肉桂酰酪胺类似物的合成与抗血小板聚集评价

为了探究肉桂酰酪胺的苯环上甲氧基取代、酪胺上羟基和酰胺上胺基被甲基化对衍生物抗血小板聚集活性的影响,以8种苯甲醛衍生物为原料,经过缩合反应及甲基化等反应制得肉桂酰酪胺类似物,经核磁共振波谱仪(NMR)、质谱(MS)、单晶衍射等技术手段表征了目标化合物结构。 基于变温核磁,探讨了化合物4a~4h中旋转异构及酰胺C-N键双键性质对氢核磁谱的影响。 采用Born比浊法对目标化合物进行活性筛选,9个类似物的活性均强于柄果花椒酰胺,特别是化合物2c、4c、4f在200 μmol/L时显示出强的抑制率,分别为50.03%、60.87%、53.33%。 该类化合物的构效关系是4位甲氧基取代对化合物的抗ADP(二磷酸腺苷)诱导血小板聚集活性最为有利,甲基化B环中的羟基和结构中的酰胺氮原子时,在某种程度上可增强化合物活性。     

Design and Synthesis of Proteolysis Targeting Chimeras for Inducing BRD4 Protein Degradation

In this paper, we synthesized a series of proteolysis targeting chimeras(PROTACs) using VHL E3 ligase ligands for BRD4 protein degradation. One of the most promising compound 19g exhibited robust potency of BRD4 inhibition with IC₅₀ value of (18.6±1.3) nmol/L, respectively. Furthermore, compound 19g potently inhibited cell proliferation in BRD4-sensitive cell lines RS4;11 with IC₅₀ value of (34.2±4.3) nmol/L and capable of inducing degradation of BRD4 protein at 0.4—0.6 µmol/L in the RS4;11 leukemia cells. These data show that compound 19g is a highly potent and efficacious BRD4 degrader.     

不同酸解聚麦秸产物分析及其动力学

以麦秸为研究对象,解聚剂为HCl、HNO₃和H₃PO₄,对解聚产物进行定性和定量分析,并利用动力学模型描述木糖及糠醛的产生过程。 结果表明,解聚液中的产物有葡萄糖、木糖、阿拉伯糖、纤维二糖、乙酸、糠醛、5-羟甲基糠醛。 通过引入变量(α,木糖/木聚糖的比值)利用Saeman动力学模型获得了不同温度下,木聚糖的水解速率常数、木糖的转化速率常数以及糠醛的生成速率常数。 HCl、HNO₃和H₃PO₄解聚麦秸,木糖的生成活化能分别为55.5、46.3和59.8 kJ/mol。 结合反应温度、反应时间、反应速率以及木糖和糠醛的浓度,确定最佳解聚条件为:硝酸作解聚剂,在130 ℃下水解95 min。     

Highly effective binding and inverse fluorescent behavior of palmatine and l-tetrahydropalmatine alkaloids by p-sulfonatocalixarenes

The effects of pressure and solvent were examined for the inclusion complexation of phenothiazine dyes and trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium (St-4Me) with water-soluble p-sulfonatocalix[8]arene (Calix-S8). Depending on the bulkiness of the guest dyes, external pressures and solvent polarity increase the inclusion equilibrium constants of dyes with Calix-S8. From the pressure dependence of the inclusion equilibria, the reaction volumes for inclusion by Calix-S8 in the alcohol-water mixtures were estimated to be negative values (?19.8 to ?5.29 cm³ mol^?1 for the phenothiazine dyes and ?13.1 to ?9.85 cm³ mol^?1 for St-4Me). Analysis of the results of the high pressure indicated that the intrinsic volume change related to inclusion into the Calix-S8 cavity plays an important role in the inclusion of Calix-S8, depending on the bulkiness of the guest molecules. Based on ¹H NMR measurements, the structures of the inclusion complexes of Calix-S8 with phenothiazine dyes have been established and the differences in the inclusion behaviors of the phenothiazine dyes and St-4Me are discussed.     

细管电泳-激光诱导荧光检测用于多个胞内蛋白激酶的抑制剂筛选和选择性评价

发展了一种基于毛细管电泳(CE)-激光诱导荧光(LIF)检测的多个细胞内源激酶的抑制剂平行筛选及选择性评价方法。CE高效的分离能力和LIF检测器的高选择性,使得同时测试多个胞内激酶的活性成为可能。共4种细胞系、3种特异性蛋白激酶底物肽、2种选择性蛋白激酶抑制剂和1种非选择性蛋白激酶抑制剂用于方法的建立。特异性底物肽与细胞裂解液混合后孵育,被其相应的激酶选择性地磷酸化,利用CE-LIF分离检测磷酸化产物和底物肽。同时测定一个抑制剂对几种蛋白激酶的抑制活性,用于评价抑制剂的选择性。与传统的单靶标筛选模式相比,这种基于细胞裂解液的多靶标筛选方法能提供更多的信息,更加高效,且细胞裂解液作为一种廉价的激酶来源大大降低了筛选成本。     

亲水/反相二维色谱法制备桔梗中的三萜皂苷

建立了亲水/反相二维色谱用于制备桔梗中三萜皂苷单体的方法。桔梗经水煮醇沉、反相和亲水两种模式的固相萃取后得到三萜皂苷类组分。选定XAmide色谱柱（150 mm×20 mm,5 μm）,以乙腈和水为流动相,在亲水色谱模式下进行组分制备。选择时间触发模式,以1 min为单位进行馏分收集,得到6~25 min之间的20个三萜皂苷精细组分。以第18个馏分（JG23）为例,在反相色谱模式下采用Atlantis Prep T3色谱柱（100 mm×30 mm,5 μm）制备,得到两个单体化合物。通过质谱和核磁共振对其进行定性,确定分别为deapi-platycoside E和platycoside E。实验结果表明,该制备方法具有好的正交选择性,对于复杂样品中三萜皂苷类化合物的分离纯化有一定的借鉴意义。     

Using Laser Measuring and SFM Algorithm for Fast 3D Reconstruction of Objects

Effective measurement of the reflective or transparent surface of an object has always been a disadvantage in laser scanning modeling. We propose a fast and complete three-dimensional (3D) reconstruction method for small static objects using laser scanning and the structure from motion (SFM) algorithm. Meanwhile, a complete reconstruction workflow is designed and a multi-angle 3d reconstruction system is set up. To generate the complete point cloud model of the object, the SFM algorithm is used to reconstruct the surface part of the object, the data for which cannot be obtained by the laser measuring instrument. The experimental results show that this method not only improves the speed, accuracy, integrity, and visual effect of 3D reconstruction of small objects, but also extends the scope of 3D reconstruction of laser measurement.     

Exhaled gas detection by a novel Rh-doped CNT biosensor for prediagnosis of lung cancer: a DFT study

Lung cancer has received considerable attention in recent years due to its high mortality. The difficulty in awareness of such disease can be attributed to its strong insidiousness during the early stage. Therefore, the prognosis of lung cancer becomes significant so as to nip this disease in the bud. In this paper, the Rh-doped CNT-based biosensors were introduced to realise the diagnosis of lung cancer through detecting the exhaled gas of possible patients. The adsorption property and sensing mechanism of Rh-CNT towards two kinds of mainly typical gases of lung cancer, namely, C₆H₆ and C₆H₇N, were analysed based on density functional theory, aiming at evaluating the potential application of such material to be gas sensors. The results indicated that the Rh-CNT not only has good adsorption towards such two gases but also obvious conductivity increase when interacted with any of them, while presents insensitivity upon the common exhaled gas, CO₂. We suggest the Rh-CNT be prepared as biosensors applied in the field of lung cancer pre-diagnosis that can be used in our daily life without pain and complex clinical examination.     

Porous sulfated metal oxide SO<Subscript>4</Subscript><Superscript>2−</Superscript>/Fe<Subscript>2</Subscript>O<Subscript>3</Subscript> as an anode material for Li-ion batteries with enhanced electrochemical performance

Sulfated metal oxide SO₄ ^2?/Fe₂O₃ was prepared by a novel facile sol–gel method combined with a subsequent heating treatment process. The as-synthesized products were analyzed by XRD, FTIR, and FE-SEM. Compared with the unsulfated Fe₂O₃, the agglomeration of particles has been alleviated after the incorporation of SO₄ ^2?. Interestingly, the primary particle size of the SO₄ ^2?/Fe₂O₃ (about 5 nm) is similar to its normal counterparts even after the calcination treatment. More importantly, SO₄ ^2?/Fe₂O₃ exhibits a porous architecture, which is an intriguing feature for electrode materials. When used as anode materials in Li-ion batteries, SO₄ ^2?/Fe₂O₃ delivered a higher reversible discharge capacity (992 mAh g^?1), with smaller charge transfer resistance, excellent rate performance, and better cycling stability than normal Fe₂O₃. We believed that the presence of SO₄ ^2? and porous architecture should be responsible for the enhanced electrochemical performance, which could provide more continuous and accessible conductive paths for Li⁺ and electrons.     

可溶液加工蓝色聚集诱导发光小分子的合成及其器件性能

利用四苯基甲烷中碳原子特殊的sp³轨道杂化结构来打断并控制分子内共轭程度,并采用硅原子替换四苯基甲烷中的碳原子合成四苯基硅烷.将这两种结构作为核,在其四周以四苯乙烯（TPE）或三苯乙烯（triPE）修饰,设计并合成了六个具有聚集诱导发光（AIE）效应的小分子.这些分子均可以溶解在常见有机溶剂中并具有良好的热稳定性.通过溶液旋涂法将其应用到有机电致发光器件（OLED）中,得到最好的器件效率为亮度最大值（L_max）1730 cd·m^-2,电流效率最大值（L_max）2.21 cd·A^-1,功率最大值（η_p,max）0.77 lm·W^-1,外量子效率最大值（η_ext,max）1.01%.