K+ Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules Targeting Mitochondria.

Imiquimod is a small-molecule ligand of Toll-like receptor-7 (TLR7) that is licensed for the treatment of viral infections and cancers of the skin. Imiquimod has TLR7-independent activities that are mechanistically unexplained, including NLRP3 inflammasome activation in myeloid cells and apoptosis induction in cancer cells. We investigated the mechanism of inflammasome activation by imiquimod and the related molecule CL097 and determined that K+ efflux was dispensable for NLRP3 activation by these compounds. Imiquimod and CL097 inhibited the quinone oxidoreductases NQO2 and mitochondrial Complex I. This induced a burst of reactive oxygen species (ROS) and thiol oxidation, and led to NLRP3 activation via NEK7, a recently identified component of this inflammasome. Metabolic consequences of Complex I inhibition and endolysosomal effects of imiquimod might also contribute to NLRP3 activation. Our results reveal a K+ efflux-independent mechanism for NLRP3 activation and identify targets of imiquimod that might be clinically relevant.

Municipal waste incineration fly ashes: from a multi-element approach to market potential evaluation.

BACKGROUND: Fly ashes from municipal solid waste incineration contain significant amounts of (technology critical) elements. Processes to recover Cu or Zn are already in practice, but it still remains difficult to evaluate the full secondary resource potential of the ashes. One reason is the absence of a worldwide comparable analytical basis for detailed market analyses. To encounter this, (i) an advice on how to analyse 65 elements after microwave-assisted digestion by ICP-OES and ICP-MS is delivered, (ii) the heterogeneity (hours to annual cycle) is evaluated for a incineration plant, (iii) leaching efficiency with three different eluents and (iv) the market potential of the elements as commodities are evaluated. RESULTS AND CONCLUSIONS: Aqua regia digestion was found to be sufficient to evaluated the recovery potential; except for the mass constituents Al, Si, Sn, Ti and the trace components Cr, Hf, Nb, U and W, for which HF-containing digestions delivered better recoveries. On different time scales, ashes were very homogenous and HCl- as well as H2SO4-supported leaching delivered, satisfying results within an hour (exceptions are, e.g., Bi and Sb). By applying characterisation factors of the life cycle assessment impact category "Resource depletion-minerals and metals" supplemented by the list of critical raw materials of the EU: Ag, Bi, Cd, Ga, In and Sb are most interesting elements to be recovered in future activities.