The p53 cancer mutation Y220C induces formation of a cavity on the protein's surface that can accommodate stabilizing small molecules. We combined fragment screening and molecular dynamics to assess the druggability of p53-Y220C and map ligand interaction sites within the mutational cavity. Elucidation of the binding mode of fragment hits by crystallography yielded a clear picture of how a drug might dock in the cavity. Simulations that solvate the protein with isopropanol found additional sites that extend the druggable surface. Moreover, structural observations and simulation revealed the dynamic landscape of the cavity, which improves our understanding of the impact of the mutation on p53 stability. This underpins the importance of considering flexibility of the cavity in screening for optimized ligands. Our findings provide a blueprint for the design of effective drugs that rescue p53-Y220C.
Objectives: The prevalence of dental caries is high in Japan, leading to a huge burden of overall expenditure on dental caries treatment for the population. School-based fluoride mouth-rinse (S-FMR) has been implemented as a public health intervention. However, its cost-effectiveness remains unclear, where universal health insurance covers a broad range of dental treatments at relatively low cost.
Optomechanical sensors provide a platform for probing acoustic/vibrational properties at the micro-scale. Here, we used cavity optomechanical sensors to interrogate the acoustic environment of adjacent air bubbles in water. We report experimental observations of the volume acoustic modes of these bubbles, including both the fundamental Minnaert breathing mode and a family of higher-order modes extending into the megahertz frequency range.
Background: Teledentistry integrates telecommunications with dental practice, facilitating the exchange of clinical information and images for remote dental consultation and treatment planning. This approach enables dental care access across long distances, addressing the need for flexible healthcare solutions.
Aim: This study aimed to evaluate the effectiveness of teledentistry compared to clinical in-person dental diagnosis in pediatric patients during the COVID-19 pandemic.
Purpose: We aimed to characterize and further understand CSF circulation and outflow of rabbits. To our knowledge, there is no research on contrast material-enhanced MR cisternography (CE-MRC) with T1 and T2 mapping in the rabbit model using a clinical 3-T MR unit without a stereotaxic frame.
Materials And Methods: Twenty-one rabbits were included in the study.
Contemporary industrial production and human activity release numerous toxins into our environment. Metal-organic frameworks (MOFs) are potential candidates for addressing these toxins due to their ultrahigh surface area, tailored pore size, and responsiveness to stimuli. With the rise of micro/nanomotor, imparting active motion to MOFs becomes crucial for efficiently performing tasks in challenging locations.
