Discovery of Potent and Selective c-Met Degraders for Hepatocellular Carcinoma Treatment.

Targeting c-Met is a clinical trend for the precise treatment of HCC, but the potential issue of acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease treatment and overcoming drug resistance due to its special mechanism of action. In this study, we designed and synthesized two series of novel c-Met degraders and conducted a systematic biological evaluation of the optimal compound .

Discovery of potent and selective c-Met inhibitors for MET-amplified hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy worldwide. The MET gene, which encodes receptor tyrosine kinase c-Met, is aberrantly activated in various solid tumors, including non-small cell lung cancer and HCC. In this study, we identified a novel c-Met inhibitor 54 by virtual screening and structural optimization.

Cotton 4-coumarate-CoA ligase 3 enhanced plant resistance to Verticillium dahliae by promoting jasmonic acid signaling-mediated vascular lignification and metabolic flux.

Lignins and their antimicrobial-related polymers cooperatively enhance plant resistance to pathogens. Several isoforms of 4-coumarate-coenzyme A ligases (4CLs) have been identified as indispensable enzymes involved in lignin and flavonoid biosynthetic pathways. However, their roles in plant-pathogen interaction are still poorly understood.

Deep reptilian evolutionary roots of a major avian respiratory adaptation.

Vertebral ribs of the anterior thorax in extant birds bear bony prongs called uncinate processes, which improve the mechanical advantage of mm. appendicocostales to move air through the immobile lung and pneumatic air sacs. Among non-avian archosaurs, broad, cartilaginous uncinate processes are present in extant crocodylians, and likely have a ventilatory function.

Discovery of Novel Phosphoinositide-3-Kinase α Inhibitors with High Selectivity, Excellent Bioavailability, and Long-Acting Efficacy for Gastric Cancer.

Phosphoinositide-3-kinase (PI3K) overexpressed in many tumors is a promising target for cancer therapy. However, due to toxicity from the ubiquitous expression of PI3K in many tissues, the development of PI3K inhibitors with high selectivity and low toxicity has become an urgent need for tumor treatment. Herein, based on the , we designed and synthesized a series of 6-(4,6-dimorpholino-1,3,5-triazin-2-yl)benzo[]oxazol-2-amine derivatives as potent, selective, and long-acting PI3Kα inhibitors.

Taphonomy and taxonomy of a juvenile lambeosaurine (Ornithischia: Hadrosauridae) bonebed from the late Campanian Wapiti Formation of northwestern Alberta, Canada.

Hadrosaurid (duck-billed) dinosaur bonebeds are exceedingly prevalent in upper Cretaceous (Campanian-Maastrichtian) strata from the Midwest of North America (especially Alberta, Canada, and Montana, U.S.A) but are less frequently documented from more northern regions.

Taxonomic revision of Eoalligator (Crocodylia, Brevirostres) and the paleogeographic origins of the Chinese alligatoroids.

Background. The primarily Neotropical distribution of living alligatoroids raises questions as to when and how the ancestors of Alligator sinensis migrated to China. As phylogeny provides a necessary framework for historical biogeographic issues, determining the phylogenetic positions of the Chinese alligatoroids is a crucial step towards understanding global alligatoroid paleobiogeography.