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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
《工程(英文)》 2024年 第32卷 第1期 页码 58-69 doi: 10.1016/j.eng.2023.09.019
Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
关键词: Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells
人工智能加速GPCR配体的发现 Review
陈伟, 宋驰, 冷梁, 张三印, 陈士林
《工程(英文)》 2024年 第32卷 第1期 页码 19-29 doi: 10.1016/j.eng.2023.09.011
G蛋白偶联受体(GPCR)在多种生理过程中发挥着关键作用,是新药发现的重要靶标。然而,传统的GPCR配体发现方法需要投入大量的时间和资源。人工智能方法的出现为GPCR配体的识别和优化提供了有利的工具,改变了GPCR配体发现的研究方式。本文从数据资源、数据描述、模型设计等方面介绍了如何利用人工智能方法构建GPCR配体发现模型,并分析了人工智能方法在GPCR药物领域的应用;提出了一种基于人工智能方法整合多组学数据的GPCR配体筛选策略;探讨了人工智能方法在GPCR研究领域面临的挑战和未来发展方向。人工智能方法与多学科的交叉融合将提高GPCR配体发现的效率。
基于5 μm厚向列相液晶的高效圆极化相控阵系统的设计、校准和实验验证 Article
Xin Yu Wu,Fengshuo Wan,Hongyuan Feng,Shichao Jin,Chong Guo,Yu Wei,Dunge Liu,Yuqian Yang,Longzhu Cai,Zhi Hao Jiang,Wei Hong
《工程(英文)》 2024年 第32卷 第1期 页码 70-82 doi: 10.1016/j.eng.2023.08.013
This paper presents a systematic investigation and demonstration of a K-band circularly polarized liquid-crystal-based phased array (LCPA), including the design, over-the-air (OTA) in-array calibration, and experimental validation. The LCPA contains 16 phase-shifting radiating channels, each consisting of a circularly polarized stacked patch antenna and a liquid-crystal-based phase shifter (LCPS) based on a loaded differential line structure. Thanks to its slow-wave properties, the LCPS exhibits a maximum phase-shifting range of more than 360° with a figure of merit of 78.3°·dB−1 based on a liquid crystal layer with a thickness of only 5 μm. Furthermore, an automatic OTA calibration based on a state ergodic method is proposed, which enables the extraction of the phase–voltage curve of every individual LCPA channel. The proposed LCPA is manufactured and characterized with a total profile of only 1.76 mm, experimentally demonstrating a scanned circularly polarized beam from −40° to +40° with a measured peak gain of 12.5 dBic and a scanning loss of less than 2.5 dB. The bandwidth of the LCPA, which satisfies the requirements of port reflection (|S11|) < −15 dB, an axial ratio (AR) < 3 dB, beam squinting < 3°, and a gain variation < 2.2 dB, spans from 25.5 to 26.0 GHz. The total efficiency is about 34%, which represents a new state of the art. The use of the demonstrated low-profile LCPA to support circularly polarized scanning beams, along with the systematic design and calibration methodology, holds potential promise for a variety of millimeter-wave applications.
关键词: Circularly polarized Liquid crystal Liquid-crystal-based phased array (LCPA) Phase shifter Over-the-air (OTA) calibration
堆石混凝土坝概述及下一代混凝土坝施工技术展望 Review
Feng Jin, Duruo Huang, Michel Lino, Hu Zhou
《工程(英文)》 2024年 第32卷 第1期 页码 100-106 doi: 10.1016/j.eng.2023.09.020
Over the past few decades, one of the most significant advances in dam construction has been the invention of the rock-filled concrete (RFC) dam, which is constructed by pouring high-performance selfcompacting concrete (HSCC) to fill the voids in preplaced large rocks. The innovative use of large rocks in dam construction provides engineers with a material that requires less cement consumption and hydration heat while enhancing construction efficiency and environmental friendliness. However, two fundamental scientific issues related to RFC need to be addressed: namely, the pouring compactness and the effect of large rocks on the mechanical and physical properties of RFC. This article provides a timely review of fundamental research and innovations in the design, construction, and quality control of RFC dams. Prospects for next-generation concrete dams are discussed from the perspectives of environmental
friendliness, intrinsic safety, and labor savings.
关键词: Rock-filled concrete dam Pouring compactness Effect of large rocks Intelligent quality control Unmanned dam construction
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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化
Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš
期刊论文
基于5 μm厚向列相液晶的高效圆极化相控阵系统的设计、校准和实验验证
Xin Yu Wu,Fengshuo Wan,Hongyuan Feng,Shichao Jin,Chong Guo,Yu Wei,Dunge Liu,Yuqian Yang,Longzhu Cai,Zhi Hao Jiang,Wei Hong
期刊论文