Butyrylcholinesterase (BChE) plays a pivotal role in regulating acetylcholine (ACh) levels during the progression of Alzheimer's disease (AD), so emerged as an attractive target in AD treatment. Vasicine, a naturally occurring pyrroloquinazoline alkaloid, was identified as a natural BChE inhibitor (IC = 1.47 ± 0.
View Article and Find Full Text PDFPseudouridine (Ψ) is one of the most abundant modifications in cellular RNA. However, its function remains elusive, mainly due to the lack of highly sensitive and accurate detection methods. Here, we introduced 2-bromoacrylamide-assisted cyclization sequencing (BACS), which enables Ψ-to-C transitions, for quantitative profiling of Ψ at single-base resolution.
View Article and Find Full Text PDFXanthine oxidase (XO) is an important enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid in the catabolism of purines in humans. This makes XO a well-recognized target in alleviating hyperuricemia. The present study adapted a structure-based drug discovery approach to develop potent and low-toxicity XO inhibitors with the chalcone skeleton.
View Article and Find Full Text PDFXanthine oxidase (XO) is a crucial target for hyperuricemia treatment(s). Naturally occurred XO inhibitors with minimal toxicity and high efficacy have attracted researchers' attention. With the goal of quickly identifying natural XO inhibitors, an integrated computational screening strategy was constructed by molecular docking and calculating the free energy of binding.
View Article and Find Full Text PDFGermline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo.
View Article and Find Full Text PDFThe "epigenetics" concept was first described in 1942. Thus far, chemical modifications on histones, DNA, and RNA have emerged as three important building blocks of epigenetic modifications. Many epigenetic modifications have been intensively studied and found to be involved in most essential biological processes as well as human diseases, including cancer.
View Article and Find Full Text PDFThe efficiency of DNA-enrichment techniques is often insufficient to detect mutations that occur at low frequencies. Here we report a DNA-excision method for the detection of low-frequency mutations in genomic DNA and in circulating cell-free DNA at single-nucleotide resolution. The method is based on a competitive DNA-binding-and-digestion mechanism, effected by deoxyribonuclease I (DNase) guided by single-stranded phosphorothioated DNA (sgDNase), for the removal of wild-type DNA strands.
View Article and Find Full Text PDFSelective, efficient, and controllable oxidation of cytosine modifications is valuable for epigenetic analyses, yet only limited progress has been made. Here, we present two modular chemical oxidation reactions: conversion of 5-hydroxymethylcytosine (5hmC) into 5-formylcytosine (5fC) using 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (ACTBF) and further transformation of 5fC into 5-carboxycytosine (5caC) through Pinnick oxidation. Both reactions are mild and efficient on double-stranded DNA.
View Article and Find Full Text PDFXanthine oxidase (XO) is a key target for gout treatment. Great efforts have been made towards the discovery and development of new XO inhibitors. Aureusidin (AUR), a natural compound, emerges as the second reported XO inhibitor with an aurone skeleton with an IC value of 7.
View Article and Find Full Text PDFInt J Geogr Inf Sci
May 2022
Geographic Question Answering (GeoQA) systems can automatically answer questions phrased in natural language. Potentially this may enable data analysts to make use of geographic information without requiring any GIS skills. However, going beyond the retrieval of existing geographic facts on particular places remains a challenge.
View Article and Find Full Text PDFAcute lymphoblastic leukemia (ALL) has been a huge threat for people's health and finding effective target therapy is urgent and important. WWP2, as one of E3 ubiquitin ligase, is involved in many biological processes by specifically binding to substrates. PARP1 plays a role in cell apoptosis and is considered as a therapeutic target of certain cancers.
View Article and Find Full Text PDFE3 ubiquitin ligases, an important part of ubiquitin proteasome system, catalyze the covalent binding of ubiquitin to target substrates, which plays a role in protein ubiquitination and regulates different biological process. DNA damage response (DDR) is induced in response to DNA damage to maintain genome integrity and stability, and this process has crucial significance to a series of cell activities such as differentiation, apoptosis, cell cycle. The NEDD4 family, belonging to HECT E3 ubiquitin ligases, is reported as regulators that participate in the DDR process by recognizing different substrates.
View Article and Find Full Text PDFFluorescence-based single-molecule techniques, mainly including fluorescence correlation spectroscopy (FCS) and single-molecule fluorescence resonance energy transfer (smFRET), are able to analyze the conformational dynamics and diversity of biological macromolecules. They have been applied to analysis of the dynamics of membrane proteins, such as membrane receptors and membrane transport proteins, due to their superior ability in resolving spatio-temporal heterogeneity and the demand of trace amounts of analytes. In this review, we first introduced the basic principle involved in FCS and smFRET.
View Article and Find Full Text PDF"Data Science" has taken many disciplines by storm. And for a good reason: New forms and unseen quantities of data enter nearly every scientific field, substantially changing the ways how scientists do science, and potentially allowing them to answer old questions or to pose them in novel ways. The recent success of Data Science is also reflected in corresponding study programs and curricula and the emergence of specialized branches, such as Geographic Data Science (GDS).
View Article and Find Full Text PDFBackground: The myelin sheath can be damaged by genetic and/or environmental factors, leading to demyelinating diseases, for which effective treatments are lacking. Recently, cyclooxygenase-2 (COX-2) overexpression was detected in demyelinating lesions both in patients and animal models, opening an avenue for promoting endogenous remyelination. The aim of this study was to investigate the therapeutic effect of celecoxib, a selective COX-2 inhibitor, against demyelination in a zebrafish model.
View Article and Find Full Text PDF-methyladenosine (mA) is the most abundant post-transcriptional modification in mRNA, and regulates critical biological functions via mA reader proteins that bind to mA-containing transcripts. There exist multiple mA reader proteins in the human genome, but their respective binding specificity and functional relevance under different biological contexts are not yet fully understood due to the limitation of experimental approaches. An study was devised to unveil the target specificity and regulatory functions of different mA readers.
View Article and Find Full Text PDFLung adenocarcinoma (LACA) is the leading cause of cancer-associated death worldwide. The present study intended to identify DNA methylation patterns that may serve as diagnostic and prognostic biomarkers for LACA. Data on DNA methylation and the survival data of the patients of LACA were obtained from The Cancer Genome Atlas.
View Article and Find Full Text PDFBackground: DLEC1 is a tumor-suppressor gene which plays a role in carcinogenesis. The purpose of the current study was to help establish the diagnostic performance of DLEC1 methylation in lung cancer.
Methods: PubMed, Embase, CNKI, and Wanfang databases were searched to obtain eligible studies.