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Kan, Q.

Publications and source records attributed to Kan, Q..

3 recordsLinked to original sources

The multiscale architecture of trait aggression: from meta-analytic convergence to multimodal characterization

Background. Trait aggression shows substantial interindividual variability, yet its neurobiological architecture across structural, functional, molecular, and macroscale organizational levels remains poorly understood. Methods. We developed a convergent multiscale framework to characterize the neurobiological architecture associated with trait aggression. We first integrated a large-sample voxel-based morphometry analysis (n = 922) with published neuroimaging studies using two complementary coordinate-based meta-analytic approaches, activation likelihood estimation and seed-based d mapping (total N = 3,671). Convergent meta-analytic findings were subsequently mapped onto functional connectivity networks, and their molecular signatures were characterized using imaging transcriptomics and neurotransmitter mapping. Finally, we examined whether the spatial organization of aggression-related networks was embedded within intrinsic multimodal brain hierarchies spanning morphometric, functional, transcriptomic, and neurochemical dimensions. Results. Across complementary analyses, trait aggression converged on a reproducible structural-functional network centered on the dorsomedial prefrontal cortex and dorsal anterior cingulate cortex. This architecture exhibited distinct molecular signatures, including gene-expression patterns enriched for synaptic functions and robust spatial associations with serotonergic, dopaminergic, and noradrenergic transporter systems. Moreover, the spatial organization of the aggression-related functional network was systematically predicted by the brain's intrinsic multimodal gradients, indicating that it is embedded within broader principles of cortical hierarchical organization. Conclusions. these findings move beyond the localization of aggression to discrete brain regions and identify a reproducible multiscale architecture linking aggression-related structural variation to functional network organization, molecular signatures, and the brain's intrinsic multimodal hierarchy. This integrative framework provides a systems-level account of the neurobiological basis of individual differences in trait aggression.

neuroscience↗

A Single-cell and Spatially Resolved Cell Atlas of Human Esophageal Squamous Cell Carcinoma

Tumor heterogeneity and the suppressive microenvironment are key challenges that limit the effectiveness of cancer treatment. In this study, we systematically elucidated the molecular characteristics and mechanisms underlying the suppressive immune microenvironment via a combination of single-cell RNA sequencing, spatial transcriptomics, and metabolomics for a series of human esophageal squamous cell carcinoma (ESCC) and matched nontumor tissues. We found that COL17A1+ epithelial cells presented greater malignancy, characterized by triglyceride (TG) and phosphocholine (PC) accumulation. We also identified a tumor-specific POSTN+ fibroblast subgroup. We found a unique epithelial-fibroblast niche with low infiltration of effector immune cells and substantial enrichment of lipids, composed of POSTN+ fibroblasts and COL17A1+ epithelial cells, where their crosstalk contributed to tumor progression. We confirmed that the INHBA/TP63 axis plays a key role in mediating the regulation of COL17A1+ tumor cells by POSTN+ fibroblasts. Our findings provided new insights into the characteristics of the tumor microenvironment and the crosstalk between tumor and fibroblasts, offering valuable multiomics data resources for elucidating tumor progression mechanisms.

genomics↗

METTL1/WDR4-mediated m7G Hypermethylation of SCLT1 mRNA Promotes Gefitinib Resistance in Non-small Cell Lung Cancer

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have produced durable complete responses, but the eventual development of acquired resistance presents a huge challenge in the treatment of non-small cell lung cancer (NSCLC). N7-methylguanosine (m7G), a prevalent post-transcriptional modification within RNA, play regulatory roles in RNA stability, expression dynamics, and functional diversity. Despite these insights, the contribution of m7G methylation to EGFR-TKIs resistance remains poorly characterized. Here, we identified substantial upregulation of mRNA internal m7G modifications and their associated methyltransferase complex composed of methyltransferase-like 1 (METTL1) /WD repeat domain 4 (WDR4) were significantly elevated in NSCLC specimens, correlating with therapeutic resistance. Functional assays confirmed that METTL1/WDR4 enhances gefitinib resistance in both cellular and animal models via the internal RNA m7G methyltransferase activity in NSCLC. Mechanistically, m7G MeRIP-seq coupled with RNA-seq identified sodium channel and clathrin linker 1 (SCLT1) as the m7G target of METTL1/WDR4. METTL1/WDR4 knockdown may result in a decrease in both the demethylation level and mRNA stability of the SCLT1 transcript, while overexpression of wild-type METTL1, but not its catalytically inactive mutant, rescues mRNA stability. METTL1/WDR4-mediated m7G modification of SCLT1 regulates gefitinib resistance by activating the NF-{kappa}B signaling. These results establish aberrant mRNA internal m7G modification as a novel resistance mechanism and propose therapeutic targeting of the METTL1/WDR4-SCLT1-NF-{kappa}B axis cascade to overcome EGFR-TKIs resistance.

molecular biology↗