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71.
Sang-Hyun Park Insu Shin Dr. Gun-Hee Kim Dr. Sung-Kyun Ko Prof. Dr. Injae Shin 《Chembiochem : a European journal of chemical biology》2021,22(24):3425-3430
A novel autophagy inhibitor, autophazole (Atz), which promoted cancer cell death via caspase activation, is described. This compound was identified from cell-based high-content screening of an imidazole library. The results showed that Atz was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP). This process generated nonfunctional autolysosomes, thereby inhibiting autophagy. In addition, Atz was found to promote LMP-mediated apoptosis. Specifically, LMP induced by Atz caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP). This event led to cancer cell death via caspase activation. Overall, the findings suggest that Atz will serve as a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process. 相似文献
72.
Shuya Liang Miaomiao Wang Jun Wang Guanzhi Chen 《Chembiochem : a European journal of chemical biology》2021,22(22):3184-3189
To overcome high toxicity, low bioavailability and poor water solubility of chemotherapeutics, a variety of drug carriers have been designed. However, most carriers are severely limited by low drug loading capacity and adverse side effects. Here, a new type of metal-drug nanoparticles (MDNs) was designed and synthesized. The MDNs self-assembled with Fe(III) ions and drug molecules through coordination, resulting in nanoparticles with high drug loading. To assist systemic delivery and prolong circulation time, the obtained MDNs were camouflaged with red blood cell (RBCs) membranes (RBCs@Fe-DOX MDNs) to improve their stability and dispersity. The RBCs@Fe-DOX MDNs presented pH-responsive release functionalities, resulting in drug release accelerated in acidic tumor microenvironments. The outstanding in vitro and in vivo antitumor therapeutic outcome was realized by RBCs@Fe-DOX MDNs. This study provides an innovative design guideline for chemotherapy and demonstrates the great capacity of nanomaterials in anticancer treatments. 相似文献
73.
Siriluk Ratanabunyong Dr. Niran Aeksiri Dr. Saeko Yanaka Dr. Maho Yagi-Utsumi Dr. Koichi Kato Dr. Kiattawee Choowongkomon Dr. Supa Hannongbua 《Chembiochem : a European journal of chemical biology》2021,22(5):915-923
HIV-1 RT is a necessary enzyme for retroviral replication, which is the main target for antiviral therapy against AIDS. Effective anti-HIV-1 RT drugs are divided into two groups; nucleoside inhibitors (NRTI) and non-nucleoside inhibitors (NNRTI), which inhibit DNA polymerase. In this study, new DNA aptamers were isolated as anti-HIV-1 RT inhibitors. The selected DNA aptamer (WT62) presented with high affinity and inhibition against wild-type (WT) HIV-1 RT and gave a KD value of 75.10±0.29 nM and an IC50 value of 84.81±8.54 nM. Moreover, WT62 decreased the DNA polymerase function of K103 N/Y181 C double mutant (KY) HIV-1 RT by around 80 %. Furthermore, the ITC results showed that this aptamer has small binding enthalpies with both WT and KY HIV-1 RTs through which the complex might form a hydrophobic interaction or noncovalent bonding. The NMR result also suggested that the WT62 aptamer could bind with both WT and KY mutant HIV-1 RTs at the connection domain. 相似文献
74.
75.
Summary Copolymeric poly(acrylic acid-co-methyl methacrylate) hydrogels for three different compositions: (90/10), (80/20) and (60/40),
have been studied. Drug release has been examined as a function of the hydrogel composition by HPLC (High Pressure Liquid
Cromatography). The release experiments were carried out at 37 °C. The fraction of available drug release was linear in t1/2. The values of the diffusional coefficient (0.50<n<1.0) indicate that the nafcillin release mechanism from the hydrogels
in study is non-Fickian. The diffusion coefficients for this drug release have been calculated. The molecular diffusion of
nafcillin through hydrogels is controlled by the swelling. 相似文献
76.
Karin Yaccato Alfred Hagemeyer Andreas Lesik Anthony Volpe Henry Weinberg 《Topics in Catalysis》2004,(1):127-132
High-throughput synthesis and screening methods have been developed for the discovery of highly active lead compounds for the selective catalytic reduction as well as direct decomposition of NO in the temperature range 200–300 °C. The discovery libraries for primary screening consisted of 16 × 16 catalyst arrays on 4in. square quartz wafers. Catalysts were prepared by robotic liquid dispensing techniques and screened for catalytic activity in Symyx' scanning mass spectrometer. The scanning mass spectrometer is a fast serial screening tool that uses flat wafer catalyst surfaces, local laser heating, a scanning/sniffing nozzle and a quadrupolar mass spectrometer to compare relative catalytic activities. The feed consisted of NO/NH3 mixtures with optional O2 cofeed and Kr as the internal standard in Ar carrier gas. QMS detection allowed for tracking of H2O, N2, NO, O2, N2O and Kr. Screening protocols for catalytic materials encompassed metal precursors and carriers for supported vanadia systems, extensive doping of V2O5/TiO2, and broad screening of mixed redox metal oxides and supported base and noble metal systems. More than 500 samples could be screened in a single day. Active hits (high NO consumption accompanied by corresponding N2 production) identified in discovery libraries were re-synthesized as focus libraries for lead confirmation and further optimization. These libraries used shallower compositional gradients, for example 56 points (compositions) per ternary, with four 56-point ternaries per 4in. wafer. Broad screening ternaries were generally 8 or 15 points. The focus libraries more clearly reveal the trends and provide guidelines for secondary screening and scale-up. High conversions were achieved in scanning mass spectrometer so the scalability risk is small for the short contact time reactions. 相似文献
77.
78.
Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient perme- abilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will reseal after pulsing,which leads to the rapid drop of transdermal flux.In the present study,the surfactants were added to the donor solution to hinder the shrinkage and resealing of the electropore,and to prolong the lifetime of the aqueous pathways with the consideration that the surfactants could reduce the surface energy of the electropore. These effects of surfactants were demonstrated by the dynamic electrical resistance of the skin and the fluorescent imaging of the local transport regions.Piroxicam(PIX)was transported percutaneously in the presence of surfactants in vitro.Owing to the longer lifetime of aqueous pathways,together with the promotion of PIX availability at the barrier exterior and the improvement in the partition of PIX into the aqueous pathways,the presence of surfactants led to a remarkable increase in the transdermal delivery rate during electroporation and a significant growth of the accumulative transdermal amount of PIX. 相似文献
79.
Career visual searchers such as radiologists and airport security screeners strive to conduct accurate visual searches, but despite extensive training, errors still occur. A key difference between searches in radiology and airport security is the structure of the search task: Radiologists typically scan a certain number of medical images (fixed objective), and airport security screeners typically search X-rays for a specified time period (fixed duration). Might these structural differences affect accuracy? We compared performance on a search task administered either under constraints that approximated radiology or airport security. Some displays contained more than one target because the presence of multiple targets is an established source of errors for career searchers, and accuracy for additional targets tends to be especially sensitive to contextual conditions. Results indicate that participants searching within the fixed objective framework produced more multiple-target search errors; thus, adopting a fixed duration framework could improve accuracy for career searchers. 相似文献
80.
Aqueous photoresists that are capable of higher resolutions than are currently employed by the cathode ray tube (CRT) industry were developed by combining photoactivators, which activate at shorter UV wavelengths with polyvinylpyrrolidone (PVP). Two photoactivators were synthesized: 4,4′‐diazido‐2,2′‐biphenyl disodium disulfonate (DABP), which has a maximum absorbance at 264 nm, and 4,4′‐diazido‐2,2′‐biphenylethane disodium disulfonate (DABPE), which has a maximum absorbance at 258 nm. The PVP/DABP and PVP/DABPE photoresists successfully imaged a pattern with resolution as small as 4.4 μm with photoactivator concentrations greater than 20% of the PVP concentration. Addition of silane and emulgen greatly improved the performance of the photoresists with more uniform coatings of thicknesses of up to 1.4 μm. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1637–1644, 2006 相似文献