.证明了六维严格近凯勒流形的典范丛是拟全纯平凡的,从而其Kodaira维数为0.特别地,证明了三维复射影空间CP3具有Kodaira维数不为-∞的近复结构.对于齐性的六维严格近凯勒流形,具体构造了它们典范丛的整体生成元.证明了齐性近凯勒流形F3和CP3的Hodge...     

痕量钒的分析进展

综述近年来测定痕量钒的主要方法,包括光度法如常规光度法、流动注射光度法、催化动力学光度法、萃取光度法、导数光度法以及原子吸收法、荧光法、交流示波极谱法、催化动力学离子选择电极法和流动注射化学发光法等。     

高速铁路连续箱型梁桥的动力响应与减振分析

根据列车具体的轴距和轴重,建立了和谐号动车组CRH380AL型列车简化模型;对高速铁路两跨连续梁桥采用多自由度欧拉伯努利梁单元进行主梁的模拟,并将液体黏滞阻尼器模拟为有限元阻尼单元;采用Newmark直接积分方法求解了高速列车作用下的连续梁桥运动方程,数值分析了列车车速以及液体黏滞阻尼器的阻尼系数对于高速铁路连续梁桥振动响应的影响。结果表明:黏滞阻尼器对于桥梁具有明显的减振效果,阻尼力不仅与阻尼系数有关还与列车时速有关;同一黏滞阻尼器条件下,桥梁的最大加速度并不随列车速度的增加而单调增加,而是在某些特定列车车速下桥梁的最大加速度出现了峰值,且随着黏滞阻尼器的阻尼系数增大,桥梁振动响应峰值处的最大加速度减幅不同;同一列车时速的条件下,桥梁的减振效果并不是随着阻尼系数的递增呈正比递增,而是随着阻尼系数的增大,阻尼器的减振效果增幅在减小。     

Syntheses,Crystal Structures and Fluorescence Properties of Three Complexes Based on 2,2'-Quinoline-4,4'-dicarboxylic Ligands

Crystallography Reports - Three new coordination complexes, [Mn(L)(H2O)4⋅(H2O)3]2 (1), [Mg(L)(H2O)4⋅(H2O)3]2 (2), and [Cu(L)(phen)⋅(H2O)4]2 (3) (H2L =...