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Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma.
J Immunother Cancer
January 2025
Division of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, UK
Background: Programmed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance.
View Article and Find Full Text PDFEmergence of a novel group B streptococcus CC61 clade associated with human infections in southern China.
J Infect
January 2025
National Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University, Wuhan, PR China; Hubei Hongshan Laboratory, Wuhan, PR China; Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan, PR China. Electronic address:
Objectives: Emerging human pathogens of animal origin have become an increasing public health concern in recent years. The aim of this study was to investigate the transmission of group B streptococcus (GBS) clonal complex (CC) 61 strains in the southern Chinese population and analyze their genetic characteristics.
Methods: Whole-genome sequencing was performed on 693 clinical isolates of GBS collected from southern China between 2016 and 2021, and the prevalence of human CC61 isolates was investigated by genomic epidemiology.
Selective pressure of various levels of erythromycin on the development of antibiotic resistance.
Environ Pollut
January 2025
Civil and Construction Engineering and Environmental and Ecological Engineering, Purdue University, 550 Stadium Mall Drive, West Lafayette, Indiana, United States 47907. Electronic address:
This study evaluated microbial fitness under selective pressure of various erythromycin concentrations and the development of resistance genes in Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis).
View Article and Find Full Text PDFHighly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.
J Med Chem
January 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
View Article and Find Full Text PDFEffector genes of type III secretion system and biofilm formation in virulent isolates carrying and genes in hospital environment.
J Med Microbiol
January 2025
Laboratory of Molecular Microbiology (Micromol), Institute of Biomedical Sciences, Universidade Federal de Uberlndia, Uberlndia, Minas Gerais, Brazil.
In critically ill patients, the occurrence of multidrug-resistant infection is a significant concern, given its ability to acquire multidrug-resistant, form biofilms and secrete toxic effectors. In Brazil, limited data are available regarding the prevalence of dissemination, and the impact of the type III secretion system (T3SS) on toxin production and biofilm formation in clinical isolates of . This study investigates the dissemination of virulent harbouring the and genes, the presence of T3SS genes and their biofilm-forming capability.
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