Biology subjects

Guo, D.

Publications and source records attributed to Guo, D..

At least 19 recordsLinked to original sources

bioRxiv2026

The cleaved C-terminal domain of GmERS1-1 modulates cell cycle via GmACR1

Ethylene signaling orchestrates plant development and stress adaptation, yet how post-translational modifications of its receptors coordinate growth regulation remains unresolved. Here, we uncover a proteolytic processing mechanism of the soybean ethylene receptor GmERS1-1 that directly gates cell cycle progression. The GmERS1-1 mutants exhibit elevated yield under field conditions, whereas overexpression suppresses growth and hypersensitizes plants to ethylene. Ethylene triggers nuclear translocation of C-terminal domain (GmERS1-1-CEND), which is indispensable for receptor function. Mechanistically, GmERS1-1-CEND scaffolds a trimeric complex with GmACR1 and GmCDK7, enforcing G2/M phase arrest, thereby decoupling cell division from canonical ethylene transcriptional responses. Strikingly, ethylene-induced cell cycle blockade during apple fruit maturation mirrors this pathway, suggesting deep conservation across angiosperms. Our work defines a receptor processing-dependent signaling axis that directly interlinks phytohormone perception with cell cycle control, proposing tunable targets (e.g., GmERS1-1 cleavage efficiency) for engineering crop architecture and productivity.

plant biology↗

bioRxiv2026

Photo-thermal Bidirectional Coupling Model for Transcranial Photobiomodulation

BackgroundAccurate optical-field simulation is critical for precise dosage delivery in transcranial photobiomodulation (tPBM). Current simulations neglect photon absorption-induced tissue heating which leads to temperature-dependent alterations of the optical field, thus fails to account for the bidirectional photo-thermal coupling effect. ObjectiveThis paper aims to establish a dynamic photo-thermal couple model that rigorously quantifies the bidirectional interaction between tissue heating and light propagation, and improves the optical dose prediction. ModelWe propose a Photo-Thermal bidirectional coupling Model (PTM). First, the Pennes Bioheat Equation (PBE) is employed to model the thermal response induced by photon absorption. Second, a Real-time temperature-dependent Absorption coefficient Model (RAM) is newly developed to quantify the thermal effect. Third, the PBE and RAM are integrated into the photon diffusion equation, forming the PTM. Finally, this coupled framework is solved temporally by an unconditionally stable Crank-Nicolson scheme. SimulationsBenchmarking against an analytical solution (two-layer cylindrical domain) demonstrates that PTM reduces the temperature prediction error by over 2.35% compared to the uncoupled baseline. Simulations using a realistic head model reveal that, compared to PTM, uncoupled modeling underestimates energy deposition by 150 J/m3 and overestimates photon fluence by 3 J/m2 within just one minute, and such discrepancies will be amplified with increasing exposure duration and power. Furthermore, the PTM identifies a 1.43-mm advantage in penetration depth for pulsed-wave over continuous-wave modality under iso-energy conditions, a key insight enabled by the coupled modeling approach. ConclusionThe PTM provides a high-fidelity simulation framework that captures the dynamic, bidirectional photo-thermal coupling in tPBM, explicitly quantifying the thermal feedback ignored by current models and thereby enabling more reliable treatment optimization and safer clinical translation.

neuroscience↗

bioRxiv2026

The role of the Angular Gyrus in the Elaboration of Specific and Categoric Memories

This study investigated the role of the angular gyrus (AG) and its subregions in the elaboration of specific and categoric autobiographical memories (AMs). Using a cue-word fMRI paradigm, thirty-nine participants retrieved and elaborated on episodic (specific) and semantic (categoric) memories, rating the amount of detail of each recollection. Parametric analyses revealed that AG activity, particularly in posterior AG, was positively associated with the amount of detail retrieved, regardless of memory type. Specific memories elicited greater activation in right AG subregions compared to categoric memories. These findings support the AGs involvement in both episodic and semantic memory retrieval and suggest functional differentiation between its subregions.

neuroscience↗

bioRxiv2026

Doublesex- mediated regulation of insulin signaling drives sex-specific body growth

Most animals develop sex-biased body sizes driven by sexually divergent plasticity in nutrient-dependent growth. Prior work in Drosophila, implicated the sex-determination gene transformer (tra) in regulation of sex differences in body size. However, tra does not widely mediate sex determination across insects. Thus, the unifying molecular pathway governing female-biased sexual size dimorphism (SSD) remains poorly established in non-drosophilid insects. The rice stem borer Chilo suppressalis, a devastating lepidopteran crop pest, exhibits a robust SSD, offering an ideal system to dissect underlying mechanisms. We report that female-specific splice forms of the sex-determining gene doublesex (Csdsx) are master regulators of female-biased growth. Disruption of the female-specific Csdsx exon 3 via CRISPR knockout or RNA interference drastically reduces female body size and completely erases the SSD. Csilp2, encoding a key insulin-like peptide (ILP2), is selectively upregulated in late-instar female larvae, and female CsDsx proteins directly bind and activate the Csilp2 promoter to boost transcription. Loss-of-function of Csilp2 eliminates the SSD by suppressing female somatic overgrowth. Our results identify a novel regulatory cascade: female-specific Dsx directly stimulates insulin signaling via Csilp2, bridging core sex-determination circuitry and nutrient-dependent body growth control. SignificanceSexual size dimorphism (SSD), widespread across insects with larger females, strongly shapes reproductive fitness. Yet reports on the molecular connection between sex determination and dimorphic growth are scarce. Using a major agricultural pest, the rice stem borer with a prominent female-biased SSD, we show that female-specific Doublesex (dsx) splice variants directly activate the promoter of Insulin-like peptide 2 in late larvae to trigger increased growth. Knocking out either gene in females abolishes the SSD. Our findings thus establish dsx as a novel link connecting sex-determination, insulin signaling and nutrient-dependent body growth.

Developmental Biology↗

bioRxiv2026

A high-level programming language for generative biology with Proto

Programmable composition of complex systems is a longstanding goal of biological research. Generative modeling has improved the reliability of computational design, but existing methods are highly specialized and are difficult to extend or compose. Here, we introduce Proto, a high-level programming language for generative biology. By composing a small set of abstract primitives into structured programs, Proto encodes generative design campaigns across diverse modalities and scales--spanning DNA, RNA, proteins, ligands, and their interactions. Proto readily incorporates predictive models into generative workflows, which we leveraged to design alternatively spliced introns with experimental validation in human cell lines. Proto is natively multi-objective, enabling the design of promoter-repressor pairs with leading experimental success rates for synthetic protein-DNA design. Alongside AI agents, Proto enables the specification of complex pathways and regulatory logic through natural language instructions. We openly release Proto, including software infrastructure and user interfaces, to enable widespread access to generative biological programming.

Synthetic Biology↗

bioRxiv2026

Alignment-free phylogenetic inference via hyperbolic protein language models

Conventional phylogenetic methods rely on multiple sequence alignments which are computationally intensive and often fail for highly divergent lineages. Here, we introduce LucaPhylo, an alignment-free framework that infers evolutionary relationships directly from unaligned sequences. Through a cascaded learning strategy LucaPhylo integrates protein language models with hyperbolic geometry, a representation space naturally suited to hierarchical branching, to capture deep evolutionary constraints without explicit homology matching. Using highly divergent RNA virosphere as a test case, LucaPhylo places unaligned sequences into phylogenetic trees with an accuracy comparable to leading alignment-based tree construction tools, while retaining divergent sequences that conventional pipelines frequently discard. It further enables the integration of divergent viral lineages into phylogenetic trees, thereby expanding the evolutionary landscape of RNA viruses. Together, LucaPhylo establishes an AI-driven, alignment-free paradigm for phylogenetic inference and provides a robust computational foundation for resolving deep evolutionary relationships among RNA viruses and other biological systems.

evolutionary biology↗

bioRxiv2026

The Impact of Dysregulated Lipid Metabolism on the Gut-Brain Axis in Patients with Intracerebral Hemorrhage

BACKGROUNGBisphenol A (BPA) has been linked to hypertension and disturbances in lipid metabolism; however, limited evidence is available regarding its association with hypertensive intracerebral hemorrhage (ICH). METHODSA multicenter, retrospective case-control study was conducted involving 129 participants, including individuals from an ICH group and healthy controls. Standard assays were employed to assess serum thyroid function, lipid profiles, serum fatty acid-binding [x]protein 4 (FABP4), oxidative stress markers, gap junction proteins, Wnt/{beta}-catenin signaling pathway activity, and expression changes of S100A8-mediated inflammatory cytokines involved in gut-brain interactions. Correlation analyses using Pearson and Spearman methods revealed that both BPA exposure and low T3 levels were significantly associated with elevated diastolic blood pressure, altered lipid metabolism, gut microbiota composition, and microglial activation. RESULTSGender-based disparities in lipid metabolism were identified. Changes in {beta}3-adrenergic receptor and neuromodulin-1 expression appear to influence fat regulation and attenuate oxidative stress responses. Subsequently, increased expression of gap junction proteins and activation of the Wnt/{beta}-catenin signaling pathway contribute to metabolic reprogramming and alterations in biochemical kinetics. Gut microbiota analysis demonstrated that, compared to controls, the ICH group exhibited significant dysbiosis and reduced alpha diversity. Further correlation analyses indicated that BPA levels were positively associated with FABP4 and oxidative stress markers, while S100A8 showed a strong dependence on microglial expression. CONCLUSIONThe interplay between lipid metabolism dysfunction and pro-inflammatory cytokines enhances vascular vulnerability. Collectively, BPA exposure, oxidative stress, and microglia-mediated neuroinflammation are significantly associated with an elevated risk of hypertensive ICH. China Clinical Trial Registry registration noticeFrom: China Clinical Trials Registry +To:guopingwang60a yunyanshuangfei FUNDINGThis work was supported by the Natural Science Foundation of Shanxi Province (grant no. 201701D121177) Key informationGender-specific differences were observed in lipid metabolism and oxidative stress parameters; BPA exposure was shown to induce lipid metabolic disturbances, promote excessive production of oxidative stress byproducts, and consequently elevate oxidative stress responses; BPA was associated with stress-induced alterations in thyroid hormone function, further exacerbating dysregulation of lipid metabolism and oxidative stress; Fatty acid binding protein 4 (FABP4), a key adipokine implicated in metabolic disorders and adipose tissue inflammation, exhibited a significant positive correlation with serum BPA levels, whereas low levels of triiodothyronine (T3) were negatively correlated with FABP4. These findings suggest that serum FABP4 may serve as a biochemical marker for chronic low-grade adipose tissue inflammation and metabolic dysfunction; Gap junction proteins and the Wnt/{beta}-catenin signaling pathway may contribute to microglial activation and mediate neuroinflammatory responses, nerve injury, and secondary pathological processes in obesity-related cerebral hemorrhage.

biochemistry↗

bioRxiv2026

SpaCir-VDJ: a broadly compatible circularization strategy for spatial immune repertoire profiling

Deciphering the spatial organization of immune clonal lineages is critical for understanding the evolution of adaptive immune responses. However, mainstream spatial transcriptomics platforms struggle to reconcile cost-effective short-read sequencing with the simultaneous and efficient capture of V(D)J sequences. To address this gap, we developed SpaCir-VDJ, an approach that utilizes a "multiplex PCR enrichment plus library circularization" strategy to integrate spatial barcodes and V(D)J CDR3 regions into a compact circular template optimized for standard short-read sequencing. This workflow is accompanied by an automated computational pipeline designed for circular-library data parsing, sequence reconstruction, spatial barcode deconvolution, and high-fidelity clonotype calling. In human lymphoid tissues, SpaCir-VDJ delineated germinal center (GC)-associated clonal organization and isotype-linked somatic hypermutation (SHM) patterns. Notably, lineage-based spatial analyses inferred inter-GC clonal redistribution events, suggesting that GCs in the analyzed samples may not be fully isolated reaction units. Functional perturbation provided orthogonal support for candidate SHM regulators identified by spatial analysis, with knockdown of MDM4, LYN, EAF2, and H2AFY each leading to reduced SHM. Finally, in gastric cancer, SpaCir-VDJ localized dominant BCR lineages within tertiary lymphoid structures and tumor-margin plasma cell-rich regions, with lineage patterns consistent with extension toward the tumor interior. We further observed a significant positive correlation between cumulative tumor mutations and spatial TCR diversity, consistent with a spatial association between local mutational burden and T-cell remodeling within the tumor microenvironment. Collectively, SpaCir-VDJ provides a scalable and cost-effective framework for interrogating the spatiotemporal dynamics of immune microenvironments.

immunology↗

bioRxiv2026

Targeting ALA3 with propiconazole regulates plant growth and enables discovery of promising inhibitor leads

Propiconazole (PCZ) is widely misused growth regulator in leafy Brassica vegetables. Developing green strategies for managing plant architecture has become an urgent agricultural priority. Here, we identified from a membrane-protein-defective yeast library a P4-ATP phospholipid flippase, aminophospholipid ATPase 3 (ALA3), as a target sensitive to PCZ. ALA3 exhibits high binding affinity for PCZ, which inhibits its ATPase activity. Knockdown of ALA3 rendered yeast, Arabidopsis, and Brassica rapa less sensitive to PCZ and conferred a growth-inhibited phenotype. This dwarfing phenotype is mediated through the interaction between ALA3 and CYP51G1 that jointly acts within the brassinosteroid regulatory pathway. Furthermore, we identified lead compounds A01 and A15 as ALA3-targeting agents, and compared to PCZ, they display superior binding affinity and reduced toxicity. Our work establishes ALA3 as a key mediator of PCZ-induced dwarfism and provides dual strategies--creating promising varieties through gene editing and developing targeted green pesticides--to reduce PCZ use. TeaserTargeting ALA3 reduces PCZ use through gene-edited varieties and green pesticides.

plant biology↗

bioRxiv2026

The BraALA3 Homologs Mediate Propiconazole-Modulated Plant Growth in flowering Chinese cabbage

In agriculture, propiconazole (PCZ) controls excessive growth in flowering Chinese cabbage but poses dietary safety risks due to residue accumulation. Therefore, identifying novel PCZ targets and breeding PCZ-free cultivars is critical for the safe production of flowering Chinese cabbage. Here, we identified three P4-ATPase flippase homologs aminophospholipid ATPase 3 (BraALA3a/b/c) in flowering Chinese cabbage that function as sensitive targets for PCZ. These proteins exhibit high binding affinity for PCZ, which directly inhibits their ATPase activity. Overexpression of the BraALA3 homologs enhanced plant growth and increased sensitivity to PCZ, whereas knockdown led to dwarfism and reduced sensitivity. Based on these findings, we identified editable active sites via protoplast-based screening. Genetic transformation of one such site yielded BraALA3a/braala3aK200T mutant lines, which displayed a dwarf and compact architecture. These findings provide a precise molecular target for developing PCZ-free germplasm in flowering Chinese cabbage through gene editing.

plant biology↗

bioRxiv2026

An EEG-fMRI Jointly Constrained Digital Twin Brain and Its Application in Alzheime's Disease

Current digital twin brain (DTB) models are typically optimized using single-modality functional neuroimaging data, which restricts their ability to simulate brain dynamics across multiple spatiotemporal scales. Here, we bridged this gap by developing a two-stage DTB (TS-DTB) modeling framework jointly constrained by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) data. Validation in both the healthy young and Alzheimers disease (AD) cohorts demonstrated that the TS-DTB model simultaneously captures subject-specific features of multi-scale brain dynamics. In particular, the TS-DTB models of AD patients successfully recapitulated spectral-temporal signatures of cognitive decline, mechanistically linking these deficits to excitation-inhibition (E-I) imbalances. By simulating responses to repetitive transcranial magnetic stimulation (rTMS), we further revealed that cognitive recovery in AD patients can be driven by E-I rebalancing via synaptic reconfiguration and background suppression. Overall, these findings underscore the potential of the TS-DTB to advance the mechanistic understanding of the brain and inform personalized digital therapeutics.

neuroscience↗

bioRxiv2026

Tract-explainable and underexplained synchrony play complementary roles in the functional organization of the brain

Macroscale functional connectivity emerges from a complex interplay between structural wiring and non-tract-mediated mechanisms. However, the intrinsic entanglement of these contributions obscures their specific roles in brain organization. Here, we introduce a computational modeling framework to disentangle functional synchrony into two fundamentally distinct components: tract-explainable and tract-underexplained synchrony. Validated across two large-scale human cohorts (n = 1214) and an independent marmoset dataset (n = 24), this dissociation reveals an evolutionarily conserved architectural principle. We show that tract-explainable synchrony aligns closely with structural connectomes to facilitate global integration. Conversely, tract-underexplained synchrony drives local modularity and is anchored by multiscale cortical similarity, encompassing microstructural, receptor, and transcriptomic profiles. Crucially, these components gradually dissociate from sensori-motor to higher-order association cortices, with the importance of tract-underexplained synchrony progressively increasing. Furthermore, the tract-underexplained synchrony exhibits greater individual variability and demonstrates a stronger association with individual cognitive performance. Ultimately, tract-based and non-tract-mediated mechanisms serve distinct yet complementary roles, jointly shaping a functional organization that balances conserved macroscopic stability with higher-order cognitive flexibility.

neuroscience↗

bioRxiv2026

Integrative Single-Cell Epigenomic Atlas Annotates the Regulatory Genome of the Adult Mouse Brain

Histone modifications underpin the cell-type-specific gene regulatory programs that drive the remarkable cellular diversity of the mammalian brain. Here, we jointly profiled four histone modifications and the transcriptome in 2.5 million nuclei from the adult mouse brain. By integrating these data with chromatin accessibility, DNA methylation, and three-dimensional genome organization, we constructed a unified epigenomic atlas spanning over 100 brain cell subclasses, and assigned active, primed, and repressive chromatin states across 81% of the genome. Active chromatin states marked by combinatorial histone modifications better nominate candidate enhancers with functional support than chromatin accessibility alone, while H3K27me3- and H3K9me3-marked chromatin states delineate distinct modes of cell-type-specific gene repression. Finally, this multimodal resource enables deep learning models that predict cell-type-specific epigenomic features and gene expression from DNA sequence, providing a comprehensive framework for annotating the brain regulatory genome and interpreting non-coding disease risk variants. HIGHLIGHTS- A single-cell epigenome atlas of transcription and four histone modifications across 2.5M mouse brain cells - Multimodal integration maps chromatin states across [~]81% of the adult mouse brain genome - Cell-type-resolved chromatin landscapes reveal regulatory programs mediated by enhancers, Polycomb and H3K9me3 - Deep learning models predict cell-type-specific epigenomic features and gene expression from DNA sequence

genomics↗

bioRxiv2025

Visualization of photoreceptor outer segment renewal using AAV-delivered Dendra2-tagged rhodopsin

Visualization of photoreceptor outer segment (OS) renewal dynamics is essential for vision research but has proved difficult in mice due to the small size and dense packing of their photoreceptors. Lack of effective protein "trackers" and the time-consuming generation of transgenic reporter lines add to these challenges. In this study, we evaluated AAV-mediated delivery of photoconvertible Rhodopsin/Dendra2 and Peripherin2/Dendra2 fusion proteins as a means to track OS renewal in mouse photoreceptors. OS renewal was assessed by two approaches: (1) comparing the lengths of native (green) Dendra2 domains at two post-infection time points, and (2) using photoconversion of Dendra2 to distinguish newly synthesized discs from preexisting ones within the same cell. We validated this method in both wild type mice and a Tmem138-deficient ciliopathy mutant, in which a reduced OS renewal rate was observed. Taken together, this method offers a rapid genetic tool for "real-time" evaluation of OS renewal dynamics in mice, overcoming limitations posed by the compact and densely organized photoreceptor architecture.

cell biology↗

bioRxiv2025

Overexpression of TPM4 promotes cancer progression through EMT in anaplastic thyroid cancer

Anaplastic thyroid cancer (ATC) is an undifferentiated tumour originating from thyroid follicular epithelium and represents the most malignant subtype of thyroid cancer. However, the mechanisms underlying ATC development are not fully understood. This study aimed to investigate the mechanisms driving ATC invasion and metastasis to provide novel insights into its aggressive behavior. Through an integrated bioinformatics analysis of the GEO database, we identified Tropomyosin 4 (TPM4) as a differentially expressed gene in ATC. Bioinformatic correlation and pathway enrichment analyses suggested that TPM4 expression is potentially linked to tumor cell invasion and lymph node metastasis. We showed that TPM4 was highly expressed in both ATC tissues and cell lines, and its expression levels were positively correlated with enhanced cell migration and invasion. Mechanistic studies indicated that TPM4 likely enhances tumour cell migration and invasion by facilitating cytoskeletal remodeling and promoting the epithelial-mesenchymal transition (EMT). Our findings suggest that TPM4 represents a promising diagnostic and therapeutic biomarker for ATC.

cancer biology↗

bioRxiv2025

Generative design of novel bacteriophages with genome language models

Many important biological functions arise not from single genes, but from complex interactions encoded by entire genomes. Genome language models have emerged as a promising strategy for designing biological systems, but their ability to generate functional sequences at the scale of whole genomes has remained untested. Here, we report the first generative design of viable bacteriophage genomes. We leveraged frontier genome language models, Evo 1 and Evo 2, to generate whole-genome sequences with realistic genetic architectures and desirable host tropism, using the lytic phage {Phi}X174 as our design template. Experimental testing of AI-generated genomes yielded 16 viable phages with substantial evolutionary novelty. Cryo-electron microscopy revealed that one of the generated phages utilizes an evolutionarily distant DNA packaging protein within its capsid. Multiple phages demonstrate higher fitness than {Phi}X174 in growth competitions and in their lysis kinetics. A cocktail of the generated phages rapidly overcomes {Phi}X174-resistance in three E. coli strains, demonstrating the potential utility of our approach for designing phage therapies against rapidly evolving bacterial pathogens. This work provides a blueprint for the design of diverse synthetic bacteriophages and, more broadly, lays a foundation for the generative design of useful living systems at the genome scale.

synthetic biology↗

bioRxiv2025

T2T Gap-free Genome Assembly of Gp03, a Soybean Cultivar with High Genetic Transformation Efficiency

Soybean is a major cultivated crop worldwide, serving as a crucial source of edible oil, plant protein, and animal feed. The continuous growth of the global population necessitates accelerated soybean breeding. High-quality reference genomes are foundational for soybean functional genomics and breeding research. Several telomere-to-telomere (T2T) reference genomes have been released, facilitating subsequent functional studies. However, soybean varieties show varying efficiencies in genetic transformation, with currently available reference genomes having low transformation efficiencies. Here, we report the complete T2T genome assembly of Gp03, a soybean cultivar with high genetic transformation efficiency, developed in Northeast China. Gp03 exhibited high transformation efficiency in comparative studies and favorable agronomic traits for dense planting. The assembly comprises 20 chromosomes with a total size of 1.01 GB, an N50 length of 51.5 Mb, and includes 40 telomeres and 20 putative centromere regions. Genome annotation identified 61,832 genes and 545.8 Mb of repetitive sequences, accounting for 53.8% of the genome. This work provides a valuable genetic resource for soybean breeding and is expected to accelerate molecular breeding efforts.

plant biology↗

bioRxiv2025

Multi-omics characterization of the skin microbiota reveals the anti-aging roles of Stenotrophomonas maltophilia

Shifts in the skin microbiome have shown a close link to chronological age. However, the contribution of skin microbiome in skin aging phenotypes remains unclear. To explore this, we performed phenotypic, metabolomic, metagenomic, and functional analyses on a cohort with divergent skin aging phenotypes. Genome-scale metabolic models (GEMs) integrated with metabolomic analysis revealed that Stenotrophomonas maltophilia, enriched in the younger group (categorized by AI-predicted age and skin elasticity), utilizes the glutathione cycle to maintain redox homeostasis. Cellular experiments showed its metabolites enhanced GSH synthesis and alleviated oxidative stress-induced skin aging by upregulating key genes in fibroblasts, including GCLM, PGD, SOD2, and NQO1. Additionally, GEMs highlighted its potential anti-aging roles in regulating host metabolic pathways involving betaine, lysolecithin, and porphyrin. In parallel, Acinetobacter guillouiae was found to influence host melanin metabolism by degrading dopamine (DA) and 3-methoxytyramine (3-MT), offering potential therapeutic strategies for mitigating pigmentation. Our findings highlight the dynamic interplay between skin microbiota and the host in aging, offering new insights for designing targeted anti-aging interventions.

microbiology↗