Skin rash, diarrhea and hepatotoxicity are the most common toxicities of Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. The present study investigated the effects of genetic polymorphisms of drug target, metabolizing enzymes and transporters on Gefitinib toxicities. Thirty single-nucleotide polymorphisms, including EGFR, cytochromes P450 and ATP-binding cassette (ABC), were genotyped by matrix-assisted laser desorption/ionization time-of-flight platform in 59 non-small cell lung cancer patients treated with Gefitinib. Correlation analyses were performed to evaluate their effects on Gefitinib-induced toxicities. ABCB1 rs1128503 TT genotype was a significant high-risk determinant of both skin rash and diarrhea, with 15.78- and 10.78-fold of incident risk increased, respectively. (odds ratio (OR)=15.78, 95% confidence interval (CI) 2.01-124.1, P=0.0087; OR=10.78, 95% CI 1.54-75.40, P=0.0166 vs non-TT genotypes). Patients with ABCB1 rs1128503 TT genotype had greater risk of skin rash and diarrhea. Therefore, polymorphism analyses of ABCB1 might be beneficial to optimize Gefitinib treatment.
Atmospheric reactive nitrogen (N r ) has been a cause of serious environmental pollution in China. Historically, China used too little N r in its agriculture to feed its population. However, with the rapid increase in N fertilizer use for food production and fossil fuel consumption for energy supply over the last four decades, increasing gaseous N r species (e.g. NH 3 and NO x ) have been emitted to the atmosphere and then deposited as wet and dry deposition, with adverse impacts on air, water and soil quality as well as plant biodiversity and human health. This paper reviews the issues associated with this in a holistic way. The emissions, deposition, impacts, actions and regulations for the mitigation of atmospheric N r are discussed systematically. Both NH 3 and NO x make major contributions to environmental pollution but especially to the formation of secondary fine particulate matter (PM 2.5 ), which impacts human health and light scattering (haze). In addition, atmospheric deposition of NH 3 and NO x causes adverse impacts on terrestrial and aquatic ecosystems due to acidification and eutrophication. Regulations and practices introduced by China that meet the urgent need to reduce N r emissions are explained and resulting effects on emissions are discussed. Recommendations for improving future N management for achieving ‘win-win’ outcomes for Chinese agricultural production and food supply, and human and environmental health, are described. This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Genes associated with the WNT pathway play an important role in the etiology of tooth agenesis. Low-density lipoprotein receptor–related protein 6 encoding gene ( LRP6) is a recently defined gene that is associated with autosomal dominant inherited tooth agenesis. Here, we aimed to identify novel LRP6 mutations in patients with tooth agenesis and investigate the significance of Lrp6 during tooth development. Using whole-exome sequencing, we identified 4 novel LRP6 heterozygous mutations (c.2292G>A, c.195dup, c.1095dup, and c.1681C>T) in 4 of 77 oligodontia patients. Notably, a patient who carried a nonsense LRP6 mutation (c.2292G>A; p.W764*) presented a hypohidrotic ectodermal dysplasia phenotype. Preliminary functional studies, including bioinformatics analysis and TOP-/FOP-flash reporter assays, demonstrated that the activation of WNT/β-catenin signaling was compromised as a consequence of LRP6 mutations. RNAscope in situ hybridization revealed dynamic and special changes of Lrp6 expression during murine tooth development from E11.5 to E16.5. It was noteworthy that Lrp6 was specifically expressed in the epithelium at E11.5 to E13.5 but was expressed in both dental epithelium and dental papilla from E14.5 and persisted in both tissues at later stages. Our study broadens the mutation spectrum of human tooth agenesis and is the first to identify a LRP6 mutation in patients with hypohidrotic ectodermal dysplasia and reveal the dynamic expression pattern of Lrp6 during tooth development. Information from this study is conducive to understanding the functional significance of Lrp6 on the biological process of tooth development.
Correction to: Oncogene (2018) 37, 1062–1074; doi: 10.1038/onc.2017.368; published online 6 November 2017 This article was originally published under NPG's License to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.
Bulk MgB2 with SiO2 nanoparticles added has been synthesized using a simple solid-state reaction route. The lattice constant in the c direction increases with additive content due to a small amount of Si being doped into the lattice of the MgB2; however, Tc is almost fixed at 37.2 K. The addition of SiO2 nanoparticles also improves the Jc–H and Hirr–T characteristics of MgB2 when the additive content is lower than 7%. At 20 K and 1 T, Jc for the sample with 7% additive content reaches 2.5 × 105 A cm−2. Microstructural analysis reveals that a high density of MgSi2 nanoparticles (10–50 nm) exists inside the MgB2 grains, leading to the formation of a nanocomposite superconductor.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.