Macrophage Extracellular Traps Suppress Particulate Matter-Induced Airway Inflammation.

Accumulating evidence has substantiated the potential of ambient particulate matter (PM) to elicit detrimental health consequences in the respiratory system, notably airway inflammation. Macrophages, a pivotal component of the innate immune system, assume a crucial function in responding to exogenous agents. However, the roles and detailed mechanisms in regulating PM-induced airway inflammation remain unclear. Our study revealed that PM had the ability to stimulate the formation of macrophage extracellular traps (METs) both in vitro and in vivo. This effect was found to be dependent on peptidylarginine deiminase type 4 (PAD4)-mediated histone citrullination. Additionally, reactive oxygen species were also found to be involved in the formation of PM-induced METs, in parallel with PAD4. Genetic deletion of PAD4 in macrophages resulted in an up-regulation of inflammatory cytokine expression. Moreover, mice with PAD4-specific knockout in myeloid cells exhibited exacerbated PM-induced airway inflammation. Mechanistically, inhibition of METs suppressed the phagocytic ability in macrophages, leading to airway epithelial injuries and an aggravated PM-induced airway inflammation. The present study demonstrates that METs play a crucial role in promoting the phagocytosis and clearance of PM by macrophages, thereby suppressing airway inflammation. Furthermore, it suggests that activation of METs may represent a novel therapeutic strategy for PM-related airway disorders.

A study on the correlation of the asymmetric regulation between the periaqueductal gray and the bilateral trigeminal nucleus caudalis in migraine male rats.

BACKGROUND: The study was designed to explore the correlation of the asymmetric regulation between periaqueductal gray (PAG) and bilateral trigeminal nucleus caudalis (TNC) in migraine rats through studying the changes of metabolites in pain regulatory pathway of acute migraine attack. METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into three groups: blank, control, model groups. Then, blank group was intraperitoneally injected with ultrapure water, while control group injected with saline and model group injected with Glyceryl Trinitrate (GTN). Two hours later, PAG and bilateral TNC were removed respectively, and metabolite concentrations of PAG, Left-TNC, Right-TNC were obtained. Lastly, the differences of metabolite among three brain tissues were compared. RESULTS: The relative concentrations of rNAA, rGlu, rGln, rTau, rMI in PAG or bilateral TNC had interaction effects between groups and sites. The concentration of rLac of three brain tissues increased in migraine rats, however, the rLac of LTNC and RTNC increased more than that of PAG. Besides, the concentrations of rNAA and rGln increased in RTNC, while rGABA decreased in RTNC. CONCLUSIONS: There is correlation between PAG, LTNC and RTNC in regulation of pain during acute migraine attack, and the regulation of LTNC and RTNC on pain is asymmetric.

Visual Search May Not Require Target Representation in Working Memory or Long-Term Memory.

We spend a lot of time searching for things. If we know what we are looking for in advance, a memory representation of the target will be created to guide search. But if the identity of the search target is revealed simultaneously with the presentation of the search array, is a similar memory representation formed? In the present study, 96 observers determined whether a central target was present in a peripheral search array. The results revealed that as long as the central target remained available for inspection (even if only in iconic memory), observers reinspected it after each distractor was checked, apparently forgoing consolidation of the target into working memory. The present findings challenged the assumption that evaluating items in a search array must involve comparison with a template in working memory.

Multiple visual items can be simultaneously compared with target templates in memory.

When we search for something, we often rely on both what we see and what we remember. This process can be divided into three stages: selecting items, identifying those items, and comparing them with what we are trying to find in our memory. It has been suggested that we select items one by one, and we can identify several items at once. In the present study, we tested whether we need to finish comparing a selected item in the visual display with one or more target templates in memory before we can move on to the next selected item. In Experiment 1, observers looked for either one or two target types in a rapid serially presented stimuli stream. The time interval between the presentation onset of successive items in the stream was varied to get a threshold. For search for one target, the threshold was 89 ms. When look for either of two targets, it was 192 ms. This threshold difference offered a baseline. In Experiment 2, observers looked for one or two types of target in a search array. If they compared each identified item separately, we should expect a jump in the slope of the RT × Set Size function, on the order of the baseline obtained in Experiment 1. However, the slope difference was only 13 ms/item, suggesting that several identified items can be compared at once with target templates in memory. Experiment 3 showed that this slope difference was not just a memory-load cost.

Rapamycin Exacerbates Staphylococcus aureus Pneumonia by Inhibiting mTOR-RPS6 in Macrophages.

Purpose: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism. Methods: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models. Results: Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus. Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia. Conclusion: Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage.

Flanker tasks based on congruency manipulation are biased measures of selective attention in perceptual load studies.

Flanker tasks based on a flanker-target congruency manipulation are widely used in perceptual load studies to investigate under what circumstances task-irrelevant flankers may be processed. An implicit assumption underlying the congruency manipulation is that the three types of flankers (congruent, incongruent, and neutral) attract attention homogeneously. However, in the present study, we provide evidence to demonstrate that this assumption is wrong: We discovered that incongruent/congruent flankers attracted more attention than the neutral flanker did. To avoid this attentional bias induced by the flanker-target congruency manipulation, we developed a new flanker paradigm in which the extent of flanker processing was evaluated by comparing the threshold stimulus exposure durations (TSEDs) for successfully performing a target identification task when a task-irrelevant flanker was presented versus when the flanker was absent. The flanker was processed if the TSED was longer when the flanker was present than when it was absent. This new paradigm provides an unbiased measure of selective attention when neutral flankers are used. The present data, obtained with neutral flankers in the new paradigm, were consistent with the dilution theory of selective attention, but inconsistent with the perceptual load theory of selective attention.