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Design and synthesis of dansyl-labeled inhibitors of steroid sulfatase for optical imaging
摘要： Steroid sulfatase (STS) is an important enzyme regulating the conversion of sulfated steroids into their active hydroxylated forms. Notably, the inhibition of STS has been shown to decrease the levels of active estrogens and was translated into clinical trials for the treatment of breast cancer. Based on quantitative structure-activity relationship (QSAR) and molecular modeling studies, we herein report the design of fluorescent inhibitors of STS by adding a dansyl group on an estrane scaffold. Synthesis of 17α-dansylaminomethyl-estradiol (7) and its sulfamoylated analog 8 were achieved from estrone in 5 and 6 steps, respectively. Inhibition assays on HEK-293 cells expressing exogenous STS revealed a high level of inhibition for compound 7 (IC50 = 69 nM), a value close to the QSAR model prediction (IC50 = 46 nM). As an irreversible inhibitor, sulfamate 8 led to an even more potent inhibition in the low nanomolar value (IC50 = 2.1 nM). In addition, we show that the potent STS inhibitor 8 can be employed as an optical imaging tool to investigate intracellular enzyme sub-localization as well as inhibitory behavior. As a result, confocal microscopy analysis confirmed good penetration of the STS fluorescent inhibitor 8 in cells and its localization in the endoplasmic reticulum where STS is localized.
关键词： Danzyl derivative,Steroid,Fluorescent agent,Enzyme inhibitor,Steroid sulfatase
更新于2025-09-19 17:13:59
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Study on the oxidation and release of gases in spontaneous coal combustion using a dual-species sensor employing laser absorption spectroscopy
摘要： Coal spontaneous combustion (CSC) is a common hazard in coal mines and a significant reason for the loss of coal in stockpiles and mines. To investigate the oxidation and release of gas due to of CSC, a miniature purpose-built laser-based sensor system capable of precise gas measurement and data processing was configured. A distributed feedback (DFB) diode laser with a central wavelength of 2.33 μm, in conjunction with a Herriot-type cell and wavelength modulation spectroscopy (WMS), was used for the simultaneous detection of methane (CH4) and carbon monoxide (CO) during coal combustion. The second-harmonic of WMS was applied to ensure sensor robustness and sensitivity with long-term performance for the system being evaluated by calculating the Allan-Werle deviations for the concentrations of CH4 and CO. The limits of detection (LoDs) for CH4 and CO were 0.05 ppm based on integration times of 120 s and 70 s, respectively. The dual-species sensor was employed for real-time and in situ investigations of coal samples for temperatures ranging from 85 °C to 200 °C and was considered suitable for integration into field monitoring equipment, especially for online early warning forecasting applications in CSC.
关键词： Wavelength modulation spectroscopy,Spontaneous coal combustion,Chemical inhibitor,Laser-based dual-species sensor,Self-heating oxidation
更新于2025-09-12 10:27:22
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Quaternary Solar Cells with 12.5% Efficiency Enabled with Non‐Fullerene and Fullerene Acceptor Guests to Improve Open Circuit Voltage and Film Morphology
摘要： Vaccines and antivirals to combat dengue, Zika, and other flavivirus pathogens present a major, unmet medical need. Vaccine development has been severely challenged by the antigenic diversity of these viruses and the propensity of non-neutralizing, cross-reactive antibodies to facilitate cellular infection and increase disease severity. As an alternative, direct-acting antivirals targeting the flavivirus envelope protein, E, have the potential to act via an analogous mode of action without the risk of antibody-dependent enhancement of infection and disease. We previously discovered that structurally diverse small molecule inhibitors of the dengue virus E protein exhibit varying levels of antiviral activity against other flaviviruses in cell culture. Here, we demonstrate that the broad-spectrum activity of several cyanohydrazones against dengue, Zika, and Japanese encephalitis viruses is due to specific inhibition of E-mediated membrane fusion during viral entry and provide proof of concept for pharmacological inhibition of E as an antiviral strategy in vivo.
关键词： viral entry inhibitor,envelope protein inhibitor,dengue virus,antiviral,fusion inhibitor,flavivirus
更新于2025-09-11 14:15:04
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Light Processing Enables Efficient Carbon-Based, All-Inorganic Planar CsPbIBr <sub/>2</sub> Solar Cells with High Photovoltages
摘要： Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (MptpB) is an important virulence factor for Mtb that contributes to survival of the bacteria in macrophages. The absence of a human ortholog makes MptpB an attractive target for new therapeutics to treat tuberculosis. MptpB inhibitors could be an effective treatment to overcome emerging TB drug resistance. Adopting a structure-based virtual screening strategy, we successfully identified thiobarbiturate-based drug-like MptpB inhibitor 15 with an IC50 of 22.4 μM, and as a non-competitive inhibitor with a Ki of 24.7 μM. Importantly, not only did it exhibit moderate cell membrane permeability, compound 15 also displayed potent inhibition of intracellular TB growth in the macrophage, making it an excellent lead compound for anti-TB drug discovery. To the best of our knowledge, this novel thiobarbiturate is the first class of MptpB inhibitor reported so far that leveraged docking- and pharmacophore-based virtual screening approaches. The results of preliminary structure-activity relationship demonstrated that compound 15 identified herein was not a singleton and may inspire the design of novel selective and drug-like MptpB inhibitors.
关键词： Docking,Tuberculosis,Thiobarbiturate scaffold,MptpB inhibitor,Virtual screening,Pharmacophore
更新于2025-09-11 14:15:04
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A carbapenem-based fluorescence assay for the screening of metallo-β-lactamase inhibitors
摘要： Reported herein is a fluorescence assay for the rapid screening of metallo-β-lactamase (MBL) inhibitors. This assay employs a fluorogenic carbapenem CPC-1 as substrate and is compatible with all MBLs, including B1, B2 and B3 subclass MBLs. The efficiency of this assay was demonstrated by the rapid inhibition screening of a number of molecules against B2 MBL CphA and 2,3-dimercaprol was identified as a potent CphA inhibitor.
关键词： Fluorescence,Inhibitor,Screening assay,Metallo-β-lactamase
更新于2025-09-10 09:29:36
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Saponin synthesis and cotton growth is antagonistically regulated by solar UV-B radiation
摘要： Background: Earlier we have reported that the exclusion of solar UV-B increased the growth and yield of cotton plants as compared with ambient UV-B. The UV-B radiation effects on the saponins and the impact of ambient and reduced UV-B on the accumulation of saponins has not been investigated yet. Thus a field experiment was conducted to study the influence of solar UV-B on the growth response and saponin synthesis in cotton (Gossypium hirsutum) var. Vikram plants by the exclusion of UV-B. The cotton plants were grown in specially designed iron chambers, wrapped with filters that excluded UV-B (<315 nm), or transmitted ambient UV-B. Results: Exclusion of ambient UV-B enhanced the growth of cotton plants in terms of plant height and leaf area. Greater plant height in UV-B excluded plants was due to elongated internode and more number of nodes. Enhancement in growth was accompanied by a decrease in the accumulation of saponins, which was quantified by the spectrophotometric, TLC and HPLC methods. Solvent extraction of saponins from the internodes and leaves were used for the bioassay of Amaranthus hypocotyl growth and expansion of cucumber cotyledons. Extracts obtained from the UV-B excluded plants (leaves and internodes) promoted the growth to a larger extent as compared with the extracts obtained from ambient grown plants. Conclusions: The result indicates that solar UV-B may possibly suppress the plant growth by regulating the synthesis of natural growth inhibitor’s like saponin.
关键词： Bioassay,Inhibitor,Growth,Cotton,UV radiation,Saponin
更新于2025-09-09 09:28:46
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Corrosion Inhibition of Aluminium Alloy AA6063-T5 by Vanadates: Local Surface Chemical Events Elucidated by Confocal Raman Micro-Spectroscopy
摘要： Chemical interactions between aqueous vanadium species and aluminium alloy AA6063-T5 were investigated in vanadate-containing NaCl solutions. Confocal Raman and X-ray photoelectron spectroscopy experiments were utilised to gain insight into the mechanism of corrosion inhibition by vanadates. A greenish-grey coloured surface layer, consisting of V+4 and V+5 polymerized species, was seen to form on the alloy surface, especially on top of cathodic micrometre-sized IMPs, whereby suppressing oxygen reduction kinetics. The results suggest a two-step mechanism of corrosion inhibition in which V+5 species are first reduced to V+4 or V+3 species above cathodic IMPs, and then oxidized to mixed-valence V+5/V+4 polymerized compounds.
关键词： B. XPS,B. Raman Spectroscopy,C. Vanadate Inhibitor,A. Aluminium,B. SEM,A. Alloy
更新于2025-09-04 15:30:14
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[IEEE 2018 IEEE 7th International Conference on Photonics (ICP) - Kuah (2018.4.9-2018.4.11)] 2018 IEEE 7th International Conference on Photonics (ICP) - Characterizing Inhibitor Content of Transformer Oil in the UV-Visible Waveband
摘要： Over the years, transformer oil has been used in majority of the power transformers to provide a reliable insulating system that is effective against dielectric stresses. Oxidation often occurred in transformer oil in the presence of oxygen and moisture which will affect the stability and insulating properties of the oil. The oxidation process cannot be eliminated but it can be delayed with the presence of inhibitor content. Even though inhibitor content can reduce the oxidation rate, the amount of inhibitor content still depletes over time. Thus, a monitoring system to detect the inhibitor content concentration is very crucial as it will be able to prolong the life span of the transformer. This paper focuses on the optical characterization of inhibitor content in transformer oil by utilizing the ultraviolet-visible (UV-Vis) spectroscopy technique. It was found that oil samples with inhibitor content produce multiple absorbance peaks in the range of 350 nm to 500 nm. A clear difference in peak absorbance near 450 nm indicates the difference in the inhibitor content concentrations. Based on the results of this work, a portable and low cost optical sensing device can potentially be developed for the detection of inhibitor content in transformer oil using UV-Vis spectroscopy.
关键词： Inhibitor,Visible spectroscopy,Power Transformers,Transformer Oil
更新于2025-09-04 15:30:14