Biology subjects

Qiu, N.

Publications and source records attributed to Qiu, N..

3 recordsLinked to original sources

bioRxiv2025

Disgust propensity, not disgust sensitivity, shapes the reactivity of a subjective disgust circuit in humans

Disgust constitutes an evolutionary adaptive defensive-avoidance response, yet humans vary markedly in their dispositional tendency to experience disgust (disgust propensity) and in their negative appraisal of such experience (disgust sensitivity). Conceptual frameworks and neuroimaging studies suggest that these traits may differentially modulate neural responses to disgust-eliciting stimuli; however, methodological constraints have left their precise roles unresolved. Our comparably large fMRI study (n = 142) therefore aimed to systematically determine how trait disgust modulates neural responses to carefully selected and validated disgust-specific visual stimuli across varying levels of subjective disgust experience. The whole-brain voxel-wise regression analyses revealed a neural dissociation between the two disgust traits, with disgust propensity, but not disgust sensitivity, modulating disgust-related neural activity in the anterior, middle, and posterior insula, as well as the caudate, putamen, thalamus, hippocampus, and parahippocampal gyrus. Mediation and network-level analyses further supported this dissociation by showing that disgust propensity shapes disgust experience via insula - striatal - hippocampal pathways. Together, these findings provide evidence for a neurofunctional dissociation of disgust propensity and sensitivity and elucidate how trait disgust shapes subjective experiences. They further suggest that disgust propensity and the identified systems may represent promising targets for the regulation of disgust-related pathology.

neuroscience↗

bioRxiv2024

Does Unfairness Evoke Anger or Disgust? A Quantitative Neurofunctional Dissection Based on 25 Years of Neuroimaging

Over the last decades, the traditional Homo economicus model has been increasingly challenged by convergent evidence underscoring the impact of emotions on decision-making. A classic example is the perception of unfairness operationalized in the Ultimatum Game where humans readily sacrifice personal gains to punish those who violate fairness norms. While the emotional mechanism underlying costly punishments has been widely acknowledged, the distinct contributions of moral emotions (anger or disgust) remain debated, partly due to methodological limitations of the conventional experiments. Here, we capitalize on a quantitative neurofunctional dissection approach by combining recent developments in neuroimaging meta-analyses, behavioral-level, network-level, and neurochemical-level decoding and data from 3,266 participants from functional neuroimaging studies to determine the common and distinct neural representations between unfairness and the two moral emotions. Experience of unfairness engaged a widespread bilateral network encompassing insular, cingulate, and frontal regions, with dorsal striatal regions mediating the decision to reject unfair offers. Disgust engaged a defensive-avoidance circuit encompassing amygdalar, occipital, and frontal regions, while anger engaged non-overlapping systems including mid-cingulate, thalamic, and frontal regions. Unfairness and anger or disgust respectively commonly engaged the anterior and mid-insula, while the latter additionally showed common recruitment of ventrolateral prefrontal and orbitofrontal cortices. Multimodal network, behavioral, and serotonergic decoding provided a more granular and convincing dissection of these results. Findings indicate a shared neuroaffective basis underlying the impact of emotions on unfairness-induced punishment behavior and suggest a common brain circuit has been evolutionarily shaped to protect individuals from personal harm and enforce societal norms.

neuroscience↗

bioRxiv2023

Discovery of a Novel Chemotype as DYRK1A Inhibitors against Alzheimer's disease: Computational Modeling and Biological Evaluation

Dual specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) plays an essential role in tau and A{beta} pathology closely related to Alzheimers disease (AD). Accumulative evidence has demonstrated DYRK1A inhibition is able to reduce the pathological features of AD. Nevertheless, there is no approved DYRK1A inhibitors for clinical use as anti-AD drugs. This is somewhat the lack of effective and safe chemotypes of DYRK1A inhibitors. To address this issue, we carried out in silico screening, in vitro assays and in vivo efficacy evaluation with the aim to discover a new class of DYRK1A inhibitors for potential treatment of AD. By in silico screening, we selected and purchased 16 potential DYRK1A inhibitors from the Specs chemical library. Among them, compound Q17 (Specs ID: AO-476/40829177) potently inhibited DYRK1A. The hydrogen bonds between compound Q17 and each of three amino acid residues named GLU239, LEU241 and LYS188, were uncovered by molecular docking and molecular dynamics simulation. The cell-based assays showed that compound Q17 could protect SH-SY5Y cells from okadaic acid (OA)-induced injury by targeting DYRK1A. More importantly, compound Q17 significantly improved cognitive dysfunction in 3xTg-AD mice, ameliorated pathological changes, and reduced the expression of DYRK1A, GSK-3{beta} and GSK-3{beta} (pSer9), attenuated tau hyperphosphorylation and A{beta} deposition as well. In summary, our computational modeling strategy is effective to identify novel chemotypes of DYRK1A inhibitors with great potential to treat AD, and the identified compound Q17 in this study is worthy of further study. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/565431v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@75abecorg.highwire.dtl.DTLVardef@16a3611org.highwire.dtl.DTLVardef@39aeborg.highwire.dtl.DTLVardef@afc8ab_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗