As wellknown persistent contaminants, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic polyaromatic hydrocarbons (Heterocyclic PAHs)'s fates in cryogenic environments are remains uncertain. Herein, strain S01 was identified as Pseudomonas fluorescens, a novel bacterium tolerant to low temperature and capable of degrading PAHs and heterocyclic PAHs. Strain S01 exhibited growth at 5-40 ℃ and degradation rate of mixed PAHs and heterocyclic PAHs reached 52% under low-temperature. Through comprehensive metabolomic, genomic, and transcriptomic analyses, we reconstructed the biodegradation pathway for PAHs and heterocyclic PAHs in S01 while investigating its response to low temperature. Further experiments involving deletion and replacement of methyl-accepting chemotaxis protein (MCP) confirmed its crucial role in enabling strain S01's adaptation to dual stress of low temperature and pollutants. Additionally, our analysis revealed that MCP was upregulated under cold stress which enhanced strain S01's motility capabilities leading to increased biofilm formation. The establishment of biofilm promoted preservation of distinct cellular membrane stability, thereby enhancing energy metabolism. Consequently, this led to heightened efficiency in pollutant degradation and improved cold resistance capabilities. Our findings provide a comprehensive understanding of the environmental fate of both PAHs and heterocyclic PAHs under low-temperature conditions while also shedding light on cold adaptation mechanism employed by strain S01.
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http://dx.doi.org/10.1016/j.jhazmat.2024.133905 | DOI Listing |
Nat Commun
January 2025
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3.
View Article and Find Full Text PDFArch Pharm (Weinheim)
January 2025
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, Novosibirsk, Russian Federation.
Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Medicines Discovery Institute, Cardiff University, Cardiff CF10 3AT, UK.
DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many malignant tumors. However, ICI-induced hyper-immune activation causes cardiotoxicity. Traditional treatments such as glucocorticoids and immunosuppressants have limited effectiveness and may even accelerate tumor growth.
View Article and Find Full Text PDFMolecules
December 2024
Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigación Lascaray (Lascaray Research Center), Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain.
The synthesis of phosphorous indenoquinolines and their biological evaluation as topoisomerase 1 (TOP1) inhibitors and antiproliferative agents were performed. First, the preparation of new hybrid 5-indeno[2,1-]quinolines with a phosphine oxide group was performed by a two-step Povarov-type [4+2]-cycloaddition reaction between the corresponding phosphorated aldimines with indene in the presence of BF·EtO. Subsequent oxidation of the methylene present in the structure resulted in the corresponding indeno[2,1-]quinolin-7-one phosphine oxides .
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