Biology subjects

Xu, Y.

Publications and source records attributed to Xu, Y..

At least 325 records · Page 18Linked to original sources

bioRxiv2025

Carbon monoxide exposure stimulates growth and activity of primary producers in diverse soil ecosystems

Carbon monoxide (CO) is both a potent poison for many aerobic organisms and a desirable energy source for diverse microorganisms. Atmospheric emissions of this gas have increased since industrialization and their levels are highly elevated in many urban and natural environments; however, it is unresolved whether elevated levels of CO at environmentally relevant concentrations are primarily stimulatory or inhibitory to soil microbial communities. Here, we showed that CO exposure minimally affects microbial abundance, richness, and composition in diverse ecosystem soils, suggesting most microbes are tolerant of this gas. Genome-resolved metagenomic profiling showed that these soils harbored diverse bacteria capable of using CO an electron donor for aerobic respiration and carbon fixation. CO stimulated the growth of several of these putative CO-oxidizing bacteria in a dose-dependent manner, especially widespread proteobacterial and actinobacterial lineages. Additionally, we found a strong relationship between CO oxidation and carbon fixation and observed an enrichment of several carboxydotrophic MAGs capable of carbon fixation in most soil types. These findings highlight that environmentally relevant CO levels do not inhibit soil microbes, but instead foster the growth of distinct carboxydotrophic bacteria, suggesting a robust soil CO sink that could help mitigate anthropogenic CO emissions and contribute to carbon cycling in terrestrial ecosystems.

biochemistry↗

bioRxiv2025

Enhancer Dynamics and Spatial Organization Drive Anatomically Restricted Cellular States in the Human Spinal Cord

Here, we report the spatial organization of RNA transcription and associated enhancer dynamics in the human spinal cord at single-cell and single-molecule resolution. We expand traditional multiomic measurements to reveal epigenetically poised and bivalent active transcriptional enhancer states that define cell type specification. Simultaneous detection of chromatin accessibility and histone modifications in spinal cord nuclei reveals previously unobserved cell-type specific cryptic enhancer activity, in which transcriptional activation is uncoupled from chromatin accessibility. Such cryptic enhancers define both stable cell type identity and transitions between cells undergoing differentiation. We also define glial cell gene regulatory networks that reorganize along the rostrocaudal axis, revealing anatomical differences in gene regulation. Finally, we identify the spatial organization of cells into distinct cellular organizations and address the functional significance of this observation in the context of paracrine signaling. We conclude that cellular diversity is best captured through the lens of enhancer state and intercellular interactions that drive transitions in cellular state. This study provides fundamental insights into the cellular organization of the healthy human spinal cord.

neuroscience↗

bioRxiv2025

Micromorphology and ammonium transmembrane transport characteristics in roots of rice seedlings

During the seedling stage, rice root exhibit rapid growth and absorb significant quantities of nutrients. This study involved cultivating rice seedlings in two different seedling-raising mediums characterized by high ammonium concentration (HN, NH4+ 1.2 mg g-1) and low ammonium concentration (LN, NH4+ 0.006 mg g-1). The morphology of distinct root zones (root cap, meristematic zone, elongation zone, and maturation zone) was observed under a microscope throughout root development, and variations in transmembrane flux rates of NH4+ in different root zones were assessed using Non-invasive micro-test technology (NMT). Results showed that the root caps of both seminal and adventitious roots became separated from the root tip between 9 and 12 days after root emergence. During this time, the root tip transformed from a sharp to a round shape, and the distance from the maturation zone to the root tip progressively decreased from over 900 m on 6 days after sowing (DAS) to under 500 m on DAS12. The meristematic zone was the primary site for NH4+ absorption in new root and proved to be particularly sensitive to environmental NH4+ concentration. At DAS 6, the net NH4+ flux rate was highest in the meristematic zone under both HN and LN treatments. Additionally, the external NH4+ concentration influenced the direction of NH4+ flux in the meristematic zone at DAS9, with HN being a net NH4+ influx and LN being an NH4+ efflux, and the net NH4+ influx in the meristematic zone persisted for 3 days longer in the HN treatment compared to the LN treatment. In mature roots, the root hair zone emerged as the primary site of NH4+ uptake, exhibiting an infNH4+ influx rate of 40-140 pmol cm-1 s-1, and this low rate of uptake could be sustained for up to 12 days after root emergence. By DAS15, a net NH4+ efflux was observed in the entire seminal root, signaling the loss of NH4+ absorption function 15 days post-emergence. A similar trend was noted in adventitious roots, where NH4+ uptake remained functional for 12-15 days after root emergence. As rice seedlings continued to grow, new adventitious roots replaced old ones, facilitating ongoing NH4+ uptake.

plant biology↗

bioRxiv2025

Spatiotemporal changes in soil properties predict plant health at continental scale

Abiotic and biotic soil properties are strong predictors of plant yield globally1-5, but they become unreliable over large areas when plant health is threatened by pathogen6-8. Here we present a novel approach to predict plant health based on spatiotemporal changes in soil chemical and biological properties. We first demonstrate that plant health and soil properties consistently respond to environmental change (organic fertilization) regardless of the soil type or geographical origin. Second, we experimentally show that trackable shifts in soil properties reliably explain soil suppressiveness to the Ralstonia solanacearum bacterial pathogen and that a scalable spatiotemporal model predicts plant health with 84% accuracy across multiple climatic zones and cropping systems. Our results suggest that this tight coupling between soil properties and plant health could facilitate the development of agricultural practices aimed at sustainably improving crop yields while safeguarding crop health.

ecology↗

bioRxiv2025

Replay builds an efficient cognitive map offline to avoid computation online

How do humans integrate fragmented experiences into a coherent structure that supports novel inferences? Addressing this question requires tracking learning from the very first encounters. Using magnetoencephalography, we recorded human neural activity throughout the full process - from initial learning to inference. Participants first learned one-dimensional, pairwise rank relationships that collectively formed a two-dimensional (2D) conceptual map, and then inferred unobserved relationships. During rest, offline replay integrated piecemeal memories into a coherent 2D representation, predicting the emergence of a grid-cell-like code that reflected a generalizable task schema. This schema reduced the need for effortful computations during subsequent inference. During inference, two types of on-task replay emerged: a fast replay, resembling offline replay and representing the full map, and a slow replay, focused on trial-specific details. Notably, slow replay negatively correlated with both grid-like coding and inference performance. Together, these results suggest that replay builds an efficient cognitive map offline, thereby reducing reliance on deliberate computation online.

neuroscience↗

bioRxiv2025

Gait Adaptations in Step Length and Push-off Force during Walking with Functional Asymmetry

Human walking is remarkably adaptable, allowing individuals to maintain efficiency and stability across diverse conditions. This study investigates how healthy young adults adapt step length and push-off force to varying speeds and cadences under functional asymmetry induced by a unilateral knee constraint, simulating hemiparetic gait. A dataset of 19 participants walking across 30 conditions was used to examine these adaptations in both absolute terms and symmetry metrics. Results reveal that functional asymmetry disproportionately impacts propulsion, with constrained-leg force decreasing significantly at higher speeds. Step length symmetry remains stable, suggesting a prioritisation of spatial over kinetic symmetry, likely to optimise walking energetics and maintain anterior-posterior balance. Statistical models demonstrated good within-dataset performance but limited generalisability in cross-dataset predictions, where differences in population cohorts and experimental designs reduced accuracy. These findings provide insights into the mechanisms driving gait adaptations and highlight critical limitations in applying statistical models to patient populations, underscoring the importance of representative datasets and caution when extrapolating findings across populations.

biophysics↗

bioRxiv2025

Pathobiont-triggered induction of epithelial IDO1 drives regional susceptibility to Inflammatory Bowel Disease

The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions and not others remains unclear. We use a TNF-overexpressing Crohns disease (CD) model (Tnf{Delta}ARE/+), which typically presents in the terminal ileum (TI), to investigate how environmental factors interact with the hosts immune susceptibility to drive region-specific disease. We identified Chlamydia muridarum, an intracellular bacterium and murine counterpart to the human sexually transmitted C. trachomatis, as necessary and sufficient to trigger disease manifestation in the ascending colon (AC), another common site of human CD. Disease manifestation in the AC depends on indoleamine 2,3-dioxygenase (IDO1) activity induced by hypersensitive surface secretory cells in genetically susceptible hosts. Single-cell and microbial analyses of human specimens also implicates this pathobiont-epithelial IDO1 pathway in patients with a history of CD in the AC. Our findings demonstrate that genetic and microbial factors can independently drive region-specific disease and provide a unique model to study CD specific to the AC.

cell biology↗

bioRxiv2025

Using green space virtual reality to prevent stress-induced working memory impairment

Exposure to green space is associated with both physical and mental health benefits, including the potential to buffer acute stress responses, positioning it as a promising non-pharmacological approach to protect cognitive functions against stress. However, urban residents often face significant barriers in accessing green spaces, which are not equitably distributed. Virtual Reality (VR) technology offers a potential solution by simulating green space that could be made accessible to a broader demographic. Here, we explored whether VR-stimulated green space could dampen biological stress responses (i.e., heart rate and cortical response) and prevent stress-induced working memory (WM) impairment. Healthy young participants underwent acute stress induction followed by 15 minutes of VR-based green space (N=36) or control empty space (N=30) intervention. Although we observed the expected stress-induced increase in heart rates and elevated cortisol levels under stress, VR green space exposure failed to temper cortisol responses compared to the control VR space. Further, VR green space exposure did not bring benefits to protect working memory performance under stress across three WM tasks. Applying a Bayesian analysis approach throughout enabled us to find substantial evidence for the absence of an effect of VR-based green space exposure on biological markers of acute stress responses and working memory performance. Our findings suggest that VR-generated green space may not effectively replicate the stress-buffering effects of actual green space exposure. We discussed the implications of our findings regarding the potential and limitations of using VR or green space exposure to buffer stress responses.

neuroscience↗

bioRxiv2024

scRNA+TCR-seq Reveals the Proportion and Characteristics of Dual TCR Treg Cells in Mouse Lymphoid and Non-lymphoid Tissues

The rearrangement of TCR germline V(D)J genes during T cell development, including allelic exclusion and tolerance selection, ensures the clonal selection theory, which states that "a lymphocyte expresses only one type of antigen receptor" This forms the basis for T cell-specific responses. However, The existence of "dual TCR T cells" has consistently been supported by specific experimental evidence. detailed reports on the origin, proportion, tissue distribution, and CDR3 characteristics of "dual TCR Treg cells" are currently lacking. In this study, we utilized scRNA+TCR-seq technology to achieve in-depth analysis of single TCR T and dual TCR T pairings, along with their mRNA expressions, from over 5,000 T cells in each sample. Through comparative studies with shared databases, we provided a detailed analysis of the proportions and characteristics of dual TCR Tregs in mouse lymphoid and non-lymphoid tissues (such as iLN, mLN, blood, and skin). Our findings revealed a high proportion of dual TCR Tregs across various mouse tissues, with their TCR pairing patterns, V(D)J usage, and mRNA expression showing both homogeneity and certain differences compared to single TCR Tregs, as well as heterogeneity across different tissue sites. This research provides new insights and technical approaches for studying the origins, characteristics, effects, and mechanisms of Treg cells in different tissue locations.

immunology↗

bioRxiv2024

Keratin 16 spatially inhibits type I interferon responses in stressed skin

The stress-induced keratin 16 is broadly used as a biomarker in inflammatory skin disorders while pathogenic variants in KRT16 cause pachyonychia congenita (PC), a condition in which differentiation and homeostasis are disrupted in palmoplantar epidermis and epithelial appendages. How K16 impacts these disorders at a molecular level is poorly understood. Here we report that K16 spatially restricts type I interferon (IFN) signaling and innate immunity in palmoplantar keratoderma (PPK) lesions in PC patients, imiquimod- and phorbol ester-induced models of sterile inflammation in mouse skin, and poly(I:C)-treated human keratinocytes ex vivo. Mechanistically, K16 interacts with effectors of the RIG-I-like receptor (RLR) pathway, including 14-3-3{varepsilon}, and inhibits the 14-3-3{varepsilon}:RIG-I interaction upstream of IFN activation. Topical application of the JAK inhibitor Ruxolitinib reduces the severity of PC-PPK-like lesions in Krt16 null mice. These findings uncover a new paradigm for keratin-dependent regulation of innate immunity and suggest a new approach to PC treatment. One sentence summaryKRT16 negatively regulates type I interferon signaling and innate immune responses in the skin, offering insight into the pathophysiology of inflammatory skin diseases including pachyonychia congenita, psoriasis and others.

immunology↗

bioRxiv2024

Reshaping epigenomic landscapes in facilitating the speciation of bread wheat

Polyploidization is a driving force of wheat evolution and speciation, yet its impact on epigenetic regulation and gene expression remains unclear. Here, we constructed a high-resolution epigenetic landscape across leaves, spikes, and roots of hexaploidy wheat and its tetraploid and diploid relatives. Inter-species stable-expression genes exhibited conserved amino acid sequences under strong purifying selection, while dynamic-expression genes were linked to species-specific adaptation. During hexaploidization, dominant D-subgenome homoeolog expression was suppressed via reduced activating epigenetic signals, converging expression with the A and B subgenomes. Proximal chromatin regions near genes were more stable, whereas distal regions, particularly enhancer-like elements mediated by H3K27ac and H3K4me3, exhibit higher dynamism. Sequence variations in these enhancers lead to differential gene regulation, influencing traits such as spike development. For instance, the two haplotypes of dCRE region of TaDEP-B1 resulted in significant differences in its expression and spikelet numbers. We also observed a coevolution of transcription factors and their binding sites, particularly within the expanded ERF family, which regulates spike morphology. This study highlights the interplay between sequence variation and epigenetic modifications in shaping transcriptional regulation during wheat speciation, offering valuable insights for genetic improvement.

plant biology↗

bioRxiv2024

Neurodevelopmental deviations in schizophrenia: Evidences from multimodal connectome-based brain ages

BackgroundPathologic schizophrenia process originate early in brain development, leading to detectable brain alterations via structural and functional magnetic resonance imaging (MRI). Recent MRI studies have sought to characterize disease effects from a brain age perspective, but developmental deviations from the typical brain age trajectory in youths with schizophrenia remain unestablished. AimThis study investigated brain development deviations in early-onset schizophrenia (EOS) patients by applying machine learning algorithms to structural and functional MRI data. MethodsMultimodal MRI data, including T1-weighted MRI (T1w-MRI), diffusion MRI, and resting-state functional MRI (rs-fMRI) data, were collected from 80 antipsychotic-naive first-episode EOS patients and 91 typically developing (TD) controls. The morphometric similarity connectome (MSC), structural connectome (SC), and functional connectome (FC) were separately constructed by using these three modalities. According to these connectivity features, eight brain age estimation models were first trained with the TD group, the best of which was then used to predict brain ages in patients. Individual brain age gaps (BAGs) were assessed as brain ages minus chronological ages. ResultsBoth the SC and MSC features performed well in brain age estimation, whereas the FC features did not. Compared with the TD controls, the EOS patients presented widened structural BAGs, with opposite trends between childhood and adolescence. These increased absolute BAG scores for EOS patients were positively correlated with the severity of their clinical symptoms. ConclusionThese findings from a multimodal brain age perspective suggest that advanced BAGs exist early in youths with schizophrenia.

neuroscience↗

bioRxiv2024

Risk assessment of zoonotic viruses in urban-adapted wildlife

The repeated emergence of pandemic viruses underscores the linkages between land-use change and wildlife disease, and urban-adapted wildlife are of special interest due to their close proximity to humans. However, viral diversity within urban-adapted species and their zoonotic potential remains largely unexplored. We compiled a large dataset on seven priority urban-adapted mammal species and their viruses covering over 115 countries from 1574 to 2023. These urban-adapted species host 286 virus species spanning 24 orders and 38 families, 14 of which are potentially high risk for human infection. Raccoons carried the most high-risk viruses, while raccoon dogs had increased viral positivity in urban habitats compared to raccoons, wild boars, and red foxes. Many viruses in urban-adapted species were phylogenetically related to those found in humans, and we also observed evidence of possible viral spillback. These results highlight zoonotic risks associated with urban-adapted species and suggest enhanced surveillance to mitigate future outbreaks.

ecology↗

bioRxiv2024

Spatial-DC: a robust deep learning-based method for deconvolution of spatial proteomics

Spatial proteomics studies the spatial distribution of proteins within cells or tissues, providing a new perspective for comprehending cellular processes and disease mechanisms. One important challenge of current spatial proteomics technologies is low resolution, resulting in multiple cells in each spatial proteomics spot. While methods have been proposed to infer the composition of potential cell types in such spots for spatial transcriptomics, the depressed correlation and divergent quantification between transcriptome and proteome limits their capability in spatial proteomics. To enhance the utility of spatial proteomics data, we propose Spatial-DC (Spatial Digital Cytometry), a deep learning-based framework that infers cell-type composition in each spot and reconstructs spatially and cell-type resolved proteomic profiles. We achieve this by utilizing transfer learning and self-supervised learning with graph convolutional networks (GCN), which enables the incorporation of target spatial proteomics with reference single-cell or single-cell-type proteomics data. Through extensive simulations of spatial proteomics data, we demonstrate that Spatial-DC outperforms eight state-of-the-art methods in estimating cell-type composition and provides meaningful reconstructions of proteomic profiles for individual cell types. We apply Spatial-DC to different tissues measured using both multiplexed antibody-based and mass spectrometry (MS)-based spatial proteomics technologies. The results showcase Spatial-DCs superior sensitivity in providing more refined cell-type distribution maps compared to cell-type-specific marker-based distributions and its feasibility in reconstructing spatially and cell-type resolved proteomic profiles from real-world spatial proteomics data. Moreover, we validate Spatial-DC with a newly self-collected pancreatic cancer spatial proteomics data characterized by complex tumor microenvironment (TME) and identify the signaling direction and strength at both spatial and cell-type levels within the TME, suggesting cell-type-specific and spatially-resolved interactions linked to tumor outcomes. Our results highlight Spatial-DC as a versatile tool for the deconvolution of spatial proteomics data across various tissue slices, providing a reliable foundation for downstream analysis.

bioinformatics↗

bioRxiv2024

Differential metabolic biomarkers between coronary heart disease and diabetes mellitus

BackgroundCoronary heart disease (CHD), the leading cause of death globally, is a complex disease often association with metabolic disorders, particularly when co-occurring with diabetes mellitus (DM). However, the mechanisms underlying the interaction between these two chronic conditions remain poorly understood. MethodsIn this study, we enrolled 320 participants, including 103 healthy controls (HC), 62 individuals with CHD, 44 with DM, and 47 with both CHD and DM (CHDDM)) in the training set, along with 64 participants (20 HC, 18 CHD, 12 DM, and 14 CHDDM) in the test set. Plasma metabolomic profiling was performed using gas chromatograph-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based multi-platform untargeted metabolomics. ResultsUsing multi-platform metabolomics, we identified 453 distinct metabolites. Through multivariate statistical analysis, we assigned 63, 27, and 56 disease-associated metabolic biomarkers for CHD, DM, and CHDDM, respectively, followed by pathway enrichment analysis. Using an area under the receiver operating characteristic (ROC) curve (AUC) cutoff value > 0.77, we identified 10, 4, and 8 disease-specific biomarkers for CHD, DM, and CHDDM, respectively. Notably, N-Formyl-L-methionine, N-Acetyl-L-methionine, PE 36:1p (18:0p/18:1), PE 36:2p (18:0p/18:2), and PE 34:2p (16:0p/18:2) were predominant in CHD, glycerophosphocholine and turanose were distinctive to DM, and xanthine and PE 38:5p (18:1p/20:4) were unique to CHDDM. These disease-specific metabolites showed superior diagnostic performance in their respective conditions. Additionally, 23 metabolites were identified as potential biomarkers for assessing the risk of CHD in DM patients. ConclusionThis comparative metabolomics approach provided new insights into disease-specific markers and pathogenic pathways, offering potential for improved diagnosis and management of CHD and DM.

molecular biology↗

bioRxiv2024

Metformin inhibits nuclear egress of chromatin fragments in senescence and aging

Chronic inflammation is a hallmark of aging and contributes to many age-associated diseases. Metabolic intervention is a strategy to modulate inflammation. However, the connection between inflammation and metabolism during aging remains poorly understood. A mechanism driving chronic inflammation involves cytoplasmic chromatin fragments (CCFs), which appear in senescent cells and aged tissues, activating the cGAS-STING pathway. The size of the CCFs exceeds the capacity of the nuclear pore complex, raising the question of how chromatin fragments enter the cytoplasm. Here, we report that chromatin fragments exit the nucleus via nuclear egress, a membrane trafficking process at the nuclear envelope that shuttles large complexes from the nucleus to the cytoplasm. Inactivating critical nuclear egress ESCRT-III or Torsin proteins results in accumulation of chromatin fragments at the nuclear membrane, thereby impairing the activation of cGAS-STING and senescence-associated inflammation. Notably, nuclear egress of CCFs is inhibited by glucose limitation or metformin treatment. This is due to AMPK phosphorylation and autophagic degradation of the ESCRT-III component, ALIX. Metformin treatment in naturally aged mice downregulates ALIX protein and blocks cGAS activation and chronic inflammation in the small intestine. Together, our study defines a central mechanism linking nutrient sensing and chronic inflammation, two distinct hallmarks of aging, and suggests a new approach to suppress age-associated inflammation by targeting the nuclear egress of chromatin fragments.

cell biology↗

bioRxiv2024

STAT1 Promotes PD-L1 Activation and Tumor Growth in Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a cystic lung disease that primarily affects women. LAM is caused by the invasion of metastatic smooth muscle-like cells into the lung parenchyma, leading to abnormal cell proliferation, lung remodeling and progressive respiratory failure. LAM cells have TSC gene mutations, which occur sporadically or in people with Tuberous Sclerosis Complex. Although it is known that hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) due to TSC2 gene mutations contributes to aberrant cell growth in LAM lung, tumor origin and invasive mechanism remain unclear. To determine molecular drivers responsible for aberrant LAM cell growth, we performed integrative single-cell transcriptomic analysis and predicted that STAT1 interacts with Pre-B cell leukemia transcription factor (PBX1) to regulate LAM cell survival. Here, we show activation of STAT1 and STAT3 proteins in TSC2- deficient LAM models. Fludarabine, a potent STAT1 inhibitor, induced the death of TSC2- deficient cells, increased caspase-3 cleavage, and phosphorylation of necroptosis marker RIP1. Fludarabine treatment impeded lung colonization of TSC2-deficient cells and uterine tumor progression, associated with reduced percentage of PCNA-positive cells in vivo. Interestingly, IFN-{gamma} treatment increased STAT1 phosphorylation and PD-L1 expression, indicating that STAT1 aids TSC2-deficient tumor cells in evading immune surveillance in LAM. Our findings indicate that STAT1 signaling is critical for LAM cell survival and could be targeted to treat LAM and other mTORC1 hyperactive tumors.

cancer biology↗

bioRxiv2024

Unveiling the diversity, transmission, and zoonotic potential of microbes in true insectivores

The Eulipotyphla (true insectivores) is the third largest mammalian order, comprising over 500 species, and could be an important source of human infectious diseases. However, relatively little is known about the diversity of microbes in insectivores and the contribution of insectivores to virus transmission more specifically among wild hosts. In this study, we compiled a comprehensive dataset containing over 400,000 records of insectivores and their associated microbes from 1903 to 2023. Our analyses showed that insectivores host a wide spectrum of 941 microbes, 60% of which are viruses and are predominantly found in the shrew and hedgehog families. Notably, human-associated viruses harbored by shrews and hedgehogs were phylogenetically closely related to those found in humans, suggesting potential bidirectional transmission between insectivores and humans. Moreover, virus-sharing networks revealed that insectivores held the second-most central position for virus sharing, just second to bats, among all mammalian orders. Insectivores had a high proportion of cross-order transmitted viruses, including many human-associated viruses. Dietary diversity, habitat diversity, and distributional traits (e.g. geographical range size, mean latitude, and urban adaptation status) emerged as the key ecological factors contributing to this cross-species virus transmission. Our findings highlight the microbial diversity present in insectivores, indicating this order may act as potential incubators for novel viruses capable of infecting mammals and spreading viruses of public health concern.

ecology↗