Biology subjects

Hu, Y.

Publications and source records attributed to Hu, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2025

Survey of hippocampal responses to sound in naive mice reveals widespread activation by broadband noise onsets

Recent studies suggest some hippocampal (HC) neurons respond to passively presented sounds in naive subjects, but the specificity and prevalence of these responses remain unclear. We used Neuropixels probes to record unit activity in HC and auditory cortex (ACtx) of awake, untrained mice during presentation of diverse sound stimuli. A subset of HC neurons exhibited reliable, short-latency responses to passive sounds, including tones and broadband noise. HC units showed evidence of tuning for tone frequency but not spectrotemporal features in continuous dynamic moving ripples. Across sound types, HC responses overwhelmingly occurred at stimulus onset; they quickly adapted to continuous sounds and did not respond at sound offset. Among all sounds tested, broadband noise was by far most effective at driving HC activity, with response prevalence scaling with increasing spectral bandwidth and density. Responses to noise were also far more common than visual flash stimuli. Sound-evoked face movements, quantified by total facial motion energy (FME), correlated with population-level HC activity, but many individual units responded regardless of movement, indicating both auditory and motor-related inputs. These results show that abrupt, acoustic events are sufficient to activate HC neurons in the absence of learning or behavioral engagement. This suggests a possible role for HC in detecting salient environmental changes and supports the idea that auditory inputs contribute directly to HC function. Given emerging links between hearing loss and dementia, these findings highlight a potential pathway by which auditory deafferentation could impact cognitive health.

neuroscience↗

bioRxiv2025

TestNet: A Testing Method for Inferring Microbial Networks with False Discovery Rate Control, for Clustered and Unclustered Samples

Most existing methods for inferring microbial networks generate only point estimates of Pearsons correlations without assessing their significance, and none can account for clustered samples. In this article, we introduce TestNet, a novel method that delivers well calibrated results by controlling the false discovery rate (FDR). We developed a permutation-based procedure to generate valid null replicates that account for compositional effects and extensive zeros in microbiome data, and clustering structures within the samples when present. Our results demonstrate that TestNet is the only method that effectively controls the FDR while maintaining high power across a wide range of scenarios.

bioinformatics↗

bioRxiv2025

Functional relevance of CASP16 nucleic acid predictions as evaluated by structure providers

Accurate biomolecular structure prediction enables the prediction of mutational effects, the speculation of function based on predicted structural homology, the analysis of ligand binding modes, experimental model building and many other applications. Such algorithms to predict essential functional and structural features remain out of reach for biomolecular. Here, we report quantitative and qualitative evaluation of nucleic acid structures for the CASP16 blind prediction challenge by 12 of the experimental groups who provided nucleic acid targets. Blind predictions accurately model secondary structure and some aspects of tertiary structure, including reasonable global folds for some complex RNAs, however, predictions often lack accuracy in the regions of highest functional importance. All models have inaccuracies in non-canonical regions where, e.g., the nucleic-acid backbone bends or a base forms a non-standard hydrogen bond. These bends and non-canonical interactions are integral to form functionally important regions such as RNA enzymatic active sites. Additionally, the modeling of conserved and functional interfaces between nucleic acids and ligands, proteins, or other nucleic acids remains poor. For some targets, the experimental structures may not represent the only structure the biomolecular complex occupies in solution or in its functional life-cycle, posing a future challenge for the community.

biophysics↗

bioRxiv2025

CellLoop: Identifying single-cell 3D genome chromatin loops

Single-cell 3D genome mapping offers insights into chromatin architecture, yet the inherent sparsity and high dimensionality of contact maps hinder reliable identification of chromatin loops at the single-cell level. Here, we present CellLoop, a single-cell chromatin loop detection algorithm based on a density-based center detection framework that integrates intra-cellular and neighboring inter-cellular contacts via a re-voting strategy. Applied to Dip-C data from the mouse brain, CellLoop demonstrates superior accuracy based on the genome spatial distance and compartment signals at the single-cell level. It reveals cell-specific chromatin loops linked to transcriptional regulation and improved cell state classification. In HiRES embryogenesis data, CellLoop refines cell subtype definitions by minimizing cell cycle effects. Integrating GAGE-seq with MERFISH in mouse cortex, CellLoop redefines spatial domain functions through chromatin loop dynamics. Together, CellLoop enables robust, scalable, and biologically meaningful single-cell chromatin loop detection.

bioinformatics↗

bioRxiv2025

Brain Diffusion Transformer for Personalized Neuroscience and Psychiatry

Task-fMRI analyses typically focus on localized activation contrasts between stimuli, neglecting the brains dynamic hierarchy. We introduce Brain Diffusion Transformer (Brain-DiT), a deep generative model capturing recurrent processing underlying individualized neurocognitive state transitions via functional networks. Without prior assumptions, Brain-DiT identifies canonical cognitive regions in the brain and reveals replicable subgroups with distinct neural circuits in large cohorts, offering critical clinical insights overlooked by traditional methods: individuals exhibiting negative emotion bias, linked to language-related regions, had a 12-fold higher likelihood of major depression, and those with maladaptive inhibition strategies, associated with overactive medial frontal regions, showed a 9-fold increased risk of alcohol abuse. By bridging cognitive theory and psychiatric applications, Brain-DiT provides a unified analytical paradigm, paving the way for operational personalized medicine in psychiatry.

neuroscience↗

bioRxiv2025

Insights into the Biocontrol Mechanisms of a Paenibacilluspeoriae Strain on Maize Seedling Blight through Multi-Omics Analysis

Maize seedling blight, caused by the phytopathogenic fungus Fusarium verticillioides, is a common and rapidly spreading disease that negatively impacts grain quality and productivity. Control of this pathogen is complicated by its complex infection process and the tendency for resistance to conventional chemical pesticides. The use of biological control agents has been recognized as an environmentally friendly and sustainable solution for the control of plant diseases. In our study, we isolated and identified Paenibacillus peoriae 3-B4 from maize leaves, which exhibited an inhibition rate of 59.92% against F. verticillioides in greenhouse experiments. Genome sequencing of P. peoriae 3-B4 revealed a chromosome of 5,912,131 bp, featuring a GC content of 45.51% on average and 5383 annotated coding sequences. Eight gene clusters associated with secondary metabolites with antifungal activity and thirteen genes associated with induced systemic resistance and pattern-triggered immunity were identified. Transcriptomic analysis identified 8,997 differentially expressed maize genes, with key defense genes (e.g., NPR1, bZIP, MYB, LRR, WRKY) enriched in MAPK signaling and plant-pathogen interactions. 16S rRNA analysis showed significant shifts in microbial communities, particularly with an increase in the abundance of beneficial genera like Paenibacillus, Delftia, and Corynebacterium. The combined analysis of differentially expressed genes and microbial communities indicated that they synergistically enhance pathogen resistance in maize. Our findings outline the potential mechanisms by which P. peoriae 3-B4 inhibits F. verticillioides infection and open possibilities of exploiting biological control strategies to control maize seedling blight.

microbiology↗

bioRxiv2025

Lipid metabolism of hepatocyte-like cells supports intestinal tumor growth by promoting tracheogenesis

Tumors reprogram lipid metabolism in distant tissues to support their growth. In adult Drosophila, gut tumors secrete the PDGF/VEGF-like factor Pvf1, which activates the TORC1-Hnf4 pathway in hepatocyte-like oenocytes. This drives production of very long-chain fatty acids and wax esters essential for tracheal growth around the tumor. Blocking Hnf4 or the elongase mElo in oenocytes strongly suppresses tracheogenesis, tumor progression, and cachexia-like organ wasting, while extending host lifespan. The same pathway also controls tracheal development in healthy flies. Lipoprotein receptor LpR2 depletion in oenocytes rescues the observed tumor induced tracheal tracheal remodeling. This tumor-host interaction is conserved: VEGF-A induces lipid metabolism genes in human hepatocytes, and lung tumor-bearing mice show elevated hepatic Hnf4 and Elovl7. The study reveals a non-autonomous role of the TORC1-Hnf4 axis in lipid-mediated tumor progression and identifies potential therapeutic targets for cancer-associated metabolic dysfunction.

cell biology↗

bioRxiv2025

The photoreaction process of a large-Stokes-shift red fluorescence protein-LSSmCherry1

Large Stokes shift red fluorescent proteins are highly valued in fluorescence imaging due to their considerable spectral separation and minimal self-absorption. However, a notable gap remains in our understanding of these proteins excited-state dynamics. Unlocking this knowledge could potentially drive significant advancements in cellular and molecular biology. In this study, we systematically examine the excited-state dynamics of LSSmCherry1, a large Stokes shift red fluorescent protein, under varying isotopic compositions and temperatures. Our aim is to elucidate its distinctive spectral properties. Through steady fluorescence spectral experiments at different temperatures, we demonstrate that the large Stokes shift is significantly reduced by approximately 80 nm at low temperatures compared to room temperature. Using transient fluorescence and absorption spectroscopy, we dissect the excited-state dynamics of LSSmCherry1 in neutral environments. We also investigate the kinetic isotopic effect by comparing spectra in water and heavy water. These analyses allow us to delineate plausible photocyclic pathways. Our results reveal that the excited-state dynamics of LSSmCherry1 follow a model similar to that observed in other fluorescent proteins, such as Green Fluorescent Protein (GFP). Notably, we demonstrate that the excited-state proton transfer (ESPT) process is the primary origin of the large Stokes shift in LSSmCherry1. This ESPT process occurs rapidly, within approximately 365 fs after excitation in the neutral environment. This study provides crucial insights into the mechanisms underlying large Stokes shift fluorescent proteins, potentially paving the way for the development of improved fluorescent probes for biological imaging. TOC GraphicSome journals require a graphical entry for the Table of Contents. This should be laid out "print ready" so that the sizing of the text is correct. Inside the tocentry environment, the font used is Helvetica 8 pt, as required by Journal of the American Chemical Society. The surrounding frame is 9 cm by 3.5 cm, which is the maximum permitted for Journal of the American Chemical Society graphical table of content entries. The box will not resize if the content is too big: instead it will overflow the edge of the box. This box and the associated title will always be printed on a separate page at the end of the document.

biochemistry↗

bioRxiv2025

Effect of Azithromycin treatment on the microbial composition, functional dynamics and resistomes of endocervical, vaginal and rectal microbiomes of women in Fiji with Chlamydia trachomatis infection

Antibiotics disrupt mucosal microbial communities, yet the effects on microbiomes with Chlamydia trachomatis (Ct) infection remain poorly understood. Some data exist on vaginal microbiomes pre- and post-treatment, but none are available for the endocervix or rectum that are primary sites of infection. We applied metagenomic shotgun sequencing to vaginal, endocervical and rectal samples from women who, overtime, had Ct persistence, clearance, or no infection to evaluate azithromycin-induced changes in microbial composition, function, and the resistome. Our results show a shift in composition and function that support Ct post-treatment with azithromycin resistance mutations in the Ct rplV gene and significant endocervical enrichment of azithromycin resistance genes in Lactobacillus iners and Gardnerella vaginalis, the strains of which have moderate/high potential for biofilm formation. These findings highlight the unintended ecological consequences of azithromycin, including resistance gene propagation and microbiome shifts that support persistent/recurrent Ct, emphasizing the need for novel treatment and microbiome- preserving strategies.

microbiology↗

bioRxiv2025

Chemically Synthesized Ultra-long DNA as Building Blocks to Accelerate Complex Gene Construction in Synthetic Biology

Certain applications of synthetic biology rely on the construction of large and complex DNA sequences. Current DNA synthesis technologies are limited in their capacity to generate ultra-long oligonucleotide for complex gene construction with extensive repetitive motifs and uneven base distribution efficiently. Here, we report a novel platform named UCOS (short for Ultralong Complex Oligonucleotides Synthesis) that enables the efficient synthesis of long, complex, and challenging DNA fragments. This platform employs nonporous silica microspheres as the solid support instead of traditional CPG (Controlled Pore Glass) solid support, full-length enrichment based on 5 flank sequence hybridization and an error-removing enzyme for correct sequence selection, substantially enhancing the fidelity of intricate, ultralong oligonucleotides. Using this approach, we successfully synthesized challenging sequences up to 600nt in length, encompassing tandem repeats and uneven base distributions. Overall, this novel platform demonstrates exceptional efficiency and reliability in handling ultralong DNA fragments with highly repetitive and complex features. It provides a strong foundation for advancing synthetic biology and shows great potential as a powerful tool for constructing challenging genes and enabling the customized synthesis of functional genetic elements.

synthetic biology↗

bioRxiv2025

HRCHY-CytoCommunity identifies hierarchical tissue organization in cell-type spatial maps

Diverse cell types within a tissue assemble into multicellular structures to shape the functions of the tissue. These structural modules typically comprise specialized subunits, each performing unique roles. We present HRCHY-CytoCommunity, a graph neural network-based framework that leverages differentiable graph pooling and graph pruning to identify hierarchical multicellular structures in cell phenotype-annotated single-cell spatial maps. HRCHY-CytoCommunity ensures the robustness of the result by employing a hierarchical majority voting strategy. To extend the utility of HRCHY-CytoCommunity in cross-sample comparative analysis, an additional cell-type enrichment-based clustering can be used to generate a unified set of nested multicellular structures across all tissue samples. Using single-cell-resolution spatial proteomics and transcriptomics data, we demonstrate that HRCHY-CytoCommunity outperforms the existing state-of-the-art method in discerning coarse-grained tissue compartments (TCs) and fine-grained tissue cellular neighborhoods (TCNs). To further validate the utility of multi-level nested multicellular structures, we apply HRCHY-CytoCommunity to breast cancer data with clinical information and reveal that large-scale TCs and small-scale TCNs enable the stratification of patients with different prognoses in a hierarchical manner.

bioinformatics↗

bioRxiv2025

Pangenome analyses of tea plant reveal structural variations driven gene expression alterations and agronomic trait diversification

Tea plants, one of the worlds most economically significant beverage crops, exhibit extensive genetic diversity and a rich array of secondary metabolites. While structural variations (SVs) are key drivers of phenotypic innovation, their regulatory roles in transcriptional networks and agronomic trait diversification remain underexplored in this perennial crop. We constructed a pangenome from 21 representative tea accessions and their wild relatives. Comparative analysis revealed that wild relatives harbor a greater abundance of gibberellin-related genes, whereas cultivated accessions exhibit an expansion of defense-related genes. We identified 522,428 non-redundant SVs, primarily insertions/deletions (73.56%), which were enriched in promoter regions. These SVs influenced the expression of genes governing flavor compounds, including those involved in flavonoid, amino acid, and terpenoid biosynthesis. Population SV analysis of 275 tea accessions uncovered three haplotypes in the ANS3 gene promoter region, with Hap1, containing a 192 bp insertion, predominantly found in wild relatives but largely lost in modern cultivars. This insertion enhanced CtANS3 expression, increasing anthocyanin accumulation. Additionally, a 159 bp insertion in the CtLRR1 promoter reduced resistance to Colletotrichum gloeosporioides in wild relatives. Our findings underscore SVs as pivotal regulators of genomic diversity, flavor differentiation, and adaptive evolution in tea plant domestication.

genomics↗

bioRxiv2025

Cocktail Chemical Labeling for In-Depth Surfaceome Profiling of Bone-Marrow Derived Dendritic Cells

Cell surface proteins (CSPs) are crucial identifiers for cell types and states, especially in dendritic cells (DCs). Current proteomic methods for profiling CSPs are limited by their hydrophobic nature and low abundance, which often require genetic or cell surface engineering and exhibit biased and insufficient labeling efficiency. Herein, we report [Ru(bpy)3]Cl2 (Ru) for effective biotinylation on the cell surfaceome via a simple "mix and lighten" method. The versatile photoredox pathways of Ru are leveraged using a probe cocktail of biotin-phenol and biotin-hydrazide for improved substrate coverage. The "cocktail" labeling strategy results in reproducible identification of up to 733 plasma membrane proteins on HeLa cells, and is further applied to map dynamic changes in the surfaceome during the differentiation of primary bone marrow-derived dendritic cells, which demonstrates a user-friendly and deep-surfaceome-coverage tool for profiling dynamic changes in primary cells, with potential implications for cell identities, functional states, and novel drug targets.

cell biology↗

bioRxiv2025

C9orf50 is a Targetable Spliceosome Regulator for Cancer Immunotherapy

Cancer cells harbor cell-intrinsic programs capable of sculpting immunogenic landscapes, yet molecular brakes that enforce immune evasion remain poorly defined. Here, we identify C9ORF50, a previously uncharacterized intrinsically disordered protein, as a liquid-liquid phase separation-driven regulator of RNA processing and actionable immunotherapy target. Genetic ablation of C9ORF50 induces selective intron retention in spliceosome component transcripts, leading to cytoplasmic accumulation of immunogenic double-stranded RNA (dsRNA). This dsRNA activates type I interferon pathway that in turn orchestrates a chemokine secretory program critical for T cell recruitment. The resultant enhancement of tumor immunogenicity and reprogramming of tumor immune microenvironment drives robust antitumor immunity, effectively converting immunologically "cold" tumors to "hot" phenotypes. Therapeutic targeting of C9ORF50 via RNA interference achieved robust tumor suppression in syngeneic models, suggesting its translational relevance. Notably, C9ORF50 exhibits tumor-predominant expression, with minimal baseline levels detected in healthy tissues or immune cell populations, underscoring its potential safety as a therapeutic target. Our study not only identifies C9ORF50 as a novel LLPS-dependent regulator of RNA splicing but also establishes it as a promising and potentially safe therapeutic target for cancer immunotherapy.

cancer biology↗

bioRxiv2025

The conserved nature of nitrogen recycling within the bacterial pouch of Tetraponera ants

Microbial symbioses are fundamental to the nutrition of many animal groups, yet the mechanisms of nutrient provisioning remain poorly understood -- even in social insects, a diverse clade whose global ecological dominance and sophisticated caste systems make them disproportionately well-studied models for symbiosis research. Here, we investigate the functional significance of a specialized and unusual symbiotic organ-- the bacterial pouch--in four ant species within the Tetraponera nigra-group, focusing on the symbionts roles in nitrogen recycling and colony fitness. Bacterial pouch houses a microbial community consistently dominated by the core bacterial symbiont Tokpelaia. Metagenomic sequencing and targeted {superscript 1}N-labeled urea feeding experiments demonstrate that these symbionts assimilate nitrogen from urea into amino acids, transferring them to adult workers and developing larvae that incorporate recycled nitrogen into their tissues. Disruption of this nitrogen-recycling symbiosis severely impairs larval growth and overall colony fitness. Our study highlights the critical role of the bacterial pouch in sustaining colony fitness in nitrogen-limited environments, providing new insights into the pivotal role of microbial symbioses in the ecological success of social insects.

ecology↗

bioRxiv2025

Molecular Insights into Cell Wall Architecture and Xylan-Bound Cellulose Fibrils in the Wheat Straw

The plant cell wall, a highly abundant renewable resource, remains insufficiently understood in terms of its structure, particularly the architecture of cellulose microfibrils and their interactions with hemicellulose and lignin, which impede the development of efficient downstream conversion. Here we present an alternative model of xylan-bound cellulose microfibril architecture in the cell wall of intact wheat straw, using solid-state nuclear magnetic resonance (ssNMR) coupled with X-ray scattering techniques. We show that the spectroscopic and scattering data can be fit to a simple elementary microfibril consisting of 18 glucan chains, with additional contributions from 0 to 4 tightly bound flat-ribbon xylan chains across the cellulose fibril axis. These xylan-bound cellulose microfibrils are found to serve as the secondary interaction site with lignin, following the non-flat xylan domains. The loose packing of these xylan-bound cellulose fibrils results in a heterogenous hydration landscape within the cell wall, allowing water penetration while maintaining structural integrity through numerous physical contacts between the polymers. This study provides a potential framework to reconcile the mounting biochemical evidence supporting the 18-chain elementary cellulose microfibril model and cellulose synthase complex with the oversized observations from characterization techniques, which report averaged structures influenced by microfibril coalescence and hemicellulose binding. The structural insights also offer valuable information regarding recalcitrance and the potential applications of biomass in biorefinery operations.

biochemistry↗

bioRxiv2025

Improved Prediction of Bacterial Type VI Secretion Effector Proteins Using an Integrated Convolutional Neural Network Model Combining N-terminal Signal Sequences, Evolutionary Information and Pre-Trained Protein Language Features

Type VI secretion system effectors (T6SEs) are crucial for bacterial pathogenicity, making their accurate identification essential for understanding bacterial virulence mechanisms. This study analyzed the differences in amino acid composition of N-terminal signal sequences between T6SEs and non-T6SEs, uncovering distinct positional amino acid preferences in T6SEs. Using a combination of unsupervised and supervised analysis, we evaluated feature encoding methods and developed T6CNN, an ensemble model that integrates N-terminal signal sequences, evolutionary information, and pre-trained protein language features for T6SE prediction. T6CNN demonstrated outstanding performance in independent testing, outperforming existing tools with a 7.9% accuracy increase (to 0.953), a 13.2% sensitivity improvement (to 0.964), and a 6.6% specificity enhancement (to 0.951). The T6CNN model offers a reliable and accurate solution for T6SE prediction, with significant potential to advance research on bacterial pathogenicity. ImportanceThis study introduces T6CNN, a new computational model for identifying Type VI secretion system effectors used by harmful bacteria. By analyzing early protein sequences, T6CNN uncovers unique features that reliably distinguish effector proteins. Integrating evolutionary data and pre-trained protein language features, the model outperforms existing methods in accuracy, sensitivity, and specificity. This enhanced prediction tool deepens our understanding of bacterial infection mechanisms and offers researchers a valuable resource for pinpointing key virulence factors. Ultimately, T6CNN may help drive the development of more targeted antibacterial treatments and strategies to combat bacterial diseases.

bioinformatics↗

bioRxiv2025

Excessive zinc reduces histone acetylation in mouse cardiomyocytes by downregulating acetyltransferases

Zinc plays a critical role in cellular functions, but its excess may lead to detrimental effects, including cardiac abnormalities. The impact of zinc overload on cardiomyocytes is investigated in this study. For the first time, we report the regulatory relationship between zinc and histone acetylation. Excessive zinc downregulates the transcription of Bmp4 in HL-1 cell line and primary cardiomyocytes. This downregulation is linked to reduced histone acetylation (H3K9ac), mediated by the suppression of histone acetyltransferases (HATs), rather than changes in histone deacetylases (HDACs). When zinc is introduced directly into the nucleus, Bmp4 expression is upregulated, suggesting that the reduction of histone acetylation by zinc is in an indirect way. This study underscores the importance of zinc homeostasis in maintaining cardiac health and provides insights into the molecular basis of zinc-induced cardiac dysfunction.

cell biology↗