Biology subjects

Liu, X.

Publications and source records attributed to Liu, X..

At least 289 records · Page 16Linked to original sources

bioRxiv2026

DIA-based quantitative proteomics reveal the protective effects of quercetin against atopic dermatitis via attenuating inflammation and modulating immune response

Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. Quercetin is a naturally occurring flavonoid, exhibits antioxidant and anti-inflammatory properties. Previous studies have indicated its beneficial role in managing atopic dermatitis (AD); however, the precise underlying mechanism remains unclear. This study aimed to investigate the protective effects of quercetin against AD and to elucidate its potential mechanisms. We demonstrated that quercetin effectively suppressed the overexpression of pro-inflammatory effector factors--including interleukin (IL)-1{beta}, thymic stromal lymphopoietin (TSLP) and chemokine (C-X-C motif) ligand 1/10/11 (CXCL1/10/11)--in immortalized human keratinocytes (HaCaT) stimulated by TNF-/IFN-{gamma}. Proteomic analysis revealed 88 differentially expressed proteins, suggesting that quercetins therapeutic action involves multiple pathways. Notably, the NOD-like receptor signaling pathway was identified as a key factor. The key proteins related to this pathway including inhibitor of nuclear factor kappa B kinase epsilon (IKBKE), indoleamine 2,3-dioxygenase 1 (IDO1) and chemokine (C-X-C motif) ligand 9 (CXCL9) showed a significant decrease in expression levels after quercetin treatment. Collectively, these results demonstrate that quercetin alleviates AD symptoms by attenuating inflammatory responses, likely through inhibition of the NOD-like receptor signaling pathway.

pharmacology and toxicology↗

bioRxiv2026

Glucokinase links metabolism and lineage plasticity in neuroendocrine prostate cancer via interaction with AKT1

Cancer cells frequently rewire their metabolism to sustain growth and survival under stress. Despite the critical role of metabolic adaptation in tumorigenesis, how specific metabolic enzymes regulate lineage plasticity remains unclear. Here, through FDG-PET imaging and transcriptomic analyses, we reveal markedly elevated glucose uptake in neuroendocrine prostate cancer (NEPC) and identify glucokinase (GCK) as a MYCN-induced metabolic enzyme. Beyond its metabolic role, GCK is indispensable for maintaining the neuroendocrine lineage of prostate cancer cells by establishing a functional circuit with AKT1 through reciprocal regulation--AKT1 binds and phosphorylates GCK at S373, whereas GCK phosphorylates AKT1 at S473. Pharmacological disruption of this AKT1-GCK axis suppresses tumor growth in NEPC mouse models and patient-derived xenografts. Altogether, our findings uncover both the metabolic and noncanonical kinase functions of GCK and establish the AKT1-GCK axis as a key link between metabolic reprogramming and neuroendocrine lineage transition in prostate cancer.

cancer biology↗

bioRxiv2026

A comprehensive analysis of flagellar mutations in Vibrio cholerae: Trade-off mechanisms between motility loss and host adaptability

IntroductionCholera, caused by Vibrio cholerae, is a severe diarrheal disease threatening global health. The flagellum of V. cholerae functions not only for motility but also as an environmental sensor regulating virulence. The trade-off mechanism between motility loss and enhanced host adaptation remains unclear. ObjectiveThis study aimed to elucidate how flagellar mutations, which lead to a loss of motility, affect host adaptability in V. cholerae and to uncover the underlying molecular basis. MethodsWe analyzed 3,135 cholera-related samples to identify mutation hotspots in flagellar genes. A relevant flagellar mutant library was constructed and assessed for host adaptability. Multiple approaches, including molecular, genetic, transcriptomic, and proteomic analyses, were applied to dissect the FlgM-mediated pathway, with key findings revalidated in an adult mouse model using a specifically constructed 6N-labeled mutant pool. ResultsBig data analysis reveals those flagellar mutations in V. cholerae cluster in key structural and regulatory genes, including flhB, fliA, fliF, fliD, and fliM. Flagellar mutations led to a scenario where the secretion level of the regulator FlgM was negatively correlated with host adaptability. Intracellular FlgM inactivates either the {sigma}28 factor FliA directly or acts through the VarS/VarA-CsrA/BCD system, ultimately leading to the derepression of the quorum-sensing master regulator named hapR. HapR can directly bind to the promoters of genes involving in methionine transportation to regulate adaptability of V. cholerae. The 6N-labeled mutants pool experiment reconfirmed that motility loss promotes host adaptability via the FlgM-FliA-HapR-methionine axis. ConclusionOur findings demonstrate that secretion levels of the flagellar regulator FlgM drive an adaptive shift in V. cholerae from motility to host adaptability, mediated through quorum sensing and methionine metabolic reprogramming. This reveals a novel mechanism underlying bacterial evolution and pathogenicity.

microbiology↗

bioRxiv2026

Benchmarking algorithms for RNA velocity inference

RNA velocity is a computational framework for single-cell RNA sequencing (scRNA-seq) that estimates the future transcriptional state of individual cells, thereby capturing the direction and rate of cell state transitions rather than providing a purely static snapshot. Since its introduction in 2018, multiple RNA velocity methods have been developed, differing in their modeling assumptions, required inputs, computational complexity, and robustness. However, there remains limited consensus on how best to evaluate these methods or on which tools are most reliable under specific biological and technical settings. Here, we perform a systematic comparison of 29 velocity inference algorithms across 114 simulated datasets with known ground-truth cell dynamics and 62 real scRNA-seq datasets, and we extend the evaluation to spatial and multi-omics levels where velocity is increasingly applied. We benchmark RNA velocity methods using a unified framework that decomposes performance into four practical dimensions: accuracy, scalability, stability, and usability. Our results show that performance rankings vary substantially across metrics and datasets, indicating no single method is uniformly optimal and that practical deployment is often constrained by feasibility and robustness as much as by accuracy. Based on these results, we provide actionable guidance for selecting RNA velocity tools according to data modality, available priors, and computational constraints. Finally, we identify key bottlenecks that currently limit RNA velocity development and deployment, including scalability to large size of datasets, sensitivity to gene selection, and the lack of genuinely multimodal and spatially explicit velocity models for spot-based technologies.

bioinformatics↗

bioRxiv2026

Rapid sensing and relaying of cellular hyperosmotic-stress signals via RAF-SnRK2 core condensates

Hyperosmolarity caused by drought, high salinity, or cold stress inhibits plant growth and crop productivity1,2. A conserved protein-kinase cascade of cytosolic B-RAFs and SnRK2s is rapidly activated upon osmotic stresses to initiate downstream adaptive responses, which represents one of the fastest known responses to osmotic stress in plants3-8. How the kinase cascade is activated by osmotic stress is unknown. Here, we show that Arabidopsis B4 subgroup RAFs have intrinsically disordered regions and directly sense both ionic and non-ionic hyperosmolarity by reversible condensation. B4-RAFs recruit and co-condense with subclass-I SnRK2s to phosphorylate and turn on SnRK2s, evading the non-condensable inhibitory A-clade PP2C phosphatases. This straightforward osmosensing and relaying module can be fully reconstituted in E. coli by co-expressing three components or in solution in a test tube using recombinant proteins. Our findings identify B-RAFs as the chief cellular osmosensors that detect low water potential by co-condensation, forming a signal hub with SnRK2s to orchestrate adaptive responses in plants, and represent an evolutionarily conserved osmosensing mechanism across kingdoms.

plant biology↗

bioRxiv2026

Fezf2 regulates differentiation of Aire-expressing and post-Aire mimetic epithelial populations maintaining thymic homeostasis

Fezf2 has been proposed to serve principally as a transcriptional regulator of broad self-antigen expression in medullary thymic epithelial cells (mTECs). Here, we demonstrate an additional function for Fezf2 as a developmental regulator of TEC lineage commitment. Fezf2 deficiency in the thymus led to a relative expansion of lung mimetic and Ccl21+ immature mTECs at the expense of MHCII-hi Aire-expressing and all other mimetic populations. Consistent with this, the disruption of mTEC development had functional consequences, including alterations in tuft-associated iNKT polarization and microfold-associated B-cell class switching. In addition, high-resolution transcriptomics revealed that Fezf2 and Aire regulate distinct transcriptional programs, with Fezf2 driving both activation and repression of a more limited set of tissue-restricted genes compared to the broad gene activation program observed for Aire. Pure transcriptional repression at Fezf2 target loci was sufficient to partially rescue mTEC development in global Fezf2-/- (tKO) mice, potentially through suppression of Lifr expression and modulation of downstream Stat3 signaling tone. These results expand our understanding of Fezf2 in mTEC biology, highlighting transcriptional repression as a required functional facet for adult steady-state lineage patterning across the mTEC compartment.

immunology↗

bioRxiv2025

Spent Mushroom Substrate Adsorbs Fusaric Acid to Protect the Cucumber Rhizosphere Microbiome and Alleviates Fusarium Wilt

Caused by Fusarium oxysporum f. sp. cucumerinum, cucumber Fusarium wilt threatens cucumber production worldwide. In addition to pesticides, using spent mushroom substrate (SMS) has a protective effect against Fusarium infection in cucumber, partly through effects on the microbiome. Fusaric acid (FA), a phytotoxic virulence factor secreted by Fusarium, disrupts both plant physiology and the rhizosphere microbial community. Herein, we investigated the relationship between SMS and this virulence factor. Bioassays demonstrated that SMS adsorbed FA both in culture supernatants and in soil. Adsorption behaviour conformed to the Langmuir-Freundlich isotherm model, with a maximum adsorption capacity of 52.72 g/g. Kinetics followed a pseudo-second-order model, indicating physical and chemical adsorption. Scanning electron microscopy showed that SMS had a porous surface, facilitating FA capture. Fourier transform infrared spectroscopy and chemical blocking assays were used to identify secondary amide groups as the key binding sites. In a dual-compartment pot system designed to isolate adsorption from other direct effects, SMS treatment significantly reduced the FA concentration in the cucumber rhizosphere and mitigated FA-induced disease aggravation. This lowered the disease index by up to 25%. Bacterial 16S metabarcoding showed that FA disrupted the rhizosphere bacterial diversity and community structure. However, when FA was adsorbed by SMS, the microbial diversity and community stability were restored. FA reduced the abundance of sensitive taxa such as Bacillus. Meanwhile, SMS-adsorbed FA preserved its relative abundance, suggesting a selective protective effect for FA-sensitive rhizobacteria. These findings indicate that SMS protects cucumber against Fusarium by alleviating FA toxicity toward beneficial microbes. Through FA adsorption, SMS amendment stabilised the rhizosphere microbial community and reduced disease incidence. This highlights the potential of SMS as a sustainable and microbiome-friendly strategy for managing soil-borne diseases.

microbiology↗

bioRxiv2025

Distinct flagellins differentially fine tune biofilm initiation via flagellar stator-associated proteins

Helicobacter pylori relies on flagellar motility to colonize the gastric niche. While H. pylori flagella serve multiple functions, including swimming motility, it has recently been appreciated that flagellar basal body properties also contribute to biofilm initiation. The H. pylori flagellar filament contains two spatially segregated flagellins, FlaA and FlaB, but their roles in the biofilm initiation process remained undefined. Here, we confirmed that both FlaA and FlaB are required for optimal motility, but found that they exert opposite effects on biofilm initiation: cells without FlaA display low biofilm initiation, while cells without FlaB display elevated initiation. To understand the molecular basis for this divergence, cryo-electron microscopy (cryo-EM) analysis of native flagellar filaments revealed that FlaA and FlaB have distinct supercoiled waveforms. We confirmed these intrinsic waveform curvatures by analyzing filaments from {Delta}flaA and {Delta}flaB mutants, providing a physical basis for their functional specialization. Genetic epistasis experiments further demonstrated that the enhanced early biofilm formation of the {Delta}flaB mutant depends on PilO, a stator-associated component of the flagellar motor recently shown to drive a reciprocal biofilm and motility response. Our findings establish that H. pylori has developed functionally specialized flagellins that work with motor-dependent signaling to dynamically balance surface colonization and motility.

microbiology↗

bioRxiv2025

A novel dephosphorylation peptide inhibits 17β-HSD1 enzyme activity in ovarian granulosa cells and breast cancer cells

Estradiol (E2), a pivotal mammalian reproductive hormone, is closely associated with estrogen-dependent diseases. 17{beta}-hydroxysteroid dehydrogenase type 1 (17{beta}-HSD1), a critical E2 synthesis enzyme, has been understudied for its post-translational regulation-despite its potential as a therapeutic target, no clinically approved inhibitors are currently available. In our investigation of porcine follicular atresia mechanisms, we identified five differentially phosphorylated residues in 17{beta}-HSD1. Using in vitro site-directed mutagenesis and transgenic mouse models carrying point mutations, we established that Ser30 and Ser274 are critical phosphorylation sites that robustly modulate 17{beta}-HSD1 enzymatic activity. We further demonstrated that activin A and insulin-like growth factor 1 (IGF-1) enhance 17{beta}-HSD1 activity by promoting its phosphorylation at these two sites. To target these regulatory residues, we designed and synthesized cell-penetrating peptides (CPPs) that specifically suppress 17{beta}-HSD1 phosphorylation. Functional assays conclusively demonstrated that these CPPs significantly suppressed 17{beta}-HSD1 activity in vitro. Notably, they also inhibited the proliferation, migration and invasion of MCF-7 cells, as well as tumor growth in a mouse model of breast cancer. Our study provides novel mechanistic insights into the regulation of 17{beta}-HSD1 and E2 synthesis, addressing a critical gap in steroid hormone biology. The identification of Ser30/Ser274 as functional phosphorylation sites and the development of CPP-based inhibitors offer both theoretical advances and translational potential, opening new avenues for the treatment of estrogen-dependent breast cancer.

cell biology↗

bioRxiv2025

Flu Virus Infection in Juvenile Mice Leads to Lifelong Multi-Organ Damage and Parkinsonian Pathological Changes in Aging

The widespread prevalence of Long COVID underscores the potential for viral infections to exert prolonged effects on hosts long after initial recovery. Despite this recognition, the long-term and even lifelong consequences of viral infections remain poorly understood. In this study, we infected juvenile mice with influenza viruses and systematically examined the lifelong effects (from 4 to 450 days post-infection) of these infections. Pathological analysis revealed persistent lifelong damage in multiple organs, including chronic lung inflammation and fibrosis, along with significant cardiac and renal pathology. Viral infection led to substantial neuronal loss in key brain regions of mice (hippocampal CA1, CA3, and striatum) during middle and old age. Strikingly, we identified two hallmark pathological features of Parkinsons disease - dopaminergic neuron degeneration and Lewy body-like -synuclein inclusions - in middle and aged infected mice. Transcriptomic profiling demonstrated sustained upregulation of inflammation-related genes in both lung and blood tissues, correlating with observed pathological changes. Lung-derived secreted proteins, encoded by differentially expressed genes, may mediate cross-organ communication affecting cardiac, renal, and neurological function. Brain transcriptome analysis at three months post-infection revealed downregulation of neurodevelopmental genes, potentially contributing to subsequent neuronal loss and Parkinsonian pathology. These findings collectively suggest that pulmonary influenza infection can induce systemic multi-organ effects through both secretory pathways and chronic inflammatory responses. The study offers crucial insights for developing more effective strategies to prevent and manage infectious diseases and their long-term sequelae.

microbiology↗

bioRxiv2025

Sampling Function-Related Metastable States of Proteins With DASH

Rational discovery of function-specific protein modulators as well as activity-enhanced engineering proteins underscore the need to identify function-related metastable states (FMSs) of proteins. However, current experimental and computational methods struggle to generate these states directly from their native state (NS), likely because the NS [->] FMS transition is non-spontaneous. To address this challenge, we introduce Deep learning guided Adaptive sampling with seed Selection and Hopping (DASH), integrating both deep learning and physical functions to guide molecular dynamics (MD) simulation towards FMS. DASH successfully sampled NS [->] FMS transitions in 18 cases across two tasks: protein activation and cryptic allosteric site opening. DASH combined with secondary-structure collective variables is further able to sample folding of disordered regions. Compared to existing methods, DASH demonstrates superior performance while requiring comparable simulation time. Crucially, we applied DASH to sample new conformations of proteins, by which revealing new folding states, previously unknown allosteric sites, and potential activators. These predictions have been further verified in wet-lab experiments and crystal structures determinations. Collectively, our framework provides a robust strategy for function-specific pharmacy research and could accelerate future drug discovery efforts.

bioinformatics↗

bioRxiv2025

Vitreous Inflammation as an Early Indicator of Retinal Ganglion Cell Loss Following Acute Optic Nerve Injury in Mice

Retinal ganglion cell (RGC) degeneration in optic neuropathies is often preceded by neuroinflammatory changes, yet the earliest in vivo indicators of this process remain poorly defined. Here, we identified vitreous hyperreflective foci (VHRFs) by visible-light optical coherence tomography (vis-OCT) as an early inflammatory signature of RGC injury. Longitudinal vis-OCT imaging after optic nerve crush (ONC) revealed that VHRFs emerged as early as 6 hours post-injury and peaked before the significant RGC loss. Confocal analysis showed that these VHRFs corresponded to activated amoeboid microglia undergoing vertical migration from the outer to inner retina and horizontal movement toward the optic nerve head area. Similar amoeboid microglia were also observed in the anterior segment, suggesting a global ocular inflammatory response to the ONC injury. RNAscope in situ hybridization further demonstrated elevated IL-1{beta} expression in vitreous amoeboid microglia. Moreover, pharmacological blockade of IL-1 signaling with an IL-1 receptor antagonist significantly reduced VHRFs, suppressed microglial migration, and delayed RGC loss. Taken together, our findings identify VHRFs as a previously unrecognized early danger signal for RGC degeneration and highlight IL-1-mediated inflammation as a tractable early therapeutic target for preventing RGC degeneration and vision loss. Graphical Overview O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/694725v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1598c4aorg.highwire.dtl.DTLVardef@9637borg.highwire.dtl.DTLVardef@623bf4org.highwire.dtl.DTLVardef@14e21ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer's disease

Synapse degeneration is a hallmark of neurodegenerative diseases1-3, including Parkinsons and Alzheimers disease (AD). Synapse loss has been known for decades as the strongest correlate with cognition and disease progression in AD patients4-8, but the molecular mechanisms that drive synapse degeneration remain elusive. Here, we identify Sarm1, a new class of NAD+ hydrolase required for Wallerian degeneration of periphery nerves after injuries9-12, as the key mediator of synaptic degeneration in AD brains. Sarm1 knockout largely reversed synapse loss, amyloid-{beta} (A{beta}) burden, and cognitive decline in 5XFAD mice. We found that Sarm1 is enriched in synaptic terminals and becomes activated in synaptic dystrophies adjacent to A{beta} plaques, leading to synapse degeneration and subsequent neuroinflammation. Sarm1 deletion in the AD mice prevented synaptic dystrophies and rescued short-term and long-term synaptic plasticity. Further, Sarm1 deletion protected synapses from C1q tagging and phagocytosis, and C1q-MERTK signaling in complement cascades 7,13-15 was significantly reduced. The reduced synapse degeneration, in turn, broke the feed-forward loop of "glia activation-neuroinflammation-A{beta} deposition". These data suggest that Sarm1 plays a key role in driving synapse degeneration in AD before C1q-tagging and phagocytic clearance, and targeting Sarm1 may offer a novel intervention to attenuate synapse degeneration and memory loss in AD. HighlightO_LISarm1 is enriched at presynaptic dystrophies and correlated with A{beta}. C_LIO_LIGenetic deletion of Sarm1 prevents synapse degeneration in AD. C_LIO_LISarm1 depletion is sufficient to reverse synaptic dysfunction and memory loss. C_LIO_LISarm1 depletion reduces A{beta} burden and neuroinflammation C_LIO_LIC1q--MERTK axis acts downstream of synaptic Sarm1 activation. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/695860v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@bd6b12org.highwire.dtl.DTLVardef@1c089e5org.highwire.dtl.DTLVardef@19d35fborg.highwire.dtl.DTLVardef@431364_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

mMap: a comprehensive and continuously updated species distribution database facilitating the understanding of mosquito diversity and distribution patterns

Mosquitoes, as vectors of deadly diseases like malaria and dengue, exhibit complex and dynamic global distribution patterns influenced by climate change and human activity. However, gaps in species-level data and biases in existing databases hinder accurate risk assessments. Here, we present mMap (v1.01), a comprehensive and curated mosquito distribution database integrating multi-source records from literature (36,242 entries across 1,809 studies), museum collections, and field reports in 6 languages. Systematic data harmonization and validation workflows address taxonomic and spatial uncertainties, enabling family-level analyses previously constrained by fragmented data. Our results reveal significant range expansions for 28 invasive species (e.g., Aedes albopictus in Europe) and corrections to historical distributions (e.g., Ae. vexans in 22 new countries). The interactive mMap platform (accessible at https://mos-map.vercel.app/) provides open-access tools for visualizing spatial-temporal trends, automated SDM forecasting, and expert-curated species profiles. By unifying dispersed data into a scalable framework, mMap advances research on mosquito biodiversity, invasion ecology, and disease risk mapping, offering a critical resource for global health strategies in an era of rapid environmental change.

ecology↗

bioRxiv2025

Reciprocal Homoeologous Replacement of MYB Factors Drives the Evolutionary Trade-off between Yield and Fiber Quality in Cotton

The long-standing phenotypic trade-off between Upland cotton (Gossypium hirsutum, high yield) and Sea Island cotton (G. barbadense, high quality) represents a major bottleneck in cotton breeding and industrialization. Despite rapid advances in genomics, the genomic structural variations driving the divergence of these two domestication strategies, and their subsequent impact on downstream transcriptional networks, remain unclear. This study integrates multi-tissue transcriptomic atlases spanning the full growth period with pan-genomic analyses of both Upland and Sea Island cotton, proposing a "Reciprocal Selective Retention (RSR)" strategy adopted by the two species during evolution. Transcriptomic analysis revealed that while the transcriptional chassis of the two species is highly conserved, a drastic "phase inversion" occurs during fiber development. Sea Island cotton appears to trade off for quality by specifically activating a "delayed elongation" module (at 20 DPA), whereas Upland cotton initiates a "precocious filling" program to pursue yield. Further Weighted Gene Co-expression Network Analysis (WGCNA), combined with genomic Presence/Absence Variation (PAV) analysis, identified a set of key transcription factors exhibiting a "3-vs-3" reciprocal loss pattern. Upland cotton specifically retained CRF10, WIND1, and MYB93, constructing a genetic foundation of "robust root system and strong regeneration" to support high yield. Conversely, Sea Island cotton specifically retained MYB111 and ERF105/017 to maintain long-staple characteristics and environmental buffering. Whole-genome structural variation and microsynteny analyses confirmed that these differences stem from asymmetric physical deletions (e.g., a 5 kb deletion in MYB111) or fragment sequence collapse (e.g., a 15.9 kb sequence divergence in MYB93) on homologous chromosomes. The RSR model proposed in this study not only offers a novel insight into the genetic roots of the negative correlation between yield and quality but also provides clear genomic targets for precision improvement using gene-editing technologies such as CRISPR.

genomics↗

bioRxiv2025

Robust division orientation of cambium stem cells requires cortical division zone components but not the preprophase band

The control of cell division plane orientation is fundamental for organizing developmental processes and shaping bodies of multicellular organisms. In plants, radial organ growth is mediated by the cambium, a stem cell niche deeply embedded in expanding organs and continuously producing xylem and phloem in a strictly bidirectional manner. Cambium stem cells (CSCs) are unique in comparison to other plant stem cells as they consistently divide along their longest axis clearly overriding the commonly found short axis rule. Despite the topological consistency of CSC divisions and the functional importance of proper division plane orientation for CSC derivatives, the regulatory mechanisms behind this consistency remain unknown. Here, we characterized microtubule organization during CSC divisions in Arabidopsis thaliana and found that division plane orientation is established independently from spindle orientation and the preprophase band (PPB). This conclusion is based on the remarkable variability of spindle orientation during metaphase and the robustness of CSC divisions in PPB-deficient mutants. Instead, the orientation of division planes depends on the cortical division zone (CDZ) and CDZ-related PHRAGMOPLAST ORIENTING KINESIN (POK) proteins. Our results highlight the importance of wood-forming CSCs and their subcellular characterization as an instructive example for the determination of cell division orientation in plants.

plant biology↗

bioRxiv2025

Multicolored, Sonosensitizer-optimized Organic Mechanoluminescent Nanoparticles for Functional Sono-optogenetics

Light enables precise visualization and control of cellular processes, but its utility in deep tissues is fundamentally limited by poor optical penetration, particularly in the deep brain. Ultrasound-triggered mechanoluminescence offers a non-invasive strategy for remote light delivery, yet existing organic systems remain monochromatic and low-intensity, largely due to an incomplete understanding of ultrasound-induced emission. Here, we report a multicolor mechanoluminescence platform that couples reactive oxygen species-responsive chemiluminescent donors with fluorescent acceptors via Forster resonance energy transfer, generating tunable emission from blue (459 nm) to red (592 nm). Systematic screening potentially reveals that electronic energy gap-dependent reactive oxygen species generation serves as a predictive design principle for high-performance mechanoluminescent materials. The emitted spectrum and intensity are sufficient to activate ChR2 and ChRmine and inhibit eOPN3, enabling bidirectional, fiber-free neuromodulation under focused ultrasound. By integrating spatially precise ultrasound with programmable photon output, this platform establishes a non-invasive strategy for deep-tissue neural monitoring and provides a foundation for applications in bioimaging, gene editing, and precision therapeutics.

bioengineering↗

bioRxiv2025

Nuclear N-Glycosylation Redefines the Glycoscape and Directs Cell Identity

Glycans modify nucleic acids, proteins and lipids in fundamental biological processes, but have long been considered confined to the secretory pathway and cell surface. Here, we challenge this view with evidence that N-glycosylation, a ubiquitous glycan modification, occurs within cell nuclei across tissues and species, exhibiting cell type-dependent abundance and localization patterns. Using a multi-faceted approach, we show that numerous classical membrane and secreted glycoproteins localize to the nucleus with N-glycan modifications, exemplified by the cell adhesion molecule L1CAM. Mechanistically, we show that the N-glycosylated L1CAM is transported to the nucleus by KPNB1, where it transcriptionally modulates neuronal differentiation. Moreover, this nuclear N-glycosylation event contributes to neurodevelopmental disorders and is pharmacologically reversible. These findings revise the cellular geography of N-glycosylation and expand the known routes of protein trafficking, and highlight nuclear N-glycosylation pathways as potential therapeutic entry points for developmental disorders.

cell biology↗