Macrophages can be activated and regulated by high-mobility group box 1 (HMGB1), a highly conserved nuclear protein. Inflammatory functions of HMGB1 are mediated by binding to cell surface receptors, ...including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, TLR4, and TLR9. Pyroptosis is a caspase-1-dependent programmed cell death, which features rapid plasma membrane rupture, DNA fragmentation, and release of proinflammatory intracellular contents. Pyroptosis can be triggered by various stimuli, however, the mechanism underlying pyroptosis remains unclear. In this study, we identify a novel pathway of HMGB1-induced macrophage pyroptosis. We demonstrate that HMGB1, acting through RAGE and dynamin-dependent signaling, initiates HMGB1endocytosis, which in turn induces cell pyroptosis. The endocytosis of HMGB1 triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. We further confirm that HMGB1-induced macrophage pyroptosis also occurs in vivo during endotoxemia, suggesting a pathophysiological significance for this form of pyroptosis in the development of inflammation. These findings shed light on the regulatory role of ligand-receptor internalization in directing cell fate, which may have an important role in the progress of inflammation following infection and injury.
Abstract The Parkes 20 cm multibeam pulsar surveys have discovered nearly half of the known pulsars and revealed many distant pulsars with high dispersion measures. Using a sample of 1301 pulsars ...from these surveys, we have explored the spatial distribution and birth rate of normal pulsars. The pulsar distances used to calculate the pulsar surface density are estimated from the YMW16 electron-density model. When estimating the impact of the Galactic background radiation on our survey, we projected pulsars in the galaxy onto the Galactic plane, assuming that the flux density distribution of pulsars is uniform in all directions, and utilized the most up-to-date background temperature map. We also used an up-to-date version of the ATNF Pulsar Catalogue to model the distribution of pulsar flux densities at 1400 MHz. We derive an improved radial distribution for the pulsar surface density projected onto the Galactic plane, which has a maximum value at ∼4 kpc from the Galactic center. We also derive the local surface density and birth rate of pulsars, obtaining 47 ± 5 kpc −2 and ∼4.7 ± 0.5 kpc −2 Myr −1 , respectively. For the total number of potentially detectable pulsars in the galaxy, we obtain (1.1 ± 0.2) × 10 4 and (1.1 ± 0.2)×10 5 before and after applying the Tauris & Manchester beaming correction model. The radial distribution function is used to estimate the proportion of pulsars in each spiral arm and the Galactic center.
The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) ...with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR)=4.8, 95% confidence interval (CI) 2.5 to 8.9, P<0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR=3.5, 95% CI 2.0 to 6.3, P<0.001). There was a positive relationship between the grade of HT and time—hyperperfusion with the Spearman's rank correlation of 0.44 (P=0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT.
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Schematic procedure for the preparation of GN/MIPs/GCE and our concept for selective electrochemical detection of IDP.
•Uniform MIP monolayers were loaded on inert graphene surface ...using a novel strategy.•Interesting factors were discussed to efficiently control the synthesis process.•The procedures were greatly simplified to cut down the cost and improve the stability.•Adsorption isotherm and kinetics study were carried out to explain the mechanism.•The proposed sensor was successfully applied in real rice samples.
A novel and simple imprinting route based on graphene (GN) was proposed to fabricate an electrochemical sensor for sensitive and selective determination of imidacloprid (IDP) residue. In this route, p-vinylbenzoic acid (VBA) was utilized as functional monomer to immobilize onto GN in N,N-dimethylformamide (DMF) solvent via π-π interaction, directing the polymerization of uniform molecularly imprinted polymers (MIP) layers on the surface of GN sheets. Besides, quantitative control of the synthesis of MIP/GN and the preparation of MIP/GN modified glassy carbon electrode (GCE) were carried out, which were rarely found in other papers. Thus, the proposed sensor possesses highly improved stability and specific recognition ability. The adsorption isotherm study indicated that the MIP layer on GN surface is monolayer and the structure is homogeneous. The peak current of IDP on MIP/GN modified GCE is linear with IDP concentration in the range of 0.5–15μM with a detection limit of 0.10μM. In addition, the novel method was further applied to detect IDP in brown rice samples with satisfactory results.
Although synaptic behaviours of memristors have been widely demonstrated, implementation of an even simple artificial neural network is still a great challenge. In this work, we demonstrate the ...associative memory on the basis of a memristive Hopfield network. Different patterns can be stored into the memristive Hopfield network by tuning the resistance of the memristors, and the pre-stored patterns can be successfully retrieved directly or through some associative intermediate states, being analogous to the associative memory behaviour. Both single-associative memory and multi-associative memories can be realized with the memristive Hopfield network.
We here report a spectroscopic monitor for the supernova (SN) SN 2017iuk associated with the long-duration low-luminosity gamma-ray burst (GRB) GRB 171205A at a redshift of 0.037, which is up to now ...the third GRB-SN event away from us. Our spectroscopic observations and spectral analysis allow us to identify SN 2017iuk as a typical broad-line Type Ic SN. A comparison study suggests that the Type IcBL SN 2017iuk resembles SN 2006aj in the following aspects: (1) similar spectra at the nearby epochs, (2) comparable evolution of the photospheric velocity obtained from the measurements based on both the Si ii λ6355 line and spectral modeling, and (3) comparable explosion parameters. This analogy could imply the formation of a neutron star in the core collapse of GRB 171205A/SN 2017iuk as previously suggested in GRB 060218/SN 2006aj. The properties of the host galaxy are discussed, which suggest that GRB 171205A/SN 2017iuk occurred in an early-type (S0), high-mass, star-forming galaxy with low specific star formation rate and solar metallicity.
GCMs are used by many national weather services to produce seasonal outlooks of atmospheric and oceanic conditions and fluxes. Postprocessing is often a necessary step before GCM forecasts can be ...applied in practice. Quantile mapping (QM) is rapidly becoming the method of choice by operational agencies to postprocess raw GCM outputs. The authors investigate whether QM is appropriate for this task. Ensemble forecast postprocessing methods should aim to 1) correct bias, 2) ensure forecasts are reliable in ensemble spread, and 3) guarantee forecasts are at least as skillful as climatology, a property called “coherence.” This study evaluates the effectiveness of QM in achieving these aims by applying it to precipitation forecasts from the POAMA model. It is shown that while QM is highly effective in correcting bias, it cannot ensure reliability in forecast ensemble spread or guarantee coherence. This is because QM ignores the correlation between raw ensemble forecasts and observations. When raw forecasts are not significantly positively correlated with observations, QM tends to produce negatively skillful forecasts. Even when there is significant positive correlation, QM cannot ensure reliability and coherence for postprocessed forecasts. Therefore, QM is not a fully satisfactory method for postprocessing forecasts where the issues of bias, reliability, and coherence pre-exist. Alternative postprocessing methods based on ensemble model output statistics (EMOS) are available that achieve not only unbiased but also reliable and coherent forecasts. This is shown with one such alternative, the Bayesian joint probability modeling approach.
Objectives
Excessive accumulation of adipose tissue may accelerate brain aging, but the underlying mechanisms are poorly understood. Several adiposity indices were proposed to assess obesity, while ...their linkage with brain health in older adults remained unclear. Here we aimed to examine the associations of adiposity indices with global and regional cerebral blood flow (CBF) in older adults, while considering insulin resistance.
Design
This was a cross-sectional population-based study that included older adults derived from the baseline participants in the ongoing Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) study.
Setting And Participants
The study included 103 Chinese rural-dwelling older adults (age≥60 years; 69.9% women) who underwent brain magnetic resonance imaging scans.
Methods
We estimated eight adiposity indices based on anthropometric measures. We automatically quantified global and regional CBF using the arterial spin labeling scans. Insulin resistance was assessed using the triglyceride-glucose index and then dichotomized into high and low levels according to the median. Data were analyzed using general linear model and voxel-wise analysis.
Results
Of the eight examined adiposity indices, only higher waist-to-height ratio (WHtR) and body roundness index (BRI) were associated with reduced global CBF (multivariable-adjusted β-coefficients and 95%CI: −1.76; −3.25, −0.27 and −1.77; −3.25, −0.30, respectively) and hypoperfusion in bilateral middle temporal gyri, angular gyri and superior temporal gyri, left middle cingulum and precuneus (P<0.05). There were statistical interactions of WHtR and BRI with levels of insulin resistance on CBF, such that the significant associations of higher WHtR and BRI with lower global and regional CBF existed only in people with high insulin resistance (P<0.05).
Conclusion
Higher WHtR and BRI are associated with cerebral hypoperfusion in older adults, especially in people with high insulin resistance. This may highlight the pathological role of visceral fat in vascular brain aging.
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