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http://dx.doi.org/10.1161/CIRCGEN.120.003123 | DOI Listing |
ACS Omega
September 2025
Neuroscience and Ageing Biology Division, CSIR- Central Drug Research Institute (CDRI), Lucknow 226031, India.
The TRPA1 channel has recently emerged as a critical target for pain relief since its antagonists target the beginning of the pain transduction pathway and, thus, are devoid of side effects such as sedation, dizziness, somnolence, or cognitive impairment. Despite this clinical significance, currently, no TRPA1 inhibitors suitable for therapeutic usage exist to target these channels. Since ancient times, natural products have been known to be a rich source of new drugs, useful therapeutic agents, as well as pharmacological tools.
View Article and Find Full Text PDFMol Plant Pathol
September 2025
State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, China.
Superinfection exclusion (SIE) is a finely tuned virus-virus interaction mechanism closely linked to the viral infection cycle. However, the mechanistic basis of SIE remains incompletely understood in plant viruses, particularly among negative-sense, single-stranded RNA viruses. In this study, we first describe the development of an efficient reverse genetics system for the plant nucleorhabdovirus Physostegia chlorotic mottle virus (PhCMoV) by codon optimisation of the large polymerase coding sequence.
View Article and Find Full Text PDFFront Immunol
September 2025
Division of Allergy and Immunology, Department of Pediatrics and Medicine, Morsani College of Medicine, University of South Florida at Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.
WHIM syndrome is typically caused by C-terminal gain-of-function variants in , yet clinical heterogeneity suggests additional genetic modifiers. We investigated a family in which the 22-year-old proband harbored two heterozygous variants: a novel missense variant, c.1022C>A (p.
View Article and Find Full Text PDFMol Plant
September 2025
Division of Life Sciences and Medicine; Division of Molecular & Cell Biophysics, Hefei National Science Center for Interdisciplinary Sciences at the Microscale; MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics; University of Science and Technology of China, The Innovation Academy
Abiotic stresses severely threaten global food security, underscoring the need for resilient crop varieties. We identified OsSPT38, a previously uncharacterized SUMO E3 ligase in rice, and discovered a rare gain-of-function mutation (Gly212Asp) that enhances both stress resilience and yield. This phenotype was validated in 18 additional independent mutants and by base editing in the elite indica cultivar Huanghuazhan.
View Article and Find Full Text PDFMol Cancer Ther
September 2025
Novelty Nobility, Seongnam-si, Korea (South), Republic of.
Overexpression and gain-of-function mutations of c-Kit have been implicated in cancers including gastrointestinal stromal tumors (GIST), small cell lung cancer (SCLC), acute myeloid leukemia, and systematic mastocytosis. In clinics, small molecule c-Kit inhibitors often result in secondary c-Kit mutations or are ineffective despite c-Kit overexpression. We developed NN3201, a novel c-Kit targeting antibody-drug conjugate (ADC), via rational design to evaluate its anticancer activity in c-Kit-positive tumors, and preclinical pharmacologic profiles.
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