Jumu is required for the activation of JAK/STAT in Drosophila lymph gland development and epidermal wounds.

The regulatory mechanism of hematopoiesis and innate immunity in Drosophila is highly similar to that in mammals, and Drosophila has become a suitable model to understand vertebrate hematopoiesis and the immune response. JAK-STAT signaling pathway components are widely conserved during evolution, and contribute to hematopoiesis and multiple tissue damage and immune responses. Here, we demonstrate that Stat92E is widely expressed in the lymph gland, and the loss of jumu inhibits the maintenance of the JAK/STAT pathway in the CZ and MZ but not in the PSC of the lymph gland. Furthermore, we found that clean puncture wounding of the larval epidermis can lead to the activation of JAK/STAT signaling and the generation of lamellocytes, and Jumu is required for the activation of JAK/STAT in response to epidermal wounds.

ACE inhibitors from Suaeda salsa: 3D-QSAR modeling, metabolomics, molecular docking and molecular dynamics simulations.

Inhibition of ACE is considered as one of the main strategies to reduce hypertension. ACE inhibitors derived from Suaeda salsa (S. salsa) present a novel antihypertensive agent source. This study employed 3D-QSAR pharmacophore, metabolomics, docking-based screening, and molecular dynamics simulations to identify ACE inhibitors from S. salsa. A set of 53 known molecules was chemically diverse to construct a 3D-QSAR model for predictive purposes. S. salsa was characterized using UPLC-QqQ-MS/MS and UPLC-Q-TOF-LC-MS techniques, 211 and 586 kinds of bioactive metabolites were identified, respectively. A total of 680 compounds were collected for database construction and virtual screening. An ADMET assessment was conducted to evaluate drug-likeness and pharmacokinetics parameters. Moreover, molecular docking results show that six top hit compounds bind to ACE tightly. Specially, diosmin could interact with ACE by hydrogen bond, Pi-cation bond, and metal bond. Molecular dynamics (MD) simulation and MMPBSA calculations were subsequently employed to elucidate complex stability and the interaction between diosmin and ACE, indicating it a strong ACE inhibitory activity. In conclusion, this study suggests that S.salsa represents a potential source of antihypertensive agents. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00233-0.