关键词： Fuchs endothelial corneal dystrophy   Corneal endothelium   PARP   Oxidate damage   Apoptosis  

摘要： Fuchs endothelial corneal dystrophy (FECD) is one of the main causes for corneal endothelial blindness, which is characterized by the progressive decline of corneal endothelial cells. Poly (ADP-ribose) polymerase (PARP) was reported to be involved in cell death and apoptosis of several diseases. However, the role of PARP1 in the progression of FECD remains elusive. In the present study, we reported that UVA irradiation caused the corneal endothelial damage and corneal edema in mice, which was accompanied with the elevated activity of PARP1 and PAR. The PARP1 inhibitor PJ34 resolved the corneal edema and protected corneal endothelium from UVA-induced oxidative damage, mitochondrial dysfunction, and cell apoptosis. Mechanistically, PARP1 inhibition exerted its anti-apoptotic effects through downregulation of the phosphorylation levels of JNK1/2 and p38 MAPK and subsequently the increase of MKP-1. Our results suggest that PARP1 inhibition protects corneal endothelium from UVA-induced oxidative damage, which provides a potential alternative strategy for the therapy of FECD.

ISBN: (纸本)9787519862091

关键词： Numerical models   Data models   Analytical models   Soil   Geology   Solid modeling   XML   Borehole data   data processing platform (DPP)   grid ground model   numerical simulation  

摘要： There have been attempts to improve the operational efficiency of construction projects and plan response countermeasures for estimated damage following disasters through the utilization of accumulated electronic data, which constructs a digital twin that can reproduce a physical space in cyberspace and feedback the cyberspace simulation results to physical space. However, the application of such simulations is limited, unless numerical models can be automatically constructed from the data. In this study, we develop a program that utilizes a data processing platform to read, transform, and integrate data to create mediated data with a common data structure. This mediated data can be used to construct analytical models for various numerical analyses. Using the program developed, a grid model of 3-D ground surface as the mediated data was constructed based on borehole data obtained through a ground survey. Each grid point has basic material parameters of soil, and these parameters are estimated from borehole data and other investigation reports. Each grid point has general geotechnical parameters and can be easily converted to a 3-D finite-element model. When the borehole data is added or changed, the analytical model can be updated with almost no cost, whereas it would be very costly to create the model manually.

关键词： Detrital zircons geochronology   U-Pb   Software   Data filtering   Data visualizing   Data export  

摘要： Overwhelming numbers of detrital zircon (dZr) U-Pb ages have been acquired all over the globe in the last few decades, opening new horizons for employing big data approaches. However, several impediments such as frequent publication of heavily filtered data tables with omitted analyses, failure to cite the logic on "best age" computation, and generally the lack of uniformity among data treatment approaches delay the employment of this growing volume of data to the full extent. We have developed Dezirteer software to address some of the impediments. The program runs on any OS as a Python package and can be installed in Windows via an executable installer. Dezirteer imports U-Th-Pb LA-ICPMS geochronology data (either as .csv files from Iolite or Glitter, or from a manually-filled template). First, it allows the user to define and apply filters (by elevated discordance, analytical uncertainty, and U concentration). Next, the user defines computations (discordance calculation, type of Pb-correction, choosing "best age"), and Dezirteer applies them on dZr datasets. Finally, Dezirteer exports data and manipulations on them, unequivocally separated. Dezirteer permits to quickly assess the results of filters and computations visually (concordia, probability density curves, kernel density estimates, histograms, and cumulative diagrams) and numerically (Kolmogoroff - Smirnov statistics, Likeness, and Similarity coefficients, peaks locations). Thus, our program can be used as a substitute for several existing software packages and provides some unique functionality. We propose several guidelines for publishing U-Th-Pb dZr data to increase the data's trustworthiness and usability and improve the transparency of manipulations on these data. Most importantly, dZr data must be published before extensive filtering and interpretation, while all further filtering and computational aspects should be described. Such an approach will significantly simplify the use of global dZr data by

关键词： water quality testing   quality control   matters needing attention  

摘要： With the continuous improvement of water quality requirements of Chinese residents, the state and relevant departments began to gradually pay attention to the quality control of water quality monitoring and evaluation for this work. In this paper, various factors affecting the actual work of water quality monitoring are defined, the optimization method in the specific link of water quality testing is analyzed, and the specific precautions in the quality assessment of water quality testing are put forward to improve the quality control ability of water quality testing institutions, so as to ensure the stability and reliability of the testing results.

关键词： Pharmacophores   Cells   Inhibitors   Inhibition   Apoptosis  

摘要： Dual inhibition of tubulin and poly(ADP-ribose) polymerase-1 (PARP-1) may become an attractive approach for cancer therapy. Here, we discover a dual tubulin/PARP-1 inhibitor (termed as TP-3) using structure-based virtual screening. TP-3 shows strong dual inhibitory effects on both tubulin and PARP-1. Cellular assays reveal that TP-3 shows superior antiproliferative activities against human cancer cells, including breast, liver, ovarian, and cervical cancers. Further studies indicate that TP-3 plays an antitumor role through multiple mechanisms, including the disturbance of the microtubule network and the PARP-1 DNA repairing function, accumulation of DNA double-strand breaks, inhibition of the tube formation, and induction of G2/M cell cycle arrest and apoptosis. In vivo assessment indicates that TP-3 inhibits the growth of MDA-MB-231 xenograft tumors in nude mouse with no notable side effects. These data demonstrate that TP-3 is a dual-targeting, high-efficacy, and low-toxic antitumor agent.

摘要： ADP-ribosylation is an essential post-translational modification that comes in two varieties: mono-ADP-ribosylation (MAR) and poly-ADP-ribosylation (PAR). Modular interaction domains that read MAR and PAR modifications are critical for interpreting the language of ADP-ribosylation. Kliza et al. (2021) use a chemical biology approach to identify distinct MAR and PAR readers.

关键词： 治理能力   银行转型   姚辉   创新空间   技术创新   微众银行   数据处理   产品部  

摘要： 微众银行科技创新产品部负责人姚辉亚强调,银行可以通过打造开放生态、提升科技能力、构建敏捷组织与文化、加强数据处理与治理能力四个维度构建银行转型的新范式,充分释放数据要素的价值。