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Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.
Nat Commun
January 2025
Molecular and Cellular Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 T. W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
Coronaviruses evade detection by the host immune system with the help of the endoribonuclease Nsp15, which regulates levels of viral double stranded RNA by cleaving 3' of uridine (U). While prior structural data shows that to cleave double stranded RNA, Nsp15's target U must be flipped out of the helix, it is not yet understood whether Nsp15 initiates flipping or captures spontaneously flipped bases. We address this gap by designing fluorinated double stranded RNA substrates that allow us to directly relate a U's sequence context to both its tendency to spontaneously flip and its susceptibility to cleavage by Nsp15.
View Article and Find Full Text PDFEffect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study.
J Immunother Cancer
January 2025
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background: Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear.
View Article and Find Full Text PDFGenetic Insights Into Coronary Microvascular Disease.
Microcirculation
January 2025
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Coronary microvascular disease (CMVD) affects the coronary pre-arterioles, arterioles, and capillaries and can lead to blood supply-demand mismatch and cardiac ischemia. CMVD can present clinically as ischemia or myocardial infarction with no obstructive coronary arteries (INOCA or MINOCA, respectively). Currently, therapeutic options for CMVD are limited, and there are no targeted therapies.
View Article and Find Full Text PDFComputer-aided diagnosis of hepatic cystic echinococcosis based on deep transfer learning features from ultrasound images.
Sci Rep
January 2025
College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, 830017, China.
Hepatic cystic echinococcosis (HCE), a life-threatening liver disease, has 5 subtypes, i.e., single-cystic, polycystic, internal capsule collapse, solid mass, and calcified subtypes.
View Article and Find Full Text PDFAssessing asymmetric enhancement on breast MRI: Besting the diagnostic challenge with imaging and clinical clues.
Curr Probl Diagn Radiol
January 2025
Department of Medical Imaging, University of Arizona, 1501 N Campbell Ave, Tucson AZ 85724, USA; Banner University Medical Center Tucson, 1625 N Campbell Ave, Tucson AZ 85719, USA.
Breast magnetic resonance imaging (MRI) has the highest sensitivity for breast cancer detection compared to other breast imaging modalities such as mammography and ultrasound. As a functional modality, it captures the increased angiogenic activity of breast cancer through gadolinium-based contrast enhancement. Normal breast tissue also enhances, albeit in distinct patterns termed background parenchymal enhancement (BPE).
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