课程文献中心 更多>>

摘要： In this study, we present an efficient and direct strategy for the synthesis of N1,N3-disubstituted quinazoline-2,4­(1H,3H)-diones with high atom and step economy. The protocol involves a Pd­(II)-catalyzed [3 + 1 + 1 + 1] cascade carbonylation/amidation/cyclocarbonylation reaction, wherein the alkylamino moiety of simple N-substituted anilines serves as an intrinsic directing group, with CO and amines as the coupling partners. This cascade process proceeds smoothly with a variety of substrates under mild conditions, affording the target products with either identical or distinct substituents mostly in moderate to good yields.

摘要： This research evaluates a therapeutic approach based on tissue-targeted immunomodulation with a potential broad application to treat autoimmune diseases including type 1 diabetes (T1D). We generated a bispecific immune agonist that binds beta cells and suppresses autoreactive T cells. These bispecific molecules called immune modulating monoclonal–T cell receptor (TCR) against autoimmune disease (ImmTAAI), consist of a human-specific TCR–targeting domain fused with a programmed death-1 agonist. We used live pancreas slices to demonstrate targeting of ImmTAAI molecules to preproinsulin peptide–HLA-A2 complexes on human beta cells. ImmTAAI molecules protected beta cells from T cell killing by increasing T cell motility and inhibiting effector molecule and cytokine secretion. ImmTAAI treatment also increased the motility of islet-infiltrating T cells in slices from a donor with recent-onset T1D and preserved insulin secretion in slices cocultured with T cell avatars transduced with diabetogenic TCRs. These data demonstrate that ImmTAAI molecules have the potential to limit T cell activity locally, making this an attractive platform to elicit targeted immunoregulation in T1D. copyright © 2026 the Authors, some rights reserved;exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. distributed under a creative commons Attribution license 4.0 (cc BY).

关键词： Neurofibromatosis type 1   executive function   cognitive rehabilitation   neuropsychology   feasibility studies  

摘要： Children with Neurofibromatosis Type 1 (NF1) experience significant executive dysfunction interfering with outcomes across the lifespan. To date, there have been limited interventions targeting executive function impairments, and even less explored within the NF1 population. The primary purpose of this study was to determine if an existing executive functioning intervention, Unstuck and On Target! (UOT), is a feasible and acceptable intervention for children with NF1. Participants were four children with NF1 (75% male;75% Caucasian) between the ages of 9 to 12 years and their parents. Participants engaged in 20 weekly group sessions of UOT over the course of five months. Attendance rates and satisfaction ratings were primary outcomes. Attendance was >95% and attrition was null. Parent feedback and satisfaction ratings were overwhelmingly positive. In the first study of its kind, the results suggest that UOT is a feasible and acceptable cognitive intervention for children with NF1. Future development of Phase II/III studies of UOT to examine treatment dose and efficacy is supported.

关键词： Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)   semaglutide   ozempic   dulaglutide   exenatide   liraglutide   tirzepatide   accidental overdose  

摘要： Background The use of online and/or compounding pharmacies to access glucagon-like peptide-1 receptor agonists (GLP-1 RAs) increases the risk for prescription error (e.g. accidental overdose) especially in racial, ethnic, and socioeconomic disadvantaged groups. Methods We sought to evaluate accidental overdose associated with GLP-1 RAs submitted to the United States FDA Adverse Event Reporting System (FAERS). Case reports of accidental overdose reported to the FAERS were retrieved from Q4 2003 to Q1 2024 using OpenVigil 2.1. Disproportionality of accidental overdose was assessed using reporting odds ratio (ROR). Upper and lower 95% confidence intervals (CI) were calculated at an alpha level of 5%, where disproportionate reporting was considered when the lower 95% CI was greater than 1.0. Results We identified 3,348 reports of accidental overdose associated with GLP-1 RAs. The RORs were significant for all agents within the class (ROR range: 2.64-61.12, all p < 0.008), including semaglutide, dulaglutide, exenatide, liraglutide, and tirzepatide compared to niacin. Conclusions Inadequate access, availability, and affordability of GLP-1 RAs has contributed to the increased seeking via online and/or compounding pharmacies, and is associated with greater risk for prescription errors that differentially affect racial, ethnic, and socioeconomic vulnerable populations. Pharmacovigilance database analyses cannot establish causation only association.