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201.
A rapid flow-injection sandwich enzyme immunoassay suitable for the direct determination of proteins in biological samples is described. The proposed system utilizes highly active adenosine deaminase—antibody conjugates in conjunction with a flow-through immunoreactor and an ammonium ion-selective potentiometric detector. After appropriate sample/reagent injection steps, the enzyme activity bound to the reactor is measured by diverting a coninuously flowing stream of substrate (adenosine) through the packed immunocolumn and detecting liberated ammonium ions downstream with a tubular ammonium ion-selective electrode. The bound enzyme activity is directly proportional to the concentration of analyte in the original sample. By using non-equilibrium flow-rates of sample and reagent slugs, a single protein assay takes less than 12 min, including regeneration of the reactor. The proposed method is shown to be selective, reproducible and capable of determining accurately the model protein (human IgC) at sub-μg ml?1 concentrations. 相似文献
202.
The intramolecular cyclization reactions of alkyl fluoride and chloride anions1 were investigated theoretically using the AM1 method. Formation of five-membered ring was the most reactive and that of three-membered ring was the least reactive process in both series. For the fluoride series the reactivity order of n = 5 > 6 > 7 > 4 > 3 was dictated by the enthalpy (ΔH≠) effect while for the chloride series the entropy (ΔS≠) effect was found to play somewhat greater role due to the much better leaving ability of the chloride anion leading to the reactivity order of n = 5 > 6 > 4 > 7 > 3. For both series, BEP principle held and the degree of bond formation was greater with the fluoride series owing to the poor electron acceptor ability of the cleaving bond. 相似文献
203.
Supercritical fluid extraction (SFE) of the fluoroquinolones norfloxacin and ofloxacin from chicken breast muscles was examined. A liquid chromatography with fluorescence detection was used for the determination of the fluoroquinolones. Extraction conditions of the SFE were optimized by determining the extraction parameters to achieve a sufficiently high recovery of each fluoroquinolone in fortified-muscle samples. Recovery values for the extraction of the fluoroquinolones using the SFE ranged from 70 to 87%. Chickens were treated orally with each fluoroquinolone and their muscles were extracted at set time intervals for time-course determination of the fluoroquinolones in chickens. The SFE combined with liquid chromatographic analysis showed that the concentrations of the fluoroquinolones decreased gradually with time in the chicken muscles after oral treatment, giving a concentration less than 5 ng/ml in 120 h. No further sample cleanup procedures were required after the SFE. These results suggest that SFE method is an extraction method for the determination of norfloxacin and ofloxacin in chicken muscle. 相似文献
204.
Jin Young Kim Kyung Hwa Cho Bo Young Jeong Chang Gyo Park Hoi Young Lee 《Experimental & molecular medicine》2020,52(7):1152
Rab coupling protein (RCP) is upregulated in head and neck squamous cell carcinoma (HNSCC) and is correlated with the progression and survival of patients. However, the role of RCP in one of the aggressive types of HNSCC, oral squamous cell carcinoma (OSCC), remains elusive. In the present study, we identified the important role of Zeb1 in RCP-induced OSCC epithelial-to-mesenchymal transition (EMT) and invasion. RCP induces Zeb1 expression, and silencing Zeb1 expression significantly inhibits RCP-induced OSCC invasion. In addition, Zeb1 upregulates MT1-MMP expression to promote OSCC EMT and invasion. Furthermore, we observed that the β1 integrin/EGFR/β-catenin signaling cascade mediates RCP-induced Zeb1 expression to promote OSCC invasion. Notably, we provide evidence that resveratrol (REV) strongly inhibits RCP-induced Zeb1 expression through blocking β1 integrin endosome recycling and EGFR activation, leading to suppression of RCP-induced OSCC invasion, demonstrating the important role of RCP in OSCC invasion and its reversion by REV. Collectively, the present study provides evidence for the first time that RCP aggravates OSCC invasion through increasing Zeb1 expression and subsequently upregulating MT1-MMP expression and that this process is reversed by REV, providing novel biomarkers and indicating the therapeutic potential of REV in OSCC.Subject terms: Oral cancer, Cell invasion 相似文献
205.
Rapid and sensitive silver-lipopolysaccharide staining using PhastSystem in fast horizontal polyacrylamide gel electrophoresis 总被引:1,自引:0,他引:1
A rapid and sensitive silver-lipopolysaccharide staining method has been developed by using PhastSystem. The total time of the procedure (including time of Phastgel electrophoresis) is within 2 h. It is at least 10 times faster than the previous reported methods and the sensitivity is also increased. 相似文献
206.
[reaction: see text] The solid-phase synthesis of N-alkyl-beta-keto)amides and 1,2,4,5-tetrasubstituted imidazoles was demonstrated using a traceless cleavage strategy based on benzylic acylammonium chloride reactivity. The approach enables the assembly of diverse compounds in a minimal number of steps in moderate to excellent yield (23-88%) and high purity (64-100%). 相似文献
207.
Vinayak Juvekar Chang Su Lim Dong Joon Lee Sang Jun Park Gyeong Ok Song Hyuk Kang Hwan Myung Kim 《Chemical science》2021,12(1):427
Two-photon photodynamic therapy (TP-PDT) is a promising approach for the treatment of cancer because of its better penetration depth and superior spatial selectivity. Here, we describe an azo group containing cyclized-cyanine derivatives (ACC1 and ACC2) as a two-photon activated, type I based photosensitizer (PS). These small-molecule and heavy atom-free organic dyes showed marked reactive oxygen species (ROS)-generating ability under physiological conditions, as well as fast loading ability into the cells and negligible dark toxicity. Live cell analyses with one- and two-photon microscopy revealed that these dyes showed higher ROS generation ability upon two-photon excitation than upon one-photon excitation via the type I process. The PSs have superior PDT properties compared to conventional Visudyne and 5-ALA under mild conditions. These characteristics allowed for precise PDT at the target region in mimic tumor spheroids, demonstrating that the developed TP PS could be useful in efficient PDT applications and in designing various PSs.Azo containing dyes as a two-photon selective and type I based photosensitizers (PSs) were developed that exhibit excellent photodynamic therapy properties under mild condition. 相似文献
208.
Salma Kassem Alan T. L. Lee David A. Leigh Augustinas Markevicius Daniel J. Tetlow Naoyuki Toriumi 《Chemical science》2021,12(6):2065
Peptides attached to a cysteine hydrazide ‘transporter module’ are transported selectively in either direction between two chemically similar sites on a molecular platform, enabled by the discovery of new operating methods for a molecular transporter that functions through ratcheting. Substrate repositioning is achieved using a small-molecule robotic arm controlled by a protonation-mediated rotary switch and attachment/release dynamic covalent chemistry. A polar solvent mixtures were found to favour Z to E isomerization of the doubly-protonated switch, transporting cargo in one direction (arbitrarily defined as ‘forward’) in up to 85% yield, while polar solvent mixtures were unexpectedly found to favour E to Z isomerization enabling transport in the reverse (‘backward’) direction in >98% yield. Transport of the substrates proceeded in a matter of hours (compared to 6 days even for simple cargoes with the original system) without the peptides at any time dissociating from the machine nor exchanging with others in the bulk. Under the new operating conditions, key intermediates of the switch are sufficiently stabilized within the macrocycle formed between switch, arm, substrate and platform that they can be identified and structurally characterized by 1H NMR. The size of the peptide cargo has no significant effect on the rate or efficiency of transport in either direction. The new operating conditions allow detailed physical organic chemistry of the ratcheted transport mechanism to be uncovered, improve efficiency, and enable the transport of more complex cargoes than was previously possible.Peptides are transported in either direction between chemically similar sites on a molecular platform, substrate repositioning is achieved using a cysteine hydrazide transporter module and a small-molecule robotic arm controlled by a rotary switch. 相似文献
209.
CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments
Ji Hyeon Kim Jeeyoung Lee Won Hoon Choi Seoyoung Park Seo Hyeong Park Jung Hoon Lee Sang Min Lim Ji Young Mun Hyun-Soo Cho Dohyun Han Young Ho Suh Min Jae Lee 《Chemical science》2021,12(15):5599
The tau protein is a highly soluble and natively unfolded protein. Under pathological conditions, tau undergoes multiple post-translational modifications (PTMs) and conformational changes to form insoluble filaments, which are the proteinaceous signatures of tauopathies. To dissect the crosstalk among tau PTMs during the aggregation process, we phosphorylated and ubiquitylated recombinant tau in vitro using GSK3β and CHIP, respectively. The resulting phospho–ub-tau contained conventional polyubiquitin chains with lysine 48 linkages, sufficient for proteasomal degradation, whereas unphosphorylated ub-tau species retained only one–three ubiquitin moieties. Mass-spectrometric analysis of in vitro reconstituted phospho–ub-tau revealed seven additional ubiquitylation sites, some of which are known to stabilize tau protofilament stacking in the human brain with tauopathy. When the ubiquitylation reaction was prolonged, phospho–ub-tau transformed into insoluble hyperubiquitylated tau species featuring fibrillar morphology and in vitro seeding activity. We developed a small-molecule inhibitor of CHIP through biophysical screening; this effectively suppressed tau ubiquitylation in vitro and delayed its aggregation in cultured cells including primary cultured neurons. Our biochemical findings point to a “multiple-hit model,” where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process, thus indicating that targeting tau ubiquitylation may be an effective strategy to alleviate the course of tauopathies.Multiple-hit model for tau aggregation, where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process. 相似文献
210.
The thermal expansion properties of crystalline organic compounds are investigated by data mining of the Cambridge Structural Database (CSD). The mean volumetric thermal expansion coefficient is 168.8 × 10−6 K−1 and the mean uniaxial thermal expansion coefficient is 71.4 × 10−6 K−1, based on 745 and 1129 different observations, respectively. Normal and anomalous coefficients can be identified using these values and the associated standard deviations. The anisotropy of the thermal expansion is also evaluated and found to have a very broad distribution. 4719 different structures, comprising 4093 different molecular compounds and 626 additional polymorphs have been analyzed on their thermal expansion properties. Approximately 34% of these structures may have at least one orthogonal axis with negative thermal expansion, much more than generally believed. Moreover 127 structures have been identified which could have negative volumetric thermal expansion. Experimental validation using a robust protocol with data collected at more than 2 different temperatures is required to validate these cases.The thermal expansion properties of crystalline organic compounds are investigated by data mining of the Cambridge Structural Database (CSD). Negative uniaxial thermal expansion is much more common than generally believed. 相似文献