Biology subjects

Zou, Y.

Publications and source records attributed to Zou, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Development of KASP Molecular Markers and Construction of Fingerprinting for Cowpea (Vigna unguiculata (L.) Walp) unguiculata Based on ddRAD-Seq

Cowpea (Vigna unguiculata (L.) Walp.) is a globally important legume crop. However, the scarcity of efficient molecular markers has hindered molecular breeding efforts and the protection of plant breeders rights. In this study, we employed double-digest restriction-site associated DNA sequencing (ddRAD-seq) to characterize the genetic diversity of 19 core cowpea germplasm accessions. We generated 791,621 SNPs, from which 13,469 high-quality SNPs were filtered. Population structure and phylogenetic analyses revealed that these accessions cluster into three distinct groups. To facilitate cost-effective and rapid genotyping, we developed a panel of KASP (Kompetitive Allele Specific PCR) markers. Through rigorous screening for polymorphism and stability, we identified six core KASP markers located in exonic regions. These six markers alone were sufficient to discriminate all 19 accessions. Based on these core markers, we constructed a unique DNA fingerprinting profile and assigned specific QR codes for each accession. This study demonstrates that extracting core KASP markers from ddRAD-seq data is a powerful strategy for germplasm identification. The developed fingerprinting system provides a robust, low-cost tool for seed purity testing, variety authentication, and marker-assisted selection in cowpea breeding programs.

plant biology↗

bioRxiv2026

Multi-omics integration of malignant peripheral nerve sheath tumors identifies potential targets based on chromosome 8q status

BackgroundChromosome 8q (chr8q) copy number gain is associated with high-grade transformation in malignant peripheral nerve sheath tumors (MPNST), an aggressive soft tissue tumor with poor outcomes in the high-risk and metastatic settings. Although chr8q gain is associated with inferior overall survival in patients with MPNST, standard of care therapies do not currently consider stratification by genomic features, including chr8q status. MethodsWe employed a proteogenomic approach to characterize proteomic and transcriptional programs associated with chr8q and nominate drug targets for potential treatment stratification based on chr8q status. We leveraged our growing library of fully characterized MPNST patient-derived xenografts (PDX) and collected LC-MS/MS global and phospho-proteomics measurements for six of these samples. We then integrated these data with transcriptomics and copy number data to identify molecular changes that are correlated with chr8q copy number. We nominated pathways, transcription factors, and kinases that were differentially active in chr8q gain samples and posited that these samples would respond differently to drugs compared to chr8q wildtype samples. We then tested this hypothesis in vitro. ResultsOur results suggest that the chr8q gene MYC may be a key driver of downstream effects that can be targetable with inhibitors of PLK1. Conversely, EGFR inhibition may be more effective in MYC-diploid MPNSTs than those with MYC gain. These results nominate candidate pathways and drug classes to target tumor heterogeneity in MPNST through the proteogenomic integration and drug sensitivity prediction in distinct tumor subpopulations. ConclusionsWe show that integration of multiomics data can identify specific drug therapies to selectively target tumor cells based on chr8q copy number. This not only provides novel avenues for drug nomination going forward but also may be important for stratifying treatment and mitigating resistance in heterogeneous tumors.

cancer biology↗

bioRxiv2026

Adrenergic signaling induces a pro-tumorigenic B cell state in colorectal cancer

The importance of neuron-tumor crosstalk has gained increasing attention, yet its influence on the cellular and molecular landscape of colorectal cancer (CRC) remains largely unexplored. Here, we show that colonic innervation shapes the tumor immune microenvironment in a murine model of colitis-associated CRC. Although neuronal density does not affect tumor number, size, or overall burden, transcriptomic profiling of cells isolated from the tumor of hypo-innervated mice revealed extensive differential gene expression, including genes involved in immunoglobulin (Ig) signaling and the cancer-relevant hallmark avoiding immune destruction. Flow cytometry analysis of leukocyte populations demonstrated a significant reduction of B cells in the cancerous colon of hypo-innervated mice, notably a decrease in germinal center B cells and an altered class-switching profile, characterized by reduced IgA and increased IgD expression. Fluorescence and transmission electron microscopy showed that colonic B cells are primarily localized in the submucosa near neuronal processes containing varicose release sites, suggesting direct neuron-B cell interactions. Functional assays revealed that adrenergic stimulation of B cells promotes their proliferation and maturation, enhances IL-10 secretion, and alters immunoglobulin profiles. Strikingly, the transcriptome of epinephrine-treated B cells closely mirrors that of plasma cells from human CRC tissues, and the transcriptomic signature of these epinephrine-stimulated B cells associates with poorer patient survival. Together, these findings uncover an adrenergic neuron - B cell axis in CRC, providing evidence for direct neuroimmune interactions that affect B cell maturation and may influence tumor progression and therapeutic responses.

cancer biology↗

bioRxiv2026

Lab-on-a-3D-Printer for Democratized Reconfigurable Digital Microfluidics

Automation in the life sciences remains dominated by expensive, centralized robotic systems, leaving most laboratories unable to access precision robotic liquid handling. Here we present the Lab-on-a-3D-Printer (Lo3DP), a reconfigurable robotic microfluidic platform that repurposes the motion control, thermal regulation, and open-source programmability of consumer 3D printers to deliver laboratory-grade automation at a hardware cost below $500. By replacing the extruder with a multifunctional magnetic toolhead, Lo3DP actuates ferrofluid droplets with sub-100 {micro}m positioning accuracy and programmable volume control spanning 0.5-25 {micro}L, enabling the full repertoire of digital microfluidic operations within inexpensive laser-cut chips (<$3). We quantitatively validate system performance through long-term droplet transport exceeding 40,000 s without degradation, automated serial dilutions with high linearity (R{superscript 2} [≥] 0.99), and fully automated colorimetric nucleic acid amplification assays whose results match conventional benchtop workflows under tightly regulated isothermal conditions (CV {approx} 0.3%). By harnessing the global economies of scale of consumer 3D printers, Lo3DP provides accurate, reproducible, and programmable assay automation at a fraction of the cost and footprint of conventional systems, establishing a practical path toward desktop-scale, democratized laboratory robotics.

bioengineering↗

bioRxiv2025

Characterizing JP-5 Biodegradation Potential in Hawaii Soil Microbiome: Phylogeny, Growth Kinetics, and Biosurfactant Production

Soil and groundwater contamination from petroleum spills continues to present major environmental and human health challenges. A recent fuel contamination event in the Pearl Harbor region of the Island of Oahu, Hawaii, highlights the need for a better understanding of the biodegradation capabilities of the indigenous soil microbiome and potential for bioremediation. Soil sampling and subsequent cultivation-based enumeration showed that the abundance and relative abundance of JP-5 degrading bacterial biomass to be 1.9 x 104 MPN/g ({sigma}=3.4 x 104 MPN/g) and 2.4 % ({sigma}= 4.4 %), respectively. Isolation and 16S rRNA gene sequencing showed diverse phylogenetic groups of JP-5 degrading bacteria, including Achromobacter, Ralstonia, Stenotrophomonas, Pseudomonas, Acinetobacter, Staphylococcus, Bacillus, and Gordonia. Logistic modeling of batch growth experiments revealed significant variation in growth kinetic parameters amongst the soil bacterial isolates. Biosurfactant production by the JP-5-degrading bacterial isolates showed significant correlation with maximum optical density (r = 0.69, p < 0.001), relative growth rate (r = 0.41, p = 0.008), and relative lag phase duration (r = -0.36, p = 0.02), indicating an important role of biosurfactant production in enhancing hydrocarbon bioavailability. The results revealed the ubiquitous presence and phylogenetic diversity of JP-5 degrading microbial capabilities in the Hawaii soil microbiome and their potentials for bioremediation applications.

microbiology↗

bioRxiv2025

Identification and Characterization of a Small Molecule Ligand for the Huntingtin-HAP40 Complex

Huntingtons disease (HD) is caused by a CAG repeat expansion mutation, giving rise to a polyglutamine expansion in the huntingtin (HTT). However, the explicit molecular functions of HTT and opportunities for direct pharmacological modulation remain incompletely understood. Here, we report the discovery of a small molecule ligand for the full-length HTT protein in complex with its partner, HAP40. Using affinity selection mass spectrometry (AS-MS), we identified a stereoselective binder, whose binding was characterized by surface plasmon resonance, hydrogen-deuterium exchange mass spectrometry, and cryo-electron microscopy at 2.3 [A] resolution. The ligand binds HTT-HAP40 in vitro with single-digit micromolar affinity and one-to-one stoichiometry at a druggable interface previously predicted computationally. In silico studies predicted and experimental analyses confirmed the (R)-enantiomer as the eutomer and initial structure activity relationship was established experimentally. This work details a structurally-validated chemical scaffold and highlights a ligandable pocket which could enable development of chemical probes for probing HTT biology, as well as therapeutics such as degraders and imaging agents for HD.

pharmacology and toxicology↗

bioRxiv2025

MindSight: A Bio-Inspired Neural Architecture for Visual Restoration via Cortical Electrical Stimulation

Visual impairment is a common condition worldwide, and cortical electrical stimulation is one of the approaches to aid in visual restoration. However, existing methods suffer from limited precision, flexibility, and generalization in generating the desired visual perception. In this paper, we propose a novel deep learning-based algorithm for cortical electrical stimulation, named "MindSight," aimed at enhancing the clarity and accuracy of induced visual perceptions. Our framework introduces three key innovations: (1) A differentiable biophysical model simulating cortical state transitions under electrical stimulation, enabling end-to-end training; (2) A dual-path training architecture combining neural decoding fidelity with phosphene simulation constraints; (3) An attention-guided background gated network for input filtration and, a multi-channel activation constraint to ensure the effectiveness of electrical stimulation. We validated our approach through novel experiments with macaque monkeys, demonstrating superior performance in visual perception tasks. These results highlight the potential of our approach in assisting individuals with visual impairments. Codehttps://github.com/zyj9902/MindSight

bioengineering↗

bioRxiv2025

3D Hydrodynamic Flow Lithography

Continuous- and stop-flow lithography has been widely used for the fabrication of ingenious multi-dimensional microstructures, including fibers and microparticles. The flow profile of multiple co-flowing streams during the process, as one of the dimensions, dictates the cross-sectional morphology of the microstructures. Here, we introduce a three-dimensional hydrodynamic flow lithography (3D HFL) approach that enables rapid and programmable generation of desired flow profiles and their conversion into solid microstructures. By strategically combining multiple flow sculpting strategies, including variable inlet configurations, intra-channel pillar configurations, and outlet configurations, we achieved precise and versatile control over flow sculpting, as validated by computational fluid dynamics simulations and experimental production of microparticles and fibers, offering unparalleled design flexibility. Importantly, the flow sculpting device is fabricated using low-cost 3D-printed molds to cast PDMS channels with precisely aligned inlets and complex geometries that are difficult or impossible to achieve using conventional soft lithography. Our 3D HFL approach effectively overcomes the limitations of existing microfabrication techniques in device complexity, structural diversity, multi-material integration, and production throughput. Furthermore, we demonstrated the capability of this platform to produce anisotropic multi-material microparticles and fibers tailored for specific applications, such as amphiphilic particles for uniform microdroplet capture, biocompatible patterned hydrogels for controlled cell adhesion, and dual-layer fibers for temperature sensing. The simplicity of device fabrication, combined with the broad design flexibility, establishes this platform as a scalable, high-throughput, and versatile solution for engineering anisotropic microparticles and fibers with tailored functionalities, providing powerful tools for a wide range of downstream fields.

bioengineering↗

bioRxiv2025

Integrating host plants and a natural enemy into MaxEnt improves global suitability predictions for Semanotus bifasciatus

BACKGROUNDSemanotus bifasciatus is a major conifer pest that causes severe wood damage. The parasitoid Sclerodermus guani is its important natural enemy. However few studies have jointly considered host plants and enemy effects when predicting pest ranges. We applied the optimized MaxEnt model and, on this basis, constructed two models: the "host-pest" model and the "host-pest-enemy" model, to predict the potential global distribution of S. bifasciatus under future scenarios and to explore the effects of climate change and the introduction of biotic interactions. RESULTSResults showed that the climate-only model projected 2.73 x 10{square} km{superscript 2} of suitable area under the historical climate condition, concentrated in Asia, North America and Europe, with expansion toward higher latitudes. The expansion of host plants further enhanced pest habitat suitability, nearly doubling the predicted range (5.46 x 10{square} km{superscript 2}) and increasing the mean suitability. Moreover, the potential distribution of S. guani overlapped extensively with S. bifasciatus, reducing the total suitable area of S. bifasciatus by up to 2.67 x 10{square} km{superscript 2}, and mean suitability declined by nearly 40%, indicating effective suppression of pest risk. Centroid shifts were consistently northward, though magnitude and fragmentation varied among models. CONCLUSIONIntegrating host availability and enemy suppression improves the realism of distribution forecasts for S. bifasciatus. The study highlights the roles of biotic factors in shaping pest suitability and identifies potential future high-risk regions of infestation. These insights provide a solid scientific foundation for targeted monitoring, and the strategic application of biological control in adaptive forest pest management.

ecology↗

bioRxiv2025

IRG1/itaconate/NRF2/GSH axis in tumor-associated macrophages drives therapy resistance and immune evasion in BRCA1-deficient breast cancer

Tumor-associated macrophages (TAMs) are major contributors to immunosuppression and therapeutic resistance, including resistance to PARP inhibitors (PARPi) in BRCA1-deficient breast cancer. However, the mechanisms underlying TAM-mediated PARPi resistance remain unclear. Here, we demonstrate that TAM-derived glutathione (GSH) impairs the efficacy of PARPi by protecting tumor cells from DNA damage and ferroptosis while suppressing STING-mediated immune activation. Mechanistically, STAT5-driven upregulation of the IRG1/itaconate axis in TAMs rewires mitochondrial metabolism and activates NRF2-dependent GSH biosynthesis. GSH is subsequently released into the tumor microenvironment, where it is taken up by tumor cells, protecting them from PARPi-induced cytotoxicity and dampening immune responses. Pharmacological inhibition of IRG1 reverses these effects, restoring PARPi sensitivity and enhancing anti-tumor immunity in BRCA1-deficient tumor models. Collectively, these findings uncover a TAM-specific immunometabolic program that limits PARPi efficacy and highlight the IRG1/NRF2/GSH axis as a promising therapeutic target to improve treatment outcomes in BRCA1-associated breast cancer.

cancer biology↗

bioRxiv2025

ADAMTS3 as a promising novel biomarker for the diagnosis of hepatocellular carcinoma

Early diagnosis of hepatocellular carcinoma (HCC) still represents a significant challenge. The rising of obesity and non-viral liver disease associated HCC further limits the effectiveness of conventional screening approaches such as ultrasonography and alpha-fetoprotein (AFP) testing. In this context, the identification of potential effective biomarkers for rapid and precise diagnosis of HCC still represents an extremely important task. Here, we identify ADAMTS3 as a novel mechanistic serum biomarker for HCC that addresses this shifting etiological landscape. Transcriptome analysis of four independent cohorts-including HCC patients, individuals with obesity-or non-viral liver disease, and healthy controls- reveals four secreted proteins associated with HCC progression. Among them, ADAMTS3 demonstrates strong diagnostic performance by ROC (receiver operating characteristic) and LASSO (least absolute shrinkage and selection operator) analysis. High ADAMTS3 expression correlates with aggressive molecular signature, characterized by enhanced proliferative signaling, suppressed immune effector responses, and a reprogrammed immune microenvironment marked by reduced NK cell infiltration and increased accumulation of immunosuppressive tumor-associated macrophages, driven by extracellular matrix stiffening. Knockdown of ADAMTS3 in cell lines significantly reduced proliferation, and clonogenic potential. Reintroduction of ADAMTS3 partially rescued both phenotypes, further confirming its role in promoting HCC cell growth. Optical tweezer-based measurements further reveal reduced cell stiffness upon ADAMTS3 deficiency, highlighting its role in extracellular matrix (ECM) remodeling. Finally, to provide a simple strategy for HCC diagnosis based on this novel biomarker, we demonstrated a DNA origami-based SERS biosensor capable of detecting ADAMTS3 at 10-11 M. Together, these findings identify ADAMTS3 as a mechanistic biomarker and demonstrate a translational sensing strategy for non-invasive HCC early screening.

cancer biology↗

bioRxiv2025

A prevalent huge phage clade in human and animal gut microbiomes

Huge phages are widespread in the biosphere, yet their prevalence and ecology in the human gut remain poorly characterized. Here, we report Jug (Jumbo gut) phages with genomes of 360-402 kilobase pairs that comprise [~]1.1% of the reads in human gut metagenomes, and are predicted to infect Bacteroides and/or Phocaeicola. Although three of the four major groups of Jug phages shared >90% genome-wide sequence identity, their large terminase subunits exhibited only 38- 57% identity, suggesting horizontal acquisition from other phages. Over 1,500 genomes of Jug phages were recovered from human and animal gut metagenomes, revealing their broad distribution, with largely shared gene content suggestive of frequent cross-animal-host transmission. Jug phages displayed high gene transcription activities, including the gene for a calcium-translocating P-type ATPase not detected previously in phages. These findings broaden our understanding of huge phages and highlight Jug phages as potential major players in gut microbiome ecology.

microbiology↗

bioRxiv2025

in vivo Reprogramming of NG2 Glia Improves Bladder Function After Spinal Cord Injury

Neurogenic bladder is a debilitating consequence of spinal cord injury (SCI), with few treatment options that restore voluntary voiding. Here, we show that SOX2-mediated in vivo reprogramming of NG2 glia improves bladder function in a clinically relevant mouse model of contusive SCI. NG2 glia reprogramming induces adult neurogenesis, reduces glial scarring, and significantly improves urinary performance, as measured by voiding assays and conscious cystometry. Functional recovery correlates positively with neurogenesis and negatively with glial scarring. These findings demonstrate that SOX2-mediated glial reprogramming promotes autonomic repair and offers a regenerative strategy for neurogenic bladder after SCI.

neuroscience↗

bioRxiv2025

Phosphorylation and DNA Damage Resolution Coordinate SOX2-Mediated Reprogramming in vivo

The stem cell factor SOX2 can reprogram resident glial cells into neurons in the adult mammalian central nervous system (CNS), but the molecular mechanisms underlying this process remain poorly understood. Here, we show that both SOX2 phosphorylation and the PRKDC-dependent non-homologous end joining (NHEJ) pathway are essential for SOX2-mediated in vivo glia-to-neuron reprogramming. A phospho-mimetic SOX2 mutant significantly enhances reprogramming efficiency without altering neuronal fate. Conversely, loss of PRKDC or knockdown of core NHEJ components KU80 and LIG4 abolishes reprogramming. Notably, p53 knockdown restores reprogramming in PRKDC-deficient mice. These findings demonstrate that SOX2-driven glial reprogramming requires both precise posttranslational regulation and effective DNA damage repair, and suggest that targeting these pathways could enhance regenerative strategies in the CNS.

neuroscience↗

bioRxiv2025

Developmental constraints mediate the summer solstice reversal of climate effects on European beech bud set

Accurate projections of temperate tree growing seasons under climate change require representing developmental constraints that determine tree resource allocation. Recent work has identified a phenological "switch point" after the summer solstice (21 June), with pre-solstice warming advancing autumn phenology and post-solstice warming delaying it. Here, we propose this switch is flexible and occurs at the compensatory point between the antagonistic effects of early-season development and late-season temperature. We performed trans-solstice climate manipulation experiments on potted European beech (Fagus sylvatica) saplings to test (i) how spring leaf-out timing and June-August temperatures influence end-of-season timing (bud set and leaf senescence [50% loss of leaf chlorophyll content]), and (ii) whether daytime and nighttime temperatures before and after the solstice have different effects, given that trees primarily grow at night. Bud set and leaf senescence responses were tightly coupled (R2 = 0.49), with bud responses being generally stronger. Each day delay in spring leaf-out delayed bud set by 0.24 {+/-} 0.06 days and senescence by 0.22 {+/-} 0.08 days. Post-solstice full-day cooling in July delayed autumn phenology in late-leafing individuals (bud set +4.9 {+/-} 2.6 days; senescence +3.1 {+/-} 2.8 days) but had negligible impact on early-leafing trees (bud set +1.4 {+/-} 2.6 days; leaf senescence +2.2 {+/-} 2.8 days). Conversely, August full-day cooling advanced both stages. Daytime cooling before the solstice had no effect, while after the solstice it advanced autumn phenology. Nighttime cooling always delayed bud set. These findings support the Solstice-as-Phenology-Switch model and highlight the central role of developmental progression in constraining growing seasons. Faster early-season development -especially under nighttime warming- moves trees past the switch earlier, increasing sensitivity to late-season cooling and thereby triggering earlier autumn phenology. To improve growing season length projections, phenology models should account for these developmentally-mediated and diel-specific temperature responses.

ecology↗

bioRxiv2025

Meta-AlignNN: A meta-learning framework for stable brain-computer interface performance across subjects, time, and tasks

Practical application of brain-computer interfaces (BCIs) requires stable mapping between neuronal activity and behavior through various behavioral contexts and for different individuals. Due to neural activity instability, BCIs require frequent recalibration to maintain robust performance. Early approaches to addressing BCI stability issues mainly focused on tackling the challenge of neural activity changes over time. However, future BCI applications involve diversified scenarios and subjects, requiring solutions that address neural variability across time, subjects, and tasks. This study proposes a meta-learning-based algorithm to achieve BCI stability, named "Meta-AlignNN." By capitalizing on the consistency of neural population dynamics, it provides a unified solution for maintaining BCI stability, robustness, and scalability across subjects, time, and tasks. Tested over two years on four tasks with three monkeys, as well as on public datasets, the approach has achieved significantly excellent performance in both offline decoding and real-time brain-control, outperforming existing methods. Our findings provides a foundation for meeting the clinical demands of longterm, efficient, and stable usability across patients and tasks, offering a compelling solution for practical BCI applications.

bioengineering↗

bioRxiv2025

Improved Injury Detection Through Harmonizing Multi-Site Neuroimaging Data after Experimental TBI: A Translational Outcomes Project in NeuroTrauma (TOP-NT) Consortium Study

Multi-site neuroimaging studies have become increasingly common in order to generate larger samples of reproducible data to answer questions associated with smaller effect sizes. The data harmonization model NeuroCombat has been shown to remove site effects introduced by differences in site-related technical variance while maintaining group differences, yet its effect on improving statistical power in pre-clinical models of CNS disease is unclear. The present study examined fractional anisotropy data computed from diffusion weighted imaging data at 3 and 30 days post-controlled cortical impact injury from 184 adult rats across four sites as part of the Translational-Outcome-Project-in-Neurotrauma (TOP-NT) Consortium. Findings confirmed prior clinical reports that NeuroCombat fails to remove site effects in data containing a high proportion-of-outliers (>5%) and skewness, which introduced significant variation in non-outlier sites. After removal of one outlier site and harmonization using a global sham population, harmonization displayed an increase in effect size in data that displayed group level effects (p<0.01) in both univariate and voxel-level volumes of pathology. This was characterized by movement toward similar distributions in voxel measurements (Kolmogorov-Smirnov p<<0.001 to >0.01) and statistical power increases within the ipsilateral cortex. Harmonization improved statistical power and frequency of significant differences in areas with existing group differences, thus improving the ability to detect regions affected by injury rather than by other confounds. These findings indicate the utility of NeuroCombat in reproducible data collection, where biological differences can be accurately revealed to allow for greater reliability in multi-site neuroimaging studies. Significance StatementThis project demonstrates the utility of NeuroCombat in reducing site effects in multi-site rodent imaging. We also demonstrate that harmonization improves the ability to distinguish between sham and injured rats at the voxel level and increase statistical power and effect size in areas of injury. Multi-center studies are becoming more common to allow for increased efficiency in data collection, and with conservative approaches and analysis into the datasets, NeuroCombat can be utilized to improve study reliability and reproducibility.

neuroscience↗

bioRxiv2025

Molecular insights into early malignant transition of hepatocellular carcinoma

The molecular continuum of premalignant-to-malignant transition remains elusive in carcinogenesis, primarily due to the difficulty in sampling transitional lesions. Here, we present comprehensive genomic and immunological profiling of 21 very early hepatocellular carcinomas (veHCCs) arising within 17 cancer-prone DNs. Surprisingly, 82% of cancer-prone DNs harbored TERT alterations, suggesting a predisposing rather than causative role in malignancy transition. A substantial increase in CNA burden, rather than SNV, was noted, indicating a role of chromosome instability in malignancy transition. Additionally, veHCC-originating DNs showed immune inactivity, not falling into the prevailing paradigm that HCCs develop in a context of chronic inflammation. 43% of veHCCs showed an inflamed phenotype with relatively mild CNA burden but already exhibited immune evasion features. Two major evolutionary scenarios were thus proposed: 1) CNA-dominant progression and 2) early immune evasion of those with mild CNA burden. Collectively, our findings illustrate previously unexplored molecular paradigms in HCC initiation, highlighting the therapeutic potential of immunotherapy for early intervention.

cancer biology↗