Isaridin E Protects against Sepsis by Inhibiting Von Willebrand Factor-Induced Endothelial Hyperpermeability and Platelet-Endothelium Interaction.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

[Effect of Pyrolytic Temperature and Time on Characteristics of Typha angustifolia Derived Biochar and Preliminary Assessment of the Ecological Risk].

A batch of biochar was produced from pyrolysis of Typha angustifolia (TBCs) at 200-500℃ for 2 h and 6 h to investigate the effects of pyrolytic temperature and heating retention time on the physico-chemical properties. Moreover, Escherichia coli (E. coli) HB101 and the seeds of Helianthus annuus were used to preliminarily test the ecological risk of the TBCs. Results showed that the heating retention time (i.e., 2 and 6 h) had no significant effect on the properties of TBCs, while pyrolytic temperature significantly affected TBCs' characteristics. As the pyrolysis temperature increased from 200 to 500℃, the mass yield and contents of hydrogen (H) and oxygen (O) decreased, while the contents of carbon (C) and ash increased. The pH and surface pores also increased with increasing pyrolytic temperature, whereas the O-containing functional group (e.g., -COOH and -OH) decreased. These results indicated the increased carbonization and aromatization of the TBCs. For the inherent nutrients of TBCs, the total phosphorus (TP) and available potassium (K) contents significantly increased as temperature increased. The main components of dissolved organic matter (DOM) of TBCs were humic acid-like and fulvic acid-like organic compounds. As the pyrolysis temperature increased, the content of humic acid-like organic compounds decreased, while the content of fulvic acid-like organic compounds increased. All the TBCs had no significant effect on the growth of E. coli HB101 and the seed germination of Helianthus annuus, indicating the little ecological risk of TBCs under the experimental conditions. These findings provide an alternative way for resource utilization of waste wetland biomass and provide important theoretical data for screening biochar in soil reclamation.

3-(2-Amino-eth-yl)-2-[4-(trifluoro-meth-oxy)anilino]quinazolin-4(3H)-one.

In the title compound, C(17)H(15)F(3)N(4)O(2), the dihedral angle between the trifluoro-meth-oxy-substituted benzene ring and the pyrimidinone ring is 45.1 (5)°, while that between the fused benzene ring and the pyrimidinone ring is 0.67 (1)°. Part of one of the benzene rings and its trifluoro-meth-oxy substituent are disordered over two positions of approximately equal occupancy (0.51:0.49). Inter-molecular N-H⋯O and N-H⋯N hydrogen bonds contribute to the stability of the crystal structure. A weak intra-molecular C-H⋯F contact is also found. In addition, π-π stacking inter-actions, with centroid-centroid distances in the range 3.673 (6)-3.780 (8) Å, and weak C-H⋯π inter-actions are also observed.