The innate immune sensor NLRP3 assembles an inflammasome complex with NEK7 and ASC to activate caspase-1 and drive the maturation of proinflammatory cytokines IL-1b and IL-18. NLRP3 inflammasome activity must be tightly controlled, as its overactivation is involved in the pathogenesis of inflammatory diseases. Here, we show that NLRP3 inflammasome activation is suppressed by a centrosomal protein Spata2. Spata2 deficiency enhances NLRP3 inflammasome activity both in the macrophages and in an animal model of peritonitis. Mechanistically, Spata2 recruits the deubiquitinase CYLD to the centrosome for deubiquitination of polo-like kinase 4 (PLK4), the master regulator of centrosome duplication. Deubiquitination of PLK4 facilitates its binding to and phosphorylation of NEK7 at Ser204. NEK7 phosphorylation in turn attenuates NEK7 and NLRP3 interaction, which is required for NLRP3 inflammasome activation. Pharmacological or shRNA-mediated inhibition of PLK4, or mutation of the NEK7 Ser204 phosphorylation site, augments NEK7 interaction with NLRP3 and causes increased NLRP3 inflammasome activation. Our study unravels a novel centrosomal regulatory pathway of inflammasome activation and may provide new therapeutic targets for the treatment of NLRP3-associated inflammatory diseases.

5-Hydroxymethyl-2-vinylfuran (HMVF), a biomass-based solvent-free adhesive, exhibits strong adhesion to steel, copper, aluminum and glass.

No abstract

Summary Myeloid cells, including dendritic cells (DCs), granulocytes, monocytes, monocyte-derived cells and macrophages, are important players in the immune response, but their identification is not as clear as lymphocytes, especially in tissues. This protocol details the step-by-step procedure for the analysis of myeloid populations in various mouse tissues by flow cytometry. For complete details on the use and execution of this protocol, please refer to Liu et al. (2019) .

BackgroundThe results of preclinical studies suggest that baclofen may be useful in the treatment of stroke patients with persistent hiccups. This study was aimed to assess the possible efficacy of baclofen for the treatment of persistent hiccups after stroke.MethodsIn total, 30 stroke patients with persistent hiccups were randomly assigned to receive baclofen (n = 15) or a placebo (n = 15) in a double-blind, parallel-group trial. Participants in the baclofen group received 10 mg baclofen 3 times daily for 5 days. Participants assigned to the placebo group received 10 mg placebo 3 times daily for 5 days. The primary outcome measure was cessation of hiccups. Secondary outcome measures included efficacy in the two groups and adverse events.ResultsAll 30 patients completed the study. The number of patients in whom the hiccups completely stopped was higher in the baclofen group than in the placebo group (relative risk, 7.00; 95% confidence interval, 1.91–25.62; P = 0.003). Furthermore, efficacy was higher in the baclofen group than in the placebo group (P < 0.01). No serious adverse events were documented in either group. One case each of mild transient drowsiness and dizziness was present in the baclofen group.ConclusionsBaclofen was more effective than a placebo for the treatment of persistent hiccups in stroke patients.Trial registrationChinese Clinical Trials Register: ChiCTR-TRC-13004554

TSI attenuates I/R-induced brain injury in rats, supporting its clinic use for treatment of acute ischemic stroke. The role of TSI may benefit from its antioxidant activity, which is most likely implemented via inactivation of NADPH oxidase through a signaling pathway implicating AMPK/Akt/PKC.

Chinese Fir wood (Cunninghamia lanceolata (Lamb.) Hook) was subjected to extraction treatments with sodium chlorite (NaClO 2 ) for delignification, as well as with sodium hydroxide (NaOH) at different concentrations for extraction of hemicelluloses. The wood was examined using a Fourier Transform Infrared (FT-IR) spectrometer and microtension technique to track changes in the chemical and the micromechanical properties of the cell wall. The results of the microtensile tests indicated that the hemicelluloses caused more damage to the mechanical properties of the cell wall than lignin. The micromechanical properties that occurred with degradation of chemical components underlined the key role of hemicelluloses in maintaining the integrity of the cell wall.

Spectator or actor? Density functional theory calculations were performed to examine the role of the base in the nickel‐catalyzed cross‐coupling of aryl phosphates with arylboronic acids. Potassium phosphate was found to not act as a spectator base but was involved in the transmetalation step, as shown by a lower barrier than that of a base‐free process, owing to the activation of the carbonboron bond by the base. Further experimental observations support the theoretical findings.