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Zhu, R.

Publications and source records attributed to Zhu, R..

At least 37 records · Page 2Linked to original sources

Saline-free preparation for chronic in vivo imaging in adult Drosophila

Longitudinal brain imaging is essential for understanding neural mechanisms. Here, we present a saline-free, chronic preparation for repeated neural recording in adult Drosophila over multiple days. We describe steps for mounting flies, performing manual surgery on the head cuticle without external saline, and resealing the opening to create a transparent optical window. We demonstrate the utility of this approach by tracking single-neuron spiking and neuronal calcium dynamics over 7-10 days. This protocol is potentially applicable to other insect species. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/706199v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@abeb34org.highwire.dtl.DTLVardef@deaf93org.highwire.dtl.DTLVardef@1d8fc24org.highwire.dtl.DTLVardef@91a696_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Distinct Chiral Nanostructures of Graphene Quantum Dots Govern Divergent Passive and Active Enantioselective Transport across Biological Membranes

Chirality in two-dimensional nanomaterials provides a powerful lever to control biological interfaces, yet the structural origins of nanoscale chirality remain poorly understood. Here, we systematically investigate chiral ligand modulated graphene quantum dots (GQDs) and reveal how ligand stereochemistry and edge chemistry modulate the formation of diverse chiral or achiral nanostructures. Spectroscopy, microscopy, and density functional theory with ring-puckering analysis identified six structural motifs, twisted-, twisted-boat, saddle-shaped, hybrid, unbuckled, and random. Among these, twisted-, twisted-boat, and saddle-shaped GQDs exhibited genuine nanoscale structural chirality, while unbuckled, hybrid, and random conformations lacked organized distortion. Importantly, structural chirality governed passive permeation into biological membrane (e.g. lipid membrane of extracellular vesicles), whereas achiral variants relied mainly on hydrophobic interactions. In contrast, active transport across biological membrane (e.g. endocytosis) is insensitive to nanoscale structural chirality but strongly influenced by chiral ligand identity and transporter recognition. Collectively, these results establish chiral ligand conjugation as a modular route to program both chiral and achiral motifs in graphene nanostructures and highlight nanoscale structural chirality as a design principle for engineering bio-nano interactions.

bioengineering↗

IBDkb: an AI-enhanced integrative knowledge base for inflammatory bowel disease research and drug discovery

IBDkb (Inflammatory Bowel Disease Knowledge Base; https://www.biosino.org/ibdkb) is a freely accessible, integrated web-based platform that systematically curates and harmonizes multi-source data related to inflammatory bowel disease (IBD). To address the fragmentation and therapeutic gaps in existing specialized resources, IBDkb establishes a unified framework featuring advanced full-text search, interactive visualizations, cross-module knowledge graphs, and AI-powered utilities for real-time literature retrieval, trend analysis, text/PDF interpretation, and domain-specific conversational assistance. The platform currently integrates 98,453 research articles, 3,390 clinical trials, 200 investigational drugs, 200,606 bioactive compounds, 103 therapeutic targets, 77 experimental models, 12 pathogenesis summaries, and 15 treatment strategies. These integrated tools facilitate efficient exploration of complex associations among drugs, targets, trials, and mechanisms, thereby accelerating hypothesis generation and translational research in IBD. The platform is openly available without registration and supports data downloads. A case study on structure-aware drug comparison further demonstrates its utility in facilitating cross-disease drug repositioning hypotheses.

bioinformatics↗

An Advanced Humanized Systemic Lupus Erythematosus Model Enables Parallel Profiling of B Cell-Targeted Therapies

B cell-targeted therapies represent a transformative frontier for systemic lupus erythematosus (SLE) intervention, yet clinical recommendation of specific treatment is hampered by the challenge to perform head-to-head comparisons of efficacy-toxicity trade-offs and tissue-specific impacts in patients. To address this gap, an advanced Toll-like receptor 7 (TLR7) agonist-induced SLE model is developed in a NCG-M (NOD-Prkdcem26Cd52Il2rgem26Cd22Rosa26em1Cin(hCSF2&IL3&KITLG)/Gpt) human immune system (HIS) mice. This model enables parallel evaluation of multiple B cell-directed therapies within a controlled cohort study. It recapitulates core SLE pathologies--including immune effector cell augmentation, autoantibody production and glomerulonephritis--within 2 months, demonstrating greater severity and clinical fidelity than conventional pristane-induced systems. Validated through replication of clinical responses to rituximab and belimumab, the platform directly compares two emerging modalities: universal chimeric antigen receptor-T cells (UCAR-T) elicits delayed but profound B-cell reset correlating with superior reduction in renal pathology and autoantibodies, while T cell engagers (TCEs) mediate rapid yet partial B-cell depletion and transient efficacy. UCAR-T concurrently induces greater acute inflammatory responses, aligning with its distinct toxicity profile. By resolving therapy-specific effects on human immune dynamics and symptom control, this study empowers context-specific therapeutic selection for SLE, advancing tailored management strategies.

immunology↗

High-PepBinder: A pLM-Guided Latent Diffusion Framework for Affinity-Aware Target-Specific Peptide Design

Peptides, as therapeutic molecules, offer unique advantages in targeting complex protein surfaces, yet their rational design remains limited by the vastness of the sequence space and the constraints of traditional approaches. Here, we propose High-PepBinder, a sequence-only conditional diffusion framework for target-specific peptide generation. Guided by the target protein sequence, High-PepBinder adopts a dual encoder architecture that integrates protein language models (pLMs) with the diffusion model. This approach cascades the peptide generation model with an affinity classifier and enables the generation process to capture affinity-related features of the peptides through lightweight joint optimization. Due to the scarcity of protein-peptide affinity data, we constructed PepPBA, to our knowledge the most comprehensive dataset to date, and established a structure- and physics-based screening pipeline to prioritize top candidates. Results show that High-PepBinder demonstrates competitive performance across multiple peptide generation and affinity-related tasks. For representative targets, including KEAP1, XIAP, and EGFR, the generated peptides preserve key binding geometries and interface patterns of reference peptides in predicted complexes, while maintaining sequence diversity and favorable predicted properties. Overall, High-PepBinder contributes toward a general and sequence-only strategy for peptide design, offering a computational framework for expanding peptide discovery against challenging targets.

bioinformatics↗

Multi-Omics Reveals Activated Fibroblasts with Dual Functional Roles in Repair and Negative Barrier in the CD8+ T Cell Cytotoxic Niche for Lung Cancer Neoadjuvant Therapy

A major challenge in elucidating immune activation and tolerance is that single-omics technologies are inherently limited. Since single-cell transcriptomics lacks spatial information and spatial transcriptomics lacks resolution or depth, neither can adequately model the multidimensional tumor immune microenvironment (TiME) features. We present NICHE (Niche Integrated Cellular Heterogeneity Elucidator), an integrative multi-omics framework. By aligning physical cell-cell interactions with single-cell ligand-receptor (L-R) expression, NICHE leverages single-cell transcriptomics, spatial proteomics, and AI modeling to systematically decode the composition, spatial interactions, and communications within immune functional niches. To validate NICHEs capabilities, we applied it to human tonsil tissue. The framework successfully identified key structural and functional units and deeply elucidated the cell-cell interactions and molecular crosstalk within them. Furthermore, these results were validated through orthogonal methods, including single-cell spatial transcriptomics and multiplexed immunofluorescence, which confirmed the accuracy and reproducibility of our analyses. In non-small cell lung cancer (NSCLC) patients undergoing neoadjuvant immunotherapy, CD8+ T cell cytotoxic niches mediate tumor clearance with variable outcomes, to define the cellular and molecular drivers behind this functional spectrum, we utilized NICHE to analyze the TiME from patients with complete versus partial pathological response, both pre- and post-treatment. We found that neoadjuvant immunotherapy may induce the activation of CXCL12+, NECTIN2+, POSTN+, and COL6A1+ fibroblasts through the activation of cytotoxic T cells. Paradoxically, these fibroblasts support tissue repair but also establish an immunosuppressive niche that protects residual tumor cells, ultimately attenuating treatment efficacy. Our work establishes a multidimensional framework for dissecting dynamic immune activity, with direct implications for understanding tumor immunology and identifying novel therapeutic targets.

immunology↗

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits

Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, we perturbed all expressed genes across 22 million primary human CD4+ T cells from four donors and developed a probe-based perturb-seq platform to measure the transcriptome effects in cells at rest and after stimulation. These data allow us to map genes that regulate known and novel pathways, including novel regulators of cytokine production. Importantly, active regulators and the gene programs they control change dramatically across stimulation conditions. Perturbation signatures enabled us to model T cell states observed in population-scale transcriptomic atlases, nominating regulators of Th1 and Th2 polarization and of age-related T cell phenotypes. Finally, we leveraged perturb-seq to implicate context-specific gene regulatory pathways in autoimmune disease risk. Our data provide a foundational resource to decode human immune function and genetic variation and for new approaches to study gene regulatory networks.

genetics↗

Lifelong maintenance of locomotion by embryonically active dopamine neurons

Locomotor skills arise early in life and are maintained throughout an animals lifespan, yet how this continuity is achieved despite major neural remodeling remains unclear. Using Drosophila, which undergoes complete metamorphosis, we show that the activity of embryonically established dopamine neurons (DANs) is essential for locomotion across all developmental stages and adulthood. Through stage-specific behavioral assays, optogenetics, in vivo brain imaging, and fluorescent neuronal tracking, we identify a subset of ventral nervous system (VNS) DANs that modulate locomotor function throughout life. Transcriptomic analyses reveal that they maintain expression of developmental transcription factors. Knocking down these factors, particularly Antp and Pdm2, in post-mitotic VNS DANs reduces neurite arborization and impairs adult locomotion. These findings uncover a previously overlooked function for embryonic DANs and suggest that stable locomotion during nervous system maturation relies on persistent developmental regulator expression coupled with structural remodeling.

neuroscience↗

Mapping Protein Occupancy on DNA with an Unnatural Cytosine Modification in Bio-orthogonal Contexts

The epigenome provides a dynamic layer of gene regulatory control above the static genetic sequence. DNA base modifications are key epigenetic regulators, predominantly found within CpG contexts in mammalian genomes. Working in tandem with these DNA modifications, chromatin-associated proteins and transcription factors further control gene expression. Given the interplay of these factors, concurrent mapping of DNA base modifications with protein-DNA occupancy can greatly aid in interpreting the epigenome. Existing multi-modal mapping methods include the use of DNA methyltransferases to mark accessible, protein-unbound DNA in non-CpG contexts. However, such approaches can either confound readouts with native DNA modifications or constrain users to third-generation sequencing approaches. To circumvent these limitations, we explored the possibility of introducing an unnatural DNA base modification, 5-carboxymethylcytosine, as an alternative label for protein occupancy. Here, we report our efforts to rationally engineer non-CpG-specific DNA methyltransferases to take on neomorphic DNA carboxymethyltransferase (CxMTase) activities. We find that DNA carboxymethylation of cytosines in GpC contexts shows broad compatibility with the most widely used epigenetic detection methods and can be used to reliably report on protein occupancy states. Using this approach, we reveal the single-molecule binding patterns of LexA, a master repressor in the bacterial DNA damage (SOS) response, at its self-regulated and endogenously methylated promoter. We thus show that unnatural DNA modifications in bio-orthogonal contexts can uncover biological insights and potentiate new approaches to multimodal epigenetic profiling. TOC GRAPHIC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/690163v3_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1817a46org.highwire.dtl.DTLVardef@182ca09org.highwire.dtl.DTLVardef@19e3572org.highwire.dtl.DTLVardef@1c6e1a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Quantitative profiling of whole-brain connectomes at single-axon resolution using deep learning and high-resolution light sheet microscopy

Revealing how individual axons create a brain-wide connectome would be indispensable for understanding brain function and behavior, yet remains technically challenging. We introduce MAPL3, an end-to-end pipeline that integrates self-supervised learning with an innovative deep architecture to capture local and global brain-wide axonal projections. MAPL3 enables subject- and population-level quantitative laminar analysis, generalizes across experiments, and outperforms state-of-the-art methods. We showcase its ability to map the circuitry of the orbitofrontal cortex from single axons to whole-brain projectome.

neuroscience↗

StrainOptimizer empowers rational cell factory design through multi-scale metabolic models with expression and proteome constraints

The rational design of microbial cell factories for high bioproduction remains a key challenge in metabolic engineering. While advanced modelling frameworks incorporating protein resource allocation, such as enzyme-constrained models (ecGEMs) and Expression and Thermodynamic Flux (ETFL), provide superior predictive power, their application is limited by a lack of user-friendly computational tools. Here, we present strainOptimizer, a comprehensive computational platform for rational strain design that systematically evaluates key resource allocation principles: the coupling of gene expression with metabolism, subcellular compartmentalization, and enzyme capacity limitations. Our benchmark analyses demonstrate that each principle offers distinct advantages: models coupling metabolism and expression (like ETFL) enable the identification of non-metabolic targets, organelle-level proteomic constraints improve precision for high-protein-cost products, and protein-usage-based objectives consistently outperformed traditional flux-based approaches. To demonstrate its practical utility, we applied strainOptimizer to an engineered sclareol-overproducing Saccharomyces cerevisiae strain. The platform identified novel targets, and experimental validation confirmed a 67% success rate, increasing the final sclareol titer by 14-26% and productivity by up to 45%. StrainOptimizer bridges the gap between resource allocation theory and applied engineering, providing a powerful, validated tool to accelerate the development of high-performance cell factories.

bioengineering↗

M1 Macrophage-Derived Small Extracellular Vesicles as Synergistic Nanotherapeutics: Harnessing Intrinsic Anticancer Activity and Drug Delivery Capacity

Small extracellular vesicles (sEVs) have emerged as next-generation multifunctional nanotherapeutics due to their parental-cell traits and role in intercellular communication. Among them, immune cell-derived sEVs are uniquely positioned to couple innate immunomodulatory activities with therapeutic payload delivery, making them highly attractive for cancer therapy. In particular, M1 macrophage-derived sEVs (M1-sEVs) preserve the tumor-suppressive functions of their parent cells, including tumor microenvironment (TME) reprogramming, immune activation, and inhibition of cancer progression. However, the mechanisms by which these activities are coordinated within the TME, and whether they act independently or synergistically, remain poorly understood. Clarifying these mechanisms is crucial for harnessing their intrinsic bioactivity in combination with their natural capacity as drug delivery nanocarriers to optimize therapeutic efficacy. Here, we demonstrate that M1-sEVs exhibit intrinsic stability and circulation longevity via do not eat me ligands, as well as tumor-homing ability revealed by proteomic profiling, enabling efficient uptake and deep infiltration in breast cancer models. Functionally, M1-sEVs deliver antiproliferative microRNAs that suppress tumor metabolism, growth, and progression by inhibiting self-renewal, adhesion, migration, motility, and invasion. Importantly, by integrating this endogenous bioactivity with exogenous doxorubicin loading, we achieved synergistic efficacy: a 3-fold reduction in IC50 in vitro (0.46 M vs. 1.45 M for free drug) and 70.18% tumor growth inhibition in vivo. These findings highlight M1-sEVs as dual-action nanotherapeutics that combine innate immune-regulatory and tumor-inhibitory functions with efficient drug delivery, advancing their development as powerful platforms for cancer therapy.

bioengineering↗

Psoralen Enhances Direct Cardiac Reprogramming via PPARα Activation and Promotion of Mitochondrial Fission

BACKGROUNDCell-based therapy is a promising strategy for heart repair and regeneration. However, its clinical application has been hampered by the low efficiency of cell direct reprogramming and the immature state of the inducing cells. Developing novel strategies to enhance direct reprogramming efficiency and yield mature functional cardiomyocytes remains a critical challenge. METHODSWe evaluated the effect of Psr on cardiac reprogramming using RepSox and Forskolin (RF) as the baseline cocktail. Reprogramming efficiency, cardiomyocyte marker expression, and calcium handling were assessed by RT-qPCR, immunofluorescence. Ultrastructural features were examined by transmission electron microscopy. Metabolic profiles were analyzed using Seahorse assays. Transcriptomic changes were explored by RNA sequencing, followed by pathway and protein-protein interaction analyses. A myocardial infarction (MI) mouse model was used for in vivo validation. RESULTSSupplementation with Psr (10 M) markedly enhanced the induction of induced cardiomyocytes (iCMs), leading to earlier appearance of beating clusters (day 1 vs. day 6-8), improved sarcomere organization, robust calcium transients, and higher energy metabolism. Transcriptomic profiling identified activation of the PPAR signaling pathway, with PPAR, RXRG, and UCP1 as central regulators. Mechanistically, Psr promoted mitochondrial fission, thereby facilitating metabolic remodeling essential for cardiomyocyte maturation. In vivo, RF+Psr treatment significantly improved cardiac function and reduced fibrosis after MI compared to RF alone. CONCLUSIONPsr enhances direct cardiac reprogramming by activating PPAR signaling and promoting mitochondrial fission. These findings provide a novel mechanistic framework and suggest psoralen as a promising natural enhancer for cardiac regeneration strategies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/681288v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@13a5d27org.highwire.dtl.DTLVardef@b9cce5org.highwire.dtl.DTLVardef@3afef8org.highwire.dtl.DTLVardef@1398972_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Nanochirality-programmed Type-I photosensitizer enables deep-tumor photodynamic therapy by reducing extracellular-matrix adhesion

Tumor hypoxia and poor penetration of therapeutics across tumor-microenvironment barriers remain major obstacles to effective cancer therapy, including photodynamic therapy (PDT). Here we introduce a nanochirality-programmed assembly (L-Chi-GAIN) in which nanochirality drives site-selective assembly that activates oxygen-independent Type-I reactive oxygen species (ROS) generation and reduces hyaluronan-mediated matrix adhesion, thereby permitting deep intratumoral therapy. Glycosylation imparts structural chirality to graphene quantum dots (GQDs), directing site-selective assembly of indocyanine green (ICG) that turns on photoinduced electron transfer (PET), producing a 64-fold increase in ROS relative to free ICG. Nanochirality also modulates assembly-extracellular matrix (ECM) interactions. L-GQDs show a less favorable hyaluronan binding free energy ({Delta}Gbind), thus accelerating interstitial transport and resulting in [~]21-fold deeper tumor penetration by L-Chi-GAIN than conventional nanocarriers. Under near-infrared irradiation, L-Chi-GAIN elicits strong oxidative stress and triggers Gasdermin-D (GSDMD)-dependent pyroptosis, leading to significant suppression of tumor growth. This work offers a nanochirality-guided design strategy for PDT in deep tumors by coupling site-selective assembly with stereoselective navigation of the ECM.

bioengineering↗

Unraveling the Molecular and Physiological Roles of Signal Peptide Peptidase A (SppA) in Flavobacterium columnare

Columnaris disease, caused by Flavobacterium columnare, represents one of the most economically devastating bacterial infections in global freshwater aquaculture. Despite its significant impact, the molecular mechanisms underlying F. columnare pathogenesis remain largely unexplored due to the challenge in targeted genomic manipulation. Signal peptide peptidase A (SppA) plays a crucial role in bacterial protein secretion by degrading residual signal peptides after protein translocation, yet its function in F. columnare physiology and virulence has not been characterized. Here, we employed a targeted gene deletion approach to investigate the role of sppA in F. columnare. The {Delta}sppA mutant exhibited pleiotropic phenotypes including increased outer membrane vesicle (OMV) production (3.8-fold higher compared to the wild type), reduced biofilm formation, and loss of gliding motility. Transcriptomic analysis of the {Delta}sppA mutant revealed significant upregulation of genes involved in membrane stress response and efflux pump system, including algU, osmC and the genes in the MacAB-TolC efflux system, compared to the wild-type state. Importantly, the artificial infection experiment demonstrated the mutants significantly attenuated virulence in freshwater Medaka (Oryzias latipes), with a 20% higher survival rate of fish compared to the wild type. Our findings reveal that SppA is essential for maintaining membrane homeostasis in F. columnare and serves as one of the virulence factors during columnaris infection. These results provide important insights into the biological function of the sppA gene in F. columnare and highlight the complex relationship between bacterial protein secretion, membrane integrity, and pathogenesis. ImportanceF. columnare causes significant economic loss in freshwater aquaculture. Understanding the molecular mechanisms underlying F. columnare pathogenesis is crucial for developing new ways for disease control. Our findings reveal that SppA is essential for gliding motility, adhesion, biofilm formation and maintaining membrane homeostasis in F. columnare, which serves as one of the virulence factors during columnaris infection. In addition, outer membrane vesicles (OMVs) and MacA/MacB/TolC tripartite efflux pump served as a compensatory mechanism for enhanced peptide metabolites secretion to manage the accumulation of misfolded proteins resulting from the sppA deficiency. These results provide important insights into the biological function of the sppA gene in F. columnare and highlight the complex relationship between bacterial protein secretion, membrane integrity, and pathogenesis.

genetics↗

AI-Guided Design of Cyclic Peptide Binders Targeting TREM2 Using CycleRFdiffusion and Experimental Validation

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a central role in regulating microglial function in the central nervous system and has emerged as a promising therapeutic target for Alzheimers disease. Despite advances in antibody-based therapeutics, small molecules and peptides capable of modulating TREM2 remain limited. Here, we present a cyclic peptide design pipeline that integrates CycleRFdiffusion, ProteinMPNN for sequence design, and HighFold for structural prediction and screening. Using the TREM2 structure as input, we generated and screened 1,500 peptide-target complexes, prioritizing four candidates that met structural and energetic criteria. Subsequent biophysical evaluation identified TP4 as a TREM2 binder, demonstrating consistent binding in spectral shift, microscale thermophoresis, and surface plasmon resonance. Pharmacokinetic profiling indicated that TP4 possesses favorable plasma stability and moderate metabolic stability, supporting its tractability for further optimization. This study establishes a generalizable framework for AI-driven cyclic peptide discovery and provides the first proof-of-concept demonstration of TREM2-targeted cyclic peptide binders.

pharmacology and toxicology↗

The Fengshu Large Model for Wugu Fengdeng: An Innovation Engine for Knowledge Integration in the Soybean Field

Against the backdrop of global population growth and the continuous escalation of food demand, the acceleration of agricultural modernization has emerged as the core pathway to safeguard food security. As the worlds fourth-largest food crop, soybean (Glycine max) possesses multiple strategic values for food security, livestock feed, and industrial raw materials, thanks to its high protein content (accounting for over 40% of the dry weight of seeds) and oil resource attributes. However, the soybean industry is confronted with multiple challenges: the long cycle of genetic breeding (8-10 years required by traditional methods), annual losses from diseases and pests reaching 40% (data from FAO 2023), and the reliance on empirical decision-making in field management, all of which urgently call for intelligent solutions.At present, agricultural knowledge is experiencing explosive growth - more than 4,000 new soybean-related literatures are added annually in PubMed, and agricultural technology Q&A platforms (Zhihu, Baidu Tieba, etc.) generate over 3,000 daily questions. However, this multi-source heterogeneous knowledge is scattered in books, literatures, Q&A communities, and gene databases, lacking systematic integration, resulting in a knowledge utilization rate of less than 30%. In response to this, this paper proposes the "Fengshu-Agri" large model, an agricultural knowledge integration and innovation engine based on the collaboration of Retrieval-Augmented Generation (RAG) and Knowledge Graph (KG). The model achieves breakthroughs through the following core technological innovations: O_LIDeep integration of multi-source heterogeneous data: For the first time, a systematic integration of 256 agricultural monographs (covering standardized knowledge such as planting techniques and pest control), 66,772 cutting-edge research literatures (genomics, agronomic trait analysis, etc.), 880,000 production practice Q&A (covering scenarios such as pest diagnosis and environmental stress response), and 120,000 gene annotation data (functional genes, expression regulation mechanisms) has been carried out to construct the largest knowledge graph in the agricultural field - containing 2 million entity nodes, realizing full-chain knowledge modeling from molecular-level gene regulation to field management. C_LIO_LIDouble-layer collaborative retrieval mechanism: Innovatively integrating RAG semantic vector retrieval with KG structured reasoning to solve problems such as low recall rate (<65%) and semantic ambiguity in traditional systems. Specifically, it achieves dual matching through local keywords (entity-level) and global keywords (relationship-level); C_LIO_LIOptimization of domain-specific generation engine: Based on the QWEN-QWQ32B large language model, a three-stage fine-tuning is carried out (pre-training, agricultural instruction fine-tuning, and reinforcement learning from human feedback) [15], which improves the professionalism of generated texts by 35% (manual evaluation index) and significantly reduces the LLM hallucination problem [12]. Experimental results show that Fengshu-Agri achieves an accuracy rate of 89.6% in soybean knowledge retrieval tasks (a 25.4% improvement over traditional RAG models), a recall rate of 87.3% (20.5% higher than pure KG reasoning models), and an F1 score of 88.4%. It can efficiently answer complex questions involving multi-entity associations (such as "the impact mechanism of CRISPR-editing the GmSWEET gene on lepidopteran pest resistance"). Analysis of typical cases indicates that the models responses not only cover technical principles (sgRNA design, Agrobacterium transformation procedures) but also integrate metabolomics data (70% improvement in insect resistance with no significant yield reduction), demonstrating cross-modal knowledge fusion capabilities. In the future, this model will be expanded to crops such as maize and potato to construct an agricultural intelligent ecosystem covering the entire process of cultivation management and breeding improvement, promoting the upgrading of precision agriculture toward a data-driven model. C_LI

plant biology↗

Genomic structural equation modeling of impulsivity and risk-taking traits reveals three latent factors distinctly associated with brain structure and development

BackgroundImpulsivity is a multifaceted transdiagnostic trait that emerges in childhood. Research has identified genetic loci and brain systems associated with different facets of impulsivity and risk-taking. However, how these genetic underpinnings overlap across different facets, and how they are associated with brain development during childhood remain unknown. MethodsUsing genomic structural equation modeling on 17 impulsivity and risk-taking traits, we identified latent factors capturing overlapping genetic architecture. We then calculated polygenic scores for these factors using Adolescent Brain Cognitive Development Study data (N = 4,142) and examined their associations with brain structure, development, and behavior in children aged 9-14 years. Finally, we tested whether socioeconomic status modulated the associations between latent polygenic scores and brain structures. ResultsWe identified three distinct genetic latent factors, which we label lack of self-control, reward drive, and sensation seeking. In children, polygenic scores for the three factors showed associations with distinct brain patterns: lack of self-control associated with reduced prefrontal cortical thickness, reward drive with increased subcortical cellular density, and sensation seeking with increased cortical surface area and white matter integrity. Longitudinally, lack of self-control predicted slower white matter development. The association between polygenetic score for lack of self-control and white matter mean diffusivity was modulated by socioeconomic status. ConclusionsWe identified three genetically distinct dimensions of impulsivity and risk-taking with separable neurodevelopmental origins. These genetic predispositions manifested as distinct brain patterns as early as ages 9-10. Environmental experience modulated some of the genetic effects on brain development.

neuroscience↗