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Background: Inflammatory pain mediated by nuclear factor kappa-B (NF-κB) signal pathway has become an increasingly important clinical issue in the last decade. As a potent antioxidant, Nodakenetin has been shown to have a prominent inhibitory effect on inflammation. However, the therapeutic effects and underlying pharmacological mechanisms of Nodakenetin for inflammatory pain remain unclear. Methods: Intraplanar injection of complete Freund’s adjuvant (CFA) was used to establish a model of chronic inflammation pain in C57BL/6 mice. The chronic neuropathic pain model was conducted by the sciatic nerve ligation surgery. QRT-PCR was performed to estimate the RNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Western blot was used to demonstrated the protein levels of phospho-IkappaBα (IκBα), p50, and p65 in HEK293T cells. Results: The bioactive components of the traditional Chinese medicine Notopterygium forbesii boiss mainly include Nodakenetin, isoimperatorin, and pregnenolone. Nodakenetin significantly alleviated CFA-induced inflammatory pain but showed no significant therapeutic effect on surgically induced neuralgia in a mouse model. In contrast, isoimperatorin and pregnenolone did not relieve CFA-induced inflammatory pain. Mechanistically, Nodakenetin inhibited IL-1β-induced activation of the NF-κB pathway and phosphorylation of IκBα in HEK293T cells. Furthermore, Nodakenetin treatment suppressed the expression of IL-6, TNF-α, and IL-1β in mouse bone marrow-derived macrophages. Conclusion: Nodakenetin alleviates inflammatory pain induced by CFA injection in vivo and modulates NF-κB signal pathway in vitro.

Although we are surrounded by various kinds of rumors during the coronavirus disease pandemic, little is known about their primary content, what effect they might have on our emotions, and the potential factors that may buffer their effect. Combining qualitative (study 1 extracted 1907 rumors from top rumor-refuting websites using the Python Web Crawler and conducted content analysis) and quantitative (study 2 conducted an online survey adopting a three-wave design,The online version contains supplementary material available at 10.1007/s12144-022-03508-x.

The causal influence of the dorsolateral prefrontal cortex (DLPFC) in voluntary forgetting remains unclear. Here, we employed repetitive transcranial magnetic stimulation (rTMS) over the right DLPFC to temporarily disrupt function of this brain region and examined its influence on an item-method directed forgetting (DF) task with both neutral and negative emotional memories. Participants were assigned to either an active or a sham rTMS group, in which we administered stimulation for 20 min before the DF task. We then examined the explicit and implicit DF effects with an explicit recognition and an implicit word completion test. We found that while participants in the sham group showed the classic DF effects in both explicit and implicit memory tests, temporally disrupting activity of the right DLPFC selectively reduced the DF effect on explicit recognition, but not on implicit word completion test. Our findings provide novel evidence that the right DLPFC plays a causal role in voluntary forgetting and support the direct inhibition account of voluntary memory control. Intriguingly, preserved implicit DF effects in the active stimulation group suggest that unintentional expressions of unwanted memories may be more sensitive to DF and less dependent on the right DLPFC.

Objective MicroRNAs (miRNAs) have become the focus of most recent efforts in cancer research. However, there have been inconsistencies in the literature regarding the suitability of circulating miRNAs for early detection of gastrointestinal cancers. This study aims to assess the diagnostic performance of circulating miRNAs in detection of gastrointestinal cancer through a meta-analysis. Methods Eligible studies were selected by conducting a systematic literature search of public databases. The sensitivity and specificity were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the SROC curve (AUC). The between-study heterogeneity was evaluated by Q test and I2 statistics. Subgroup analyses and meta-regression were further performed to explore the potential sources of heterogeneity. All analyses were performed using the STATA 12.0 software. Results A total of 107 studies from 42 articles were included for the meta-analysis according to the inclusion criteria. The overall analysis of all gastrointestinal cancers showed that circulating miRNAs have a relatively good diagnostic performance in gastrointestinal cancers, with a sensitivity of 0.75, a specificity of 0.81 and an AUC of 0.85. In addition, subgroup analyses based on different type of miRNA assay suggested that single-miRNA assay displayed a relatively low diagnostic performance with the AUC values of 0.84 for gastric cancer (GC) and 0.79 for colorectal cancer (CRC), while multiple-miRNAs assay significantly improved the diagnosing accuracy with AUC rising to 0.92 for GC and 0.89 for CRC. Another interesting finding was that plasma-based miRNA assay reach a higher accuracy compared with serum-based one for GC, while opposite conclusion was drawn for CRC. Conclusions In conclusion, circulating miRNAs, particularly the combination of multiple miRNAs, may present as promising biomarkers for the diagnosis of gastrointestinal cancers. Further large-scale prospective studies are necessary to validate their potential applicability in human cancer diagnosis.

Generally, successful cooperation can only be established when the interacting persons believe that they would not be betrayed; this belief can be updated by observing the other persons' actual choices. Thus, the process of belief updating plays an important role in conditional cooperation. Using the Prisoner's Dilemma Game (PDG) with event-related potential (ERP) hyperscanning, this study investigated the dynamics of belief updating in a dyad. During the task, participants were asked if they believed that their opponent would cooperate in the next trial, and their answers functioned as a self-reported index of reciprocal belief. The results suggested that this index shows strong associations with participants' behavioral choices (cooperate/betray). At the individual level, the amplitudes of the ERP components frontal P3a and parietal P3b elicited by the decision outcome were sensitive to belief updating. At the interpersonal level, the between-subject synchronization in P3b was higher than those in the other conditions when the paired participants confirmed each other's reciprocal beliefs. Since previous studies have linked the P3b with memory updating, we suggest that a cooperative relationship is built up when the memory systems (which support belief updating) of two interacting persons reach a high level of coordination. These findings may help explain how conditional cooperation develops between strangers.

Emerging evidence has revealed significant roles for long noncoding RNA (lncRNA) in various biological processes, including cell proliferation, apoptosis and invasion. The lncRNA distal‑less homeobox 6 antisense 1 (DLX6‑AS1) has been reported to serve as a vital oncogene during tumorigenesis and progression. However, the expression levels and functional roles of DLX6‑AS1 in cervical cancer are not yet well understood. In the present study, DLX6‑AS1 expression was identified to be significantly upregulated in cervical cancer tissues and cell lines by reverse transcription‑quantitative polymerase chain reactions. Knockdown of DLX6‑AS1 inhibited cell proliferation and induced cell apoptosis. Bioinformatics analysis predicted that micro RNA (miR)‑199a was a direct target of DLX6‑AS1. Overexpression of miR‑199a counteracted the role of DLX6‑AS1 in facilitating proliferation and inhibiting apoptosis in in vitro rescue assays. The present results suggest that DLX6‑AS1 acting as a sponge for miR‑199a may serve a critical role in the development and progression of cervical cancer.

This paper is devoted to the numerical solution of large-scale linear ill-posed systems. A multilevel regularization method is proposed. This method is based on a synthesis of the Arnoldi-Tikhonov regularization technique and the multilevel technique. We show that if the Arnoldi-Tikhonov method is a regularization method, then the multilevel method is also a regularization one. Numerical experiments presented in this paper illustrate the effectiveness of the proposed method.

There is abundant evidence suggesting that the right ventrolateral prefrontal cortex (rVLPFC) plays an important role in down-regulating the emotional response to social exclusion. However, a causal relationship between rVLPFC function and explicit emotional regulation is not clear in the context of social exclusion. This study employed anodal transcranial direct current stimulation (tDCS) to activate rVLPFC while participants used emotional regulation to reappraise pictures of social exclusion. Forty-four participants were randomly assigned to an active tDCS group or a sham group. Both groups viewed social exclusion images under two conditions: in the no-reappraisal condition, participants were instructed to passively view social exclusion images; in the reappraisal condition, they reappraised the images to down-regulate negative emotional responses. Compared to sham stimulation, anodal tDCS over the rVLPFC resulted in less negative emotion ratings, and produced significantly smaller pupil diameter in the reappraisal, compared to no-reappraisal block. The tDCS also led to longer fixation durations to rejectees and shorter fixation durations to rejecters. Taken together, these findings suggest a causal role for rVLPFC in down-regulation of negative emotions produced by social exclusion. This study has implications for clinical interventions targeting emotional regulation deficits.