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.

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 H 2 SO 4-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.

Urban mining from fly ash resulting from municipal solid waste incineration (MSWI) is becoming more and more important due to the increasing scarcity of supply-critical metals. Metal extraction from acid fly ash leaching has already been established. In this context selective Cu recovery is still a challenge. Therefore, our purpose was the separation of Cu(II) from MSWI fly ash extracts by polymer-assisted ultrafiltration (PAUF). We investigated three polyethyleneimines (PEIs) with regard to metal retention, Cu(II) selectivity, Cu(II) loading capacity, and the viscosity of the PEI containing solutions. A demanding challenge was the highly complex matrix of the fly ash extracts, which contain up to 16 interfering metal ions in high concentrations and a chloride content of 60 g L−1. Overcoming that, Cu(II) was selectively enriched and separated from real fly ash extract at pH 3.0. At pH 1.0, a PEI-free Cu(II) concentrate was obtained and PEIs could be regenerated for reuse in further separation cycles. The PAUF conditions developed at laboratory scale were successfully transferred to pilot scale, and hyperbranched PEI (HB-PEI) was found to be the most suitable reagent for PAUF in a technical scale. Moreover, HB-PEI enables photometric control of the Cu(II) enrichment.

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