Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C. 相似文献
Many phospholipase Ds (PLDs) are known to catalyze transphosphatidylation as well as hydrolysis of phospholipids. Transphosphatidylation of lysoplasmalogen (LyPls)‐specific phospholipase D (LyPls‐PLD), which catalyzes hydrolysis of ether lysophospholipids such as LyPls and 1‐hexadecyl‐2‐hydroxy‐sn‐glycero‐3‐phosphocholine (Lyso‐PAF), still remains unclear. This study aims to reveal the transphosphatidylation activity of LyPls‐PLD, that is, the production of cyclic ether lysophospholipid. The enzymatic reaction is conducted in a buffer system, and the reaction products of a novel LyPls‐PLD from Thermocrispum sp. are investigated using mass spectrometry (MS). MS analyses demonstrate the reaction products to consist of 100% 1‐hexadecyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate (cLyPA) and choline from Lyso‐PAF; however, 1‐alkenyl‐2‐hydroxy‐sn‐glycero‐2,3‐cyclic‐phosphate from 1‐O‐1′‐(Z)‐octadecenyl‐2‐hydroxy‐sn‐glycero‐3‐phosphocholine and 1‐O‐1′‐(Z)‐octadecenyl‐2‐hydroxy‐sn‐glycero‐3‐phosphoethanolamine is not produced. These results are expected to help in elucidating the catalytic mechanism of LyPls‐PLD, that is, the rate‐limiting step, and indicate LyPls‐PLD to be useful for the one‐pot synthesis of cLyPA. Practical Applications: A novel phospholipase D, LyPls‐PLD, can exclusively synthesize cLyPA from Lyso‐PAF using a one‐step enzymatic reaction without an organic solvent. cLyPA could be expected to show bioactivities similar to those of cyclic phosphatidic acid, which promotes normal cell differentiation, hyaluronic acid synthesis, antiproliferative activity in fibroblasts, and inhibitory activity toward cancer cell invasion and metastasis. 相似文献
A variety of process-based models have been developed for predicting nitrogen (N) dynamics in agro-ecosystem; however, no reliable models have been validated for N leaching from soils receiving a long-term application of different types of animal manure composts. The Leaching Estimation and Chemistry Model (LEACHM) was recently modified by incorporating the basic structure of Rothamsted Carbon Model for extending its ability to describe soil organic matter decomposition and subsequent N leaching in soils rich in organic matter. We evaluate the applicability of the modified LEACHM in cropped Yellow soils receiving 10-year application of cattle or swine manure compost in addition to chemical fertilizers, where high-frequency field monitoring data of soil water contents, soil N contents and leachate N concentrations were available for the last 3 years. Particular attention was paid to determine all input parameters from independent measurements, parameterization from known soil properties or databases without optimisation to fit the measured field data. The model reasonably predicted temporal changes in the soil NH4-N and NO3-N contents, and inorganic N concentrations in the leachate as well as their differences due to different manure compost/chemical fertilizer applications. The simulations of leached N concentration yielded a Willmott index of agreement (IA) of 0.62–0.68, with those for soil moisture, soil nitrate content and crop N uptake all within an acceptable IA range. In view of the good performance without site-specific calibrations, the modified LEACHM appears to be a valuable tool for predicting N leaching from cropped soils receiving long-term manure compost applications. 相似文献
This article addresses a new pattern mining problem in time series sensor data, which we call correlated attribute pattern mining. The correlated attribute patterns (CAPs for short) are the sets of attributes (e.g., temperature and traffic volume) on sensors that are spatially close to each other and temporally correlated in their measurements. Although the CAPs are useful to accurately analyze and understand spatio-temporal correlation between attributes, the existing mining methods are inefficient to discover CAPs because they extract unnecessary patterns. Therefore, we propose a mining method Miscela to efficiently discover CAPs. Miscela can discover not only simultaneous correlated patterns but also time delayed correlated patterns. Furthermore, we extend Miscela to automatically search for correlated patterns with any time delays. Through our experiments using three real sensor datasets, we show that the response time of Miscela is up to 20.84 times faster compared with the state-of-the-art method. We show that Miscela discovers meaningful patterns for urban managements and environmental studies.
Herein we report the synthesis, photophysical properties, positron emission tomography (PET) imaging and photodynamic therapy (PDT) efficacy of methyl 3-(1′-m-iodobenzyloxy)ethyl-3-devinyl-verdin 4 (with or without the 124I isotope). The PET imaging ability and ex vivo biodistribution of [124I] 4 were compared with the well-studied methyl [3-(1241′-m-iodobenzyloxy)ethyl]-3-devinyl-pyropheophorbide-a methyl ester (PET-ONCO or [124I] 2 ) and [18F]fluorodeoxyglucose ([18F]FDG) in BALB/c mice bearing colon-26 tumors. Whole-body PET images of [124I] 4 containing a fused methoxy cyclohexenone ring system showed excellent tumor contrast with time (72>48>24 h post-injection). Ex vivo biodistribution results indicate that relative to the current clinical standard [18F]FDG and [124I] 2 in 2 % ethanol formulation, [124I] 4 , at the same radioactive dose (25 μCi per mouse), showed higher tumor uptake at 24 h post-injection and longer tumor retention. In biological environments, compound 4 showed lower fluorescence and lower singlet oxygen yield than 2 , which is possibly due to higher aggregation caused by the presence of a fused cyclohexenone ring system, resulting in limited in vitro/in vivo PDT efficacy. Therefore, the chlorophyll-a analogue [124I] 4 provides easy access to a novel PET imaging agent (with no skin phototoxicity) to image cancer types—brain, renal carcinomas, pancreas—in which [18F]FDG shows limitations. 相似文献
This paper provides a fundamental analysis of a power supply and rectifiers for wireless power transfer using magnetic resonant coupling (MRC). MRC enables efficient wireless power transfer over middle‐range transfer distances. MRC for wireless power transfer should operate at a high frequency in the industry science medical band, such as 13.56 MHz, because the size of the transfer device decreases at higher transfer frequencies. Therefore, the output frequency of the power supply on the transmitting side should be 13.56 MHz. In addition, the rectifier on the receiving side is operated at a high frequency. This paper focuses on the reflected power in the power supply and rectifiers. Thus, the parametric design method is clarified for the power supply, including a low‐pass filter to match the output, the impedance of the power supply with the characteristic impedance of the transmission line. In addition, the effects on the rectifiers of silicon carbide and gallium nitride diodes are confirmed by performing an experiment and a loss analysis. 相似文献
In a plant consisting of parallelized microreactors (MRs), the product quality is lowered because of a lack of flow uniformity among them when blockage occurs. It is not practical to install sensors in every MR from the viewpoint of cost when detecting the blocked MRs. In the previous study, the multiple blockage detection (MBD) method using a small number of sensors was proposed, but its performance became low when the number of sensors decreased. Here, the conventional algorithm for MBD is improved by considering the process behavior on blockage occurrence, and the effectiveness of the improved algorithm is demonstrated through a numerical case study. The effects of flow distributor types and sensor types on the MBD performance are numerically investigated. 相似文献
In this study, new rGO-silica xerogel nanocomposites (SX-rGO) and its glass fiber reinforced composites (GFR-SX-rGO) were prepared, and its microstructure and thermal properties were evaluated. The raw material was a mixed dispersion prepared by adding 0.01–2.5?wt% of reduced graphene oxide (rGO) to waterglass (6% SiO2). A hydrogel was prepared via sol-gel reaction of this raw material, which was then immersed in hydrochloric acid, hydrophobized in a siloxane/2-propanol reaction system, and then dried at ambient pressure to obtain a hydrophobic carbon-silica xerogel composite. The obtained samples were characterized by N2 physisorption (at 77?K), solid 29Si Magic angle spinning nuclear magnetic resonance spectroscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, hydrophobicity, and thermal conductivity. It was found that as the amount of rGO was increased, the specific surface area of the nanocomposite decreased by ~25% from 535 to 403?cm2/g, and the average pore size and pore volume were almost halved. The thermal decomposition temperature of the SX-rGO was increased markedly by the addition of rGO. Moreover, the GFR-SX-rGO-0.5 showed low density (0.208?g/cm3), high contact angle (146°) and low thermal conductivity (0.0199?W/mK). 相似文献