The metabolites and biotransformation pathways in vivo after oral administration of ocotillol,RT5, and PF11

Ocotillol, pseudo-ginsenoside RT5 (RT₅), and pseudo-ginsenoside F₁₁ (PF₁₁) are ocotillol-type saponins that have the same aglycone structure but with different numbers of glucose at the C-6 position. In this study, the metabolites of ocotillol, RT₅, and PF₁₁ in rat plasma, stomach, intestine, urine, and feces after oral administration were investigated by ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry. The results showed that RT₅ was easily biotransformed into metabolites in vivo, whereas PF₁₁ and RT₅ were difficult to be biotransformed. Hydrogenation, dehydrogenation, dehydration, deglycosylation, deoxygenation, hydration, phosphorylation, deoxidation, glucuronidation, and reactions combining amino acid were speculated to be involved in the biotransformation of ocotillol, RT₅, and PF₁₁. Based on the structural analysis of metabolites, it was deduced that hydrogenation, dehydration, deoxidation, and reactions combining amino acid occurred on the aglycone structure, whereas deglycosylation, hydration, and phosphorylation occurred on the glycosyl chain. Further, metabolites in plasma, urine, feces, and tissues were different: First, glucuronidation products were found in urine, stomach, intestine, and feces, but not in plasma. Second, the ocotillol prototype was not identified in urine samples. Third, the RT₅ prototype was found in stomach, intestine, feces, and urine, but not in plasma.     

A multifunctional silicotungstic acid-modified Li-rich manganese-based cathode material with excellent electrochemical properties

Journal of Solid State Electrochemistry - Li-rich layered oxide (LrLO) cathode has attracted much attention for Li-ion batteries in recent years due to its superior capacity of exceeding...     

A New Quassinoid from Brucea javanica

Chemistry of Natural Compounds - A new quassinoid, dehydrobruceantinol B (1), was isolated from the seeds of Brucea javanica, together with two known compounds, bruceantinol (2) and bruceine A (3)....     

二氢嘧啶并[4,5-d]嘧啶类衍生物作为集落刺激因子-1受体激酶抑制剂的分子对接和定量构效关系研究

集落刺激因子-1受体激酶（CSF-1R）属于Ⅲ型受体酪氨酸激酶家族成员，其在调控单核巨噬细胞系中发挥重要作用。CSF-1R及其配体异常表达与肿瘤发展过程密切相关。因此，CSF-1R信号传导可成为抗肿瘤治疗的有吸引力的靶标。本文用比较分子场分析法（CoMFA）和比较分子相似性指数分析法（CoMSIA）研究了54个二氢嘧啶并[4,5-d]嘧啶类CSF-1R激酶抑制剂的三维定量构效关系（3D-QSAR）。基于配体叠合，CoMFA和CoMSIA模型的交叉验证系数（q2）分别为0.725和0.636，拟合验证系数（r2）分别为0.960和0.958，结果表明这两种模型均具有较好的预测能力。所建模型的等势图能直观反映分子不同取代基对活性的影响，其中立体场和疏水场对活性的贡献较大。通过分子对接研究显示，氨基酸残基Cys666、Asp796在配体和受体结合过程中产生作用，分子对接的结合模式与3D-QSAR得到的结果一致。这些信息为进一步优化CSF-1R激酶抑制剂提供了理论基础。     

Syntheses and structures of two novel fluorescent metal–organic frameworks generated from a tridentate donor–acceptor motif ligand

The tridentate organic ligand 4,4′,4′′‐(4,4,8,8,12,12‐hexamethyl‐8,12‐dihydro‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐2,6,10‐triyl)tribenzoic acid ( H₃L ) has been synthesized (as the methanol 1.25‐solvate, C₄₈H₃₉NO₆·1.25CH₃OH). As a donor–acceptor motif molecule, H₃L possess strong intramolecular charge transfer (ICT) fluorescence. Through hydrogen bonds, H₃L molecules construct a two‐dimensional (2D) network, which pack together into three‐dimensional (3D) networks with an ABC stacking pattern in the crystalline state. Based on H₃L and M(NO₃)₂ salts (M = Cd and Zn) under solvothermal conditions, two metal–organic frameworks (MOFs), namely, catena‐poly[[triaquacadmium(II)]‐μ‐10‐(4‐carboxyphenyl)‐4,4′‐(4,4,8,8,12,12‐hexamethyl‐8,12‐dihydro‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐2,6‐diyl)dibenzoato], [Cd(C₄₈H₃₇NO₆)(H₂O)₃]_n, I , and poly[[μ₃‐4,4′,4′′‐(4,4,8,8,12,12‐hexamethyl‐8,12‐dihydro‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐2,6,10‐triyl)tribenzoato](μ₃‐hydroxido)zinc(II)], [Zn₂(C₄₈H₃₆NO₆)(OH)]_n, II , were synthesized. Single‐crystal analysis revealed that both MOFs adopt a 3D structure. In I , partly deprotonated HL ^2? behaves as a bidentate ligand to link a Cd^II ion to form a one‐dimensional chain. In the solid state of I , the existence of weak interactions, such as O—H…O hydrogen bonds and π–π interactions, plays an essential role in aligning 2D nets and 3D networks with AB packing patterns for I . The deprotonated ligand L ^3? in II is utilized as a tridentate building block to bind Zn^II ions to construct 3D networks, where unusual Zn₄O₁₄ clusters act as connection nodes. As a donor–acceptor molecule, H₃L exhibits fluorescence with a photoluminescence quantum yield (PLQY) of 70% in the solid state. In comparison, the PL of both MOFs is red‐shifted with even higher PLQYs of 79 and 85% for I and II , respectively.     

多层面验证共培养微环境诱导法诱导骨髓间充质干细胞心肌样分化

为了多层面探讨共培养微环境诱导法定向诱导骨髓间充质干细胞(MSCs)心肌样分化的可行性,取第3代MSCs与原代心肌细胞(CMs)进行共培养。在显微镜下观察诱导1周后的MSCs形态学变化,用免疫荧光和实时荧光定量聚合酶链式反应(RT-PCR)分别检测诱导的MSCs中心肌肌钙蛋白I(cTnI)、α-肌动蛋白(α-actin)、Nkx-2.5和GATA-4的基因表达变化情况。采用超高效液相色谱-串联质谱(UPLC-MS/MS)分别检测诱导组和对照组的代谢产物。诱导1周后的MSCs形态呈心肌样改变,cTnI、α-actin、Nkx-2.5和GATA-4的基因表达均明显升高,正交偏最小二乘法判别分析(OPLS-DA)模型显示诱导的MSCs代谢物向CMs转变趋势明显。通过多元和单元统计分析筛选差异变量,根据一级质谱和二级质谱比对结果,最终确定12种差异代谢物。与未经诱导的MSCs相比,经诱导的MSCs与CMs中变化趋势相同的差异代谢物有7种,变化趋势不同的差异代谢物有5种。实验结果表明,无论从形态、基因、蛋白质还是代谢层面看,MSCs通过与CMs间接接触共培养后均发生了心肌样改变,但是与CMs仍存在差异。