98%
921
2 minutes
20
A palladium-catalyzed multicomponent reaction involving -bromobenzaldehydes and two different isocyanides was developed to assemble series of isoindolinones with spiroindolenine or azepinoindole skeletons. This sequential insertion reaction features mild conditions, a wide substrate scope, and high efficiency. Preliminary mechanistic study indicated that the difference in steric hindrance between isocyanide components is crucial when regulating the reaction sequence, whereas the ligand also played an important role during the whole process.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/acs.orglett.3c00393 | DOI Listing |
Mol Oncol
September 2025
Department of Internal Medicine - Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Retroelements in the human genome are silenced via multiple mechanisms, including DNA methylation, to prevent their potential mutagenic effect. Retroelement activity, demonstrated by their expression and somatic retrotransposition events, was shown to be deregulated in multiple tumors but not yet in leukemia. We hypothesized that treatment with hypomethylating agents, commonly used in myelodysplastic syndromes and acute myeloid leukemia, could lead to increased retroelement activity and somatic retrotranspositions, thus contributing to disease progression.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
School of Science, Technology and Engineering, University of the Sunshine Coast, Petrie, Queensland, Australia.
Drug release using polymeric microneedles (MNs) plays a significant role in medical applications and the treatment of various diseases. However, conventional MNs are often limited by complex fabrication procedures and inadequate mechanical strength. This study introduces a dual-function core/shell MN patch fabricated through a novel method that integrates 3D printing and casting techniques.
View Article and Find Full Text PDFPerioper Med (Lond)
September 2025
Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background: Painless gastroscopy is preferred by both patients and physicians, as it minimizes discomfort during the procedure. Alfentanil, a short-acting opioid analgesic, possesses pharmacological properties that make it suitable for inducing analgesia during gastroscopy. However, research on the optimal dosage of alfentanil when used in combination with propofol for gastroscopy is limited.
View Article and Find Full Text PDFNat Commun
August 2025
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
While altered pre-mRNA splicing is a frequent mechanism by which genetic variants cause disease, the regulatory architecture of human exons remains poorly understood. Antisense oligonucleotides (AONs) that target pre-mRNA splicing have been approved as therapeutics for various pathologies including patient-customised treatments for rare diseases, but AON discovery is currently slow and expensive, limiting the wider adoption of the approach. Here we show that deep indel mutagenesis (DIM) -which can be made experimentally at very low cost - provides an efficient strategy to chart the regulatory landscape of human exons and rapidly identify candidate splicing-modulating oligonucleotides.
View Article and Find Full Text PDFBMC Med Genomics
August 2025
The Central Laboratory of Birth Defects Prevention and Control, The Affiliated Women and Children's Hospital of Ningbo University, Ningbo, China.
Background: Hemophilia A (HA) is an X-linked recessive bleeding disorder caused by pathogenic variants in the gene, resulting in deficient coagulation factor VIII activity. Although intron 22 and intron 1 inversions (Inv22 and Inv1) accounts for approximately 50% of severe HA cases, complex structural rearrangements mediated by intron 22 homologous region ( repeats have rarely reported and poorly characterized.
Methods: In this study, we investigated a Chinese severe HA pedigree with a complex rearrangement of gene by integrating 750 K SNP arrays, long-read sequencing (Oxford Nanopore Technologies, ONT), and optical genome mapping (OGM).