Biomedical subjects

Xiaoyu Li

Publications and source records attributed to Xiaoyu Li.

4 recordsLinked to original sources

PubMed2026

Construction and evaluation of an independently generated transgenic mouse model carrying mutated human HRAS genes for short-term carcinogenicity assessment.

The study aimed to construct and evaluate an independently generated transgenic mouse model applied to the short-term carcinogenicity assessment. Mutated human HRAS fragment containing an intron point-mutation was inserted into C57BL/6JGpt mice via bacterial artificial chromosome transgenic technology, eventually generating BALB/c;B6J-Tg(hHRAS)16/Gpt mice, abbreviated as HRAS mice. The inserted human HRAS fragment in HRAS mice was characterized, revealing five tandem copies at chromosome 19. Baseline profiles, including biochemical, hematological, immunophenotypic, survival, and carcinogenic data of HRAS mice, were collected. To evaluate the tumor susceptibility in HRAS mice, we applied N-Nitroso-N-methylurea (MNU) to HRAS mice in a short-term carcinogenicity assessment conducted according to Good Laboratory Practice. The genetic characteristics of HRAS mice include five tandem arrays of mutated human HRAS fragments located in genomic coordinate 7,755,606 on chromosome 19 and the duplication of a 9-kilobase genome sequence (genomic coordinate 7,755,606-7,746,509) located on chromosome 19. HRAS mice showed a relatively lower incidence and range of spontaneous tumor formation during long-term observation compared to CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) transgenic mice. The short-term carcinogenicity assessment showed a strong tumor response to MNU, with high incidences of lymphoma (≥ 90%) and stomach squamous cell papilloma (≥ 90%) in both male and female HRAS mice. The HRAS mice showed susceptibility to MNU and exhibited baseline characteristics distinct from those of Tg.rasH2 mice. The co-expression of HRAS and MKI67 at the cellular localization level was found in neoplasms of HRAS mice. These findings preliminarily evaluated the feasibility of HRAS mice applied to the short-term carcinogenicity assessment.

Animals↗

PubMed2026

Exogenous ABA enhances cold tolerance of Rhododendron yedoense var. poukhanense under subzero temperature: integrating physiology, transcriptome, and proteome.

Low temperature limits the growth and ornamental value of evergreen shrubs. Rhododendron yedoense var. poukhanense, an important ornamental shrub from Northeast China, frequently suffers freezing damage during winter. While exogenous abscisic acid (ABA) enhances cold tolerance in many plants, its molecular mechanisms at subzero temperatures remain poorly understood in non-model species lacking chromosome-level reference genomes. This study investigated the effects of exogenous ABA on freezing tolerance in R. yedoense var. poukhanense at -4 °C using an integrated physiological, transcriptomic, and proteomic approach. Cutting seedlings were subjected to four treatments: CK (22°C control), A (22°C + ABA), LT (-4°C), and ALT (-4°C + ABA). Photosynthetic pigments, osmotic regulation substances, antioxidant enzyme activities, and malondialdehyde (MDA) content were measured. Transcriptome sequencing and quantitative proteomics were performed, and transcriptome data were validated by quantitative real-time PCR (qRT-PCR) of 15 selected genes. ABA pretreatment reduced visible cold injury severity, partially preserved photosynthetic pigments, decreased MDA content by 28.7%, and promoted recovery of catalase (+43.6%), superoxide dismutase (+31.1%), and peroxidase (+20.0%) activities under freezing stress. Transcriptome analysis revealed 8, 444 differentially expressed genes (DEGs) in LT versus CK and 6, 481 DEGs in ALT versus CK, representing a 23% reduction in transcriptional reprogramming scope attributable to ABA priming. The ALT versus LT comparison identified only 1, 690 additional DEGs, indicating that most cold-responsive genes were pre-activated during the ABA priming phase. Proteome analysis identified 1, 461 differentially expressed proteins (DEPs) in ALT versus CK. Integrated analysis revealed extensive post-transcriptional regulation, with transcript-protein concordance of only 1.0-4.1%, and co-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in both omics layers. qRT-PCR validation confirmed high reliability of the transcriptome data (R2 = 0.8500). These findings demonstrate that exogenous ABA enhances freezing tolerance through multi-layered molecular regulation encompassing transcriptional buffering, translational reprogramming, and functional reallocation from photosynthesis to stress protection. This study provides the first integrated physiology-transcriptome-proteome framework for ABA-mediated freezing tolerance in an evergreen ornamental shrub and offers theoretical support for ABA-based winter protection strategies.

Rhododendron yedoense var. Poukhanense↗

PubMed2025

Streamlining large-scale genomic data management: Insights from the UK Biobank whole-genome sequencing data.

Biobank-scale whole-genome sequencing (WGS) studies are increasingly pivotal in unraveling the genetic bases of diverse health outcomes. However, managing and analyzing these datasets' sheer volume and complexity presents significant challenges. We highlight the annotated genomic data structure (aGDS) format, substantially reducing the WGS data file size while enabling seamless integration of genomic and functional information for comprehensive WGS analyses. The aGDS format yielded 23 chromosome-specific files for the UK Biobank 500k WGS dataset, occupying only 1.10 tebibytes of storage. We develop the vcf2agds toolkit that streamlines the conversion of WGS data from VCF to aGDS format. Additionally, the STAARpipeline equipped with the aGDS files enabled scalable, comprehensive, and functionally informed WGS analysis, facilitating the detection of common and rare coding and noncoding phenotype-genotype associations. Overall, the vcf2agds toolkit and STAARpipeline provide a streamlined solution that facilitates efficient data management and analysis of biobank-scale WGS data across hundreds of thousands of samples.

Humans↗

PubMed2024

Crosstalk between epitranscriptomic and epigenomic modifications and its implication in human diseases.

Crosstalk between N6-methyladenosine (m6A) and epigenomes is crucial for gene regulation, but its regulatory directionality and disease significance remain unclear. Here, we utilize quantitative trait loci (QTLs) as genetic instruments to delineate directional maps of crosstalk between m6A and two epigenomic traits, DNA methylation (DNAme) and H3K27ac. We identify 47 m6A-to-H3K27ac and 4,733 m6A-to-DNAme and, in the reverse direction, 106 H3K27ac-to-m6A and 61,775 DNAme-to-m6A regulatory loci, with differential genomic location preference observed for different regulatory directions. Integrating these maps with complex diseases, we prioritize 20 genome-wide association study (GWAS) loci for neuroticism, depression, and narcolepsy in brain; 1,767 variants for asthma and expiratory flow traits in lung; and 249 for coronary artery disease, blood pressure, and pulse rate in muscle. This study establishes disease regulatory paths, such as rs3768410-DNAme-m6A-asthma and rs56104944-m6A-DNAme-hypertension, uncovering locus-specific crosstalk between m6A and epigenomic layers and offering insights into regulatory circuits underlying human diseases.

Humans↗