Probing metabolic alterations in breast cancer in response to molecular inhibitors with Raman spectroscopy and validated with mass spectrometry

Rapid and accurate response to targeted therapies is critical to differentiate tumors that are resistant to treatment early in the regimen. In this work, we demonstrate a rapid, noninvasive, and label-free approach to evaluate treatment response to molecular inhibitors in breast cancer (BC) cells with Raman spectroscopy (RS). Metabolic reprogramming in BC was probed with RS and multivariate analysis was applied to classify the cells into responsive or nonresponsive groups as a function of drug dosage, drug type, and cell type. Metabolites identified with RS were then validated with mass spectrometry (MS). We treated triple-negative BC cells with Trametinib, an inhibitor of the extracellular-signal-regulated kinase (ERK) pathway. Changes measured with both RS and MS corresponding to membrane phospholipids, amino acids, lipids and fatty acids indicated that these BC cells were responsive to treatment. Comparatively, minimal metabolic changes were observed post-treatment with Alpelisib, an inhibitor of the mammalian target of rapamycin (mTOR) pathway, indicating treatment resistance. These findings were corroborated with cell viability assay and immunoblotting. We also showed estrogen receptor-positive MCF-7 cells were nonresponsive to Trametinib with minimal metabolic and viability changes. Our findings support that oncometabolites identified with RS will ultimately enable rapid drug screening in patients ensuring patients receive the most effective treatment at the earliest time point.

Rapid and accurate response to targeted therapies is critical to differentiate tumors that are resistant to treatment early in the regimen.     

A density functional study on magnetic exchange interaction between Mn(II) ion and nitronyl nitroxide radical in <Emphasis Type="Italic">trans</Emphasis>-and <Emphasis Type="Italic">cis</Emphasis>-metal-radical complexes

The magneto-structural correlation between a Mn(ll) ion, coordinated in an octahedral environment, and two nitronyl nitroxide radical ligands in trans- and cis-metal-radical complexes is investigated by the broken symmetry (BS) approach within density functional theory (DFT). The dependences of coupling constants J on three structural parameters: (i) bond angle θ (Mn-O-N (nitroxide)); (ii) rotating angle ψ, defined by the nitronyl nitroxide radical plane rotating around the axial Mn-O (nitroxide); (iii) bond distance R (Mn-O (nitroxide)) are directly calculated. Our calculations showed that both trans- and cis-Mn(ll)-radical complexes behave a stronger antiferromagnetic interaction, consistent with experiments. In view of molecular orbital theory, the direct exchanges, including σ-type and π-type exchanges, are responsible for the magnetic exchange pathways. There is a preferable linear correlation between the calculated coupling constants J and the overlap integral squares S b between the local magnetic orbitals at the various rotating angle ψ at the fixed bond angle θ and bond distance R, in both trans- and cis-Mn(ll)-radical complexes.     

2,6-O-二戊基-3-O-三氟乙酰β-环糊精和聚硅氧烷混合手性石英毛细管柱分离对映体

本文合成了部分烷基化三氟乙酰化的β-环糊精手性固定相(DP-TFA-β-CD),并把它与普通聚硅氧烷OV-7混合制备出了柱效高、热稳定性好的手性石英毛细管柱。与直接涂DP-TFA-β-CD相比,混合固定相能在较短分析时间内对卤代烃、醇、酯、γ-内酯、胺等对映体有更好的拆分。     

Carbonylation of Benzyl Halides Over Two-Phase Catalyst of Iron Pentacarbonyl

Carbonylation of benzyl halides to phenylacetic acid was studied in a two-phase system with iron pentacarbonyl as the catalyst precursor. The solutions consisted of a benzyl halide and iron pentacarbonyl in benzene and tetrabutylammonium hydrogen sulfate in aqueous sodium hydroxide. Stirring under carbon monoxide readily produced phenylacetic salts in aqueous phase which were then acidified and extracted with ether. The yields of phenylacetic acid from benzyl iodide and from benzyl bromide were similar at a evel of about 50percnt;, that of the latter being higher by 1%. The yield from benzyl chloride was far less, at a level of only 21%. The rate as studied with gas chromatography was found to decrease in the order benzyl iodide>benzyl bromide>benzyl chloride.     

3—（3,5—二氨基—2,4,6—三硝基苯基）氨基—5—硝基—1,2,4—三唑的合成

多硝基多氨基三唑类衍生物作为含能材料,具有高氮、致密、钝感等优点。本文通过3-氨基-1,2,4-三唑和三硝基三氯苯的缩合,再经过三唑碳原子上的硝化反应和芳环上的氨化反应,合成并鉴定了标题化合物。     

超高效液相色谱-串联质谱法测定茶叶中游离氨基酸成分

建立了使用超高效液相色谱-串联质谱（UHPLC-MS/MS）高效、快速直接测定茶叶中游离氨基酸的方法。通过对质谱、色谱条件及氨基酸提取条件的优化，以含0.2%（体积分数）甲酸的5 mmol/L乙酸铵水溶液和甲醇为流动相进行梯度洗脱，在电喷雾离子（ESI）源正离子扫描模式下检测，通过UHPLC-MS/MS测定，共解析了茶叶中的20种氨基酸。结果表明，茶氨酸（Thea）、Arg、Asn和Asp在50~500 μg/L范围内线性关系良好，其他氨基酸在10~250 μg/L范围内线性关系良好，相关系数均大于0.99；加标回收率为92.3%~109.2%，相对标准偏差为2.00%~9.88%，检出限为0.001~0.011 mg/L，定量限为0.010~0.053 mg/L。该方法灵敏、准确，具有良好的重复性和稳定性，可有效检测出茶叶中的20种氨基酸及氨基类成分。     

手性高效液相色谱法测定1—（6‘—甲氧基萘）乙醇不对称氢酯基化反应

在自制的硅基纤维素－三（３，５－二甲基苯基氨基甲酸酯）高效液相色谱手性固定相上（ＨＰＬＣ－ＣＳＰ），优化了１－（６＇－甲氧基萘）乙醇氢酯基化反应产物－萘普生甲酯手性分离的条件，测定了相应的一系列不对称氢酯基化反应产物的对映体过剩值（ｅ．ｅ．值）。结果表明，在ＣＤＭＰＣ－ＣＳＰ手性柱上用ＨＰＬＣ测定此类不对称催化反应的光学产率，评价催化剂体系的手性选择是一种非常理想的方法。     

Probing water interactions and vacancy production on gadolinia-doped ceria surfaces using electron stimulated desorption

Polycrystalline gadolinia-doped ceria (GDC) surfaces were studied using low-energy (5-400 eV) electron stimulated desorption (ESD). H(+), O(+), and H(3)O(+) were the primary cationic desorption products with H(+) as the dominant channel. H(+), H(3)O(+), and O(+) have a 22 eV threshold followed by a yield change around 40 eV. H(+) also has an additional yield change approximately 75 eV and O(+) has an additional change approximately 150 eV. The O(+) ESD yield change approximately 150 eV may indicate bond breaking of Gd-O and the involvement of oxygen vacancies. The H(+) and H(3)O(+) threshold data collectively indicate the presence of hydroxyl groups and chemisorbed water molecules on the GDC surfaces. ESD temperature dependence measurements show that the interaction of water with GDC surface defect sites, mainly oxygen vacancies, influences the desorption of H(+), O(+), and H(3)O(+). The temperature dependence of the O(+) ESD at 400 eV incident electron energy yields a 0.21 eV activation energy. This is close to the energy needed for oxygen vacancy production next to a pair of Ce(3+) on a CeO(2) surface. These results may indicate a correlation between the O(+) ESD yield and oxygen vacancy density on GDC surfaces and a potential correlation of O(+) ESD and GDC ionic conductivity.     

缝管原子捕集原子吸收光谱法测定维生素B12

本文研究了Ａｌ２Ｏ２涂层的开缝石英管原子捕集法测定ＣＯ的条件并通过测ＣＯ间接测定维生素Ｂ（１２）。结果表明，在优化条件下Ｃｏ的特征浓度为８×１０（－３）μｇ·ｍＬ（－１），比常规火焰原子吸收法的灵敏度提高８倍。采用本法测定腺苷辅酶维生素Ｂ（１２）中ＶＢ（１２）的含量，相对标准偏差１．１％，加标回收率９８．２～１００．４％。     

低分子量溴代聚苯乙烯的制备及应用

用溶液法合成了一系列低分子量的聚苯乙烯，其溴化产物（Ｂｒ－ＰＳ）的溴含量和热稳定性与美国同类产品Ｐｙｒｏ－Ｃｈｅｋ ＬＭ相当，分别用作聚苯乙烯树脂的阻燃剂，极限氧指数测定结果表明，其阻燃性也达到了Ｐｙｒｏ－Ｃｈｅｋ ＬＭ的水平。