Lack of high-efficiency, cost-efficient, and well-stocked oxygen evolution reaction (OER) electrocatalysts is a main challenge in large-scale implementation of electrolytic water. By regulating the electronic structure of isolated single-atom metal sites, high-performance transition-metal-based catalysts can be fabricated to greatly improve the OER performance. Herein, we demonstrate single-atom manganese coordinated to nitrogen and sulfur species in two-dimensional graphene nanosheets Mn-NSG (NSG means N- and S- codoped graphene) as an active and durable OER catalyst with a low overpotential of 296 mV in alkaline media, compared to that of the benchmark IrO₂ catalyst. Theoretical calculations and experimental measurements reveal that the Mn-N₃S sites in the graphene matrix are the most active sites for the OER due to modified electronic structure of the Mn site by three nitrogen and one sulfur atoms coordination, which show lower theoretical overpotential than the Mn-N₄ sites and over which the O-O formation step is the rate-determining step.

The design of diatomic catalysts with uniformly dispersed metal atoms is expected to improve catalytic performance, which is conducive to the intensive comprehending of the synergistic mechanism between dual-metal sites for the oxygen evolution reaction (OER) at the atomic level. Herein, we design a strategy to immobilize bimetallic Fe-Co atoms onto nitrogen-doped graphene to obtain a diatomic catalyst (DA-FC-NG) with FeN₃-CoN₃ configuration. The DA-FC-NG shows excellent OER activity with a low overpotential (η₁₀ = 268 mV), which is superior to commercial iridium dioxide catalysts. Theoretical calculations uncover that the excellent activity of DA-FC-NG is due to the interaction between Fe and Co diatoms, which causes charge rearrangement and induces the adsorption of intermediates on the Fe–O–Co bridge structure, thus improving the catalytic OER performance. This work is of great significance for the design of highly active diatomic catalysts to replace noble metal catalysts for energy-related applications.

The emergence and wide spread of multi-drug resistant Staphylococcus aureus (S. aureus) requires the development of new therapeutic agents with alternative modes of action. Anti-virulence strategies are hoped to meet that need. Sortase A (SrtA) has attracted great interest as a potential drug target to treat infections caused by S. aureus, as many of the surface proteins displayed by SrtA function as virulence factors by mediating bacterial adhesion to specific organ tissues, invasion of host cells, and evasion of the host-immune responses. It has been suggested that inhibitors of SrtA might be promising candidates for the treatment and/or prevention of S. aureus infections. In this study, we report that Chlorogenic acid (CHA), a natural compound that lacks significant anti–S. aureus activity, inhibit the activity of SrtA in vitro (IC50=33.86±5.55μg/ml) and the binding of S. aureus to fibrinogen (Fg). Using molecular dynamics simulations and mutagenesis assays, we further demonstrate that CHA binds to the binding sites of C184 and G192 in the SrtA. In vivo studies demonstrated that CHA prevent mice from S. aureus-induced renal abscess, resulting in a significant survival advantage. These findings indicate that CHA is a promising therapeutic compound against SrtA during S. aureus infections.

Alpha-hemolysin (α-HL) is a self-assembling, channel-forming toxin produced by most Staphylococcus aureus strains as a 33.2-kDa soluble monomer. Upon binding to a susceptible cell membrane, the monomer self-assembles to form a 232.4-kDa heptamer that ultimately causes host cell lysis and death. Consequently, α-HL plays a significant role in the pathogenesis of S. aureus infections, such as pneumonia, mastitis, keratitis and arthritis. In this paper, experimental studies show that oroxylin A (ORO), a natural compound without anti-S. aureus activity, can inhibit the hemolytic activity of α-HL. Molecular dynamics simulations, free energy calculations, and mutagenesis assays were performed to understand the formation of the α-HL-ORO complex. This combined approach revealed that the catalytic mechanism of inhibition involves the direct binding of ORO to α-HL, which blocks the conformational transition of the critical “Loop” region of the α-HL protein thereby inhibiting its hemolytic activity. This mechanism was confirmed by experimental data obtained from a deoxycholate-induced oligomerization assay. It was also found that, in a co-culture system with S. aureus and human alveolar epithelial (A549) cells, ORO could protect against α-HL-mediated injury. These findings indicate that ORO hinders the lytic activity of α-HL through a novel mechanism, which should facilitate the design of new and more effective antibacterial agents against S. aureus. The mechanism controlling protein-ligand interactions is one of the most important processes in rational drug design. X-ray crystallography is a traditional tool used to investigate the interaction of ligands and proteins in a complex. However, protein crystallography is inefficient, and the development of crystal technology and research remains unequally distributed. Thus, it seems impractical to explore the structure of the α-hemolysin-ORO monomer complex by crystallography. Therefore, we used molecular dynamics simulations to investigate the receptor-ligand interaction in the α-HL-ORO monomer complex. In this study, we found that oroxylin A (ORO), a natural compound with little anti-S. aureus activity, can inhibit the hemolytic activity of α-HL at low concentrations. Through molecular docking and molecular dynamics simulations, we determined the potential binding mode of the protein-ligand interaction. The data revealed that ORO directly binds to α-HL, an interaction that blacks the conformational transition of the critical “Loop” region in α-HL and thus prevents the formation of the α-HL heptameric transmembrane pore, which ultimately inhibits the hemolytic activity of α-HL. This mechanism was confirmed by experimental data. Furthermore, we demonstrated that ORO could protect against α-HL-mediated injury in human alveolar epithelial (A549) cells.