Rational Design of a Two-Photon Fluorescent Probe for Human Cytochrome P450 3A and the Visualization of Mechanism-Based Inactivation

Mechanism-based inactivation (MBI) can mediate adverse reactions and hepatotoxicity from drugs, which is a result of their conversion into highly reactive metabolites catalyzed by enzymes such as cytochrome P450 3A (CYP3A). In the present research, we optimized the key interaction domain of the fluorophore with the target protein to develop a two-photon fluorescent probe for CYP3A that is involved in the metabolism of more than half of all clinical drugs. The developed BN-1 probe exhibited appropriate selectivity and sensitivity for the semi-quantitative detection and imaging of endogenous CYP3A activity in various living systems, thereby providing a high-throughput screening system enabling evaluation of MBI-associated hepatotoxicity by CYP3A. Using BN-1 as a fluorescent molecular tool facilitates the efficient discovery and characterization of CYP3A-induced MBI in natural systems.</p

Writing for Local Government Schools: Authors and Themes in Song-dynasty School Inscriptions

A hallmark of the Song dynasty\u27s achievements was the creation of a national network of state-sponsored local schools. This engendered an exponential growth of commemorative inscriptions dedicated to local government schools. Many authors used these inscriptions as an avenue to expound and disseminate their visions of schools and education. Using the methods of network analysis and document clustering, this article analyzes all the inscriptions extant from Song times for local government schools. It reveals a structural schism in the diffusion of ideas between the Upper Yangzi and other regions of the Song. It also demonstrates the growing intellectual influence of Neo-Confucian ideologues that gradually overtook that of renowned prose-writers. Methodologically, this article provides an example of how diverse digital methods enable us to handle a large body of texts from multiple perspectives and invite us to explore connections we might not have otherwise thought of. Free access link: https://www.cambridge.org/core/journals/journal-of-chinese-history/article/writing-for-local-government-schools-authors-and-themes-in-songdynasty-school-inscriptions/8917993FA5EC53FC837961E6B929856F/share/eb301b0b72c9781fb464765a830a50b029453e6

Enhanced strong interaction between nanocavities and p-shell excitons beyond the dipole approximation

Large coupling strengths in exciton-photon interactions are important for the quantum photonic network, while strong cavity–quantum dot interactions have been focused on s-shell excitons with small coupling strengths. Here we demonstrate strong interactions between cavities and p-shell excitons with a great enhancement by the in situ wave-function control. The p-shell excitons are demonstrated with much larger wave-function extents and nonlocal interactions beyond the dipole approximation. Then the interaction is tuned from the nonlocal to the local regime by the wave function shrinking, during which the enhancement is obtained. A large coupling strength of 210     μ eV has been achieved, indicating the great potential of p-shell excitons for coherent information exchange. Furthermore, we propose a distributed delay model to quantitatively explain the coupling strength variation, revealing the intertwining of excitons and photons beyond the dipole approximation