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Biomedical subjects

Lili Li

Publications and source records attributed to Lili Li.

3 recordsLinked to original sources

Pan-genome characterization of the maize 4CL gene family and its dynamic responses to abiotic stress.

1.Pan-genome analysis across 26 maize inbred lines identified 13 Zm4CL genes (nine core and four near-core) classified into three evolutionary clades.2.Structural variations (SVs) are significantly associated with the expression and altered conserved protein domains of key Zm4CL genes.3.Zm4CL genes exhibit distinct tissue-specific expression patterns and dynamic enzymatic and transcriptional responses to stresses, particularly cold and drought.4-Coumarate:CoA ligase (4CL) is a key enzyme in the phenylpropanoid pathway and plays important roles in plant growth, development, and responses to environmental stresses. However, a comprehensive pan-genome analysis of the 4CL gene family in maize is still lacking. In this study, 13 Zm4CL genes were identified from a maize pan-genome comprising 26 diverse inbred lines, including nine core genes and four near-core genes. Phylogenetic analysis classified these genes into three evolutionary clades, while Ka/Ks analysis indicated that most members have been maintained under purifying selection, although several genes exhibited greater evolutionary divergence and relatively relaxed evolutionary constraints. Structural variation (SV) analysis revealed significant associations between SVs and the expression of Zm4CL2 and Zm4CL3, while sequence comparisons suggested that SVs were also associated with alterations in conserved protein domains in some genotypes. Transcriptome analyses revealed distinct tissue-specific expression patterns and diverse transcriptional responses to abiotic and biotic stresses. Enzyme activity assays showed that cold stress significantly increased 4CL activity at 12 h, whereas heat, salt, and alkali stresses caused an initial decrease followed by recovery, while drought had no significant effect. Time-course RT-qPCR further validated dynamic expression changes of representative Zm4CL genes under cold and drought stresses. Overall, this study provides a comprehensive pan-genome framework for understanding the evolutionary conservation, regulatory diversification, and stress-responsive characteristics of the maize Zm4CL gene family, providing valuable resources for future functional studies and the genetic improvement of stress tolerance in maize.

Zea mays

RADX protects against intestinal inflammation by restraining IFI16-mediated innate immunity.

Genomic instability is increased in patients with inflammatory bowel disease (IBD), yet whether it contributes directly to disease pathogenesis remains unclear. Here, we identify RADX, a structural antagonist to RAD51 and a key regulator of replication fork stability, as a critical suppressor of intestinal inflammation by limiting innate immune sensing of replication-associated DNA damage. RADX deficiency exacerbates experimental colitis, with macrophages serving as the principal mediators of this phenotype. Mechanistically, RADX competes with the DNA sensor IFI16 for binding to single-stranded DNA (ssDNA). Loss of RADX promotes ssDNA accumulation, triggering IFI16-dependent activation of NF-κB signaling and inflammasome assembly, thereby driving intestinal inflammation. Consistent with these findings, two RADX variants identified in patients with IBD associate with reduced RADX protein expression, increased DNA damage signaling, and elevated IL-1β levels. Pharmacological inhibition of RAD51 with RI-1 alleviated colitis in both wild-type and Radx-deficient mice. Together, these findings establish a mechanistic link between genome instability and intestinal inflammation, identify a RADX-IFI16 checkpoint that restrains pathogenic innate immune activation, and nominate modulation of replication stress as a therapeutic strategy for IBD.

Animals

Gut microbiota dysbiosis and host metabolite-immune crosstalk drives the pathogenesis of neonatal lupus erythematosus: a multi-omics analysis.

BACKGROUND: Neonatal lupus erythematosus (NLE) is a rare autoimmune condition triggered by the transplacental transfer of maternal antibodies. Despite its recognized clinical manifestations, the underlying pathogenesis remains incompletely understood. This study seeks to explore the disruption of the gut microbiota-host metabolism-immune axis in anti-Ro/La-positive neonates, and to assess its potential role in the development of NLE. METHODS: This multicenter, cross-sectional study included 90 neonates, divided into three groups: 30 with neonatal lupus erythematosus (NLE), 30 with positive antibodies but without clinical manifestations (No-NLE), and 30 healthy controls. We performed 16 S rRNA sequencing to analyze gut microbiota composition, untargeted plasma metabolomic profiling, and proteomic analysis to identify alterations associated with the pathogenesis of NLE. RESULTS: We identified significant alterations in the gut microbiota, plasma metabolome, and proteome profiles of anti-Ro/La-positive neonates. NLE infants exhibited marked enrichment of Enterobacteriaceae and depletion of Bifidobacterium and Clostridium butyricum. Metabolomic analysis revealed hyperactivation of β-alanine and purine metabolism, along with impaired α-linolenic acid metabolism and endocannabinoid signaling. Proteomic profiling indicated aberrant protein expression that modulated IFN signaling, particularly within the C-type lectin receptor pathway. Dysregulation of the spleen tyrosine kinase (SYK) and high-affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) decoupling was observed, correlating with elevated IFN-α and NF-κB p65 levels. Integrated correlation analysis revealed significant associations among differential microbial taxa, plasma metabolites, and proteins. Notably, E. coli-associated metabolites and proteins displayed inverse relationships with those associated with C. butyricum. CONCLUSIONS: These findings represent comprehensive evidence of dysregulation along the "gut microbiota-host metabolism-immune" axis in neonatal lupus erythematosus (NLE), providing novel insights into the disease's underlying heterogeneity.

Humans