Biology subjects

Wang, X.-Q.

Publications and source records attributed to Wang, X.-Q..

6 recordsLinked to original sources

bioRxiv2026

Individualized Functional Connectivity-Guided TMS Targeting Theory of Mind Network for Autism Spectrum Disorder

Transcranial magnetic stimulation (TMS) shows promise in autism spectrum disorder (ASD), but variable outcomes may reflect suboptimal targeting. We developed a functional-connectivity (FC)-guided individualized TMS approach by identifying an ASD-relevant effective region and selecting superficial targets. In a multi-site mega-analysis of Autism Brain Imaging Data Exchange I data (298 ASD, 348 controls), the region with the greatest regional homogeneity (ReHo) abnormality was defined as the effective region. Individualized dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) targets were localized as sites with strongest FC to this region. Group differences, symptom associations, and a six-patient case series were examined. The posterior cingulate cortex (PCC) showed the greatest ReHo abnormality and was implicated in theory-of-mind (ToM) circuitry. PCC-guided targets showed weaker FC in ASD in the right IPL, correlating with Autism Diagnostic Interview social scores; left DLPFC FC differences lacked symptom associations. In the case series, individualized PCC-IPL-guided TMS reduced ToM-related symptoms and Childhood Autism Rating Scale scores. PCC-IPL FC-guided TMS is a biologically informed intervention for modulating ToM circuitry in ASD.

neuroscience↗

bioRxiv2025

IGP receptors act as redox sensors to mediate broad-spectrum disease resistance induced by cellooligomers

Cys-oxidation is a well-established post-translational regulator of intracellular protein function, yet its role in extracellular receptor-mediated signaling remains poorly understood. Here, we investigate the LRR-Malectin receptor-like kinase IGP1, a key receptor for plant cell wall damage-associated molecular patterns (DAMPs). We demonstrate that IGP1 directly recognizes cellooligomers with a degree of polymerization [≥] 3 via a conserved binding groove in its LRR domain, not the malectin domain as anticipated. Strikingly, a pair of cysteines within the malectin domain functions as a redox sensor, undergoing hydrogen peroxide-induced oxidation that sterically reduces ligand binding affinity and attenuates immune signaling. Phylogenetic analyses reveal that IGP originated after the terrestrialization of plants, and is an evolutionarily conserved redox sensor in land plants. Functional studies in Arabidopsis (Arabidopsis thaliana), wheat (Triticum aestivum), and soybean (Glycine max) confirm that the IGP-cellooligomer module confers broad-spectrum disease resistance. Our work uncovers a unique mechanism where ligand perception and redox sensing are integrated into a single receptor to regulate DAMP-triggered immunity.

plant biology↗

bioRxiv2024

Peptide Information Compression Technology (PICT): A New Frontier in Therapeutic Peptide Discovery

Therapeutic peptides hold tremendous market potential, yet the discovery methods for active peptides lag considerably behind those for small molecules and biological macromolecule drugs. Due to their respective limitations, traditional peptide compound synthesis and display libraries fail to meet the growing demands of the peptide drug market. Here, we introduce a novel Peptide Information Compression Technology (PICT) and, based on this technology, a large-scale physical peptide library and its accompanying high-throughput screening (HTS) platform. By screening for inhibitors of TSLP/TSLPR/IL7R and antagonists of MC3R at both the molecular and cellular levels, we have identified active molecules in the single-digital micromolar and nanomolar ranges, respectively. This demonstrates the immense application value of Peptide Information Compression Technology in the efficient discovery of peptide drugs.

molecular biology↗

bioRxiv2024

Nearly complete genome assembly of a critically endangered pine illuminates evolution and conservation of conifers

Population genetic theory predicts that severe bottlenecks and extremely small effective population sizes (Ne) should reduce the ability of natural selection to eliminate harmful mutations. Under this framework, deleterious alleles are expected to accumulate and even fix, eroding fitness, constraining evolutionary rescue, and potentially precipitating mutational meltdown. Yet, empirical tests of these predictions in species at the extreme lower bound of Ne remain rare. We address this gap using Pinus squamata, one of the rarest tree species on Earth, with only 35 wild individuals remaining. We generated a near-complete reference genome (29.2 Gb) for this species and performed population genomic analyses across nearly all of its extant individuals, together with two closely related species. P. squamata exhibits extraordinarily low nucleotide diversity ({pi} = 3.35 x 10-), the lowest reported for any plant. Demographic inference reveals a recent and severe bottleneck ([~]20 generations ago) that reduced Ne to [~]2.7 and resulted in intense inbreeding. Contrary to theoretical expectations, we uncover evidence for highly efficient purifying selection: strongly deleterious mutations are markedly depleted, indicating substantial purging despite the extremely small Ne. Genome-wide patterns further implicate selection at linked sites--including background selection and pseudo-overdominance--as dominant forces shaping genomic variation in the species. These results challenge the prevailing view that drift overwhelms selection in extremely small populations. Instead, they suggest that, under certain genomic and demographic conditions, purifying selection can remain unexpectedly effective, potentially mitigating the risk of mutational meltdown in the rarest species.

genomics↗

bioRxiv2024

Multi-view graph learning for deciphering the dominant cell communication assembly of downstream functional events from single-cell RNA-seq data

Cell-cell communications (CCCs) from multiple sender cells collaboratively affect downstream functional events in receiver cells, thus influencing cell phenotype and function. How to rank the importance of these CCCs and find the dominant ones in a specific downstream functional event has great significance for deciphering various physiological and pathogenic processes. To date, several computational methods have been developed to focus on the identification of cell types that communicate with enriched ligand-receptor interactions from single-cell RNA-seq (scRNA-seq) data, but to the best of our knowledge, all of them lack the ability to identify the communicating cell type pairs that play a major role in a specific downstream functional event, which we call it "dominant cell communication assembly (DCA)". Here, we proposed scDCA, a multi-view graph learning method for deciphering DCA from scRNA-seq data. scDCA is based on a multi-view CCC network by constructing different cell type combinations at single-cell resolution. Multi-view graph convolution network was further employed to reconstruct the expression pattern of target genes or the functional states of receiver cells. The DCA was subsequently identified by interpreting the model with the attention mechanism. scDCA was verified in a real scRNA-seq cohort of advanced renal cell carcinoma, accurately deciphering the DCA that affect the expression patterns of the critical immune genes and functional states of malignant cells. Furthermore, scDCA also accurately explored the alteration in cell communication under clinical intervention by comparing the DCA for certain cytotoxic factors between patients with and without immunotherapy. scDCA is free available at: https://github.com/pengsl-lab/scDCA.git.

bioinformatics↗

bioRxiv2017

Multiethnic Meta-analysis Identifies New Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), African (N=8,429), Asian (N=9,959), and Hispanic/Latino (N=11,775) ethnicities. We identified over 50 novel loci at genome-wide significance in ancestry-specific and/or multiethnic meta-analyses. Recent fine mapping methods incorporating functional annotation, gene expression, and/or differences in linkage disequilibrium between ethnicities identified potential causal variants and genes at known and newly identified loci. Sixteen of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.

genetics↗