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Mitochondria-Targeting Identification of a Fluorescent Apoptosis-Triggering Molecule by Mass Spectrometry Unravels Drug Tracking
摘要: The real-time tracking of localization and dynamics of small molecules in organelles helps to understand their function and lock their potential targets at the subcellular resolution. To identify the mitochondria-targeting effect of small molecules (NA-17 and NA-2a) in cancer cells, we used mass spectrometry to study the distribution and enrichment of small molecules in mitochondria and the residual cytoplasm, which enables to trace action process of therapeutic molecules. Colocalization analysis with an image-guided way suggests that both NA-17 and NA-2a have mitochondria-targeting effect. However, Mass Spectrometry (MS) analysis reveals that only NA-2a has mitochondria-targeting and enrichment effect, whereas NA-17 only distributes in the residual cytoplasm. A combination of mitochondria imaging, immunoblotting, and MS analysis in mitochondria indicate that NA-17 neither have the ability to enter mitochondria directly nor possess mitochondria-targeting effect. Further studies reveal that NA-17 could not enter mitochondria even though mitochondrial permeability has changed after NA-17 treatment in cells, evident by the ROS generation and cytochrome C release. In the process of cellular metabolism, NA-17 itself is firmly locked in the cytoplasm during the metabolic process, and its metabolites containing fluorophores could enrich in mitochondria for cell-imaging. Our present studies furnish new insights into drug metabolism process.
关键词: small molecule,mitochondria-targeting,mass spectrometry,drug tracking
更新于2025-09-10 09:29:36
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[IEEE 2018 Conference on Precision Electromagnetic Measurements (CPEM 2018) - Paris, France (2018.7.8-2018.7.13)] 2018 Conference on Precision Electromagnetic Measurements (CPEM 2018) - New Silicon Crystals for a Redefined Kilogram and Mole: Isotopic Composition of the First Two Crystals
摘要: The isotopic compositions (molar mass, M) of the first and new silicon crystals highly enriched in 28Si (> 99.99 %) used for the determination of the Avogadro constant were measured using a high resolution multicollector ICP mass spectrometer and applying a modified isotope dilution mass spectrometry technique. Relative uncertainties urel(M) < 1 × 10-9 were obtained: a reduction by almost three orders of magnitude in ten years. This study compares the homogeneities in M(Si) of the first “AVO28” crystal and the first crystal (Si28-23Pr11) of the “Kilogram-2” project.
关键词: isotopic composition,enriched silicon,Avogadro constant,mass spectrometry,“Kilogram-2” project,homogeneity
更新于2025-09-10 09:29:36
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?Lab on a Chip“; Lab on a Chip;
摘要: Background. Miniaturization has not only driven microelectronics and generated new unforeseen options but has also dramatically changed sensors and analytics. Developments. The Lab on a Chip (LOC) technology enables laboratory processes to run fully automated in canals in the micrometre range. The biggest challenge for LOC is to keep production costs low despite miniaturization and application-specific design. If this is achieved medical laboratory analyses can usually be carried out faster and with less hands on time. This explains why LOCs are already integrated into many laboratory instruments and why point-of-care testing (POCT) can no longer be imagined without it. New markers, such as in liquid biopsies and measurement techniques, such as Raman spectroscopy and mass spectroscopy, create further potentials that will enable faster and more specific laboratory analyses to be made using LOC technology. Conclusion. The LOC technology has the potential of changing the medical practice especially in cases when the central laboratory is not available or is unable to provide results fast enough.
关键词: Laboratory diagnostics,Mass spectrometry,Point-of-care testing,Spectrum analysis, Raman,Microfluidics
更新于2025-09-10 09:29:36
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226Ra determination in complex samples using liquid scintillation counting
摘要: A co-precipitation method followed by a liquid–liquid extraction and liquid scintillation counting is proposed to get low 226Ra detection limits when measuring complex samples. The sensitivity of the method is determined with an analysis of interfering agents on it. The ion-exchange followed by alpha spectrometry is also described and an analysis of the advantages and disadvantages of both methods is carried out. Then, a comparison between both methods, considering also time and cost analysis, is realised. Conclusions show that both methods provide similar values for uncertainties, critical values and chemical yields when similar sample size and measuring times are chosen.
关键词: Liquid scintillation counting,226Ra activity,Complex sample,Alpha-spectrometry
更新于2025-09-10 09:29:36
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Simulation Study of the Beam Trajectory Effect on the Magnetic Field Distribution of a Duoplasmatron
摘要: Recently, a gas interface system was developed for accelerator mass spectrometry with a cesium sputtering ion source. A gaseous ion source was proposed and designed to eliminate the solidification and graphitization process in radiocarbon dating. A simulation study of the ion source for a gas sample analysis system was conducted to investigate the characteristics of the ion source when different anode shapes were used, and the results are reported in this paper. The use of different anode shapes revealed the influence of magnetic field penetration on the plasma within the expansion cup. An axial magnetic field constrains the discharge, producing greater ionization density. The ion beam trajectories from the ion source were calculated using the SIMION program to examine the dependence of the changes in the magnetic field distribution on the shape of the ion source’s anode.
关键词: Accelerator mass spectrometry,Ion source,Beam trajectory
更新于2025-09-10 09:29:36
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Determination of Sulfite in Botanical Medicine Using Headspace Thin-Film Microextraction and Surface Enhanced Raman Spectrometry
摘要: A facile method using headspace thin-film microextraction (HS-TFME) coupled with surface enhanced Raman spectrometry (SERS) has been developed for the determination of sulfite in traditional Chinese herbal medicine. The extraction substrate was synthesized by depositing urchin-like ZnO micron particles on glass sheets using chemical liquid phase deposition. Under the optimal conditions, the intensity of the SERS signal at 630–640 cm?1 provided a good linear relationship with the concentration of sulfite from 25 to 400 mg/kg, and the linear correlation coefficient (R) was 0.996 with a detection limit of 6 mg/kg. The method was employed for the determination of sulfite in herbal medicines, and the results were confirmed by a traditional distillation-titration method. Therefore, this developed HS-TFME-SERS method may play an important role in the rapid, simple, and selective determination of sulfite residues in Chinese herbal medicine and become a potentially universal method for this analyte in various solid samples.
关键词: Headspace thin-film microextraction (HS-TFME),scanning electron microscopy (SEM),X-ray diffraction (XRD),surface enhanced Raman spectrometry (SERS),transmission electron microscopy (TEM)
更新于2025-09-10 09:29:36
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Discriminating Normal Regions within Cancerous Hen Ovarian Tissue Using Multivariate Hyperspectral Image Analysis
摘要: Identification of subregions under different pathological conditions on cancerous tissue is of great significance for understanding cancer progression and metastasis. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry (IR-MALDESI-MS) can be potentially used for the diagnostic purpose since it can monitor spatial distribution and abundance of metabolites and lipids in biological tissues. However, the large size and high dimensionality of hyperspectral data make analysis and interpretation challenging. To overcome these barriers, multivariate methods were applied to IR-MALDESI data for the first time, aiming at efficiently resolving mass spectral images, from which these results were then used to identify normal regions within cancerous tissue.
关键词: Mass Spectrometry Imaging,Multivariate curve resolution-Alternating Least Squares,IR-MALDESI,Ovarian Cancer,Principle Component Analysis
更新于2025-09-10 09:29:36
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Reference Module in Chemistry, Molecular Sciences and Chemical Engineering || Photoionization
摘要: The ionization of analyte molecules is of vital importance to mass spectrometric analysis because mass spectrometry takes only ions as the object for analysis. The most commonly used ionization source in mass spectrometry is electron-impact (EI) ionization source with electrons impacting to analyte with an energy of 70 eV. The kinetic energy of 70 eV is much higher than the ionization energy of organic molecules, and the ionization process approaches the maximal ionization efficiency. Thus, a large number of fragment peaks are usually observed in an EI mass spectrum. These fragments act as fingerprints of molecules, which can be used for identification of unknown molecules by searching EI-MS library, for example NIST Mass Spectral Library. This statistically based identification is particularly convenient and effective when analyzing a single component, for example a preseparated analyte by GC. However, there are many cases that analytes cannot be preseparated, for example very active components in a reaction, or fast on-line observation of evolving analytes. Consequently, the extensive fragmentation by EI-MS turns to a severe disadvantage: if each compound of a mixture produces a certain amount of fragment peaks, serious interference can be made, which will bring muscular obstacles to peak assignment. The best strategy is to use a “soft” ionization source with high selectivity. Here, “soft” means fragment-free or fragment-controllable.
关键词: SPI,Photoionization,APPI,REMPI,VUV Lamps,Synchrotron Radiation,Lasers,Mass Spectrometry
更新于2025-09-10 09:29:36
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A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis, Characterization and Biological Studies
摘要: The silver(I) NHC (N-heterocyclic carbene) complex bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) chloride, ([Ag(EIA)2]Cl) hereafter, bearing two anthracenyl fluorescent probes has been synthesized and characterised. [Ag(EIA)2]Cl is stable in organic solvents and under physiological-like conditions, and shows in vitro potent cytotoxic effects toward human SH-SY5Y neuroblastoma cells. The interactions of [Ag(EIA)2]Cl with a few model biological targets have been studied here as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalisation. Notably, [Ag(EIA)2]Cl does not react with a few model proteins, but is capable to bind the C-terminal dodecapeptide of thioredoxin reductase hTrxR(488-499). Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C-terminal dodecapeptide with concomitant release of the silver cation. This mode of interaction, to the best of our knowledge, is reported here for the first time for Ag(NHC)2 complexes; consequently, a potent enzyme inhibition is measured.
关键词: thioredoxin reductase,fluorescence,mass spectrometry,anticancer drugs,silver carbene complexes
更新于2025-09-10 09:29:36
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Efficiency calibration of a coaxial HPGe detector-Marinelli beaker geometry using an 152Eu source prepared in epoxy matrix and its validation by efficiency transfer method
摘要: In this study, an in-house 152Eu calibration source was produced from a custom epoxy matrix with a density of r ? 1.14 g cm(cid:2)3, which is chemically stable and durable form after its solidification. The homogeneity of 152Eu in matrix was obtained better than 98%. For a Marinelli beaker geometry, an efficiency calibration procedure was applied to a n-type, coaxial, 78.5% relative efficient HPGe detector in the energy range of 121.7e1408.0 keV by using in-house 152Eu calibration source. Then the measured efficiencies for Marinelli geometry were compared with the results calculated by MEFFTRAN and ANGLE softwares for the validation. Although MEFFTRAN and ANGLE have two different efficiency transfer algorithms to calculate the efficiencies, they usually need to use a reliable and accurate reference efficiency values as input data. Hence, reference efficiency values were obtained experimentally from a multinuclide standard source for the same detector- Marinelli geometry. In the present source characterization, the corrections required for self-absorption and true coincidence summing effects for 152Eu gamma-rays were also obtained for a such close counting geometry condition. The experimental results confirmed the validity of efficiency calculations obtained by MEFFTRAN and ANGLE softwares that are calculation tools.
关键词: In-house source preparation,Epoxy,Efficiency transfer,MEFFTRAN,Marinelli geometry,152Eu,ANGLE,Gamma-ray spectrometry
更新于2025-09-10 09:29:36