A novel ruthenium-catalyzed intramolecular cyclization of a nitrile and an azetidine was developed to achieve a one-step synthesis of the fused tricyclic 1H-2,3-dihydropyrimido[1,2-a]quinoline, which is the core skeleton for more than 100 natural pyoverdines and is also responsible for their fluorescence.
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http://dx.doi.org/10.1021/acs.orglett.7b01330 | DOI Listing |
Genet Epidemiol
January 2025
Interdisciplinary Program of Bioinformatics, College of Natural Science, Seoul National University, Seoul, South Korea.
In this article, we proposed a new method named fused mixed graphical model (FMGM), which can infer network structures associated with dichotomous phenotypes. FMGM is based on a pairwise Markov random field model, and statistical analyses including the proposed method were conducted to find biological markers and underlying network structures of the atopic dermatitis (AD) from multiomics data of 6-month-old infants. The performance of FMGM was evaluated with simulations by using synthetic datasets of power-law networks, showing that FMGM had superior performance for identifying the differences of the networks compared to the separate inference with the previous method, causalMGM (F1-scores 0.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Macau, Institute of Chinese Medical Sciences, Avenida da Universidade, N22, Taipa, CHINA.
Engineered immune cell therapy has proven to be a transformative cancer treatment despite the challenges of its prohibitive costs and manufacturing complexity. In this study, we propose a concise "lipid droplet fusion" strategy for engineering macrophages. Because of the integration of hydrophobic alkyl chains and π-conjugated structures, the mildly synthesized sp2C-conjugated covalent organic framework (COF) UM-101 induced lipid droplet fusion and metabolic reprogramming of macrophages, thus promoting their antitumor classical activation.
View Article and Find Full Text PDFJ Agric Food Chem
January 2025
State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, PR China.
4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial herbicide target in current research, playing an important role in the comprehensive management of resistant weeds. However, the limited crop selectivity and less effectiveness against grass weeds of many existing HPPD inhibitors, limit their further application. To address these issues, a series of novel HPPD inhibitors with fused ring structures were designed and synthesized by introducing an electron-rich indazolone ring and combining it with the classical triketone pharmacophore structure.
View Article and Find Full Text PDFCommun Biol
January 2025
Institut Pasteur, CNRS UMR 3528, Université Paris Cité, Structural Microbiology Unit, F-75015, Paris, France.
MoeA, also known as gephyrin in higher eukaryotes, is an enzyme essential for molybdenum cofactor (Moco) biosynthesis and involved in GABA and GlyR receptor clustering at the synapse in animals. We recently discovered that Actinobacteria have a repurposed version of MoeA (Glp) linked to bacterial cell division. Since MoeA exists in all domains of life, our study explores how it gained multifunctionality over time.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230031, Anhui, China.
Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.
Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.
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