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A conserved element in the first intron of has a lineage specific, TCR signal-responsive, canonical enhancer function that matches the timing of cell surface CD4 upregulation required to prevent lineage choice error.
Front Immunol
January 2025
Integrative Immunobiology Department, Duke University, Durham, NC, United States.
Introduction: The regulation of expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage.
View Article and Find Full Text PDFDesign, synthesis and evaluation of (E)-1-(4-(2-(1H-pyrazol-5-yl)vinyl)phenyl) derivatives as next generation selective RET inhibitors overcoming RET solvent front mutations (G810C/R).
Eur J Med Chem
January 2025
College of Chemistry and Materials Science, Zhejiang Normal University, No. 688 Yingbin Road, Jinhua, Zhejiang Province, 321004, China. Electronic address:
RET is a well-recognized drug target for cancer treatment. Despite the promising efficacy of selective second-generation RET inhibitors Selpercatinib and Pralsetinib, the clinical benefits have been compromised due to the quickly developed resistance to these drugs. RET G810 mutations at the solvent front site have been identified as the major on-target mutations contributing to resistance against Selpercatinib and Pralsetinib.
View Article and Find Full Text PDFCD146 promotes resistance of NSCLC brain metastases to pemetrexed via the NF-κB signaling pathway.
Front Pharmacol
January 2025
Department of Radiation Oncology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China.
Introduction: Pemetrexed is a first line drug for brain metastases from lung cancer, either as monotherapy or combined with other drugs. The frequent occurrence of initial and acquired resistance to pemetrexed results in limited treatment effectiveness in brain metastases. CD146 was recently found to play important roles in chemoresistance and tumor progression.
View Article and Find Full Text PDFCase report: Multisystemic smooth muscle dysfunction syndrome: a rare genetic cause of infantile interstitial lung disease.
Front Pharmacol
January 2025
Respiratory Department II, National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Multisystemic smooth muscle dysfunction syndrome (MSMDS) is an autosomal dominant disorder caused by mutations in the gene, resulting in variable clinical manifestation and multi-organ dysfunction. Interstitial lung disease (ILD) is a rare phenotype of this condition. We describe a rare infant case of an 8-month-old boy who presented with progressively worsening dyspnea, along with intermittent episodes of respiratory distress and cyanosis since birth.
View Article and Find Full Text PDFValine metabolite, 3-hydroxyisobutyrate, promotes lipid metabolism and cell proliferation in porcine mammary gland epithelial cells.
Front Nutr
January 2025
College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, China.
Improving mammary gland epithelial cells proliferation through nutrition is an important approach for enhancing sow milk production and piglet growth. An intermediate metabolite of valine, 3-hydroxyisobutyrate (3-HIB), regulates cellular lipid metabolism. In the present study, we investigated the effects of 3-HIB on porcine mammary gland epithelial cells proliferation and lipid metabolism.
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