Biology subjects

He, M.

Publications and source records attributed to He, M..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Genomic Prediction Enables Provenance-Aware Selection in 1 Sessile Oak (Quercus petraea) using Foliar Physiological Traits

Climate change is reshaping the adaptive landscape of forest ecosystems, demanding more efficient strategies to identify and deploy resilient tree genotypes. Genomic prediction offers a powerful framework to accelerate selection for complex physiological traits underlying climate adaptability in long-lived species such as sessile oak (Quercus petraea (Matt.) Liebl.). Here, we conducted genomic prediction for three key physiological traits carbon isotope composition, nitrogen isotope composition, and the carbon-to-nitrogen content ratio (C/N ratio) measured in 746 trees genotyped with dense genome-wide markers ([~]580,000 SNPs). High genomic heritabilities were estimated across traits, with within-year prediction accuracies (Pearsons r between genomic estimated values and observed phenotypes) reaching 0.77. Notably, across-year and across-provenance predictions remained substantial (0.41 < r < 0.82), with predictability declining with increasing genetic distance (FST) between training and test provenances for nitrogen isotope composition and C/N ratio. In addition, GWAS-guided SNP preselection increased heritability capture by [~]15% relative to random SNP subsets. And, the pronounced provenance-by-environment interactions observed indicated substantial phenotypic plasticity in these traits. These results demonstrate the strong potential of applying genomic prediction to foliar physiological traits as polygenic predictors for climate adaptation in plants, support provenance-aware breeding to improve forest establishment, and provide practical strategies for deploying genomic prediction in long-lived species.

genetics↗

bioRxiv2026

ProteinMCP: An Agentic AI Framework for Autonomous Protein Engineering

Computational protein design is often constrained by slow, complex, inaccessible, and highly sophiscated and expert-dependent workflows that hinder its transferrability and generalization power for broader applications. We present ProteinMCP, an agentic AI framework designed to accelerate and democratize protein engineering. ProteinMCP automates end-to-end scientific tasks, delivering dramatic gains in efficiency; for instance, a comprehensive protein fitness modeling workflow was completed in just 11 minutes. This performance is achieved by an AI agent that intelligently orchestrates a unified ecosystem of 38 specialized tools, made accessible through a Model-Context-Protocol (MCP). A cornerstone of the framework is an automated pipeline that converts existing software into MCP-compliant servers, ensuring the platform is both powerful and perpetually extensible. We further demonstrate its capabilities through the successful autonomous design and selection of high-affinity de novo binders and therapeutic nanobodies. By removing technical barriers, ProteinMCP has the potential to shorten the design-build-test cycle and make advanced computational protein design accessible to the broader scientific community.

bioinformatics↗

bioRxiv2026

Clinical Metabolomics studies in diagnosing Prediabetes and Type 2 Diabetes: Unveiling Trends through Bibliometric Analysis

BackgroundPrediabetes is the transitional stage preceding the onset of type 2 diabetes. Due to its asymptomatic nature and slow progression, conventional screening methods frequently fail to identify individuals in this prediabetic stage. Therefore, this study employs bibliometric methods to reveal the abnormal changes in clinically relevant metabolites in diabetes, providing evidence for early diagnosis, pathogenesis, and precision interventions. MethodsSearch the Web of Science Core Collection database for all papers on metabolomics related to prediabetes and type 2 diabetes clinical research from the databases inception until May 2025. Use VOSviewer and CiteSpace software to perform bibliometric analysis on the included literature. ResultsA total of 1,742 studies were ultimately included in the review of the literature. Researchers from China, the United States, and Germany, as well as institutions, have made significant contributions to metabolomics research in prediabetes and type 2 diabetes. The highest number of publications and citations was from the journals Metabolites and Diabetes. The current research hotspots in this field, as determined by keyword co-occurrence and clustering analysis, include metabolomics, insulin resistance, obesity, risk factors, biomarkers, gut microbiota, amino acids, lipidomics, and mass spectrometry. ConclusionThe outcomes of the study are instrumental in enabling scholars to comprehend the developmental trajectory of metabolites associated with prediabetes and type 2 diabetes and facilitate the rapid identification of emerging research pathways.

immunology↗

bioRxiv2026

Leveraging ONT move table values for signal aware variant calling

Oxford Nanopore Technologies (ONT) sequencing enables long-range haplotype phasing and contiguous genome assembly but still exhibits elevated error rates that challenge small variant calling, particularly for insertions and deletions (Indels). While raw electrical signals contain rich information, existing signal-aware methods require computationally intensive processing of large signal files. Here, we present Clair3 v2, a method that leverages the ONT move table--a lightweight byproduct of basecalling that maps signal events to nucleotide positions--to improve variant calling accuracy. Clair3 v2 builds upon Clair3 and integrates signal-level dwelling time to significantly enhance variant calling performance. We also propose a genome position based circular buffer to incorporate dwelling time with minimal computational overhead. Benchmarking across six Genome in a Bottle samples demonstrates substantial improvements in variant calling accuracy. With HAC basecalling, Clair3 v2 achieves a mean SNP F1-score of 97.69% at 10x depth (compared to 96.45% for baseline Clair3), and Indel F1 scores improved from 64.27% to 76.70%, while gains persisted at higher depths. The benefits were most pronounced for longer Indels and in complex genomic regions, where Indel F1 scores in long homopolymer regions improved from 14.3% to 45.2%. Benchmark results across various basecalling modes, samples, and coverage settings outperformed Clair3 baselines and other methods, including DeepVariant and Dorado Variant, and demonstrate the significant benefits of Clair3 v2. Furthermore, Clair3 v2 incurs negligible runtime compared to standard Clair3, making it practical for routine use.

bioinformatics↗

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

A lightweight, ultrafast and general embedding framework for large-scale spatial omics data

Deciphering ultra-large-scale omics data with minimal resources while maintaining high computational efficiency is a longstanding challenge in biology. Here, we present Local Pooling (LP), a lightweight, ultrafast and general framework that leverage neighbor-indexing strategy and local pooling module to generate omics embedding and compatible with variety of downstream analyses. We developed its adaptation for spatial omics, SpaLP, and evaluated it on over 20 large-scale datasets spanning 9 technology platforms. SpaLP consistently outperformed baseline methods across multiple benchmarks, including niche identification, expression reconstruction, multiple slices integration, 3D organ construction, multi-omics integration and cross-platform generalization. Notably, SpaLP processed a 1.35-million-cell mouse embryo slice in just 47 seconds, achieving up to 300-fold increase in computational efficiency compared to Graph Neural Network (GNN)-based methods. Meanwhile, SpaLP increased the average adjusted rand index (ARI) by over 30% for niche identification in simulated and realistic settings. Furthermore, we applied SpaLP to integrate 8.4 million mouse brain cells within 4 minutes on a single GPU and constructed a 3D spatial atlas. Finally, we explored SpaLPs ability of cross-platform generalization and potential for developing an omics foundation model. As a novel and general framework, we believe that LP could help more researchers develop new model on large-scale data and overcome the research barriers caused by computing resources in more fields.

bioinformatics↗

bioRxiv2026

Diet-Driven Gut Microbiome Differences Between Cohabiting Han and Yi Ethnic Groups in Liangshan, China

BackgroundWhile ethnic variations in gut microbiota are well-documented, their persistence in genetically distinct populations sharing the same geographic environment remains poorly understood. This study investigates the Han and Yi ethnic groups cohabiting rural Southwest China, where contrasting dietary traditions persist under identical environmental conditions. MethodsWe analyzed fecal samples from 100 healthy adults (50 Yi/50 Han) using 16S rRNA gene sequencing (V3-V4 region). Dietary intake was quantified via three 24-hour recalls validated with plasma biomarkers. Multivariate analyses (DESeq2, PERMANOVA) controlled for age, sex, and BMI covariates. ResultsYi individuals exhibited significantly higher Prevotellaceae (log2FC=1.82, padj=0.028) and Succinivibrionaceae (log2FC=2.15, padj=0.013) abundances, corresponding to their buckwheat-rich diet (58.5 {+/-} 12.3% vs Han 3.3{+/-}1.8%, p<0.001) Han microbiota showed enriched Bacteroidaceae (log2FC=1.24, padj=0.041), associated with higher animal fat intake (23.6% vs Yi 1.8%, p<0.001) Dietary factors (buckwheat/animal fat intake) explained greater microbiota variation than ethnic genetic ancestry (PERMANOVA R{superscript 2}=0.10 vs 0.07, p < 0.05) ConclusionCohabiting Han and Yi populations maintain distinct gut microbiota compositions primarily driven by dietary differences. These findings highlight diet as a stronger determinant than genetic ancestry in shaping microbial communities under shared environments. Future studies should validate these observations with metagenomic sequencing.

microbiology↗

bioRxiv2026

Ultra-fast genetic recovery of dead fish through cross-family germline stem cell transplantation

AbstactThe conservation of genetic resources from aquaculture species and endangered fish is increasingly challenged by large body size, long reproductive cycles, and limited opportunities for timely intervention after death. Here, we establish and validate an ultra-fast genetic platform based on germline stem cell transplantation to enable postmortem genetic recovery in fish. Using grass carp (Ctenopharyngodon idella) as a representative warm-water species, we systematically quantified the relationships among postmortem tissue freshness, germline stem cell viability, and transplantation efficiency, and demonstrated that low-temperature preservation plays a decisive role in maintaining germline activity after death. Germline stem cells isolated from deceased grass carp were transplanted into germ-cell-depleted zebrafish recipients, where they rapidly colonized recipient gonads, underwent proliferation and differentiation, and generated functional donor-derived gametes within three months. These gametes supported successful fertilization and normal embryonic development, ultimately yielding viable grass carp offspring. Our results reveal an intrinsic postmortem resilience of germline stem cells and demonstrate that cross-species transplantation into small, fast-maturing hosts can dramatically accelerate genetic recovery. This strategy overcomes key biological and logistical constraints associated with conventional breeding-based rescue approaches and provides a rapid, scalable, and broadly applicable framework for postmortem genetic resource conservation in aquaculture and endangered fish species.

zoology↗

bioRxiv2025

Systematic microcircuit reconfigurations underlie early experience-induced visual cortical plasticity

Experience-dependent reorganization of neuronal connections during a postnatal critical period (CP) is essential for the functional maturation of developing primary visual cortex (V1). However, the systematic reconfigurations across microcircuit synapses underlying this plasticity were poorly defined. Paired recording from excitatory pyramidal cells and other three major interneurons (INs) within layers 2/3 and 4 microcircuits in the developing mouse V1 monocular region, we find that monocular deprivation (MD) for one-day during the CP transiently reconfigures local excitatory synapses on inhibitory INs that specifically express parvalbumin (PV) or vasoactive intestinal peptide (VIP), whereas prolonged MD primarily strengthens inhibitory transmission from somatostatin (SST)-expressing INs to PV-INs and VIP-INs in both layers. A physiologically based microcircuit model suggests these coordinated synaptic changes in specific inhibitory neurons mediate differential MD-induced plasticity in visual responses across layer 2/3 neurons in vivo. Together, our findings define a systematic microcircuit basis for cortical critical-period plasticity. HighlightsO_LIInhibitory-to-inhibitory connectivity is conserved in cortical layer 2/3 and 4 circuits. C_LIO_LIEarly experience sequentially modifies excitatory and dis-inhibitory synapses in both layers. C_LIO_LISystematic microcircuit reconfigurations underlie plasticity of cortical visual responses. C_LIO_LIModeling suggests a pivotal role of disinhibitory microcircuits in mediating the plasticity. C_LI

neuroscience↗

bioRxiv2025

Perturbational single-cell profiling of patient tumors defines lineage- and context-specific programs of innate immune resistance

AbstractDespite promise in preclinical models, most immuno-oncology drug candidates fail in clinical trials. These failures reflect limitations in our ability to directly model the response of human tumor and immune cells to immunotherapies. To address this gap and test the effect of innate immune agonists, we developed PERCEPT, an approach that uses ex vivo perturbational single-cell RNA sequencing to compare the response of immunomodulatory treatments with unstimulated controls directly in patient samples. Using PERCEPT, we tested cytokines and innate immune agonists in melanoma and Merkel cell carcinoma (MCC) and identified the dsRNA mimetic, RIG-I agonist, Stem Loop RNA (SLR) 14 as a powerful inducer of anti-viral states and enhancer of T cell activation. We compared transcriptional responder and non-responder patient samples and identified midkine (MDK), a multifunctional cytokine, as a potent repressor of IFN signaling in both tumor and immune cells. MDK expression dampened MHC-I presentation in human tumor cells and reduced activation of antigen-presenting cells, disrupting tumor immunity at multiple levels. In contrast to prior studies, we identified MDK as specifically enriched in neuroendocrine cancers such as MCC and small cell lung cancer compared with melanoma, suggesting the importance of lineage- and context-specific targeting. Our results demonstrate the utility of high-dimensional controlled perturbation of patient samples to identify mechanisms of innate immune response and resistance and demonstrate an actionable path towards clinical development of MDK-inhibiting therapies including FDA-approved ALK inhibitors in neuroendocrine cancers.

cancer biology↗

bioRxiv2025

Design, synthesis, and pharmacological evaluation of novel PROTAC degraders targeting 11β-HSD1 for metabolic disease intervention

Hydroxysteroid 11-beta dehydrogenase 1 (11{beta}-HSD1) plays a critical role in metabolic homeostasis by catalyzing the intracellular conversion of cortisone to cortisol. Dysregulated 11{beta}-HSD1 activity is closely associated with metabolic disorders such as type 2 diabetes mellitus, obesity, and glucocorticoid-related inflammation. While small-molecule inhibitors of 11{beta}-HSD1 have shown promise, they primarily suppress enzymatic activity without modulating protein abundance. Here, we report the development of the 11{beta}-HSD1-targeting PROTAC degraders. A series of bifunctional molecules were synthesized based on CRBN- and VHL-recruiting ligands, with AZD8329-derived warheads linked via polyethylene glycol chains. Cellular assays demonstrated efficient, ubiquitin-proteasome-dependent degradation of 11{beta}-HSD1, with H-3-V identified as the most potent degrader. In vivo, H-3-V treatment improved glucose tolerance and enhanced glucose-stimulated insulin secretion in a high-fat diet-induced T2DM mouse model. Molecular dynamics simulations revealed that the H-3-V ternary complex exhibited superior binding energetics compared to less active analogs. Collectively, this study introduces a novel chemical modality for 11{beta}-HSD1 modulation and lays the groundwork for future therapeutic development targeting metabolic disease via selective protein degradation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/687522v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@60aa3borg.highwire.dtl.DTLVardef@484120org.highwire.dtl.DTLVardef@1abca2eorg.highwire.dtl.DTLVardef@166b1a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

NOVEL SMALL-MOLECULE INHIBITORS OF THE PROTEIN KINASE DYRK: POTENTIAL THERAPEUTIC CANDIDATES IN CANCER

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) is crucial for normal brain development and its disruption has been linked to various cancers. DYRK1A drives glioblastoma (GBM) progression via stabilization of epidermal growth factor receptor (EGFR). Here we describe two, selective, benzothiazole-derived DYRK inhibitors, FC-2 and FC-3, obtained by structure-activity optimization of a natural product lead. Both compounds inhibit DYRK1A with nanomolar potency and display high selectivity across a kinase panel. The co-crystal structure of FC-3 with DYRK1A revealed ATP-competitive binding, with interactions at the hinge region and the DYRK-specific phenylalanine gatekeeper residue explaining target selectivity. Generation of inhibitor-resistant mutants confirmed DYRK1A as the primary cellular target. In GBM cell-models, FC-2 and FC-3 impaired neurosphere self-renewal, cell invasion, and EGFR stability, phenocopying DYRK1A loss. Both compounds crossed the blood-brain barrier and suppressed tumor growth, to prolong survival in intracranial xenografts. These findings identify FC-2 and FC-3 as selective small-molecule inhibitors of DYRK1A with potential therapeutic utility in GBM.

cancer biology↗

bioRxiv2025

Surveillance of migratory shorebirds and seabirds in 2024 in Australia reveals incursions of a diversity of low pathogenicity avian influenza viruses, but not high pathogenicity avian influenza H5N1

The current panzootic of high pathogenicity avian influenza (HPAI) H5N1 has been catastrophic for wildlife, and following a significant sweep, clade 2.3.4.4b is found in every region aside from Oceania. Herein, we report the results of our third year of targeted surveillance of incoming migratory seabirds and shorebirds into Australia. We did not find evidence of HPAI H5N1 in any of the birds tested, and there were no reports of HPAI H5N1 in wildlife tested through other surveillance schemes in 2024. Unlike previous years, we detected a diversity of low pathogenicity avian influenza (LPAI) viruses in shorebirds. Through phylogenetic analysis we revealed that the H3N7 and H4N7 viruses recovered from Red-necked Stints were complex mosaic viruses, comprising segments of Eurasian, Australian shorebird, and Australian waterfowl segments. A H1N7 virus detected comprised a wholly Eurasian introduction, confirming this route for avian influenza viruses into Australian ecosystems. These results provide further evidence for the key role of long-distance migratory shorebirds in introducing novel LPAI viruses into Oceania. While our focus on northern migration routes remained appropriate for HPAI H5N1 surveillance in 2024, the continued spread of HPAI H5N1 to sub-Antarctic Islands demands consideration of a potential southern incursion route for Oceania in future.

microbiology↗

bioRxiv2025

Clair-Mosaic: A deep-learning method for long-read mosaic small variant calling

Mosaic variants, defined as postzygotic mutations occurring during an organisms development from zygote to adult, play critical roles in developmental biology, aging, and diseases such as cancer and neurological disorders. However, their accurate detection remains challenging due to low abundance in the genome and low variant allelic fractions (VAF). While current mosaic variant callers are primarily designed for short-read sequencing, no method is available for long-read sequencing, which can generate tens of kilobase-long reads to cover complex genomic regions inaccessible to short reads. To fill the gap, we present Clair-Mosaic, a deep-learning-based method for detecting mosaic small variants from long-read data. Clair-Mosaic was trained on hundreds of millions synthetic variants encompassing diverse read coverages and allelic fractions, enabling it to detect low-VAF mosaic variants with high sensitivity in paired-sample and single-sample modes. In addition to neural network prediction, Clair-Mosaic distinguishes genuine mosaic variants from sequencing artifacts by leveraging their inherent haplotype relationship in phased long reads. Furthermore, a Bayesian mosaic-germline discriminator is introduced to distinguish mosaic variants from germline variants. It also employs multiple post-calling filters, including a mosaic variant database and multiple germline population resources, to tag common germline and mosaic variants. Comprehensive benchmarking on synthetic datasets and real samples demonstrated Clair-Mosaics outstanding performance in ONT and PacBio. Clair-Mosaic is also applicable to short-read data and outperforms methods like MosaicHunter, MosaicForecast, DeepMosaic, and DeepSomatic. Clair-Mosaic is open-source and available at https://github.com/HKU-BAL/Clair-Mosaic.

bioinformatics↗

bioRxiv2025

In-situ Observation of Fast Chloroplast Dynamics in Intact Leaves

Chloroplast relocation is a hallmark of plant photoprotection, yet has long been regarded as a slow, minute-scale process. Here we overturn this view by directly visualizing chloroplast motility in intact leaves with the second near-infrared (NIR-II, 900-1880 nm) fluorescence confocal microscopy, an optical strategy uniquely suited for deep, in situ imaging. By harnessing the intrinsic long-wavelength fluorescence tail of chloroplasts, this method minimizes scattering, extends imaging depth, and enables simultaneous stimulation-imaging with subcellular resolution--capabilities not attainable with conventional visible fluorescence or multiphoton fluorescence microscopy. Using this approach, we discover that submerged leaves of amphibious plants exhibit remarkably rapid avoidance responses to red light, whereas aerial leaves show negligible relocation. Control experiments exclude influence of the physical structure of leaves, confirming that these contrasting responses reflect distinct physiological adaptations to environmental light regimes. Beyond revealing unexpected speed and flexibility in chloroplast dynamics, our findings establish the second near-infrared fluorescence confocal microscopy as an important tool for direct observation of fast subcellular processes in deep photosynthetic tissues and advancing plant photobiology.

plant biology↗

bioRxiv2025

Atom-level backbone engineering preserves peptide function while enhancing stability

Peptide therapeutics offer unmatched potency and selectivity but are limited by rapid proteolysis and poor pharmacokinetics. Backbone engineering provides a rational approach to enhance stability while preserving function, yet direct comparisons across strategies remain scarce. Using bradykinin as a model, we systematically evaluated four backbone modifications--D-amino acid substitution, N-methylation, -methylation, and azapeptide incorporation. Each modification produced distinct outcomes in synthesis, conformation, proteolytic stability, and receptor pharmacology. While D- and N-methyl substitutions yielded high stability, they compromised receptor binding and in vivo function. In contrast, the azapeptide analogue maintained native-like affinity and physiological activity while achieving an enhanced stability profile. These findings highlight the need to balance stability and function in peptide design and position azapeptides as an underexplored class with strong therapeutic potential. More broadly, this study establishes a framework for systematic, data-driven peptide design and optimization.

biochemistry↗

bioRxiv2025

Directed evolution of a compact TranC11a system for efficient genome editing

The recently discovered TranC systems represent programmable RNA-guided DNA endonucleases of transposon origin with compact protein sizes ideal for therapeutic delivery. However, their editing efficiency in human and plant cells is limited. Here, we evolved TranC11a and engineered its sgRNA to enhance overall editing efficiencies. TranC11a systems exhibit up to 9.2-fold higher editing activity than its parent and achieves efficiency comparable to SpCas9 across multiple human genome endogenous sites, significantly outperforming compact editors NovaIscB and enTnpB1c. TranC11a enables efficient editing of disease-relevant genes in human cells and breeding traits in maize. With its high editing activity and compact size (574 aa), TranC11a demonstrates strong potential for future in vivo genome editing and crop engineering.

synthetic biology↗

bioRxiv2025

PET-Microplastics Trigger Endothelial Glycocalyx Loss via ER Stress and ROS Unleashing IL-1β-Driven SMC Switching and Early Aortic Structural Impairment

Polyethylene terephthalate microplastics (PET-MPs), a major microplastics component identified in human vasculature, pose emerging environmental health risks. This study systemically profiled MPs in human aortic tissues and investigated the mechanisms underlying PET-MPs-induced aortic injury in vivo and in vitro. Chronic oral exposure of Sprague-Dawley rats to PET-MPs (1.0-100 mg/L) resulted in endothelial glycocalyx loss and structural impairment of aortic elastic fibers, with MPs accumulating within aortic endothelial cells. Transcriptomic and biochemical analyses revealed that PET-MPs triggered endoplasmic reticulum stress (ERS) and reactive oxygen species (ROS) generation in human aortic endothelial cells (HAECs), driving glycocalyx degradation and NF-{kappa}B-mediated inflammation. Proteomic profiling identified endothelial-derived IL-1{beta} as a key mediator, which subsequently induced phenotypic switching in human aortic smooth muscle cells (HASMCs) in vitro. Pharmacological inhibition of ERS (TUDCA), ROS (NAC), or IL-1{beta} (Canakinumab) attenuated this pathogenic cascade. Crucially, restoration of the glycocalyx using Sulodexide mitigated endothelial dysfunction and downstream HASMC phenotypic switching. These findings establish endothelial glycocalyx degradation via ERS-ROS as a novel mechanism for PET-MPs-induced vascular injury and highlight glycocalyx protection as a potential strategy against environmental microplastic hazards.

pharmacology and toxicology↗