Anti-C5a monoclonal antibody, clone 306004

A wide pressure range pyrolysis experiment of 2-ethylnorbornane (EthNB), a potential high energy-density fuel, was conducted in a micro-reactor at 773-1098 K, 0.1-3.0 MPa and 2.1-10.3 s to explore its high-pressure pyrolysis mechanism. Altogether 30 pyrolysis products are detected and quantified using online GC-MS/FID, which major products are ethylene, methane, 1,3-cyclopentadiene and benzene in descending order of importance. The first-order kinetic analysis shows that no isomerization of exo-EthNB and endo-EthNB into each other is observed and the activation energies of overall EthNB pyrolysis slightly increase from 0.1 MPa to 3.0 MPa, indicating the unfavorable effect of pressure. A detailed theoretical calculation of the EthNB initial pyrolysis is performed to explain the formation and selectivity of primary products under different pressures, which includes C-C dissociations and H-abstraction reactions leading to the diradical (BR8), C8H13 (BR1), C7H11 (BR2) and six C9H15 (R1-R4, R6, R7) radicals. These radicals undergo further decomposition via beta-C-C scission reactions to generate unstable intermediates and then the intermediates proceed to dissociate or isomerize. Finally, the other aliphatic and aromatic species may mainly come from the secondary reactions of primary products decomposition involving small radicals, C5 cyclic hydrocarbons and aromatics, as well as cross-coupling reactions of them.

Most patients with cholangiocarcinoma (CCA) develop extrahepatic malignant biliary obstructions, which require palliative drainage to normalize bilirubin levels and to improve the patients' overall survival. Here, we report that the infusion of methotrexate-containing plasma-membrane microvesicles derived from apoptotic human tumour cells into the bile-duct lumen of patients with extrahepatic CCA mobilized and activated neutrophils and relieved biliary obstruction in 25% of the patients. Neutrophil recruitment by the microvesicles was associated with an increase in uridine diphosphate glucose and complement C5, and led to the degradation of the stromal barrier of CCA. The microvesicles induced pyroptosis of CCA cells through a gasdermin E-dependent pathway, and their intracellular contents released upon CCA-cell death activated patient-derived macrophages into producing proinflammatory cytokines, which attracted a secondary wave of neutrophils to the tumour site. Our findings suggest a possible treatment for the alleviation of obstructive extrahepatic CCA with few adverse effects, and highlight the potential of tumour-cell-derived microvesicles as drug carriers for antitumour therapies. Methotrexate-loaded tumour-cell-derived microvesicles induce neutrophil-mediated antitumour activity and can relieve biliary obstructions in patients with extrahepatic cholangiocarcinoma.