The development of a universal vaccine against foot-and-mouth disease virus (FMDV) is hindered by cross-serotype antigenic diversity and by a lack of knowledge regarding neutralization of the virus in natural hosts. In this study, we isolated serotype O-specific neutralizing antibodies (NAbs) (F145 and B77) from recovered natural bovine hosts by using the single B cell antibody isolation technique. We also identified a serotype O/A cross-reacting NAb (R50) and determined virus-NAb complex structures by cryo-electron microscopy at near-atomic resolution. F145 and B77 were shown to engage the capsid of FMDV-O near the icosahedral threefold axis, binding to the BC/HI-loop of VP2. In contrast, R50 engages the capsids of both FMDV-O and FMDV-A between the 2- and 5-fold axes and binds to the BC/EF/GH-loop of VP1 and to the GH-loop of VP3 from two adjacent protomers, revealing a previously unknown antigenic site. The cross-serotype neutralizing epitope recognized by R50 is highly conserved among serotype O/A. These findings help to elucidate FMDV neutralization by natural hosts and provide epitope information for the development of a universal vaccine for cross-serotype protection against FMDV.

Foot-and-mouth disease virus (FMDV) causes a highly contagious and economically devastating disease in cloven-hoofed animals, and neutralizing antibodies play critical roles in the defense against viral infections. Here, we isolated a bovine antibody (R55) using the single B cell antibody isolation technique.

Drug addiction is a serious brain disorder with widespread somatic, psychological, psychiatric, and legal consequences, characterized by compulsive drug seeking, craving, withdrawal, and relapse, particularly with psychostimulants. A key feature of drugs commonly abused by humans is their ability to enhance dopamine (DA) neurotransmission in mesolimbic circuits, thereby activating DA receptors and altering emotional and motivational behaviors. Recent studies have demonstrated that dopamine D2 receptors (D2Rs), existing both as monomers and as D1/D2 receptor heteromers with dopamine D1 receptors (D1Rs), are critically involved in the neurobiological mechanisms underlying drug addiction. Furthermore, Ca²⁺/calmodulin-dependent protein kinase II alpha (CaMKIIα), which interacts with D2Rs and associates with D1/D2 receptor heteromers, plays a pivotal role in regulating the molecular mechanisms of the reward system, primarily through its phosphorylation. In addition, fatty acid-binding protein 3 (FABP3), by forming a complex with the long isoform of the D2 receptor (D2LR), has been shown to contribute significantly to the development of drug addiction. This article first reviews the roles of D2Rs and D1/D2 receptor heteromers in addiction, followed by a discussion of the underlying mechanisms of CaMKII signaling. We further highlight recent advances identifying FABP3 as a potential pharmacological target to mitigate addiction and prevent relapse, offering new avenues for therapeutic development and future clinical interventions.

Coumarins and pyrazoles are two essential heterocyclic scaffolds in medicinal chemistry, which are extensively applied in the drug discovery and development process owing to their various biological activities. Through the molecular heterocyclic strategy to construct coumarin-pyrazole hybrid heterocyclic molecules, the pharmacokinetic and pharmacodynamic characteristics of the parent compounds can be effectively optimized. According to the structural connection modes, these heterocyclic compounds can be categorized into three main types: fused type, condensed type, and heterocyclic type linked by connecting groups. Among these categories, the condensed type and the linked type can be further subdivided according to the connection positions on the coumarin skeleton, such as derivatives substituted at the C3, C4, C6, C7, and C8 positions. This review summarizes the biological activities, structure-activity relationships (SAR), and action mechanisms of different types of coumarin-pyrazole heterocyclic compounds, intending to provide a reference for the design of novel drugs based on this heterocyclic framework.