质子转移反应质谱对肺癌患者呼气中特征性VOCs的筛选及研究

利用质子转移反应质谱(PTR-MS)对40名肺癌患者、32名健康志愿者呼出气体中的挥发性有机物(VOCs)进行检测,Mann-Whitney秩和检验与多因素logistic回归的结果表明,呼气中VOC 33、VOC 39、VOC 45可能为肺癌人群的呼气标志物,同时VOC 45在小细胞肺癌和非小细胞肺癌患者之间存在显著差异。以肺癌人群的呼气标志物作为自变量,采用二元logistic回归分析和Fisher判别分析分别建立肺癌预测模型。logistic回归模型的受试者工作曲线下面积(AUC)达到0.878,灵敏度和特异性分别为85.5%和63.5%。Fisher判别模型的受试者工作曲线下面积(AUC)达到0.822,灵敏度和特异性分别为82.5%和62.5%。两种模型对肺癌的预测均具有统计学意义。     

基于呼气中特异性VOCs筛查的肺癌早期诊断与模型评估

采用气相色谱-质谱联用仪（GC-MS）检测了180例受试者的呼出气样品,包括79名肺癌患者和101名健康志愿者。每个受试者采集3个平行样品,以及1个室内空气样品。对所有呼气样品中检测的92种挥发性有机物（VOCs）进行定量分析。结合Mann-Whitney检验和正交偏最小二乘判别分析（OPLS-DA）模型筛选出10种肺癌患者呼气特异性VOCs,包括苯甲醛、顺式-2-丁烯、2-丁酮、萘、乙酸乙烯酯、乙烯、2,2,4-三甲基戊烷、3-甲基戊烷、己醛和2-甲基戊烷。利用统计学方法研究其在不同人群中的代谢差异和可能相关的代谢机制,通过建立机器学习模型验证候选标志物对疾病的诊断性能,结果显示,随机森林模型诊断的准确度、精准率、灵敏度和特异性分别为96.25%、96.21%、95.76%、96.67%,马修斯相关系数（MCC）为0.93,曲线下面积为0.96。上述10种化合物可作为肺癌患者的潜在呼气VOCs标志物,为肺癌的早期诊断提供了丰富的基础数据。     

质子转移反应-飞行时间质谱检测呼出气体中痕量挥发性有机物

通过对自主研制的质子转移反应飞行时间质谱(PTR-TOF-MS)进样口的改造,实现了对呼出气体的实时、在线定量检测,并对23名志愿者(11名男性健康受试者、11名女性健康受试者和1名胃病患者)的呼出气体进行28天的实时在线监测。结果表明,健康人群呼出气体中主要的挥发性有机物(VOCs)为甲醛、丙烯、乙醛、丙酮、异丙醇和异戊二烯等,浓度基本服从对数正态分布,且甲醛、丙烯、异丙醇主要集中在40~100 ppb浓度范围内,乙醛的浓度主要集中在80~180 ppb浓度范围内,丙酮主要集中在500~1500 ppb浓度范围内,异戊二烯主要集中在8~20 ppb的浓度范围内;呼出气体浓度在性别上也存在差异,其中,受试人群中男性呼出气体中丙酮的浓度高于女性,而乙醛和异丙醇浓度低于女性。胃病患者的呼出气体中甲醛和丙酮含量明显高于健康人群;乙醇和乙醛是饮酒者呼出气体的主要标志物,乙醛是乙醇的代谢产物,随着乙醇浓度的变化而变化。     

基于气相离子迁移谱研究肺隐球病患者呼出气中特征挥发性有机物

该文采用气相色谱离子迁移谱(GC-IMS)对81例受试者呼出气样品进行了检测,包括临床确诊的20例肺隐球菌病患者,以及28例临床确诊的肺曲霉病患者和33例健康个体的对照样品,单个样品分析仅需10 min。结果显示,所有呼气样品中共检出19种挥发性有机物(VOCs)。通过主成分(PCA)分析发现,肺隐球病患者呼气中VOCs与健康对照组差异显著,但与肺曲霉病患者呼气中VOCs差异不显著。正交偏最小二乘判别模型(OPLS-DA)分析显示,与健康人群相比,肺隐球菌病患者呼气中特征VOCs为2-甲基-1-丙醛、异丙苯、2-戊酮、4-甲基-2-戊酮、丁醛和己醛;肺曲霉病患者的呼气特征VOCs为2-丁酮、2-戊酮、异丙苯、2-甲基-1-丙醛、4-甲基-2-戊酮和3-戊酮。此外,2种肺部感染患者呼气中特征性VOCs均包括2-甲基-1-丙醛、异丙苯、4-甲基-2-戊酮和2-戊酮,这表明丁醛和己醛在肺隐球菌病患者呼气中特异性略强,而2-丁酮和3-戊酮在肺曲霉病患者呼气中特异性更好。综上,采用GC-IMS可快速检出肺隐球病患者呼气中的VOCs,可用于后续数百例甚至数千例大样本分析,为更客观地评价呼气用于肺部真菌感染诊断的可行性提供必要的基础数据。     

高危儿在顺产与剖腹产中娩出时产生糖代谢紊乱的研究分析

目的分析高危儿在顺产与剖腹产中娩出时血糖的特点,探讨防治糖代谢紊乱路径。方法选取2013年12月至2014年6月于广东省连州市妇幼保健计划生育服务中心产科娩出的85例高危儿为研究对象,按娩出方式分为剖腹产组43例,顺产组42例,应用罗氏血糖检测仪分析高危儿娩出后血糖水平(全血血糖低于2.2 mmol/L诊断为低血糖,全血血糖高于7.0 mmol/L诊断为高血糖),并针对血糖异常制定糖代谢紊乱预防方案,比较两组出生后24 h内的血糖水平。结果顺产组糖代谢紊乱率11.9%显著低于剖腹产组30.2%(P0.05);娩出时剖腹产新生儿脐血的血糖(2.14±0.37)mmol/L明显低于顺产组(2.63±0.59)mmol/L(P0.05),出生后24 h内剖腹产组血糖水平与顺产组比较无显著差异(P0.05)。结论剖宫产高危儿较容易发生血糖异常,出现糖代谢紊乱,故在高危儿出生后应及时监测血糖变化,并采取措施防治血糖异常引起的糖代谢紊乱。     

热脱附-气相色谱-质谱法筛查分析溶剂型涂料中挥发性有机化合物

为检测溶剂型涂料中挥发性有机物(VOCs)的释放量,利用1m~3气候箱,在温度(23±2)℃和相对湿度(50±5)%、箱内空气换气率为1次·h~(-1)的条件下,以钢化玻璃板(30cm×30cm)为基材,将涂料样品(约10g)涂覆在玻璃板上,置于气候箱中,关闭箱门并开始计时。此前已将老化的Tenax TA吸附管靠近吸附剂的一端与气候箱连接,另一端与采样连接,调节流量为0.20L·min~(-1),采集2h时的空气样品。将吸附管放入热脱附-气相色谱-质谱仪器系统中,按工作条件对65种VOCs进行分离和测定。样品经热脱附并流经HP-VOC色谱柱,恒压模式,在35～250℃之间程序升温进行VOCs的分离,进入质谱仪,在电子轰击离子源(EI)全扫描模式进行测定。试验结果表明:二氯甲烷、四氯化碳和乙二醇的信号较弱,标准曲线的线性不佳,其余62种VOCs的标准曲线的线性范围均在0.01～0.20μg之间,其检出限(3S/N)在0.018～0.25μg·kg~(-1)之间,此62种VOCs的加标回收率在85.0%～116%之间。对市售的8种溶剂类涂料,按本方法进行筛查和分析,被检出频次较高的为芳香烃、醇、烷烃、酯醚等4大类;从所检测得到的VOCs的含量可见,其中芳香烃和酯醚类VOCs的释放占大部分,8种涂料第2h采样VOCs的释放总量分别为2.51,2.29,1.54,1.47,1.64,13.01,3.37,17.14mg·kg~(-1)。     

高效液相色谱-程序波长紫外检测法同时测定血浆中的色氨酸及其代谢物

建立了一种高效液相色谱-程序波长紫外检测法同时测定血浆中色氨酸(Trp)及其主要代谢产物犬尿氨酸(Kyn)和5-羟色胺(5-HT)。以茶碱为内标(IS),采用BDS-Hypersil-C8柱(150 mm×4.6 mm, 5 μm)分离。流动相为10 mmol/L醋酸钠缓冲液(pH 4.5)-乙腈(94:6, v/v),流速为0.6 mL/min;柱温为25 ℃;紫外检测波长设定: Kyn和IS为360 nm, 5-HT为220 nm, Trp为302 nm。3种物质的平均回收率为87%～113%;线性范围分别为3.97～400 μmol/L(Trp), 0.421～20.2 μmol/L(Kyn), 4.36～980 nmol/L(5-HT);检出限分别为0.134 μmol/L(Trp), 0.0160 μmol/L(Kyn), 2.03 nmol/L(5-HT)。利用该方法对15例抑郁症患者和15例健康志愿者的血浆进行测定,结果表明两组间Trp的代谢存在显著的差异。     

呼气中挥发性硫化物的质子转移反应质谱在线检测

利用自主研制的高灵敏呼气检测质子转移反应质谱(PTR-MS),对一名口臭受试者的口腔吹出气体、鼻子呼出气体和口腔内气体分别进行多组分实时监测,发现了该受试者呼气中3种引起口臭的挥发性硫化物(VSCs)的来源并不相同,其中甲硫醇主要来源于口腔,硫化氢和二甲基硫则主要来源于肺或呼吸道.本研究不仅发现了口腔内气体在PTR-MS呼气监测过程中的特征变化趋势,还分析了呼出气体中3种VSCs的来源,对于呼气的正确采样和检测具有重要的指导意义.     

主成分分析-近红外光谱法快速测定婴儿配方乳粉中必需脂肪酸

利用主成分分析法将婴儿乳粉的近红外光谱数据与必需脂肪酸含量建立校正模型,并采用交互验证和外部检验两种方式来考察模型的可靠性。得到模型校正相关系数(R2)0.8704,均方估计残差(RMSEC)和交互校验均方残差(RMSECV)分别为0.6275和0.8907,应用所建立的必需脂肪酸近红外模型对婴儿乳粉必需脂肪酸含量进行预测,并将预测值和化学测量值进行配对t检验,结果表明两者无显著差异。     

气相色谱-质谱法测定空气清新剂中23种挥发性有机物

应用气相色谱-质谱联用法测定空气清新剂中23种挥发性有机物(VOCs)的含量。取经预处理的样品0.500 0g于10mL刻度管中,加入混合内标溶液0.10mL作为定量依据,用三乙酸甘油酯定容至10.0mL,加入无水硫酸钠3g,涡旋脱水并静置1h后取上清液1.0mL,经滤膜过滤,取滤液按仪器工作条件进行操作。经试验,在样品的稀释以及内标溶液和VOCs标准溶液的配制中均选用三乙酸甘油酯作为稀释溶剂。混合内标溶液中包含两种化合物(丙二醇乙醚和溴苯),两者的质量浓度均为200mg·L-1;测定23种VOCs中的3种醚类化合物时用丙二醇乙醚为内标,测定其余化合物时以溴苯为内标。GC分离中选用DB-FFAP极性色谱柱和DB-1非极性色谱柱作为分离柱,DB-FFAP柱对23种VOCs和2种内标物均能达到良好分离,但由于样品含大量乙醇和水,干扰了苯、甲苯、α-蒎烯、丁酸乙酯和乙酸丁酯的分离,因此选用DB-1柱对以上5种化合物分离。所测定的23种VOCs的线性范围均在0.50～10.00mg·L-1之间,其检出限(3S/N)均小于10mg·kg-1。在10,20,100,200mg·kg-1等4个浓度水平上进行加标回收试验,测得回收率在88.3%～113%之间;测定值的相对标准偏差(n=6)除丙酮在加入量为10mg·kg-1时为6.5%,其他均小于5.0%。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.