Biology subjects

Zuo, K.

Publications and source records attributed to Zuo, K..

5 recordsLinked to original sources

bioRxiv2025

A cytosolic function of DNMT1 controls neuronal morphogenesis via microtubule regulation

Proteins traditionally confined to a single cellular compartment are increasingly recognized to exert non-canonical functions in alternative domains. The DNA methyltransferase 1 (DNMT1), classically defined as the maintenance methyltransferase that preserves DNA methylation patterns during replication, exemplifies this versatility. Beyond its canonical role, DNMT1 is highly expressed in the developing and adult brain, where it contributes to transcriptional regulation in postmitotic neurons. Notably, cytoplasmic DNMT1 localization has been observed in neural cells, and emerging evidence links DNMT1 to mitochondrial function with implications for neurodegenerative disease, whereby the underlying functional mechanisms remain to be fully elucidated. Here, we identify a previously unrecognized cytosolic function of DNMT1 in developing cortical excitatory neurons. Through genetic perturbation, proteomics, and high-resolution imaging, we show that DNMT1 regulates dendritic and axonal branching independently of its catalytic activity and nuclear localization. Instead, DNMT1 operates as a cytosolic scaffold interacting with the polarity regulator DOCK7 to modulate Rac1-STMN1 signaling, microtubule dynamics, and organelle trafficking. These findings expand the conceptual framework of DNMT1 from a genome guardian to a dual-compartment regulator that coordinates cytoskeletal remodeling and mitochondrial positioning. Beyond advancing our understanding of neuronal morphogenesis, this work provides mechanistic insight into how DNMT1 mutations may lead to neurodegenerative diseases.

neuroscience↗

bioRxiv2025

HEAL-KGGen: A Hierarchical Multi-Agent LLM Framework with Knowledge Graph Enhancement for Genetic Biomarker-Based Medical Diagnosis

The discovery and validation of genetic biomarkers across diverse diseases demand intelligent systems capable of integrating complex multi-omics data with clinical relevance. We introduce HEAL-KGGen, an end-to-end framework that enhances Large Language Models (LLMs) through a hierarchical multi-agent architecture and an automatically constructed medical knowledge graph. The system includes a General Practitioner (GP) agent for initial biomarker triage and specialist agents for genomics, transcriptomics, proteomics, and clinical interpretation. The core innovation of HEAL-KGGen lies in its dynamic knowledge graph pipeline, which combines entity extraction based on patterns and semantics, ontology-aligned normalization (using UMLS, MeSH, SNOMED CT) and the construction of multi-source relationships from biomedical databases and literature. Retrieved subgraphs are transformed into contextual prompts that guide LLM reasoning via structured, explainable pathways. Our experiments show that HEAL-KGGen significantly improves question-answering accuracy across multiple mainstream large language models, with the highest improvement observed on Claude 3.5 Sonnetachieving a 43.75% increase in accuracy., confirming the value of domain-specific graph knowledge in advancing LLM performance for genetic and molecular diagnostics.

bioinformatics↗

bioRxiv2022

Signaling pathways involved in the repression of root nitrate uptake by nitrate in Arabidopsis thaliana

In Arabidopsis thaliana, root high-affinity nitrate (NO3-) uptake depends mainly on NRT2.1, 2.4 and 2.5, which are repressed by high NO3- supply at the transcript level. For NRT2.1, this regulation is due to the action of (i) feedback downregulation by N metabolites and (ii) repression by NO3- itself mediated by the transceptor NRT1.1(NPF6.3). However, for NRT2.4 and NRT2.5 the signaling pathway(s) remain unknown along with the molecular elements involved. Here we show that unlike NRT2.1, NRT2.4 and NRT2.5 are not induced in a NO3- reductase mutant but are strongly upregulated following replacement of NO3- by ammonium (NH4+) as the N source. Moreover, increasing NO3- concentration in a mixed nutrient solution with constant NH4+ concentration results in a gradual repression of NRT2.4 and NRT2.5, which is suppressed in a nrt1.1 mutant. This indicates that NRT2.4 and NRT2.5 are subjected to repression by NRT1.1-mediated NO3- sensing, and not to feedback repression by reduced N metabolites. We further show that key regulators of NRT2s transporters, such as HHO1, HRS1, PP2C, LBD39, BT1 and BT2, are also regulated by NRT1.1-mediated NO3- sensing, and that several are involved in NO3- repression of NRT2.1, 2.4 and 2.5. Finally, we provide evidence that it is the phosphorylated form of NRT1.1 at the T101 residue, which is most active in triggering the NRT1.1-mediated NO3- regulation of all these genes. Altogether, these data led to propose a regulatory model for high-affinity NO3- uptake in Arabidopsis, highlighting several NO3- transduction cascades downstream the phosphorylated form of the NRT1.1 transceptor. One sentence summaryCharacterisation and identification of molecular elements involved in the signaling pathways repressing NRT2s transporters and root nitrate uptake in response to nitrate.

plant biology↗

bioRxiv2022

Arabidopsis CPK6 regulates drought tolerance under high nitrogen by the phosphorylation of NRT1.1

Nitrogen is an essential macronutrient for plant growth and development, and its availability to some extent is regulated by drought stress. Calcium-dependent protein kinases (CPKs) are a unique family of Ca2+ sensors with diverse functions in nitrogen and drought signaling pathways. However, which and how CPKs involve in the crosstalk between drought stress and nitrogen transportation remains largely unknown. Here we identified the drought tolerant function of Arabidopsis CPK6 under high nitrogen condition. The CPK6 expression is induced by the treatments of ABA and drought. The mutant cpk6 is insensitive to the ABA treatment, but sensitive to drought only under high nitrogen condition. CPK6 interacts with and phosphorylates the Thr571 in NRT1.1 protein, and thus represses its NO3- transporting activity under drought stress. Taken together, we showed the evidences that CPK6 regulates Arabidopsis drought tolerance through the phosphorylation of NRT1.1, and that enriches the knowledge of nitrogen uptake in plants during drought stress.

genetics↗

bioRxiv2020

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

Specific alterations of gut microbiota (GM) in atrial fibrillation (AF) patients, including elevated microbial diversity, particularly perturbed composition, imbalanced microbial function, and associated metabolic pattern modifications have been described in our previous report. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation, and to construct a GM-based predictive model for RAF. Gut microbial composition and metabolic profiles were assessed based on metagenomic sequencing and metabolomic analyses. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and the non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter, and the species Faecalibacterium sp. CAG:82, Bacillus gobiensis, and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. An elevated area under curve (0.954) and positive net reclassification index (1.5601) for predicting RAF compared with traditional clinical scoring (AUC=0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance. These data provide novel evidence that supports incorporating the GM factor into future recurrent risk stratification.

genomics↗