Biology subjects

Xia, Y.

Publications and source records attributed to Xia, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Fatty acid synthase coordinates mTOR signaling and histone crotonylation during cardiomyocyte hypertrophy

Background: Epigenetic modifications are central to the regulation of cardiac gene expression during disease. Among these, histone crotonylation (Kcr) has recently emerged as a key modulator of chromatin structure and transcriptional activity. Here, we identify a novel signaling axis linking fatty acid synthase (FASN) to mTOR activation and hypertrophic gene expression through histone crotonylation. Methods: FASN expression, mTOR activation, and histone crotonylation were assessed in mouse hearts and isolated cardiomyocytes using immunoblotting. FASN was silenced by siRNA or inhibited pharmacologically using TVB-2640. Hypertrophic gene expression was quantified by RT-qPCR. Cardiomyocyte hypertrophy was evaluated by immunofluorescence-based cell size analysis. p300 acetylation and crotonylation were assessed by immunoprecipitation and immunoblotting. CUT&RUN-seq and RNA-seq were performed to identify FASN- and Histone H3K18cr-regulated genes during hypertrophic stimulation. Bioinformatic analyses of human RNA-seq and genome-wide association study (GWAS) data were conducted to investigate the clinical relevance of these findings. Results: Histone crotonylation was markedly elevated in hypertrophic myocardium and cardiomyocytes. This increase was driven by upregulated FASN expression in response to hypertrophic stimuli. Genetic or pharmacological inhibition of FASN suppressed histone crotonylation, hypertrophic gene expression, and cardiomyocyte enlargement. Mechanistic studies suggested that FASN regulates histone crotonylation through mTOR-associated signaling and changes in p300 activity. Transcriptomic analyses further revealed that FASN enhances the expression of hypertrophy-associated genes enriched for histone crotonylation marks. Analysis of human sequencing datasets demonstrated a positive association between FASN expression and molecular markers of hypertrophy in patients with hypertrophic cardiomyopathy (HCM). Furthermore, GWAS analysis identified a variant at the FASN locus associated with heart failure as the underlying cause of death and increased FASN expression in cardiomyocytes. Conclusions: Our findings identify FASN as an important regulator of mTOR signalling and histone crotonylation during cardiomyocyte hypertrophy. These results support a potential mechanism linking altered lipid metabolism to epigenetic regulation and pathological cardiac remodelling.

cell biology↗

bioRxiv2026

Creator 1.0: Phylogeny-Guided Stagewise Pretraining for Plant Genome Foundation Models across 1,000 Species

Genomic language models have advanced DNA sequence analysis, but their applicability to plant-specific tasks and representation changes during pretraining remain poorly characterized. Here, we present Creator 1.0, a 2-billion-parameter parameter plant genome foundation model pretrained on 1,000 plant genomes using phylogeny-guided stagewise pretraining (PGSP). Training comprised 83 consecutive stages and produced 52 cumulative checkpoints associated with distinct plant orders. On GENEB, the stage 83 checkpoint ranked first among 46 models across 10 plant-related tasks, with a mean Matthews correlation coefficient (MCC) of 0.565, and fourth across all 100 tasks. Evaluation of 52 checkpoints on six plant lncRNA tasks identified different optimal stages under full-data, 10-shot and 1-shot settings, corresponding to stages 71, 72 and 29, respectively. Checkpoint performance varied across tasks, without consistent advantages for corresponding plant orders. These findings demonstrate the competitive performance of Creator 1.0 and highlight the potential of PGSP to provide task-adaptable checkpoints for plant genomic applications.

genomics↗

bioRxiv2026

Dual phage sensing activates an RNA-targeting reverse transcriptase for anti-phage defense

Defense-associated reverse transcriptases (DRTs) mediate diverse antiphage responses, yet how they sense phage infection and couple unconventional DNA synthesis to antiviral effector activation remains poorly understood. Here, we characterize DRT4 as a dual-sensor immune system that integrates two distinct phage-derived signals. Cryo-EM analysis reveals that DRT4 assembles into a dimer-of-trimers hexamer, with each protomer catalyzing protein-primed, template-independent synthesis of a covalently linked ssDNA product. DRT4 displays a strong preference for purine nucleotides, determined by base-specific interactions within the polymerase active site. Using phage escape genetics, we identify two independent activators of DRT4: the phage ribonucleotide reductase NrdAB, which increase intracellular dNTP levels, and the SSB-like protein 0087, which directly binds the DRT4-generated ssDNA. Activated DRT4 exhibits dNTP-dependent RNase activity, linking phage sensing to RNA cleavage and abortive infection. Together, our findings show DRT4-generated ssDNA as a signaling intermediate that integrates phage-induced metabolic changes with direct recognition of viral replication proteins, revealing how protein-primed DNA synthesis can be repurposed for infection sensing and antiviral effector activation.

microbiology↗

bioRxiv2026

The effects of DNA repair factor-Cas9 fusions on homing drive performance

CRISPR-based homing gene drives achieve super-Mendelian inheritance by converting wild-type alleles into drive alleles through homology-directed repair (HDR). However, competing end-joining repair can generate resistance alleles that limit drive spread. Although fusing Cas9 to DNA repair-associated proteins has improved HDR in conventional genome editing systems, its effectiveness in gene drives remains unclear. Here, we systematically evaluated in Drosophila melanogaster eight Cas9 fusion constructs previously reported to improve HDR in other systems. Although none of the fusion constructs significantly increased HDR-associated signals in S2 cells, several candidates retained relatively high activity comparable to standard Cas9. These candidates were then tested in vivo across multiple split drive systems, regulatory elements, target loci, and parental sexes. Cas9-POLD3 significantly increased female drive inheritance in contexts with low baseline efficiency or substantial nonfunctional resistance formation, likely by increasing effective cutting rate and potentially also by biasing repair outcomes toward drive conversion. Cas9-Geminin degron generally maintained germline drive performance while reducing embryo resistance. Together, these findings identify Cas9-POLD3 and Cas9-Geminin degron as complementary, context-specific tools for enhancing drive conversion and limiting embryo resistance, respectively. These results highlight the importance of matching fusion modules to the regulatory and genetic context of individual drive systems.

genetics↗

bioRxiv2026

Efficacy of Tumor Treating Fields (TTFields) in triple negative breast cancer cells and synergy with PARP inhibitor talazoparib

Breast cancer is the most diagnosed cancer worldwide. Triple-negative breast cancer (TNBC) is a subtype with a poor prognosis because of its aggressiveness and high likelihood of relapse, making its treatment particularly challenging. We explored the effect of Tumor Treating Fields (TTFields) as a novel treatment option for breast cancer, which can be used together with other therapies, such as PARP inhibitors. TTFields use alternating electric fields to inhibit cell growth and induce cellular damage. Our findings indicate that TTFields increase expression of the universal cell cycle CDK inhibitory protein p21(WAF1)/CDKN1A independently of TP53 mutational status. Moreover, when used together with the PARP inhibitor talazoparib, the combination further upregulates p21 protein. Both TTFields alone and together with talazoparib induce cell death as documented by PARP cleavage while reducing markers of cell growth and anti-apoptotic proteins, including p-STAT3, STAT3, and MCL-1. Additionally, TTFields together with talazoparib induce DNA damage, as indicated by increased {gamma}H2AX expression. The combination of talazoparib plus TTFields treatment decrease PDL-1 levels and given its utility in predicting response to PD-1/PD-L1 by mediating immune evasion, this raises the possibility of future combination for immune modulation in cancer therapy. Our preclinical results suggest TTFields alone or together with PARP inhibitors such as talazoparib as a promising therapeutic approach for further development for the treatment of breast cancer.

cancer biology↗

bioRxiv2026

Pannexin 1 Ablation Disrupts Cell Cycle Progression and Compromises the Structure of Melanoma Tumours

Pannexin 1 (PANX1) is a channel-forming glycoprotein that has been implicated in regulating melanoma cell properties such as growth, migration, and invasion. Here we report that the CRISPR-Cas9 mediated ablation of PANX1 or channel inhibition with probenecid shifted A375-P cell cycle distribution towards G2/M, while channel inhibition with spironolactone stalled cell cycle progression at the G1/S checkpoint regardless of PANX1 expression. Bulk RNA sequencing revealed cell cycle related gene expression was downregulated with PANX1 targeting strategies and this was exacerbated when PANX1 deficient cells were treated with spironolactone. When grown as spheroids, we found the deletion and inhibition of PANX1 disrupted spheroid compaction, with spheroids displaying poorly defined borders and reduced circularity. The deletion of PANX1 increased spheroid fragmentation, and this phenotype was intensified when spheroids devoid of PANX1 were treated with spironolactone, highlighting a potential synthetic lethal effect. Using liquid chromatography mass spectrometry, we sought to determine whether PANX1 had binding partners that may act to stabilize spheroid integrity and found that PANX1 co-immunoprecipitated various cell adhesion molecules such as {beta}-actin and F-actin-capping protein subunit -1, suggesting PANX1 and its interacting partners may stabilize cell-cell contacts. When control and PANX1 ablated cells were grown in chick chorioallantoic membrane xenografts to assess their tumour growth characteristics, we discovered that the deletion of PANX1 reduced tumour surface area and viability. Our findings indicate that PANX1 regulates cell cycle progression and the structural architecture of A375-P melanoma tumours, highlighting the therapeutic utility of targeting PANX1 in melanoma.

cancer biology↗

bioRxiv2026

Extracts of Bacillus proteolyticus strain OSUB18 exhibit cytostatic activity

Although therapeutic advancements have dramatically improved outcomes for cancer patients in recent decades, advanced cancer remains a significant challenge. There is still an urgent need for new and more effective strategies that minimize toxicity and improve survival outcomes in cancer patients. Natural products from microorganisms are a rich and promising source of bioactive compounds with substantial therapeutic potential in cancer treatment. Recently, B. proteolyticus strain OSUB18, isolated from switchgrass, has been demonstrated to promote plant growth and regulate reactive oxygen species (ROS) production. Here, we investigated the anticancer potential of this plant-associated microbe and demonstrated that its crude extracts exhibited broad-spectrum cytostatic activity across diverse solid tumor cell lines. Importantly, OSUB18 extracts displayed limited cytotoxicity toward normal human mammary epithelial cells and mouse fibroblasts. This potentially selective cytostatic activity was retained within a water soluble, heat-labile, and protease-resistant fraction. The extracts primarily suppressed cell proliferation, accompanied by increased lipid peroxidation, with preliminary evidence suggesting the potential involvement of ferroptosis. These findings suggest that the bioactive component may be a selective cytostatic agent with multifaceted mechanisms of action.

cancer biology↗

bioRxiv2026

An agentic AI environment to support biomedical research in collaborative academic environments

Agentic artificial intelligence (AAI) is increasingly used by biomedical scientists, where it has substantially lowered the difficulty of integrating computational, statistical and data-science approaches into day-to-day research activities, assisting with project design, analysis and manuscript preparation. Significant barriers remain, however, which are unlikely to be removed solely by releasing more capable AI models. Meaningful use still demands a technical fluency that many biomedical researchers lack: a PI and their lab members must learn how to use the AAI system, establish standard operating procedures (SOPs) for managing, sharing and curating data, and enforce rules that address data privacy and security. Existing commercial AAI systems, which were designed primarily for software engineering purposes, need to be significantly re-purposed for biomedical-related data science. We present Murmurent, shared software that sits beneath the agentic AI and provides the skills, procedures and protections to address the concerns above, removing the need for a lab to develop them independently. This includes (1) infrastructure to support projects and so-called choreographies} involving multiple group members; (2) a set of specialized agents each dedicated to typical biomedical data science tasks including software and statistical development, data visualization, literature search, equity, diversity, inclusion, and decolonization (EDID) review, and others; (3) a tiered memory which can retain important research decisions, intermediate, derived outputs and sensitive data, and which can exploit this information to automatically build better contexts in AAI sessions; (4) traceability records which are used by the AAI session to better plan and execute data analyses and software builds by, for example, helping to avoid repeating decisions that lead to dead-ends; (5) enforcement of SOPs for data maintenance and data governance across all lab members; and (6) multi-user capacity to allow groups to interact and collaborate. We use the system to identify putative inhibitors of Peptidyl-prolyl cis-trans Isomerase NIMA-interacting 1 (Pin1), a protein with a shallow catalytic site making it difficult to target. We describe the construction of several approaches to identify Pin1 inhibitors and the results they yield. Murmurent is open source.

bioinformatics↗

bioRxiv2026

MiRNA let-7a-5p Ameliorates Pulmonary Fibrosis by Suppressing TGFBR1-Mediated Endothelial-to-Mesenchymal Transition

Background Idiopathic Pulmonary Fibrosis (IPF) is a fatal chronic lung disease with limited therapeutic options. While alveolar epithelial injury and fibroblast activation are well-studied, endothelial-mesenchymal transition (EndoMT) is emerging as a critical pathogenic mechanism. The regulatory role of exosomal miRNAs in pulmonary fibrosis remains unclear. This study investigates serum exosomal miRNAs, particularly let-7a-5p, in modulating EndoMT during the onset of pulmonary fibrosis. Methods Clinical cohorts of IPF patients and healthy controls were enrolled. Serum exosomal miRNAs were profiled, followed by differential expression and functional enrichment analyses. In vitro experiments involved human pulmonary artery endothelial cells (HPAECs) transfected with let-7a-5p mimic or inhibitor. Dual-luciferase reporter assays confirmed the binding between let-7a-5p and TGFBR1. HPAECs were co-cultured with lung epithelial cells to examine paracrine signaling. In vivo studies used a bleomycin-induced mouse model with let-7a-5p agomir administration. Assessments included histopathological staining, hydroxyproline content, Western blot, qPCR, micro-CT, and pulmonary function tests. Results Let-7a-5p was significantly downregulated in serum exosomes from IPF patients, correlating with clinical indicators. Mechanistically, let-7a-5p directly bound the TGFBR1 3'UTR to inhibit its expression. Inhibition of let-7a-5p upregulated -SMA, FN1, smad2/3 phosphorylation, and collagen I, while downregulating CD31 and VE-cadherin. Therapeutically, let-7a-5p mimic reversed bleomycin-induced EndoMT and suppressed epithelial-mesenchymal transition (EMT) via paracrine signaling. Mice administered agomir showed reduced fibrosis, improved lung function, and suppressed TGF-{beta}/Smad signaling. Conclusion Serum exosomal let-7a-5p suppresses pulmonary fibrosis by targeting TGFBR1 to inhibit EndoMT. Its downregulation in IPF patients correlates with disease progression, highlighting its biomarker potential.

molecular biology↗

bioRxiv2026

Heart rate dynamics embed a shared representation of individual brain organization and cognitive function

Idiosyncratic brain functional organization shapes intricate cardiac dynamics through central-peripheral autonomic interactions, yet a comprehensive mapping between multi-scale heart rate dynamics and whole-brain functional architecture remains lacking. Here, combining highly comparative time-series analysis with multi-modal neuroimaging and intracranial electrophysiology, we establish heart rate dynamics as a physiological fingerprint that maps onto whole-brain functional architecture. Partial least squares analysis revealed a generalizable latent axis linking reduced heart rate temporal complexity and elevated micro-scale predictability to heightened resting-state functional connectivity across default mode, salience, and sensorimotor networks. This covariance aligns spatially with serotonergic, noradrenergic, and cholinergic neuromodulatory gradients, persists across physiological confound controls and cross-session validations, derives support from human intracranial electrophysiological recordings, and extends to active cognitive states. Furthermore, brain-covarying heart rate signatures underpin the predictive capacity of heart rate dynamics for individual fluid and crystallized intelligence, demonstrating a shared representational substrate. Our findings demonstrate a robust neurovisceral coupling architecture, establishing well-characterized heart rate dynamics as a scalable, neurobiologically anchored window into human brain functional organization and cognitive traits.

neuroscience↗

bioRxiv2026

Rational antigen engineering and mucosal delivery design for next-generation RSV vaccines

Respiratory syncytial virus (RSV) prefusion F (preF) vaccines have transformed adult prophylaxis, yet unmet needs in antigen stability, pediatric safety, and mucosal protection persist. Here, we develop an integrated structure-guided RSV vaccine design platform that couples allosteric stabilization, epitope-focused immunogen engineering, and route-specific mRNA delivery for systemic and mucosal immune activations. By mapping prefusion F "breathing" motions and applying a ThermoNet-and Rosetta-guided screening funnel, we identified R296, a stabilized prefusion F immunogen that reinforces the 1-5 hinge and interprotomer interfaces while preserving key neutralizing epitopes. Cryo-EM confirmed that R296 retains a native-like prefusion architecture. And mRNA-LNP vaccination elicited potent, durable, and broadly protective neutralizing responses in mice, rats, and cotton rats, with clearance of detectable infectious virus and no evidence of Th2-skewed enhanced respiratory disease. To address pediatric safety, we designed a stalkless nanoparticle immunogen, Head38-50AB-3, which enriches high-potency apical epitopes while excluding stalk regions associated with low-potency or non-protective responses, conferring protection without VAERD-like pathology. Finally, we engineered an intranasal-delivered LNP that enables intranasal R296 mRNA delivery, inducing systemic neutralization together with robust nasal and bronchoalveolar secretory IgA (sIgA). R296 has now advanced to Phase 1 clinical trials. These results establish a modular framework for next-generation RSV vaccines.

microbiology↗

bioRxiv2026

FXR-mediated recruitment of PPP1CB suppresses SMAD2/3 phosphorylation to mitigate pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options and poorly understood molecular underpinnings. Dysregulated TGF-{beta}/SMAD signaling is a key driver of fibrotic remodeling, promoting persistent myofibroblast activation and excessive extracellular matrix deposition. Here we identify the Farnesoid X receptor (FXR), a bile acid activated nuclear receptor, as a previously unrecognized suppressor of pulmonary fibrosis. FXR expression is significantly reduced in lung tissues from patients with PF and in myofibroblasts derived from BLM-induced mouse models, correlating inversely with fibrosis severity. Genetic ablation of FXR exacerbates BLM-induced pulmonary fibrosis by promoting fibroblast hyperactivation and dysregulation of the TGF-{beta}/SMAD signaling pathway. Mechanistically, we identify PPP1CB as a previously unrecognized FXR-interacting protein in primary myofibroblasts derived from IPF patients. We further show that FXR both increases chromatin accessibility at the PPP1CB locus and assembles a functional complex with PPP1CB, which in turn promotes SMAD2/3 dephosphorylation and suppresses their nuclear translocation. Notably, the clinical-stage FXR agonist TERN101 exhibits potent therapeutic efficacy in a BLM-induced mouse pulmonary fibrosis model. These findings establish FXR as a critical antifibrotic regulator in lung tissue and suggest that pharmacological activation of FXR may offer a promising therapeutic strategy for IPF.

cell biology↗

bioRxiv2026

Adipose GPD2 Couples Glycolytic Signals to Epigenetic Control of Metabolic Homeostasis

The glycerol-3-phosphate shuttle (G3PS) is a classic reducing equivalent transferring system, yet its role in adipose metabolism remains poorly understood. Here, we identify mitochondrial glycerol-3-phosphate dehydrogenase (GPD2), the core enzyme of G3PS, as a critical orchestrator of adipose thermogenesis and systemic metabolic homeostasis. Adipocyte-specific GPD2 knockout mice exhibited impaired thermogenic capacity and energy expenditure, rendering them susceptible to obesity and metabolic dysfunction. Mechanistically, GPD2 deficiency elevated cytosolic NADH, which suppressed glycolysis and decreased the levels of key metabolites, such as acetyl-CoA, thereby diminishing H3K27ac at thermogenic gene loci and silencing these genes. NADH depletion with an NADH oxidase rescued both glycolysis and thermogenic gene expression. In support of this mechanism, we defined a previously undescribed enhancer of Ucp1 whose H3K27ac was tightly controlled by GPD2. Remarkably, replenishing the acetyl-CoA pool or directly restoring H3K27ac at the Ucp1 enhancer reversed UCP1 expression in GPD2-deficient adipocytes. Importantly, we find that human adipose GPD2 expression is inversely correlated with BMI, WHR, and HOMA-IR, underscoring its clinical relevance. Collectively, our findings establish GPD2 as an essential node in the metabolic-epigenetic axis that governs thermogenic activation and energy balance.

biochemistry↗

bioRxiv2026

An engineered IdeS variant with enhanced activity and performance for IgG degradation

IgG-degrading enzymes have emerged as innovative therapeutic agents for treating conditions driven by pathogenic antibodies. Here, we used structure-guided rational design to engineer IdeSM33, a double mutant (K167R/D226E) of the IgG-specific bacterial protease IdeS from Streptococcus pyogenes, with improved catalytic efficiency. Biolayer interferometry revealed a fourfold increase in binding affinity relative to wild-type IdeS (IdeSWT). This enhancement is likely attributable to mutations that strengthen hydrogen bonding at the enzyme-IgG Fc interface. In vitro, IdeSM33 has higher performance than IdeSWT in cleaving serum IgG. In vivo studies in rabbits demonstrated that IdeSM33 effectively depleted circulating IgG and showed better performance at a dose of 0.005 mg/kg than the IdeSWT. Although doses greater than 0.2 mg/kg demonstrated higher plasma concentrations of IdeS and a larger AUClast, they did not show a significant enhancement in the pharmacodynamics of IgG degradation. Importantly, a single dose of IdeSM33 (0.2 mg/kg) potently degraded binding and neutralizing antibodies against AAV9 within 1-2 days and restored hepatic AAV9 transduction in pre-immunized animals. Together, these findings highlight IdeSM33 as a potent and safe engineered enzyme with therapeutic potential for autoimmune disorders, transplant rejection, and overcoming pre-existing humoral immunity in gene therapy.

bioengineering↗

bioRxiv2026

Identifying Ecological Restoration Priority Areas through a Function-Structure-Dynamic Framework: Integrating Ecological Security Patterns and Future Land-Use Simulation in the Anhui Section of the Yangtze River Basin

Rapid urbanization has intensified ecological degradation and threatened ecosystem sustainability in the Yangtze River Basin. This study proposes a Function-Structure-Dynamic (FSD) framework integrating ecological protection importance assessment, ecological security pattern (ESP) construction, and future land-use simulation to identify ecological restoration priorities in the Anhui section of the Yangtze River Basin. Ecologically important areas were identified by coupling ecosystem services and ecological vulnerability. MSPA, landscape connectivity analysis, resistance surface modeling, and circuit theory were applied to construct the ESP, while the PLUS model simulated land-use change and ecological risks in 2032. Results identified 37 ecological sources covering 6,901.39 km{superscript 2} and 84 ecological corridors with a total length of 916.80 km. Ecological pinch points, barrier areas, and 17 ecological warning areas were further delineated. Based on these findings, four ecological restoration zones were proposed with differentiated management strategies. The FSD framework effectively integrates ecological functions, spatial structure, and future dynamics, providing scientific support for ecological restoration and sustainable territorial spatial planning in rapidly urbanizing regions.

ecology↗

bioRxiv2026

ARID4 Modulates Stomatal ABA Signaling and Stress-Responsive Gene Expression to Confer Drought Tolerance in Arabidopsis

To identify novel regulators of plant drought tolerance, we performed a forward genetic screen using thermal infrared imaging to detect alterations in leaf temperature, a proxy for transpiration. This screen identified AT-rich Interacting Domain Protein 4 (ARID4), a protein involved in chromatin remodeling, as a modulator of transpiration. arid4 loss-of-function mutants exhibited cooler leaves, increased water loss from detached leaves, and heightened susceptibility to drought relative to wild-type plants. Stomata of arid4 mutants were hyposensitive to abscisic acid (ABA), displaying reduced ABA-induced reactive oxygen species (ROS) production and impaired stomatal closure. Transcriptome profiling under drought revealed extensive misregulation of genes involved in stress-responses, redox homeostasis, iron acquisition, and photosynthesis. These findings indicate that ARID4 modulates the expression of key regulatory genes to maintain redox homeostasis and photosynthetic efficiency, thereby conferring drought stress tolerance.

Plant Biology↗

bioRxiv2026

Entanglement-governed protein networks enable mechanically adaptive artificial skin for transplantation-scale skin replacement

Artificial skin substitutes that simultaneously achieve mechanical robustness, regenerative bioactivity, and transplantation-scale tissue integration remain challenging to engineer. Here we report a mechanically adaptive bilayer artificial skin based on entanglement-mediated protein networks. By integrating protein chain entanglement, flexible molecular linkers, and photo-triggered intermolecular crosslinking, we establish a hierarchically organized protein matrix with enhanced toughness, structural adaptability, and regenerative compatibility. Spatial biofunctionalization further enables integration of an antibacterial Zn{superscript 2}-coordinated epidermal layer and a regenerative CLP-EGF-functionalized dermal layer within a unified construct. The engineered skin promotes cellular proliferation through PI3K-AKT-mTOR activation, exhibits sustained antibacterial activity, and supports large-area full-thickness skin replacement covering approximately 40% of the dorsal skin surface in mice. The construct further accelerates diabetic wound repair and extracellular matrix remodeling in vivo. These findings establish entanglement-mediated protein engineering as a strategy for mechanically adaptive regenerative biomaterials and provide a platform for transplantation-scale skin regeneration.

bioengineering↗

bioRxiv2026

OryzaG3: A Single-species Genomic Foundation Model Pretrained on Rice Pangenome

While multi-species genomic language models have advanced biological representation learning, high-quality, single-species foundation models for crops remain scarce. Leveraging recently expanded rice pangenome resources, we introduce OryzaG3, a species-specific DNA language model with 700M parameters. OryzaG3 was pretrained on 59.20 Gb of chromosome-level sequences from 149 high-quality rice genomes using a non-overlapping 3-mer tokenization strategy and a causal language modeling objective, featuring context-length variants up to 32k tokens. On the Plants Genomic Benchmark polyA prediction task, OryzaG3 achieves competitive predictive performance against leading multi-species models while delivering a four-fold increase in inference throughput under identical long-context conditions. Ultimately, OryzaG3 demonstrates that lightweight, single-species foundation models trained on high-quality pangenomes can match multi-species benchmarks while significantly reducing computational overhead. This work provides a scalable framework for rice functional genomics, molecular breeding, and targeted crop foundation model development.

bioinformatics↗