uld be clinically useful in pathologies associated with low RGS2 protein levels, such as hypertension, heart failure, and anxiety.Enzymes of the human UDP-glycosyltransferase (UGT) superfamily typically catalyze the covalent addition of the sugar moiety from a UDP-sugar cofactor to relatively low-molecular weight lipophilic compounds. Although UDP-glucuronic acid (UDP-GlcUA) is most commonly employed as the cofactor by UGT1 and UGT2 family enzymes, UGT2B7 and several other enzymes can use both UDP-GlcUA and UDP-glucose (UDP-Glc), leading to the formation of glucuronide and glucoside conjugates. An investigation of UGT2B7-catalyzed morphine glycosidation indicated that glucuronidation is the principal route of metabolism because the binding affinity of UDP-GlcUA is higher than that of UDP-Glc. Currently, it is unclear which residues in the UGT2B7 cofactor binding domain are responsible for the preferential binding of UDP-GlcUA. Here, molecular dynamics (MD) simulations were performed together with site-directed mutagenesis and enzyme kinetic studies to identify residues within the UGT2B7 binding site responsible for the selective cofacto the elucidation of UGT-aglycone interactions.Cytochromes P450 (P450, CYP) metabolize a wide variety of endogenous and exogenous lipophilic molecules, including most drugs. Sterol 14α-demethylase (CYP51) is a target for antifungal drugs known as conazoles. Using X-ray crystallography, we have discovered a domain-swap homodimerization mode in CYP51 from a human pathogen, Acanthamoeba castellanii CYP51 (AcCYP51). Recombinant AcCYP51 with a truncated transmembrane helix was purified as a heterogeneous mixture corresponding to the dimer and monomer units. Spectral analyses of these two populations have shown that the CO-bound ferrous form of the dimeric protein absorbed at 448 nm (catalytically competent form), whereas the monomeric form absorbed at 420 nm (catalytically incompetent form). AcCYP51 dimerized head-to-head via N-termini swapping, resulting in formation of a nonplanar protein-protein interface exceeding 2000 Å2 with a total solvation energy gain of -35.4 kcal/mol. In the dimer, the protomers faced each other through the F and G α-helices, thus bg-bound AcCYP51 was monomeric. In the AcCYP51-isavuconazole complex, the protein target failed to refold 74 N-terminal residues, suggesting a fundamentally different mechanism of AcCYP51 inactivation than only blocking the active site. Proteolytic degradation of a structurally aberrant enzyme would explain the superior potency of isavuconazole against A. castellanii.Loss of DCAF1 and resulting ROS leads to Treg aging and inflammation.Bacterial flagellin can elicit production of TLR5-mediated IL-22 and NLRC4-mediated IL-18 cytokines that act in concert to cure and prevent rotavirus (RV) infection. This study investigated the mechanism by which these cytokines act to impede RV. Although IL-18 and IL-22 induce each other’s expression, we found that IL-18 and IL-22 both impeded RV independently of one another and did so by distinct mechanisms that involved activation of their cognate receptors in intestinal epithelial cells (IEC). IL-22 drove IEC proliferation and migration toward villus tips, which resulted in increased extrusion of highly differentiated IEC that serve as the site of RV replication. In contrast, IL-18 induced cell death of RV-infected IEC thus directly interrupting the RV replication cycle, resulting in spewing of incompetent virus into the intestinal lumen and causing a rapid drop in the number of RV-infected IEC. Together, these actions resulted in rapid and complete expulsion of RV, even in hosts with severely compromised immune systems. These results suggest that a cocktail of IL-18 and IL-22 might be a means of treating viral infections that preferentially target short-lived epithelial cells.Patients with cancer with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti-PD-1 immunotherapy. The mechanism of liver metastases-induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic suppression of antitumor immunity. The immune suppression was antigen specific and associated with the coordinated activation of regulatory T cells (Tregs) and modulation of intratumoral CD11b+ monocytes. The dysfunctional immune state could not be reversed by anti-PD-1 monotherapy unless Treg cells were depleted (anti-CTLA-4) or destabilized (EZH2 inhibitor). Thus, this study provides a mechanistic understanding and rationale for adding Treg and CD11b+ monocyte targeting agents in combination with anti-PD-1 to treat patients with cancer with liver metastasis.Quantum dots have innate advantages as the key component of optoelectronic devices. For white light-emitting diodes (WLEDs), the modulation of the spectrum and color of the device often involves various quantum dots of different emission wavelengths. Here, we fabricate a series of carbon quantum dots (CQDs) through a scalable acid reagent engineering strategy. The growing electron-withdrawing groups on the surface of CQDs that originated from acid reagents boost their photoluminescence wavelength red shift and raise their particle sizes, elucidating the quantum size effect. These CQDs emit bright and remarkably stable full-color fluorescence ranging from blue to red light and even white light. Full-color emissive polymer films and all types of high-color rendering index WLEDs are synthesized by mixing multiple kinds of CQDs in appropriate ratios. The universal electron-donating/withdrawing group engineering approach for synthesizing tunable emissive CQDs will facilitate the progress of carbon-based luminescent materials for manufacturing forward-looking films and devices.Students who speak English as a second language (ESL) are underserved and underrepresented in postsecondary science, technology, engineering, and math (STEM) fields. To date, most existing research with ESL students in higher education is qualitative. Drawing from this important body of work, we investigate the impact of a social-belonging intervention on anticipated changes in belonging, STEM GPA, and proportion of STEM credits obtained in students’ first semester and first year of college. Using data from more than 12,000 STEM-interested students at 19 universities, results revealed that the intervention increased ESL students’ anticipated sense of belonging and three of the four academic outcomes. Phosphoramidon Moreover, anticipated changes in belonging mediated the intervention’s effects on these academic outcomes. Robustness checks revealed that ESL effects persisted even when controlling for other identities correlated with ESL status. Overall, results suggest that anticipated belonging is an understudied barrier to creating a multilingual and diverse STEM workforce.