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Bicyclo[1.1.0]butanes (BCBs), which possess multiple switchable reactive sites, serve as the most direct modular scaffolds for constructing benzene ring bioisosteres. Herein, we describe the precise modulation of BCB reactive sites through Lewis/Brønsted acid switching to enable the synthesis of challenging spirocycles and bridged frameworks. The divergent reaction outcomes, arising from the precise control of catalysts over the switchable reactive sites of BCBs, are achieved without any substrate modification.
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http://dx.doi.org/10.1021/acs.orglett.5c02160 | DOI Listing |
Mol Ther Methods Clin Dev
September 2025
Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
genome editing with CRISPR-Cas9 systems is generating worldwide attention and enthusiasm for the possible treatment of genetic disorders. However, the consequences of potential immunogenicity of the bacterial Cas9 protein and the AAV capsid have been the subject of considerable debate. Here, we model the antigen presentation in cells after gene editing by transduction of a human cell line with an AAV2 vector that delivers the Cas9 transgene.
View Article and Find Full Text PDFFuture Med Chem
September 2025
Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, P.R. China.
The nuclear receptor binding SET domain (NSD) family of histone methyltransferases, which comprised NSD1, NSD2, and NSD3. They play a pivotal role in catalyzing mono- and dimethylation of histone H3 at lysine 36 (H3K36me1/2), a modification critical for maintaining chromatin structure and transcriptional fidelity. Dysregulation of NSD enzymes, often through overexpression, mutation, or chromosomal translocation, has been implicated in a broad spectrum of malignancies and various diseases.
View Article and Find Full Text PDFNano Lett
September 2025
School of Materials and Chemistry, University of Shanghai for Science & Technology, Shanghai 200093, China.
Developing low-temperature gas sensors for parts per billion-level acetone detection in breath analysis remains challenging for non-invasive diabetes monitoring. We implement dual-defect engineering via one-pot synthesis of Al-doped WO nanorod arrays, establishing a W-O-Al catalytic mechanism. Al doping induces lattice strain to boost oxygen vacancy density by 31.
View Article and Find Full Text PDFJCI Insight
September 2025
Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
The regulation of follicular (F) and germinal center (GC) immune reactivity in human lymph nodes (LNs), particularly during the acute stages of viral infection, remains poorly understood: We have analyzed lung-draining lymph nodes (LD-LNs) from COVID-19 autopsies using multiplex imaging and spatial transcriptomics to examine the immune landscape with respect to follicular immune reactivity. We identified three groups of donors based on the Bcl6 prevalence of their Reactive Follicles (RFs): RF-Bcl6no/low, RF-Bcl6int, and RF-Bcl6high. A distinct B/TFH immune landscape, associated with increased prevalence of proliferating B-cell and TFH-cell subsets, was found in RF-Bcl6high LD-LNs.
View Article and Find Full Text PDFNucleic Acids Res
September 2025
Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, is catalyzed by Clr4/Suv39. Clr4/Suv39 contains two conserved domains-an N-terminal chromodomain and a C-terminal catalytic domain-connected by an intrinsically disordered region (IDR). Several mechanisms have been proposed to regulate Clr4/Suv39 activity, but how it is regulated under physiological conditions remains largely unknown.
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