Multiplex metal-detection based assay (MMDA) for COVID-19 diagnosis and identification of disease severity biomarkers

The ongoing COVID-19 pandemic caused by SARS-CoV-2 highlights the urgent need to develop sensitive methods for diagnosis and prognosis. To achieve this, multidimensional detection of SARS-CoV-2 related parameters including virus loads, immune response, and inflammation factors is crucial. Herein, by using metal-tagged antibodies as reporting probes, we developed a multiplex metal-detection based assay (MMDA) method as a general multiplex assay strategy for biofluids. This strategy provides extremely high multiplexing capability (theoretically over 100) compared with other reported biofluid assay methods. As a proof-of-concept, MMDA was used for serologic profiling of anti-SARS-CoV-2 antibodies. The MMDA exhibits significantly higher sensitivity and specificity than ELISA for the detection of anti-SARS-CoV-2 antibodies. By integrating the high dimensional data exploration/visualization tool (tSNE) and machine learning algorithms with in-depth analysis of multiplex data, we classified COVID-19 patients into different subgroups based on their distinct antibody landscape. We unbiasedly identified anti-SARS-CoV-2-nucleocapsid IgG and IgA as the most potently induced types of antibodies for COVID-19 diagnosis, and anti-SARS-CoV-2-spike IgA as a biomarker for disease severity stratification. MMDA represents a more accurate method for the diagnosis and disease severity stratification of the ongoing COVID-19 pandemic, as well as for biomarker discovery of other diseases.

A MMDA platform is developed by using metal-tagged antibodies as reporting probes combined with machine learning algorithms, as a general strategy for highly multiplexed biofluid assay.     

遗传光度法用于地质样品中多组分同时测定

将遗传算法（ＧＡ）用于地质样品中１５个稀土元素同时测定,分析结果与ＩＣＰ法进行了比较,大多数组分浓度的相对误差小于１０％,个别小于１６．２％,初步验证,遗传算法可以摆脱对校准模型的依赖。文中还讨论了变异概率,交配概率,种群数大小等因素的影响。     

Binuclear iron carbonyl nitrosyls: bridging nitrosyls versus bridging carbonyls

The iron carbonyl nitrosyls Fe 2(NO) 2(CO) n ( n = 7, 6, 5, 4, 3) have been studied by density functional theory (DFT) using the B3LYP and BP86 methods, for comparison of their predicted structures with those of isoelectronic cobalt carbonyl derivatives. The lowest energy structures for Fe 2(NO) 2(CO) 7 and Fe 2(NO) 2(CO) 6 have two NO bridges, and the lowest energy structure for Fe 2(NO) 2(CO) 5 has a single NO bridge with metal-metal distances (BP86) of 3.161, 2.598, and 2.426 A, respectively, corresponding to the formal metal-metal bond orders of zero, one, and two, respectively, required for the favored 18-electron configuration for the iron atoms. The heptacarbonyl Fe 2(NO) 2(CO) 7 is thermodynamically unstable with respect to CO loss to give Fe 2(NO) 2(CO) 6. The favored structures for the more highly unsaturated Fe 2(NO) 2(CO) 4 and Fe 2(NO) 2(CO) 3 also have bridging NO groups but avoid iron-iron bond orders higher than two by formal donation of five electrons from bridging NO groups with relatively short Fe-O distances. The lowest energy structures of the unsaturated Fe 2(NO) 2(CO) n derivatives ( n = 5, 4, 3) are significantly different from the isoelectronic cobalt carbonyls Co 2(CO) n +2 owing to the tendency for Fe 2(NO) 2(CO) n to form structures with bridging NO groups and metal-metal formal bond orders no higher than two.     

Synthesis, Characterization and Thermal Decomposition Mechanism of Cetyltrimethyl Ammonium Tetrathiotungstate

The synthesis, characterization and thermal decomposition mechanism of cetyltrimethyl ammonium tetrathiotungstate （CTriMATT） were studied herein. The as-synthesized CTriMATT was characterized by Elemental analysis, X-ray diffraction （XRD）, Fourier transform infrared （FT-IR）, Ultraviolet visible （UV-Vis） spectra. The results showed that the as-synthesized CTriMATT had high purity and good crystallinity. The introduction of alkyl groups induced a shift of the stretching vibration band of W-S bond to lower wavenumber, while it had no influence on the position of WS4^2-. Thermogravimetric analysis （TG）, differential thermal analysis （DTA） and in situ XRD characterizations revealed that CTriMATT began to decompose at 423 K in nitrogen and was converted to WS2 eventually. In addition, the decomposition product of CTriMATT at 673 K in nitrogen was characterized by N2 adsorption （BET） and scanning electron microscopy （SEM）. The results demonstrated that WS2 with higher specific surface area, and pore volume could be obtained from the thermal decomposition of CTriMATT in nitrogen.     

MnOx/Al2O3/Ce0.45Zr0.45M0.10Oy （M = Mn, Y, La） catalysts used for ethanol catalytic combustion

MnOx/Al2O3/Ce0.45Zr0.45M0.10Oy (M = Mn,Y,La) catalysts were prepared by impregnation method and characterized by BET,TPR and XRD analyses.The catalytic activities toward ethanol combustion were investigated in a microreactor.The results demonstrated that the catalytic activity of MnOx/Al2O3/Ce0.50Zr0.50O2 monolithic catalyst could be improved by doping Mn,Y and La into Ce0.50Zr0.50O2.When doping Y into Ce0.50Zr0.50O2,the catalyst MnOx/Al2O3/Ce0.45Zr0.45Y0.10O1.95 showed the highest activity.The 100% conversion temperature of ethanol was 230 ℃.Furthermore,once the conversion of ethanol started,the complete conversion was quickly achieved.The doping of Mn,Y and La led to better activity for ethanol combustion and lower temperature reduction peaks in TPR profiles.The doping of Mn resulted in enhanced oxygen storage capacity (OSC),larger area of the reduction peaks,and excellent reactivity,and the doping of Y resulted in the lowest reduction temperature and the best activity.     

2,5-二甲氧基-4-氯硝基苯与硫化钠的反应

硫化钠和二硫化钠分别在95%乙醇中与2,5-二甲氧基-4-氯硝基苯反应, 原本期望得到2,5-二甲氧基-4-氯苯胺, 然而对产物结构的1H NMR, 13C NMR, MS以及元素分析结果表明, 2,5-二甲氧基-4-氯硝基苯中的硝基没有被硫化钠和二硫化钠还原成氨基, 而是其中的氯原子被硫离子(或二硫离子)取代, 分别生成了4,4’-硫代-2,2’,5,5’-四甲氧基-双硝基苯和4,4’-双硫代-2,2’,5,5’-四甲氧基-双硝基苯. 根据这个实验事实, 讨论了上述亲核取代反应的机理.     

含喹唑啉二酮片段的新型三酮类化合物的合成及生物活性

对羟苯基丙酮酸双氧化酶(EC 1.13.11.27, HPPD)是一个重要的除草剂作用靶标. 为了寻找具有高效除草活性的新型HPPD抑制剂, 在前期研究的基础上设计合成了24个含有喹唑啉二酮结构的三酮类化合物9a～9x. 所合成的化合物均经过¹H NMR, ¹³C NMR和 HRMS的表征. 以来源于拟南芥的HPPD (AtHPPD)为测试对象进行酶抑制活性筛选, 结果表明所合成的大部分化合物对AtHPPD均表现出了较好的抑制效果, 其中化合物9i的K_i 值为0.005 μmol/L, 显著优于商品化对照药剂硝磺草酮(K_i=0.013 μmol/L). 进一步温室盆栽筛选结果表明, 多数化合物在150 g ai/ha的剂量下对六种供试杂草中的至少一种表现出80%以上的防效, 特别是化合物9g在37.5 g ai/ha的低剂量下对所测试的六种杂草中的四种仍表现出了大于85%的抑制效果, 同时9g 在150 g ai/ha的剂量下对水稻和小麦均表现出了很好的作物安全性, 可以作为先导化合物供进一步深入研究.     

具有双螺旋链结构的3-吡啶丙烯酸镝配合物的水热合成及晶体结构

采用水热法制备了一种新型稀土配位聚合物[Dy(3-PA)3(H2O)]n(3-PA=3-吡啶丙烯酸)(1),并通过X射线单晶衍射结构分析、元素分析、红外光谱、热重分析对配合物1进行了结构表征.结构分析表明,标题配合物属于三斜晶系,Pī空间群,晶胞参数为:a=0.617 16(5)nm,b=1.270 45(11)nm,c=1.564 03(13)nm,α=111.557 0(10)°,β=90.307 0(10)°,γ=95.342 0(10)°,V=1.134 54(16)nm3,Z=2.金属离子Dy(III)通过配体3-AP羧基的桥联作用,链接成为一维双螺旋链状配位聚合物.     

Rapid finding and quantification of the major antioxidant in water extracts of three marine drug organisms from China by online HPLC-DAD/MS-DPPH

A method based on high-performance liquid chromatography (HPLC) with diode array detector coupled with electrospray ionisation-mass spectrometry and an online detection system for radical scavenging was established and used to rapidly find and quantify antioxidant compounds in the water extracts of Hippocampus japonicus Kaup, Hippocampus kuda Bleeker and Syngnathus acus Linnaeus. The online screening results revealed the presence of one major radical scavenging compound identified as hypoxanthine by comparison of mass data and retention time with the standard. Subsequently, the developed HPLC method was applied to quantify hypoxanthine in different H. japonicus, H. kuda and S. acus samples. The results indicated that the developed HPLC method is simple and reliable for the quantification of hypoxanthine with a detection limit at 0.002 μg mL(-1), and a high recovery from 96.3% to 102.1%. This method provides a powerful tool for rapid identification and quantification of free radical scavenging compounds in complex marine natural products.     

Enhanced indirect fluorescence detection of p-nitrophenol, 2,4-dinitrophenol and trinitrophenol by micellar electrokinetic capillary chromatography with in-column optical-fiber LED-induced fluorescence detection

Enhanced indirect fluorescence detection with in-column optical-fiber LED-induced fluorescence (LED-IF) detection has been developed for the simultaneous separation and determination of p-nitrophenol, 2,4-dinitrophenol and trinitrophenol. The instrumental set-up is simple, cost-effective and the detection method is stable. Different experimental parameters have been studied. The optimum conditions were determined as: running buffer (pH 9.1) composed of 10 mM borate, 80 mM sodium dodecylsulfate and 0.18 μM fluorescein (as a background reagent); applied voltage of 15 kV; working temperature of 25.0 °C. The limits of detection (S/N = 3) were 11, 18 and 16 μM for p-nitrophenol, 2,4-dinitrophenol and trinitrophenol, respectively. The nitrophenols were completely separated in 13 min and the number of theoretical plates for p-nitrophenol, 2,4-dinitrophenol and trinitrophenol were 8.1 × 10(6), 6.5 × 10(6) and 8.4 × 10(6), respectively. The RSDs (n = 6) for the migration time and the peak area were better than 0.85 and 0.91%, respectively. Our proposed method possesses the advantages of rapidness and good separation efficiency.