Biology subjects

Huo, S.

Publications and source records attributed to Huo, S..

8 recordsLinked to original sources

bioRxiv2026

A Urinary Metabolomic Signature Associated with Small Intestinal Bacterial Overgrowth in Children with Short Bowel Syndrome

Direct sampling of the small intestinal microbiome is challenging. Urinary metabolites may offer a noninvasive approach to studying microbial functional activity. We used clinically available gas chromatography/mass spectrometry to profile urinary organic acids in 94 children with short bowel syndrome, comparing those with clinically defined small intestinal bacterial overgrowth (SIBO; n=21) with those without SIBO (n=73). SIBO-associated metabolites included microbial fermentation products, dietary derivatives, and host metabolic intermediates. Metabolites enriched in SIBO mapped to aromatic amino acid metabolism, including tryptophan and tyrosine pathways, consistent with altered microbial fermentation. Many associations persisted after adjustment for intestinal anatomy, age, antibiotic exposure, and nutritional composition. These findings identified a urinary metabolic profile associated with clinically defined SIBO in children with short bowel syndrome and support further evaluation of urinary metabolomics as a noninvasive approach to studying small intestinal microbial function.

microbiology↗

bioRxiv2026

Proteomic and Transcriptomic Differences in Ischemic Stroke Patients with Atrial Fibrillation Versus Carotid Atherosclerosis

BackgroundIschemic stroke occurring in the setting of atrial fibrillation (AF) or carotid atherosclerosis (CA) may reflect distinct underlying biological processes. We integrated proteomic, transcriptomic, and genetic data from different sources to identify circulating proteins and molecular pathways associated with ischemic stroke in patients with AF versus CA. MethodsWe conducted a nested proteomic study within the UK Biobank comparing plasma protein levels among ischemic stroke patients with AF (n=539) and CA (n=127). Linear regression models were used to evaluate 2,923 proteins measured using the Olink Explore platform (false discovery rate [FDR] <0.05). In a separate Yale cohort, we evaluated expression of genes encoding identified proteins in thrombectomy clot single-cell RNA sequencing data from ischemic stroke patients with AF (n=7) or CA (n=7), including cell type-specific expression patterns. We then used summary statistics to perform 2-sample Mendelian randomization analyses using cis-protein quantitative trait loci to evaluate associations between genetically predicted levels of proteins identified in prior analyses and ischemic stroke subtypes. Exploratory pathway enrichment analyses were also performed. ResultsTwelve circulating proteins differed significantly between ischemic stroke patients with AF versus CA. AF was associated with higher levels of NTproBNP, NPPB, and ACP5, and lower levels of APCS, ANGPT2, PAMR1, PRCP, PROS1, LARP1, F7, F10, and LEO1 (all FDR<0.05). Clot transcriptomic analyses showed corresponding differential expression of ACP5, PRCP, LARP1, ANGPT2, and LEO1 across AF versus CA patients. Pathway analyses suggested enrichment of coagulation-related pathways among proteins associated with CA and natriuretic peptide signaling pathways among proteins associated with AF. Mendelian randomization analyses demonstrated associations between genetically predicted protein levels and ischemic stroke subtypes (AF or CA), including cardioembolic stroke for NTproBNPand ischemic stroke for ANGPT2, ACP5, APCS, and PAMR1. ConclusionComplementary proteomic, transcriptomic, and genetic analyses identified differing molecular profiles among ischemic stroke patients with AF versus CA. These findings support established biomarkers, including NTproBNP and coagulation-related proteins, while identifying additional candidate pathways that may contribute to biological differences between these stroke-associated conditions. Further validation in clinically adjudicated and longitudinal cohorts is needed.

neuroscience↗

bioRxiv2026

Posterior Periodic Alpha Power as a Neural Marker of Early Biliteracy Skills: The Mediating Role of Rapid Automatized Naming in Chinese-English Bilingual Children

In school-aged children, resting-state posterior alpha activity has been linked to thalamocortical signal coordination and literacy-related cognition. However, findings are mixed, partly because conventional band power measures conflate oscillatory (periodic) activity with the broadband aperiodic (1/f) background. We tested Chinese-English bilingual children in Grades 1 to 5 (N = 121; 72 families; mean age = 8.23 years, SD = 0.81) to examine if posterior periodic alpha power (8-12 Hz), isolated from aperiodic components, predicts foundational biliteracy skills (Chinese and English word reading and dictation). We also tested whether Chinese digit rapid automatized naming (CDRAN) mediates these associations. In regression models that accounted for family clustering and controlled for age, socioeconomic status (SES), and aperiodic components (exponent and offset), higher periodic alpha power uniquely predicted better performance on all four literacy outcomes. In structural equation models that accounted for family clustering, periodic alpha power predicted CDRAN ({beta} = .213, p = .011), and CDRAN significantly predicted Chinese word reading ({beta} = .442, p < .001), Chinese dictation ({beta} = .346, p = .003), English word reading ({beta} = .302, p < .001), and English dictation ({beta} = .349, p < .001). Indirect effects via CDRAN were significant for all outcomes. These findings suggest that aperiodic-adjusted periodic alpha power is associated with biliteracy variation across Chinese and English and that its association with biliteracy operates in part through rapid serial naming efficiency.

neuroscience↗

bioRxiv2026

Hex-MASP for Mapping the Whole-tissue Spatial Proteome and the Intra-brain Distribution of Monoclonal Antibodies

Whole-tissue spatial proteomics level provides critical insights into region-specific biological regulations but remains challenging. Previously, we introduced the Micro-scaffold Assisted Spatial Proteomics (MASP) concept for whole-tissue mapping. However, this prototype required substantial development in spatial resolution, practicality, and throughput for practical application. Here we present a next-generation MASP technique (hex-MASP) featuring i) a new design of hexagonal-micro-wells fabricated with optimized Projection Micro-Stereolithography (P{micro}SL) 3D-printing, achieving high spatial resolution, sampling robustness and mechanical strength for reproducibly compartmentalizing even tough tissues; ii) enhanced throughput/effectiveness in sample preparation and LC-MS analysis with high quantitative quality. Applied to mouse brain, hex-MASP for the first time achieved in-depth, whole-tissue mapping for >6,000 proteins in mouse brains, with high spatial accuracy and excellent data quality. The substantially improved resolution revealed critical regional details across the entire brain, that were not previously captured, enabling precise depiction of protein distribution heterogeneity. This technique enabled the discovery of many unreported regionally-enriched proteins across brain structures. We further applied hex-MASP to investigate the intra-brain distribution of intracerebroventricularly-dosed antibody therapeutics and related proteins, which to our knowledge, enabled whole tissue mapping of protein drugs for the first time and revealed novel mechanistic insights into antibody distribution and localized treatment effects. Hex-MASP represent a robust, scalable platform for whole-tissue spatial proteomics.

pharmacology and toxicology↗

bioRxiv2025

Deviant functional connectivity patterns in the EEG and their potential use for dyslexia screening

Developmental dyslexia (DD) is a common learning disorder with potential neural origins. While EEG-based brain activation measures combined with machine learning have shown promise for DD screening, these approaches often lack validation on independent participants, which is a crucial step for practical application. This study developed an EEG-based screening approach and investigated the neural correlates of DD in Chinese children. EEG signals were recorded from 130 children (82 with DD, 48 typically developing) aged betweeen 7 and 11 during resting-state and working memory tasks. The EEG data were preprocessed into clean segments to compute functional connectivity (FC) matrices across four frequency bands (delta, theta, alpha, beta). The segments were split into two independent samples, ensuring independence at the participant level: Sample 1, used for training and five-fold cross validation of the convolutional neural networks, and Sample 2, used for cross-sample validation with the trained model. The beta-band FC index in the eyes-open condition achieved the highest within-sample classification accuracy (98%) and cross-sample accuracy (70%, p < .001). Discriminative FC patterns revealed that children with DD exhibited reduced temporal-parietal and central connectivity but increased frontal-central connectivity, likely reflecting compensatory mechanisms. Within the DD group, stronger FCs showed significant negative correlations with Chinese word reading accuracy and fluency. These findings suggest that EEG-based FC measures can effectively distinguish DD and reveal neural markers associated with impaired reading performance. This approach shows promise for noninvasive screening and deeper insight into the neural basis of DD, particularly in non-alphabetic language systems.

neuroscience↗

bioRxiv2022

Focal adhesion protein vinculin inhibits Mef2c-driven sclerostin expression in osteocytes to promote bone formation in mice

The focal adhesion (FA) is the structural basis of the cell-extracellular matrix crosstalk and plays important roles in control of organ formation and function. Here we show that expression of FA protein vinculin is dramatically reduced in osteocytes in patients with aging-related osteoporosis. Deleting vinculin using the mouse 10-kb Dmp1-Cre transgenic mice causes a severe osteopenia in both young and aged mice by impairing osteoblast function without affecting bone resorption. Vinculin loss impairs the anabolic response of skeleton to mechanical loading in mice. At the molecular level, vinculin knockdown increases, while vinculin overexpression decreases, sclerostin expression in osteocytes without impacting expression of Mef2c, a major transcriptional regulator of the Sost gene, which encodes sclerostin. Vinculin interacts with Mef2c and vinculin loss enhances Mef2c nuclear translocation and binding to the Sost enhancer ECR5 to promote sclerostin production in osteocytes. Deleting Sost expression reverses the osteopenic phenotypes caused by vinculin loss in mice. We demonstrate that estrogen is a major regulator of vinculin expression in osteocytes and that more importantly vinculin loss mediates estrogen deficiency induction of bone loss in mice. Thus, we demonstrate a novel mechanism through which vinculin inhibits the Mef2c-driven sclerostin expression in osteocytes to promote bone formation.

developmental biology↗

bioRxiv2021

SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from non-VOC COVID-19 patients and vaccinated individuals. Here, serum of Beta variant infected patients revealed reduced cross-neutralization of non-VOC virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of novel VOC-specific clonotypes and accommodation of VOC-defining amino acids into a major non-VOC antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with non-VOC-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge independent of VOC mutations. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics. One sentence summarySARS-CoV-2 Beta variant elicits lineage-specific antibodies and antibodies with neutralizing breadth against wild-type virus and VOCs.

immunology↗

bioRxiv2019

Artificial intelligence method to design and fold alpha-helix structural proteins from the primary amino acid sequence

The development of rational techniques to discover new proteins for use in variety of applications ranging from agriculture to biotechnology remains an outstanding materials design problem. The key barrier is to design a sequence to fold into a predictable structure to achieve a certain material function. Focused on alpha-helical proteins, we report a Multi-scale Neighborhood-based Neural Network (MNNN) model to learn how a specific amino acid sequence folds into a protein structure. The algorithm predicts the protein structure without using a template or co-evolutional information at a maximum error of 2.1 [A]. We find that the prediction accuracy is higher than other models and the prediction consumes less than six orders of magnitude time than ab initio folding methods. We demonstrate that MNNN can predict the structure of an unknown protein that agrees with experiments, and our model hence shows a great advantage in the rational design of de novo proteins.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC=\"FIGDIR/small/660639v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (66K):\norg.highwire.dtl.DTLVardef@8771fcorg.highwire.dtl.DTLVardef@4c7255org.highwire.dtl.DTLVardef@e63f1eorg.highwire.dtl.DTLVardef@39e4ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗