Inflammasome-Independent NALP3 Contributes to High-Salt Induced Endothelial Dysfunction

Backgrounds and Aims: Na+ is an important nutrient and its intake, mainly from salt (NaCl), is essential for normal physiological function. However, high salt intake may lead to vascular injury, independent of a rise in blood pressure (BP). Canonical NALP3 inflammasome activation is a caspase-1 medicated process, resulting in the secretion of IL-18 and IL-1β which lead to endothelial dysfunction. However, some researches uncovered a direct and inflammasome-independent role of NALP3 in renal injury. Thus, this study was designed to investigate the possible mechanisms of NALP3 in high salt induced endothelial dysfunction.Methods and Results: Changes in endothelial function were measured by investigating mice (C57BL/6J, NALP3-/- and wild-type, WT) fed with normal salt diet (NSD) or high salt diet (HSD) for 12W, and thoracic aortic rings from C57BL/6J mice cultured in high-salt medium. Changes of tube formation ability, intracellular reactive oxygen species (ROS), and NALP3 inflammasome expression were detected using mouse aortic endothelial cells (MAECs) cultured in high-salt medium. Consumption of HSD for 12W did not affect BP or body weight in C57BL/6J mice. Endothelium-dependent relaxation (EDR) decreased significantly in C57BL/6J mice fed with HSD for 12W, and in isolated thoracic aortic rings cultured in high-salt medium for 24 h. Results from the aortic ring assay also revealed that the angiogenic function of thoracic aortas was impaired by either consumption of HSD or exposure to high-salt medium. NALP3-/- mice fed with HSD showed a relatively mild decrease in EDR function when compared with WT mice. Tube length of thoracic aortic rings from NALP3-/- mice was longer than those from WT mice after receiving high-salt treatment. Inhibiting NALP3 with a NALP3 antagonist, small interfering (si) RNA experiments using si-NALP3, and decomposing ROS significantly improved tube formation ability in MAECs under high salt medium. NALP3 expression was increased in MAECs cultured with high salt treatment and inhibiting NALP3 reversed the down-regulation of p-eNOS induced by high salt in MAECs.Conclusion: High salt intake impairs endothelial function, which is at least in part mediated by increasing NALP3 expression

Integration of motion and form cues for the perception of self-motion in the human brain

When moving around in the world, the human visual system uses both motion and form information to estimate the direction of self-motion (i.e., heading). However, little is known about cortical areas in charge of this task. This brain-imaging study addressed this question by using visual stimuli consisting of randomly distributed dot pairs oriented toward a locus on a screen (the form-defined focus of expansion (FoE)) but moved away from a different locus (the motion-defined FoE) to simulate observer translation. We first fixed the motion-defined FoE location and shifted the form-defined FoE location. We then made the locations of the motion- and the form-defined FoEs either congruent (at the same location in the display) or incongruent (on the opposite sides of the display). The motion- or the form-defined FoE shift was the same in the two types of stimuli but the perceived heading direction shifted for the congruent but not the incongruent stimuli. Participants (both sexes) made a task-irrelevant (contrast discrimination) judgment during scanning. Searchlight and region-of-interest based multi-voxel pattern analysis (MVPA) revealed that early visual areas V1, V2, and V3 responded to either the motion- or the form-defined FoE shift. After V3, only the dorsal areas V3a and V3B/KO responded to such shifts. Furthermore, area V3B/KO shows a highly significant higher decoding accuracy for the congruent than the incongruent stimuli. Our results provide direct evidence showing area V3B/KO does not simply respond to motion and form cues but integrate these two cues for the perception of heading. Human survival relies on accurate perception of self-motion. The visual system uses both motion (optic flow) and form cues for the perception of the direction of self-motion (heading). Although human brain areas for processing optic flow and form structure are well identified, the areas responsible for integrating these two cues for the perception of self-motion remain unknown. We conducted fMRI experiments and used MVPA analysis technique to find human brain areas that can decode the shift in heading specified by each cue alone and the two cues combined. We found that motion and form information are first processed in the early visual areas and then are likely integrated in the higher dorsal area V3B/KO for the final estimation of heading

Low level constraints on dynamic contour path integration

Contour integration is a fundamental visual process. The constraints on integrating discrete contour elements and the associated neural mechanisms have typically been investigated using static contour paths. However, in our dynamic natural environment objects and scenes vary over space and time. With the aim of investigating the parameters affecting spatiotemporal contour path integration, we measured human contrast detection performance of a briefly presented foveal target embedded in dynamic collinear stimulus sequences (comprising five short 'predictor' bars appearing consecutively towards the fovea, followed by the 'target' bar) in four experiments. The data showed that participants' target detection performance was relatively unchanged when individual contour elements were separated by up to 2° spatial gap or 200ms temporal gap. Randomising the luminance contrast or colour of the predictors, on the other hand, had similar detrimental effect on grouping dynamic contour path and subsequent target detection performance. Randomising the orientation of the predictors reduced target detection performance greater than introducing misalignment relative to the contour path. The results suggest that the visual system integrates dynamic path elements to bias target detection even when the continuity of path is disrupted in terms of spatial (2°), temporal (200ms), colour (over 10 colours) and luminance (-25% to 25%) information. We discuss how the findings can be largely reconciled within the functioning of V1 horizontal connections

Advances in methods for detection of anaerobic ammonium oxidizing (anammox) bacteria

Anaerobic ammonium oxidation (anammox), the biochemical process oxidizing ammonium into dinitrogen gas using nitrite as an electron acceptor, has only been recognized for its significant role in the global nitrogen cycle not long ago, and its ubiquitous distribution in a wide range of environments has changed our knowledge about the contributors to the global nitrogen cycle. Currently, several groups of methods are used in detection of anammox bacteria based on their physiological and biochemical characteristics, cellular chemical composition, and both 16S rRNA gene and selective functional genes as biomarkers, including hydrazine oxidoreductase and nitrite reductase encoding genes hzo and nirS, respectively. Results from these methods coupling with advances in quantitative PCR, reverse transcription of mRNA genes and stable isotope labeling have improved our understanding on the distribution, diversity, and activity of anammox bacteria in different environments both natural and engineered ones. In this review, we summarize these methods used in detection of anammox bacteria from various environments, highlight the strengths and weakness of these methods, and also discuss the new development potentials on the existing and new techniques in the future

Endovascular treatment of acute ischemic stroke with a fully radiopaque retriever: A randomized controlled trial

ObjectiveThe Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed.MethodsAcute ischemic stroke patients aged 18–80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared.ResultsA total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, −9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054).ConclusionThe Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO).Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757