Biology subjects

Gu, Y.

Publications and source records attributed to Gu, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Structure of the Chimalliviridae bacteriophage Goslar reveals host recognition and infection machinery

Large-genome bacteriophages (phages) of the Chimalliviridae family possess a distinctive life cycle, building compartments inside infected bacterial cells that broadly protect their genomes from host defenses. Here, we use cryoelectron microscopy to determine a high-resolution structure of the E. coli-infecting Chimalliviridae phage Goslar, generating a composite model with 2,888 protein chains from 28 different structural proteins, totaling over 1.4 million amino acid residues. Our structure reveals the architecture of the Goslar capsid, portal, tail, and baseplate, highlighting structural similarities and differences with other tailed phages. Combining our structural data with quantitative mass spectrometry of Goslar virions, we identify several high-copy virion-associated proteins that likely play key roles when injected into host cells upon infection. We also identify a Chimalliviridae-specific family of proteins that form long, flexible filaments anchored at the phage baseplate and which incorporate carbohydrate-binding domains, suggesting a key role in host recognition.

microbiology↗

bioRxiv2026

A Rapid and Universal Pipeline for High-Resolution GPCR Structure Determination through In Silico Construct Optimization and de novo Protein Design

G protein-coupled receptors (GPCRs) are critical regulators of human physiology and major drug targets. Although structural studies have provided valuable insights, determining GPCR structures remains challenging, especially for inactive state receptors. Recent advances in cryo-electron microscopy (cryo-EM) have enabled structural determination of small GPCRs by using fusion partner proteins and binders to increase molecular weight. However, current methods require extensive experimental screening of fusion constructs. Widely adopted strategies, such as BRIL-Fab complexes, also face limitations due to inherent flexibility. Here, we introduce a streamlined and universal pipeline that integrates an in silico fusion construct screening program, NOAH (NOAH: NOn-experimental, AI-assisted High-throughput construct screening), with a de novo designed fusion protein called ARK1 (ARtificially-designed fiducial marKer). We validate the efficacy of NOAH by determining the structures of the vasopressin V2 receptor (V2R) bound to the clinical antagonist tolvaptan and the partial agonist OPC51803, as well as the bradykinin B2 receptor (B2R) bound to the clinical antagonist icatibant, thereby elucidating their activation and deactivation mechanisms. Furthermore, we demonstrate the capability of NOAH-ARK1 by solving the tolvaptan-bound V2R structure at higher resolution and showcase the methods versatility by determining the structure of lysophosphatidic acid receptor 2 (LPA2) bound to the antagonist Ki16425. This approach eliminates the need for time-consuming and labor-intensive construct optimization, providing a rapid and widely applicable solution for high-resolution GPCR structure determination and drug discovery.

biophysics↗

bioRxiv2026

Chromosomal rearrangements 1 and sequence similarity drivepreferential allosyndetic introgression from a wild relative into wheat

Recombination in polyploid genomes is generally constrained to homologous or homoeologous chromosomes; however, how chromosomal rearrangements influence recombination between chromosomes remains unclear. Here, we demonstrate that large-scale chromosomal rearrangements in the wild relatives of wheat are associated with recombination involving non-homoeologous chromosomes or arms during alien gene introgression under conditions that permit homoeologous recombination mediated by ph1b. Using a wheat chromosome 6A monosomic-induced 6AS*6CL Robertsonian translocation combined with ph1b-mediated recombination, we generated 17 independent recombinants carrying a new stem rust resistance gene, Sr69, from Aegilops caudata chromosome arm 6CL. Unexpectedly, 94.1% (16 of 17) of recombinants resulted from exchanges with wheat group-7 chromosomes rather than with the homoeologous group-6 chromosome. Comparative sequence- and marker-based analyses identified a 67-Mb rearranged interval on Ae. caudata 6CL that corresponds to telomeric regions of the long arms of wheat group-7 chromosomes. Sequence similarity within this interval was quantitatively associated with recombination frequency, with higher similarity corresponding to more frequent translocations. Physical and optical mapping showed that recombination within the rearranged interval generated compensating 7A/6C, 7B/6C, and 7D/6C translocations, whereas recombination outside this region produced non-compensating 6A/6C exchanges. An independent case involving the powdery mildew resistance gene Pm7C showed a similar correspondence between a rearranged 7CL region and preferential introgression into wheat 7DS. Together, these results indicate that ph1b-mediated recombination involving structurally altered chromosomes is driven by local chromosomal structure and sequence similarity rather than strict homoeologous group identity. This provides a mechanistic basis for harnessing untapped beneficial genes from structurally rearranged alien genomes. Significance StatementAlien gene introgression is a powerful strategy for wheat improvement, typically relying on ph1b-mediated recombination between homoeologous chromosomes. The genomic basis and outcomes of introgression from structurally rearranged alien chromosomes remain unclear. Here, we show that ph1b-induced recombination can efficiently target wheat-allosyntenic blocks in rearranged alien genomes, preferentially transferring genes from structurally altered alien segments into their syntenic regions on wheat chromosomes of different homoeologous groups. Crossover formation is governed by extended sequence similarity within corresponding intervals rather than strict collinearity across entire homoeologous chromosomes. As many wild species exhibit extensive genome rearrangement, these findings and methodologies expand access to underexploited genetic diversity embedded within highly rearranged wild genomes for wheat improvement.

genetics↗

bioRxiv2026

Complete genome-derived metabolic interactions reveal impact of gut ecology on human health

Metabolic interactions govern gut microbiome assembly, yet functional rules remain obscured by genomic incompleteness and fragmentation. Here, we leverage 1,150 complete genomes to construct genome-scale metabolic models, demonstrating that draft genomes introduce systemic artifacts missing critical transport functions. We observe that metabolic interactions are intrinsically driven by genomic traits and niche specialization rather than random association. We stratifies strains into four ecological groups, including active players, resource predators, utilizers, and contributors, each of which exhibits distinct metabolite exchange/competition signatures. This functional architecture is strongly coupled to secondary metabolism. Applying this framework to inflammatory bowel disease revealed distinct temporal dynamics of ecological groups across disease subtypes, where group-specific dysbiosis predicted clinical phenotypes better than whole community profiles. Furthermore, integrating metabolic and co-occurrence networks to identify keystone for classifiers as features significantly improved disease diagnosis. Our study provides novel insights into gut metabolic interaction landscape, bridging the gap between genomic potential and clinical utility for precision microbiome therapeutics.

microbiology↗

bioRxiv2026

Complete Genomes of Cultivated Gut Bacteria Reveal Mobile Genetic Element-Driven Functional Diversity with Therapeutic Implications

Cultivated bacterial isolates are essential for elucidating gut microbiota functions, yet reliance on fragmented draft genomes and limited mobile genetic element (MGE) annotation has constrained high-resolution analyses. Here, we present the Cultivated Complete Genome Reference (CCGR), a comprehensive compendium of 1,150 fully circularized human gut bacterial genomes. Overcoming draft limitations, CCGR achieves chromosome-scale resolution and reveals distinct evolutionary strategies shaping gene topological organization in response to bacterial growth. Furthermore, we decode the dynamic landscape of MGEs, demonstrating that broad-host-range phages follow strict positional patterns by integrating at conserved chromosomal hotspots flanked by nutrient transporter loci. Importantly, we provide mechanistic in vivo evidence that accessory genomic elements drive strain-level functional heterogeneity. Specifically, the plasmid-encoded scrK gene in Levilactobacillus brevis involved in fructose catabolism is required to mitigate fructose-diet-exacerbated colitis. Collectively, CCGR establishes a framework linking chromosomal architecture and MGEs to bacterial evolution and host health, enabling precise, strain-resolved functional investigations.

microbiology↗

bioRxiv2026

Lipoxins Regulate Intercalated Disk-Associated Signaling and Immune Remodeling in Dilated Cardiomyopathy

We investigated whether pro-resolving lipid mediators of the lipoxin family can attenuate fibrosis and inflammation in muscle LIM protein knockout (MLPko) mice, a model of dilated cardiomyopathy (DCM). Male and female MLPko mice received either vehicle or a mix of lipoxin-A4 and lipoxin-B4 three times per week for six weeks. Cardiac function was assessed using echocardiography, and fibrosis and DCM-associated cardiac signaling was evaluated through histology, immunofluorescence and immunoblot analyses. Flow cytometry and RNA sequencing (RNAseq) was performed to identify changes in cardiac gene expression and characterize macrophage subpopulations, respectively. Flow cytometry showed increased inflammatory CD11c+ M1-like macrophages and reduction of CD206+ M2-like macrophages in MLPko hearts compared to wild-type controls. Lipoxin treatment partially reversed the macrophage imbalance and showed mild improvements in cardiac physiology in MLPko males. RNAseq analyses revealed sex-dependent alterations in the expression of pro-fibrotic and inflammation-related genes, suggesting changes in extracellular matrix (ECM) integrity and composition, and to the adaptive immune response. Intriguingly, several ECM proteins showed unexpected localizations at cardiac intercalated disks, which are known to be involved in DCM etiology. Further analysis identified lipoxin-dependent reduction in the DCM-associated expression of intercalated disk components only in lipoxin-treated MLPko males. Lipoxins also modulated key cardiac signaling pathways in a sex-specific manner, including Erk1/2 and PKC-linked Ankrd1/Carp1, which is associated with DCM development in MLPko mice. While lipoxins do not directly reverse cardiac dysfunction or fibrosis in MLPko mice, they may provide sex-specific protective effects by modulating DCM-related cardiac signaling pathways and by influencing immune-cell populations.

cell biology↗

bioRxiv2026

GPNMB overexpression- a marker of resistance to CDK4/6 inhibitors

Resistance to cyclin-dependent kinase 4/6 inhibitors remains a major clinical challenge in treating estrogen receptor-positive breast cancer, with no reliable predictive biomarkers currently available for patient selection. To investigate resistance mechanisms, we generated drug-tolerant persisters (DTPs) to abemaciclib and palbociclib in a panel of estrogen receptor-positive breast cancer cell lines. Functional analyses revealed that DTPs showed resistance to CDK4/6 inhibition, maintained G1 arrest, and exhibited increased senescence phenotype. To identify clinically relevant markers of resistance, we compared transcriptomic profiles from DTPs with publicly available gene-expression data from the phase III PEARL trial. Glycoprotein non-metastatic B (GPNMB) emerged as one of the most strongly upregulated transcripts in DTPs, and also was amongst the genes associated with resistance in the PEARL dataset. We further verified that GPNMB overexpression (GPNMB-OE) in sensitive cells conferred resistance to CDK4/6 inhibition, and enhanced migratory capacity. Overexpression of GPNMB drove substantially faster tumor progression and eliminated the growth-inhibitory effect of abemaciclib, which remained highly effective in control tumors. Across all treatment arms, GPNMB-OE tumors failed to respond to CDK4/6 blockade, highlighting a strong resistance phenotype. These results identify GPNMB as a potent promoter of tumor progression and a key mediator of resistance to abemaciclib. Our findings position GPNMB as a potential biomarker and therapeutic target that may help identify patients unlikely to benefit from CDK4/6 inhibition.

cancer biology↗

bioRxiv2026

Relation Extraction for Diet, Non-Communicable Disease and Biomarker Associations (RECoDe): A CoDiet study

Diet plays a critical role in human health, with growing evidence linking dietary habits to disease outcomes. However, extracting structured dietary knowledge from biomedical literature remains challenging due to the lack of dedicated relation extraction datasets. To address this gap, we introduce RECoDe, a novel relation extraction (RE) dataset designed specifically for diet, disease, and related biomedical entities. RECoDe captures a diverse set of relation types, including a broad spectrum of positive association patterns and explicit negative examples, with over 5,000 human-annotated instances validated by up to five independent annotators. Furthermore, we benchmark various natural language processing (NLP) RE models, including BERT-based architectures and enhanced prompting techniques with locally deployed large language models (LLMs) to improve classification performance on underrepresented relation types. The best performing model gpt-oss-20B, a local LLM, achieved an F1-score of 64% for multi-class classification and 92% for binary classification using a hierarchical prompting strategy with a separate reflection step built in. To demonstrate the practical utility of RECoDe, we introduce the Contextual Co-occurrence Summarisation (Co-CoS) framework, which aggregates sentence-level relation extractions into document-level summaries and further integrates evidence across multiple documents. Co-CoS produces effect estimates consistent with established dietary knowledge, demonstrating its validity as a general framework for systematic evidence synthesis. AvailabilityThe code, models, and data will be made freely available upon acceptance.

bioinformatics↗

bioRxiv2026

A Translational Model of MASLD-Associated HFpEF Defines Mitochondrial Dysfunction and Cardiac Plasticity During Disease Progression and Regression

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are strongly linked to cardiac dysfunction, particularly, heart failure with preserved ejection fraction (HFpEF), yet the mechanisms underlying this association remain unclear because robust integrative preclinical models are lacking and the liver and heart are rarely studied as a coordinated system. Here we show that Alms1-/- (Foz/Foz) mice fed a Western diet develop MASH with advanced liver fibrosis accompanied by a HFpEF-like phenotype characterized by left ventricular hypertrophy, impaired cardiomyocyte contractility, reduced {beta}-adrenergic reserve, elevated BNP, and increased mortality despite ejection fraction >50%. Liver fibrosis emerged as a parameter strongly associated with the cardiac dysfunction. Remarkably, dietary reversal improved hepatic architecture, normalized cardiac function, and improved survival, revealing marked plasticity of the liver-heart axis. Analyses of left ventricular (LV) remodeling revealed mitochondrial dysfunction, altered substrate utilization, and extracellular matrix remodeling in the LV, with consistent concordance to human HFpEF transcriptomic signatures. Ultrastructural studies confirmed mitochondrial injury and sarcomeric disorganization, linking metabolic failure to impaired cardiomyocyte performance. Together, these findings identify mitochondrial dysfunction as an important feature of MASLD-associated HFpEF-like cardiac dysfunction and establish the Foz/Foz model as a powerful platform for investigating pathophysiological pathways linking metabolic liver disease to cardiac dysfunction and for testing mechanism-based therapeutic strategies. STRUCTURED ABSTRACTO_ST_ABSBackgroundC_ST_ABSMetabolic dysfunction associated steatotic liver disease (MASLD) and its advanced form, MASH, are closely linked to cardiac dysfunction, particularly heart failure with preserved ejection fraction (HFpEF). However, the mechanisms underlying MASLD-associated HFpEF and its reversibility remain poorly understood, largely due to the lack of robust preclinical models. Here, we established a translational model of MASLD-associated cardiac dysfunction that recapitulates the key features of human HFpEF. We applied functional and transcriptomic analyses of the left ventricle (LV) to define the pathways associated with cardiac dysfunction and its reversibility. MethodsAlms1-/- (Foz/Foz) mice and wild-type littermates were fed normal chow (NC) or Western diet (WD) for up to 36 weeks (wk). Reversibility was modeled by switching WD-fed Foz/Foz mice at 12wk back to NC for 12wk. Cardiac assessment included echocardiography, invasive hemodynamics with dobutamine stimulation, histopathology, electron microscopy and isolated cardiomyocyte contractility. LV transcriptomes were profiled by bulk RNA sequencing and analyzed by differential expression and pathway enrichment. ResultsFoz/Foz mice on WD for 24wk developed metabolic syndrome and MASH with advanced liver fibrosis. Cardiac phenotyping showed LV hypertrophy, impaired cardiomyocyte contractility, reduced {beta}-adrenergic reserve, elevated plasma BNP, and increased mortality while the ejection fraction was preserved (>50%), consistent with HFpEF. The progression of cardiac dysfunction was closely associated with liver fibrosis that developed during MASH. Switching WD-fed Foz/Foz mice at 12wk to normal chow diet reversed hepatic fibrosis, restored LV function, and reduced mortality, demonstrating plasticity of the liver-heart axis. LV transcriptomic analysis revealed that cardiac impairment in these mice was associated with mitochondrial dysfunction, altered substrate utilization, extracellular matrix remodeling, and metabolic stress; pathways that are similarly dysregulated in human HFpEF. Cardiac electron microscopy revealed swollen mitochondria with disrupted cristae, which improved following dietary intervention. ConclusionsMitochondrial dysfunction and fibroinflammatory remodeling are prominent features of MASLD-associated cardiac dysfunction. Reversal of hepatic and cardiac phenotypes with dietary intervention, together with elucidation of underlying pathways, establish the Foz/Foz model as a useful translational platform for studying liver-heart axis in MASLD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/708088v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@60bd2aorg.highwire.dtl.DTLVardef@1234a09org.highwire.dtl.DTLVardef@1d1c5aborg.highwire.dtl.DTLVardef@1086089_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2026

Hopx expression marks Aβ clearance astrocytes in Alzheimers disease

SUMMERYAstrocytic dysfunction is closely associated with nearly all types of neurological diseases. Targeting astrocyte regulation has thus emerged as an important potential therapeutic strategy for neurological disorders. However, mechanisms that induce astrocyte dysfunction under pathological conditions have not been fully elucidated. In this study, we identified that Homeodomain-only protein X (Hopx) is downregulated in astrocytes across inflammatory models, Alzheimers disease (AD) mouse models, and brain tissues from AD patients. In the brains of AD mice, Hopx-positive astrocytes exhibit efficient {beta}-amyloid (A{beta}) plaque clearance, while knockout of Hopx leads to astrocytic dysfunction. Conversely, astrocyte-specific overexpression of Hopx not only significantly enhances their A{beta} phagocytic function but also effectively reduces the generation of neurotoxic astrocytes while increasing protective astrocytes. In summary, this study demonstrates the core regulatory mechanism underlying astrocytic dysfunction under AD pathological conditions and provides important potential targets for developing therapeutic strategies for AD by targeting astrocyte regulatory pathways.

neuroscience↗

bioRxiv2026

Self-amplifying RNA-based CAR T cell therapy with enhanced duration and multi-genic logic function

Chimeric antigen receptor T (CAR-T) cell therapy is transforming the treatment landscape of hematological malignancies. However, manufacturing with integrating viral vectors is costly, slow, and carries risks including insertional mutagenesis, prolonged B cell aplasia, and other long-term toxicities. Expression of CAR with mRNA can reduce cost, manufacturing timelines, and improve safety. However, the short-lived expression necessitates frequent repeat dosing. Here, we describe a modified self-amplifying RNA (saRNA) platform for engineering CAR T cells with prolonged CAR expression and enhanced durability of tumor control relative to mRNA CAR T cells. In an acute lymphoblastic leukemia (ALL) xenograft model, saRNA CAR T cells achieve superior tumor suppression and prolong survival. Further, a single-strand modified saRNA supports the co-expression of multiple proteins, enabling the construction of advanced CAR systems, such as OR- and AND-gated logic CAR T cells. Together, these results highlight saRNA as a powerful and versatile platform for CAR T cell engineering with favorable safety, efficacy, and accessibility.

bioengineering↗

bioRxiv2026

Cell Type Architecture and Positional Gene Gradients in an Adult Animal at Subcellular Resolution

The spatial organization of cell types and gene expression underlies tissue architecture and organismal physiology. However, resolving complete cellular and molecular landscapes within a three-dimensional context remains challenging, particularly in organisms with high cellular heterogeneity and complex geometry. Here, we developed a semi-supervised workflow to reconstruct high-resolution three-dimensional spatial transcriptomic models of the planarian Schmidtea mediterranea at single-cell resolution. Planarians are basal bilaterians capable of regenerating body structures after injury. Our reconstruction maps the distribution of cell types and spatially patterned gene expression across the intact organism and identifies 119 candidate positional control genes (PCGs). These genes are expressed across muscle, neural, and epidermal populations. Functional perturbation of selected candidates, including pitx3, ptpn11, pi4ka, upf3b, and cul1, revealed roles in regeneration following injury. In addition, we identify intestinal cells as prominent components of the microenvironment surrounding adult tgs1 pluripotent stem cells (neoblasts). Together, these results demonstrate the utility of three-dimensional spatial transcriptomic reconstruction for mapping cellular architecture and positional gene regulation in complex adult organisms.

developmental biology↗

bioRxiv2026

4D Single-Cell Spatial Transcriptomics Reveals Dynamic Morphogenetic Gradients and Regenerative Domains in Planarians

Regeneration relies on precise spatiotemporal gene expression and cellular responses to establish tissue identity and body patterning. Using high-resolution Stereo-seq (715 nm) on 353 sections from 16 whole animals at 8 regeneration timepoints, we constructed a 4D spatiotemporal transcriptomic map of planarian regeneration. Our analysis captured 36 refined cell types from 3,508,004 segmented cells, enabling genome-wide transcriptional imputation of gene expression dynamics across body axes at cellular, tissue, and organismal scales. We identified dynamic positional gradients and distinct spatially distributed cell types during regeneration, including an injury-induced Anterior Regenerative Zone (ARZ). The ARZ exhibited enriched positional signals in epidermal, muscle, and neural cells and was regulated by Mediator 8, which is crucial for polarity remodeling and blastema formation. This study provides a comprehensive spatial molecular and cellular map of regenerative processes, highlighting injury-induced spatial domains and key regulatory factors in planarian regeneration. We also provide an interactive web portal, offering a valuable resource for exploring and analyzing regeneration mechanisms in a spatiotemporal context.

developmental biology↗

bioRxiv2026

Base-resolution DNA methylome of human MDS hematopoietic stem cell reveals TET2-GFI1 epigenetic axis repressing MDS

Dysfunctional hematopoietic stem cells (HSCs) drive the initiation of myelodysplastic syndromes (MDS), yet the genome-wide DNA methylation landscape in MDS primitive HSCs and its mechanistic contribution to disease pathogenesis remain poorly defined. Here, we establish single-base resolution DNA methylomes of bone marrow HSCs from MDS patients and healthy donors. We uncover widespread hypermethylation within CpG islands, alongside hypomethylation in repetitive elements such as Alu. Differentially methylated regions (DMRs) are enriched for genes involved in cancer-related pathways, as well as extrinsic signaling pathways and intrinsic transcriptional networks essential for HSC function. Among these, we identify GFI1 and BMI1 as key targets of DNA methylation dysregulation in MDS. Notably, using either MDS or Tet2-deficient mouse model, we demonstrate that loss of Tet2, a frequently mutated epigenetic regulator in MDS, induces promoter hypermethylation and transcriptional repression of Gfi1, contributing to expansion of the MDS or aged hematopoietic stem and progenitor cell pool. Our study not only charts the base-resolution DNA methylome of human MDS HSCs but also reveals a TET2-GFI1 axis that safeguards HSC homeostasis. These findings provide mechanistic insight into how aberrant DNA methylation drives HSC dysfunction in MDS and offer an epigenomic resource for discovering novel regulators and therapeutic targets at the stem cell level.

immunology↗

bioRxiv2026

The genetic repertoire of the deep sea: from sequence to structure and function

The deep sea as the largest and maybe most hostile environment on Earth is still underexplored especially regarding its genetic repertoire. Yet, previous work has revealed significant habitat-specific deep-sea biodiversity. Here, we present an integrated deep-sea genetic dataset comprising 502 million nonredundant genes from 2,138 samples and 2.4 million predicted structures, and used it to link specific protein structures with genetic variants associated with life in the deep sea and to assess their biotechnology potential. Combining global sequence analysis with biophysical and biochemical measurements revealed unprecedented sequence diversity, yet substantial structural conservation of proteins. Especially proteins involved in replication, recombination, and repair were identified to be under rapid evolution and with specialized properties. Among these, a structurally divergent helicase exhibited advantages in controlling nanopore sequencing speed. Thus, our work positions the deep sea as a unique evolutionary engine that generates and hosts genetic diversity and bridges genetic knowledge with biotechnology.

bioinformatics↗

bioRxiv2026

Effect of C6-HSL and chlorogenic acid on spoilage characteristics of Serratia liquefaciens in mutton

Quorum sensing (QS) is a bacterial cell-cell communication system that coordinates group behaviors via self-produced signaling molecules. Serratia liquefaciens, a common mutton spoilage bacterium, precisely regulates its spoilage capacity through the AHL-mediated QS system. The results demonstrated that 20 mol/mL C6-HSL concentration-dependently enhanced AHL activity 1.26-fold, increased biofilm formation by 51.55%, and elevated protease activity and siderophore production by 37% and 26.78%, respectively. In contrast, 80 g/mL chlorogenic acid significantly inhibited AHL activity (by 26.19%), biofilm formation (by 42.54%), protease activity (by 28.92%), and motility (by 38.34%). In stored mutton, chlorogenic acid treatment reduced total plate counts by 6.1% and pH by 5.26%. Transcriptomic analysis revealed that C6-HSL treatment altered metabolic pathways such as flagellar assembly, ABC transporters, two-component systems, and secondary metabolite synthesis, in which spoilage-related genes (slyB, fimA, fliJ, iucD, cheW) were significantly up-regulated. In contrast, chlorogenic acid treatment affected pathways including amino acid metabolism, sulfur metabolism, and carbohydrate metabolism, with spoilage-related genes (fimA, tuf, ibpA, clpS, metQ) significantly down-regulated. These findings demonstrate that AHL activity plays a key role in regulating the spoilage capacity of Serratia liquefaciens, and suggest chlorogenic acid as a potential QS inhibitor with promising application in mutton preservation. ImportanceSerratia liquefaciensis a common spoilage bacterium in refrigerated foods and proliferates extensively in meat, making it one of the primary spoilage organisms. The significance of our research lies in investigating how changes in the activity of the signaling molecule AHL affect both spoilage capacity and mutton quality. Additionally, transcriptomic analysis was employed to elucidate the regulatory mechanisms by which altered AHL activity influences the spoilage potential of S. liquefaciens. The results demonstrated that variations in AHL activity significantly impacted key spoilage-related traits of S. liquefaciens, including biofilm formation, protease activity, and motility, while also contributing to improved meat quality during storage. Furthermore, the study revealed that AHL activity regulates metabolic pathways associated with spoilage as well as the expression of spoilage-related genes. These findings provide a theoretical basis for developing preservation strategies for mutton.

microbiology↗

bioRxiv2026

The Red Rice Bran Extract (RRBE) Mitigates Photoaging by Targeting Mitochondrial Oxidative Stress and Regulating Thermal Damage Responses

The photoprotective efficacy of natural skin-active complexes is well recognized, yet their ap-plication is often hindered by the challenge of deciphering their complex, multi-component, and multi-target mechanisms. To bridge the gap between established phenotypes and molecular mechanisms, we developed an AI-driven integrated platform that combines phytochemical profiling, network pharmacology, and deep learning-based target prediction with rigorous biophysical validation. We applied this platform to investigate RRBE, a bioactive complex refined from red rice bran extract. In vivo clinical studies confirmed that RRBE significantly accelerates the resolution of UV-induced erythema, while cellular and 3D tissue models demonstrated robust suppression of oxidative stress and DNA damage responses. To decode its material basis, the platform deconstructed RRBE into 10 distinct chemical modules. Leveraging our SCOPE-DTI deep learning model for global target prediction, we identified flavonoids (Module 1) and phenolic acids (Module 10) as the primary bioactive drivers relevant to photoprotection. These computational predictions were structurally supported by molecular docking and definitively validated in a physiological environment via Cellular Thermal Shift Assay-Mass Spectrometry (CETSA-MS). Mechanistically, RRBE functions through a synergistic polypharmacology: (1) Module 1 components, represented by procyanidin B2, target NDUFA7 to stabilize mitochondrial function and mitigate ROS; (2) Module 10 components, exemplified by caffeic acid, ferulic acid, and p-coumaric acid, engage FKBP11 and HSP90AA1 to regulate protein homeostasis and stress responses. This work not only deciphers the polypharmacological basis of RRBEs photoprotective action but also validates a scalable "AI-guided, cell-validated" discovery pipeline, offering a rational paradigm for uncovering the protective benefits of complex natural extracts.

systems biology↗

bioRxiv2026

Context-Dependent Motor Feedback Underlies Choice-Related signals in Visual Cortex

Choice-related neural activity, reflecting trial-by-trial correlation with subjects perceptual choice, is commonly observed in sensory cortices and has been implied in sensory readout. Recent studies suggest an alternative source from motor-reporting, yet its precise nature remain elusive due to limitations in conventional experimental paradigms. Here we quantitatively identified motor component by training macaques to discriminate visual motion directions via making saccade to spatial-independent, colored choice targets appeared under two contexts: at stimulus onset, or after its offset. Neural recordings in visual areas MT/MST revealed a dominant motor-related choice signal when the saccade goal was known in advance; this signal vanished with delayed target onset. By comparing with downstream sensory-motor transformation areas and employing a recurrent network model, we demonstrated that this motor component reflected feedback. Our work clarifies that a major portion of "decision" activity in sensory neurons is attributable to motor-reporting processes, highlighting the profound influence of behavioral context.

neuroscience↗