Biology subjects

Liu, X.

Publications and source records attributed to Liu, X..

At least 217 records · Page 12Linked to original sources

bioRxiv2026

High-Field Multinuclear MRI Reveals Sodium Relaxation Heterogeneity in Cortical Organoids

Sodium magnetic resonance imaging (23Na MRI) provides a unique opportunity to probe ionic microenvironments in neural tissue because sodium ions play central roles in membrane electrophysiology, ion transport, and cellular homeostasis. Unlike conventional proton ({superscript 1}H) MRI, which primarily reflects water distribution and tissue structure, {superscript 2}3Na MRI is sensitive to ionic compartmentation and quadrupolar interactions arising from the spin-3/2 nature of the sodium nucleus. However, sodium MRI remains technically challenging due to intrinsically low signal sensitivity and rapid biexponential relaxation, particularly when imaging small biological systems. Here, we establish a high-field multinuclear MRI platform for imaging human cerebral organoids at 14 Tesla. Cerebral organoids derived from human induced pluripotent stem cells provide a simplified three-dimensional neural tissue model that enables investigation of ionic microenvironments without vascular or systemic confounds. Using a dual-tuned {superscript 1}H/{superscript 2}3Na radiofrequency coil, we performed co-registered structural, diffusion, and sodium imaging of individual fixed organoids. High-resolution {superscript 1}H MRI (33-100 m) revealed pronounced microstructural heterogeneity, while multi-echo {superscript 2}3Na MRI (300-400 m) enabled voxel-wise characterization of quadrupolar relaxation behavior. Bi-exponential analysis of the sodium signal decay identified distinct relaxation components (T2*short {approx} 1 ms and T2*long {approx} 12 ms) and revealed spatial heterogeneity in sodium microenvironments across the organoid tissue. These results demonstrate the feasibility of quantitative sodium relaxometry in cortical organoids and establish a multinuclear imaging platform for investigating ionic microenvironment dynamics in three-dimensional neural tissue models.

bioengineering↗

bioRxiv2026

A phosphorylation switch in PAGE4 drives MED12-mutant fibroid pathogenesis

Recurrent somatic mutations in MED12, found in [~]70% of uterine leiomyomas (ULs), define the dominant molecular subtype of these highly prevalent tumors, yet the downstream effector mechanisms remain poorly understood. Using an integrated multi-omics workflow, encompassing discovery-phase DDA proteomics of matched leiomyoma-myometrium pairs, validation-phase DIA proteomics across genetically stratified cohorts (MED12 p.G44D, RAD51B-HMGA2, IRS4/FH subtypes), phosphoproteomics, immunohistochemistry, and AP-MS interactomics, we identify prostate-associated gene 4 (PAGE4) as a central effector of MED12-mutant UL pathogenesis. PAGE4 emerged as one of the most significantly upregulated proteins in MED12-mutant ULs and harbored the highest-occupancy hyperphosphorylation sites (T51, T85) in the tumor phosphoproteome, a pattern confirmed by immunohistochemistry and orthogonal phosphoproteomics. Kinase-substrate enrichment nominated HIPK2 as the primary upstream kinase, with supporting evidence from the broader CMGC family. Subsequent analysis revealed that phosphorylation acts as a molecular switch, fundamentally restructuring the PAGE4 interactome to favor the Mediator complex and RNA Pol II transcriptional machinery. This rewiring was functionally validated by ChIP-seq and luciferase reporter assays, which demonstrated corresponding shifts in transcription factor occupancy and downstream pathway activity. Collectively, these data establish phospho-PAGE4 as a critical mechanistic node downstream of MED12 mutation, expand PAGE4 biology from prostate cancer to female reproductive tumors, and nominate it as a mechanistic biomarker and candidate therapeutic vulnerability in the most prevalent molecular subtype of uterine leiomyomas.

systems biology↗

bioRxiv2026

FoTO1 is an epoxide isomerase in paclitaxel biosynthesis

Paclitaxel biosynthesis is limited by the instability of taxadiene-4(5)-epoxide, which readily diverts to the non-productive byproduct 5(12)-oxa-3(11)-cyclotaxane (OCT) instead of rearranging to taxadiene-5-ol. Although FoTO1 suppresses OCT accumulation, its molecular function has been unclear. Here we identify FoTO1 as a dedicated epoxide isomerase that directs productive rearrangement. Biochemical characterization, site-directed mutagenesis, and QM/MM calculations reveal a pre-organized D68-D149 dyad that electrostatically activates epoxide ring opening and stereospecific rearrangement. Modular dissection of the C-terminal extension further reveals a functional partition between catalytic integrity and productive coupling with T5OH, mediated by specific hydrophobic contacts that enforce precise geometric complementarity at the binary complex interface. These results demonstrate how electrostatic activation and enzyme association cooperate to control the fate of a highly reactive intermediate in paclitaxel biosynthesis.

biochemistry↗

bioRxiv2026

No genetic evidence yet for hinnies at Mazongshan (400-160 BCE), northwestern China

In their recent study entitled "Ancient DNA reveals the co-existence of domestic horses, donkeys and their hybrids in the prehistorical northwestern China", Li and colleagues (2026) report the genetic identification of three horses, three donkeys and four first-generation hinny hybrids dating to 400-160 BCE from the Mazongshan jade mining site in northwestern China. While a re-analysis of their ancient DNA sequence data confirms the horse and donkey identifications, it indicates that the four putative hinny specimens were, in fact, donkeys. This revision removes the primary evidence originally shown for the presence of hinnies at this site. Therefore, new data from the Mazongshan bone assemblage are required to support the proposed role of hinny hybrids as integral components of trans-regional trade networks during the Late Warring States and Early Han periods.

evolutionary biology↗

bioRxiv2026

Multicopper oxidase mediated single-carbon insertion for skeletal remodeling

Modern drug discovery demands efficient strategies for generating structurally diverse compound libraries. Skeletal editing--a transformative paradigm enabling precise atom-level modifications within molecular frameworks, offers a sustainable alternative to traditional synthetic routes. While carbene insertion-mediated approaches have dominated single-carbon insertion strategies, current methodologies are limited by their reliance on hazardous, unstable carbene precursors and harsh reaction conditions. Herein, we report a multicopper oxidase (MCO)-catalyzed skeletal editing that enables the direct, one-step transformation of phenolic and indole derivatives into functionalized tropones and quinoline analogues through exogenous single-carbon insertion. This platform employs stable and safe nitroalkanes as carbon sources and O2 as the sole terminal oxidant. It accommodates a broad substrate scope and yields products with superior antibacterial activity against to multidrug-resistant strains relative to their parent compounds. This work introduces the first biocatalytic platform for exogenous single-carbon insertion skeletal editing. This sustainable and scalable strategy overcomes key limitations of synthetic approaches, offering efficient skeletal remolding and rapid expansion of bioactive compound libraries. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/714988v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@1f1d09borg.highwire.dtl.DTLVardef@b67c65org.highwire.dtl.DTLVardef@a0cd4dorg.highwire.dtl.DTLVardef@106afe5_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2026

MAMGL: A memory-augmented meta-graph learning framework for adolescent major depression disorder diagnosis

BackgroundAdolescent major depressive disorder (AMDD) is a prevalent and heterogeneous psychiatric condition that emerges during a critical period of brain development. Neuroimaging-based biomarkers derived from resting-state functional magnetic resonance imaging (rs-fMRI) hold promise for objective diagnosis; however, pronounced inter-individual variability and limited sample sizes pose major challenges for robust model development. MethodsWe propose a memory-augmented Meta-Graph Convolutional Network (BrainMetaGCN) to classify AMDD using rs-fMRI functional connectivity. Individual functional connectivity matrices were constructed by parcellating rs-fMRI time series into cortical regions of interest and computing pairwise correlations. A meta-graph generator dynamically learned subject-specific graph structures, which were processed by lightweight graph convolutional layers. A memory neural network was incorporated to encode population-level prototypical connectivity patterns and generate individualized representations via attention-based retrieval. Model performance was evaluated across multiple independent datasets and compared with state-of-the-art deep learning approaches. Additionally, network interpretability was examined through cortical hierarchy analysis and functional enrichment of discriminative network components. ResultsThe proposed BrainMetaGCN consistently outperformed baseline models, including convolutional and transformer-based approaches, achieving higher accuracy, area under the receiver operating characteristic curve, sensitivity, and specificity. Memory-module-derived functional networks exhibited clear modular organization and showed a significant positive correlation with cortical functional hierarchy, supporting their neurobiological validity. Functional enrichment analyses implicated synaptic transmission, axon guidance, receptor tyrosine kinase signaling, and immune-related pathways, suggesting neurodevelopmental and neuroimmune mechanisms underlying AMDD. Ablation analyses confirmed that memory augmentation and dynamic meta-graph construction were critical for robust performance under small-sample conditions. ConclusionsThis study introduces a robust and interpretable memory-augmented graph learning framework for AMDD classification. By effectively balancing individual specificity and population-level generalization, BrainMetaGCN advances neuroimaging-based precision diagnosis and provides new insights into the neural and biological mechanisms of adolescent depression.

neuroscience↗

bioRxiv2026

Astrocyte targeted SMN1 gene therapy and forskolin application improves astrocyte filopodia actin defects and motor neuron synaptic dysfunction in human SMA disease pathology

BackgroundPeri-synaptic astrocyte processes (PAPs) play a fundamental role in synapse formation and function. Central afferent synapse loss and astrocyte dysfunction greatly impede sensory-motor circuitry in spinal muscular atrophy (SMA) disease progression, however mechanisms underpinning tripartite synapse dysfunction remains to be fully elucidated. The aims of this study were to further define PAP and motor neuron synaptic defects in human SMA disease pathology and implement a therapeutic intervention strategy to improve motor neuron function. MethodsWe derived astrocyte monocultures and motor neuron astrocyte co-cultures from healthy and SMA patient induced pluripotent stem cell (iPSC) lines to assess intrinsic astrocyte filopodia defects and phenotypes occurring at the synapse-PAP interface, respectively, using cell surface capture mass spectrometry proteomics, confocal and super resolution microscopy, synaptogliosome isolation, and electrophysiology. ResultsSMA astrocytes demonstrated intrinsic filopodia actin defects featuring low abundance of actin-associated cell surface N-glycoproteins, and decreased filopodia density and CDC42-GTP levels after actin remodeling stimulation. This phenotype is likely driven by the significant reduction of CD44 and phosphorylated ezrin, radixin and moesin ERM proteins (pERM) within SMA astrocyte filopodia. The dual combination of SMN1 gene therapy and forskolin treatment, an adenylyl cyclase activator leading to increased cyclic adenosine monophosphate (cAMP) levels and actin signaling pathway stimulation, led to extensive branching and increased filopodia density of SMA astrocytes during actin remodeling. SMA patient-derived motor neuron and astrocyte co-cultures, particularly samples derived from male patient iPSC lines, demonstrated a significant decrease in synapse number, actin-associated pre-synaptic neurotransmitter release protein, synapsin I (SYN1), and PAP-associated expression of pERM and glutamate transporter, EAAT1. Our astrocyte-targeted SMN1 augmentation and forskolin treatment paradigm restored SYN1 protein levels within the SMA synaptogliosome, resulting in significant increases in motor neuron synapse formation and function, but did not fully restore PAP-associated proteins levels at the synapse. ConclusionsSMA astrocytes demonstrate intrinsic actin-associated defects within filopodia, which correlates with decreased pERM levels at tripartite motor neuron synapses. We also define a SMN- and cAMP-targeted treatment paradigm that significantly increases pre-synaptic neurotransmitter release protein levels to improved SMA motor neuron synapse formation and function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/714618v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1257ab8org.highwire.dtl.DTLVardef@19c0010org.highwire.dtl.DTLVardef@c84552org.highwire.dtl.DTLVardef@3f1e62_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Metabolic Analysis of Human Retinal Pigment Epithelium and Choroid Tissue in Aging and Macular Degeneration

Age-related macular degeneration is a common ocular disease that causes vision loss in the elderly, with a complex set of risk factors and proposed mechanisms of pathogenesis. A powerful method for investigating changes in disease is metabolomics, by which small molecules can be identified and quantified simultaneously. We report here the metabolic analysis of human RPE-choroid tissue in aging and macular degeneration (AMD), as well as comparisons of human macular and extramacular RPE-choroid and neural retina. Levels of 215 metabolites were determined in young donors, AMD donors (early/intermediate, geographic atrophy, and neovascularization) and age-matched controls. The largest number of metabolite differences were observed between young and healthy aged controls, as opposed to between aged controls and any stage of AMD. Two notable metabolites found to be increased in aging choroids are trimethylamine N-oxide and uric acid, both of which were significant after Bonferroni correction. A mouse endothelial cell line treated with a high concentration of uric acid exhibited reduced migration in a wound closure assay. This study provides initial insights into the metabolome of human choroids in varying states of age and macular degeneration, as well as functional implications of these changes in the aging choroid.

cell biology↗

bioRxiv2026

Uncovering zebrafish embryonic proteome dynamics across 16 time points during the first 24 hours of development

Defining how proteins change over developmental time is amenable to studies deciphering regulatory genetic networks in vertebrate development, biology, and pharmacology. In an approach toward such quantitative studies of dynamic network behavior, we produced an atlas using the mass spectrometry-based method to investigate protein expression changes across 16 time points from the zygote to the early pharyngula stage zebrafish embryos. We systematically summarize 8 clusters for interrogating changes in protein expression associated with the development of zebrafish embryos. Specifically, we identified a class of zinc finger-related transcription factors primarily located on the long arm of chromosome 4, which are highly expressed during zygotic genome activation. Furthermore, we highlight the power of this analysis to assign developmental stage-specific expression information to chromosomes and tissues. Time-resolved analyses reveal significant discordance between differential transcript and protein expression, whereas no time lag is observed for proteins involved in stable and fundamental biological processes, such as metabolism (e.g., Ppt2a and Gatm), cytoskeletal organization (e.g., Col18a1), and the translation machinery (e.g., Eif4enif1). This atlas offers high-resolution and in-depth molecular insights into zebrafish development, providing a resource for developmental biologists to generate hypotheses for functional analysis of proteins during early vertebrate embryogenesis. HighlightsO_LIA global protein expression database with high time resolution is created for zebrafish embryos. C_LIO_LIDistinct patterns of protein expression correlate with biological processes. C_LIO_LITranscription factors have a burst of expression from the gastrulation stage. C_LIO_LIDevelopmental stage-specific protein expressions were assigned to chromosomes and tissues. C_LIO_LIHigh-resolution embryonic transcriptome and proteome datasets were compared and connected. C_LI

developmental biology↗

bioRxiv2026

Paternal behavior is controlled by preoptic Trpc5 neurons

Male parenting behavior is highly conserved and activated only after offspring are born. Here we show that the behavioral switch from infanticide in virgin male mice to caregiving in wild-type sires is associated with enhanced expression and activation of Transient receptor potential channel 5 (Trpc5) in estrogen receptor (Esr1)-expressing neurons in the hypothalamic medial preoptic area (MPOA). While selective deletion of Trpc5 from Esr1MPOA neurons diminishes paternal behavior in sires, overexpression of Trpc5 in these neurons converts the otherwise infanticidal virgin males to exhibit care to pups. Mechanistically, Trpc5-dependent changes in neuronal excitability underlie fatherhood-associated Esr1MPOA neuron plasticity. Notably, Trpc5 overexpression also enhances escape behavior and elicits exploratory diving behavior, suggesting that these neurons control a broader adaptive parenting response in males. These findings establish a Trpc5-dependent MPOA neural signal as a critical regulator of paternal behavior.

neuroscience↗

bioRxiv2026

The enhanced multi-tissue atlas of regulatory effects in cattle

Cattle are integral to global food security, yet the molecular architecture of their complex traits remains poorly understood. Here, we present the Cattle Genotype-Tissue Expression (CattleGTEx) Phase 1 resource (https://cattlegtex.farmgtex.org/), a substantial expansion of the pilot study. By leveraging 12,422 RNA-seq profiles across 43 tissues and 82 breeds, we characterized 433,972 primary and 161,428 non-primary regulatory effects spanning seven molecular phenotypes. This high-resolution atlas resolves 75% of GWAS signals for 44 complex traits, significantly addressing the "missing regulation" in livestock. We propose a genetic regulatory model demonstrating how variants across multiple biological layers interact with specific biological contexts to shape phenotypic variation. Furthermore, CattleGTEx elucidates mechanisms underlying adaptive evolution between Bos taurus and Bos indicus, as well as artificial selection in dairy and beef breeds. Finally, by mapping evolutionary constraints on these regulatory effects, we demonstrate the translational value of this resource for prioritizing causal variants in human complex diseases. Together, Phase 1 of CattleGTEx provides a transformative framework for functional genomics, precision breeding, and comparative genetics.

genetics↗

bioRxiv2026

Hierarchical Flows of Human Cortical Activity

Ongoing brain activity unfolds as structured spatiotemporal patterns across the cortex, yet quantifying the direction and strength of this propagation on the folded cortical sheet is challenging within and across individuals. We introduce geodesic cortical flow, a surface-based optical-flow framework that estimates millisecond-resolved surface-tangent propagation fields from source-imaged magnetoencephalography (MEG) data. In resting-state MEG from 608 healthy adults, spontaneous propagation was anisotropic and bidirectionally aligned with the principal unimodal-to-transmodal functional gradient: slow activity (1-13 Hz) was biased toward upstream propagation from sensory to association cortex, whereas beta activity (13-30 Hz) was biased toward downstream propagation in the opposite direction. Across adulthood, this balance shifted toward weaker upstream slow propagation and stronger downstream beta propagation. Propagation strength, indexed by kinetic energy of the cortical flow, followed a robust posterior-to-anterior gradient and, within frontoparietal cortex, higher kinetic energy was associated with better fluid intelligence after adjustment for age. Kinetic-energy dynamics further identified stable-state dwell times that tracked regional neuronal timescales. Together, these findings establish geodesic cortical flow as a geometry-informed framework for quantifying frequency-resolved cortical propagation and its variation across aging and cognition.

neuroscience↗

bioRxiv2026

MATRIX: Rapid Quantification of Total and Active Microbial Cells with Single Cell Phenotypes for Environmental Microbiomes

Quantifying the abundance and activity of bacteria within populations and communities is fundamental to systems microbiology and microbiome research. Yet direct microscopic cell counting remains low-throughput, labor-intensive, and prone to user variability, leading many researchers to rely on indirect proxies such as optical density or multicopy marker-gene quantification. These indirect approaches do not distinguish between active and inactive cells and can obscure ecological interpretation. Here, we introduce MATRIX (Microbial Activity and Total cell quantification via Rapid Imaging and eXtraction), an efficient workflow that integrates sample extraction, fluorescence staining, automated microscopy and image analysis, and Bayesian statistical inference to quantify total and redox-active cells and derive single-cell measurements for environmental microbial populations and communities. We demonstrate its reproducibility and versatility using both cultured isolates and high-diversity soil communities. The resulting quantitative, phenotypic datasets provide rapid, direct measurements of population of community size and activity, enabling well-powered analyses that strengthen mechanistic insight into microbial responses and improve the ecological grounding of microbiome studies. ImportanceMicrobiome studies commonly rely on relative abundance data, which cannot distinguish whether compositional shifts reflect true population growth, declines in total community size, or both. Without explicit measurements of population and community sizes, mechanistic interpretation of microbiome dynamics remains incomplete. Here we present a rapid, throughput workflow, MATRIX, that quantifies both total and redox-active bacterial cells from environmental samples. By integrating single-cell phenotypes with community-level metrics, this approach anchors microbiome datasets in direct ecological accounting rather than proxies. These measurements can clarify whether observed changes in community structure represent shifts in abundance, activity, or both, improving inference about microbial responses to stress or environmental change. MATRIX therefore offers an efficient way to incorporate quantitative ecology into systems-microbiology and microbiome studies and to strengthen the link between microbial cellular physiology, community dynamics, and eco-system function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/712149v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@1db1d8aorg.highwire.dtl.DTLVardef@708551org.highwire.dtl.DTLVardef@140a1aforg.highwire.dtl.DTLVardef@36fe58_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2026

Syndecan-1 Promotes Alveolar Type 2 Epithelial Cell Senescence during Lung Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive, and fatal interstitial lung disease for which effective therapies remain limited. Alveolar type 2 (AT2) epithelial cells serve as facultative stem cells essential for alveolar repair; however, AT2 cell senescence disrupts epithelial regeneration and contributes to fibrotic remodeling in IPF. Syndecan-1 is a transmembrane heparan sulfate proteoglycan predominantly expressed by lung epithelial cells, but its role in AT2 dysfunction during fibrosis is poorly defined. Here, we demonstrate that syndecan-1 is robustly upregulated in AT2 cells in IPF and other fibrotic lung diseases, as well as in murine bleomycin-induced lung fibrosis. Syndecan-1 expression was further enhanced with aging and associated with increased fibrotic burden in aged mice. Using integrated human transcriptomic analyses, mouse genetic models, and epithelial cell-based systems, we show that excess syndecan-1 promotes cell-autonomous epithelial senescence and impairs AT2 progenitor function. Elevated syndecan-1 reduced AT2 renewal capacity, disrupted differentiation, and diminished surfactant protein C level, whereas genetic loss of syndecan-1 attenuated senescence and preserved epithelial function following injury. Together, these findings identify syndecan-1 as a critical epithelial regulator of AT2 senescence and maladaptive repair in pulmonary fibrosis and support targeting syndecan-1-driven epithelial dysfunction as a potential therapeutic strategy.

cell biology↗

bioRxiv2026

A Novel Hollow Fiber Infection Model (HFIM) for Antiviral PK/PD studies of CMV infection.

The hollow fiber infection model (HFIM) is a translational in vitro model that links time-varying human pharmacokinetic profiles to the associated viral dynamic responses, from which pharmacokinetic/pharmacodynamic (PK/PD) targets can be derived. Establishing such targets is essential for antiviral dose selection and optimization. This is particularly important for cytomegalovirus (CMV) infection treatment, which primarily affects vulnerable patient populations. PK/PD targets for ganciclovir, the first-line drug for treatment, are not yet defined. The lack of an undefined PK/PD target makes dose optimization challenging and may result in suboptimal exposure, prolonged toxicity, and the emergence of resistance. For the first time, we have demonstrated the use of a low-cost hemodialyzer hollow fiber cartridge with application for CMV infection using ganciclovir. We have established a system that 1) supports CMV culture for PD analysis, 2) reproduces a clinically relevant ganciclovir PK profile, and 3) maintains consistent drug exposure in the infected cells, allowing reliable PK/PD analysis. Quantitative methods such as tissue culture infectious dose 50% (TCID50) and quantitative PCR were used to assess both active virus replication and genome copies production. Ganciclovir PK was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This validation study serves as a fundamental step that can allow further PK/PD studies for ganciclovir and other antiviral agents that is still largely understudied. Consequently, this model could provide an affordable and practical platform for establishing clinically relevant PK/PD targets and guide treatment optimization.

pharmacology and toxicology↗

bioRxiv2026

Exploration of Orally Disintegrating Tablet for Sublingual Vaccination against Mucosal Bacterial Infection

Oral mucosal bacterial infections impose a substantial global disease burden, yet current clinical management typically reduces microbial load only transiently and rarely establishes durable protection at the oral surface. Analysis of 200 patients with periodontitis revealed that elevated levels of pathogen-specific salivary secretory Immunoglobulin A (sIgA) were strongly associated with reduced bacterial burden and improved clinical periodontal outcomes, identifying sIgA as a key determinant of effective oral protection. Guided by this observation, we developed a sublingual, orally disintegrating tablet vaccine (Capot) that incorporates bacterial extracellular vesicles providing a comprehensive repertoire of native antigens and multiple pathogen-associated molecular patterns, encapsulated within a calcium phosphate nanoshell to enable safe transmucosal delivery to submandibular lymph nodes. The rapidly disintegrating tablet format minimizes inadvertent swallowing and enhances local mucosal bioavailability. In mice and non-human primates, Capot induced robust and long-lasting salivary sIgA responses without overt oral mucosal or gastrointestinal inflammation and conferred strong protection against primary, recurrent, and antibiotic-resistant periodontitis. Together, these findings establish sublingual tablet vaccination as a practical strategy for selectively engaging oral mucosal immunity and preventing chronic bacterial diseases at oral mucosal surfaces.

bioengineering↗

bioRxiv2026

Convergent cortical temporal axis: common cortical oscillatory modes

Brain dynamics provide the most direct substrate for neural function and representation. Extensive prior work has demonstrated that the human brain is organized into hierarchical structures across molecular, cellular, microstructural, and macroscale network levels. However, whether these hierarchies can be directly linked through shared patterns of neural dynamics remains unresolved, and clear evidence from data-driven analyses is still lacking. A central open question is whether brain dynamics vary along a single continuous dimension, or whether they are instead composed of a limited number of reproducible coordination modes that could provide a unifying basis for cross-scale integration. Here, using source-resolved resting-state magnetoencephalography (MEG), we adopt a fully data-driven approach that imposes no a priori assumptions about cortical hierarchy or gradient structure. By characterizing full-spectrum power relationships across cortical regions, we identify a set of stable and reproducible spectral coordination modes. These modes capture how multiple frequency components jointly co-vary across space, defining distinct dynamical configurations rather than conventional band-limited oscillations or continuous gradients. The identified spectral coordination modes exhibit pronounced spatial differentiation across the cortex, distinguishing regions dominated by narrowband rhythmic activity from those characterized by broadband or multi-frequency coordination. Importantly, these modes do not correspond to predefined hierarchical axes, nor can they be reduced to existing MEG gradients or functional connectivity organizations. Instead, they emerge directly from the data, revealing a finite set of shared organizational patterns underlying cortical dynamics. Multimodal analyses further demonstrate that individual spectral coordination modes show selective associations with neurotransmitter system distributions, laminar microarchitecture, and cell-type-specific gene expression, suggesting that these dynamical patterns may serve as linking mechanisms between micro- and macroscale brain organization. Computational modeling supports this interpretation, showing that differences in local circuit parameters are sufficient to generate distinct spectral coordination states without invoking a single global dynamical hierarchy. Across the adult lifespan, these coordination modes exhibit frequency- and region-specific reorganization, indicating multiple parallel trajectories of dynamical aging. In Parkinsons disease, alterations are observed in specific spectral coordination modes, particularly within higher-order cortical regions, suggesting that the disorder preferentially disrupts distinct dynamical configurations rather than inducing a global breakdown of cortical dynamics. Together, these findings indicate that large-scale brain dynamics are not organized along a single pre-existing hierarchical axis, but instead are structured by a limited number of data-driven spectral coordination modes. This framework provides a new dynamical perspective for linking brain organization across modalities and scales, and offers a principled avenue for understanding systematic changes associated with aging and neurological disease.

neuroscience↗

bioRxiv2026

Multimodal spatial alignment and morphology mapping with MOSAICField

Recent efforts to build comprehensive tissue and tumor atlases leverage diverse spatial technologies to measure transcriptomic, proteomic, epigenetic, and other modalities with hundreds to thousands of features at thousands to millions of spatially resolved locations in a tissue slice. Integrating such data across spatial technologies that differ in molecular features, spatial resolution, and tissue morphology remains a major challenge. We introduce MultimOdal Spatial Alignment and Integration with Coordinate neural Field (MOSAICField), a unified framework for aligning spatial slices across arbitrary combinations of experimental modalities. MOSAICField computes two types of spatial alignments across multiple slices from the same tissue: physical alignment, which reconstructs a contiguous 3D model of the original tissue, and morphological alignment, which maps distinct morphological or anatomical structures, such as ducts, veins, or neurons, that may traverse the tissue at different angles relative to the direction of slicing. MOSAICField computes both alignments using a deep neural network that estimates a nonlinear deformation field with a multimodal feature loss. We evaluate MOSAICField on simulated data and a prostate cancer sample from the Human Tumor Atlas Network (HTAN), containing more than a dozen spatial slices with multimodal profiling data. MOSAICField constructs an accurate 3D tumor model, tracks the architecture of the prostatic ductal system, and improves analysis of features within and across modalities, outperforming existing methods.

bioinformatics↗