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Biomedical subjects

Xiao Han

Publications and source records attributed to Xiao Han.

8 recordsLinked to original sources

XsiAMT1.1a was identified as a novel ammonium uptake functional gene and its overexpression combined with GA4 application significantly increased yield in Arabidopsis thaliana.

Nitrogen (N) is a key limiting factor for plant yield. Ammonium is one of the main N forms absorbed by plants. Overexpression of ammonium uptake functional genes, such as ammonium transporter (AMT), can increase yield. However, the AMTs reported to enhance yield significantly is still limited. No researches have focused on the effect of overexpressing AMT combined with hormone application on yield improvement. In this study, we first investigated the role of XsiAMT1.1a, a potential ammonium uptake functional gene in an ammonium preference plant Xanthium sibiricum, in ammonium uptake by the analysis of bioinformatics, gene expression and subcellular localization, and the determination of ammonium uptake rate in endogenous silencing and heterologous overexpression plants. Subsequently, the effect of XsiAMT1.1a overexpression combined with hormone application on yield increase was further investigated in model plant Arabidopsis thaliana. Our results showed that XsiAMT1.1a shared the same conserved domains with AtAMT1 subfamily members and localized on the plasma membrane. XsiAMT1.1a was induced by N deficiency and highly expressed during the reproductive period. XsiAMT1.1a endogenous silencing and heterologous overexpression significantly decreased and increased ammonium uptake rates in X. sibiricum and A. thaliana, respectively. Overexpression of XsiAMT1.1a significantly improved total N accumulation, biomass and yield in A. thaliana, while XsiAMT1.1a overexpression combined with GA4 application had a stronger promoting effect on the above indicators. Our research identified a novel ammonium uptake functional gene, XsiAMT1.1a, and provided a new yield-increasing strategy which was verified in A. thaliana.

Arabidopsis

The circadian clock proteins PRR modulate root hair development via the RHD6/RSL module in Arabidopsis.

Root hairs, derived from trichoblasts, are critical for plant growth and environmental adaptation. Although environmental cues are known to influence root hair development, how endogenous timing systems such as the circadian clock integrate into the core transcriptional network governing root hair formation remains unclear. Here, we show that the circadian clock-associated protein PSEUDO-RESPONSE REGULATOR5 (PRR5) physically interacts with ROOT HAIR DEFECTIVE6 (RHD6) and RHD6 LIKE1 (RSL1), two basic helix-loop-helix transcription factors essential for root hair initiation. Genetic analyses suggest that PRR proteins contribute to root hair development under long-day conditions in Arabidopsis thaliana. Simultaneous disruption of PRR5, PRR7, and PRR9 results in defective root hairs, whereas PRR5 overexpression markedly increases root hair density and length. Transcriptomic and RT-qPCR analyses reveal that PRRs enhance the expression of RHD6, RSL1, and multiple downstream root hair-responsive genes, while modulating their temporal expression patterns. Furthermore, PRR5-mediated root hair promotion requires RHD6/RSL1, and PRR proteins enhance RHD6-dependent activation of the RSL4 promoter. PRRs also contribute to root hair development under phosphate-deficient and salt-stress conditions. Together, these findings establish a molecular framework in which PRR proteins regulate the RHD6/RSL network to coordinate root hair development and environmental responses.

Arabidopsis

Comparison of Medium-Coverage Whole-Genome Sequencing and Chromosomal Microarray in Prenatal Testing of Absence of Heterozygosity.

OBJECTIVE: Absence of heterozygosity (AOH) is a clinically significant genomic feature often associated with uniparental disomy and parental consanguinity in the prenatal settings. Chromosomal microarray analysis (CMA) is commonly used for AOH detection, while sequencing-based approaches may provide complementary genomic information within a single assay. This study evaluated the performance of medium-coverage whole-genome sequencing (CNV-plus) for the detection of prenatal AOH. METHODS: We analyzed 45 prenatal samples (35-CMA-positive, 10-CMA-negative). Concordance between CNV-plus and CMA was assessed at regional, genome-wide, and sample levels, with particular emphasis on the effect of AOH segment size. RESULTS: CNV-plus detected 56 AOH regions compared with 65 by CMA, yielding 68 matched segments. Segment-level sensitivity was 86.8%, showing clear size dependence: 53.3% for 5-10 Mb regions and 96.2% for regions > 10 Mb. Genome-wide overlap was high (global Jaccard index = 0.871), although boundary resolution differed between methods. At the sample level, CNV-plus achieved 97.1% sensitivity and 100% specificity, with no significant difference from CMA. CONCLUSIONS: CNV-plus demonstrates good concordance with CMA for detecting larger AOH regions in prenatal samples and may serve as a complementary approach when considering its size-dependent performance.

Humans

Population and landscape genomics provide insights into the adaptive genetic variation and future climate-induced vulnerability of the endangered tree species Phoebe bournei.

Elucidating the genomic underpinnings of adaptive variation is highly important for the conservation, landscape application, and management of ornamental trees against the backdrop of global climate change. However, research on the genetic mechanisms underlying climate adaptation in Phoebe bournei-a near-threatened subtropical tree species endemic to China, which is endowed with exceptionally high ornamental and ecological value-remains scarce. Whole-genome resequencing was conducted on 362 individuals from 27 natural populations across the geographical range of the species. Genome-environment association analyses were employed to identify 1556 climate-associated variants and 167 candidate genes associated with temperature and precipitation variables. Through functional annotation and expression profiling, pivotal genes, including TRX-M4 and FBD1, were identified as integral to drought and heat stress responses, with adaptive alleles displaying distinct geographic frequency distributions and significant phenotypic differentiation. Divergent evolutionary trajectories were deduced among populations, with southeastern populations distinguished by elevated genetic diversity and strong signatures of local adaptation. Nevertheless, projections derived from the Risk of Non-Adaptedness and gradient forest models suggest that these southeastern populations will face substantial genomic offset under future climate scenarios, signaling heightened vulnerability and the need for prioritized conservation and management. This study provides the first genome-wide perspective into the adaptive evolution of P. bournei and offers a robust foundation for its conservation and climate-resilient management.

Journal Article

Telomere-to-telomere genome of Phoebe chekiangensis reveals that age-dependent CHG hypomethylation promotes floral transition via MADS-box gene activation.

Phoebe species are renowned for their highly valuable 'golden thread' timber; however, their protracted juvenile phase presents a significant obstacle to mechanistic investigations of floral induction. Phoebe chekiangensis, a rare early-flowering representative within this genus, provides a unique model system for dissecting the vegetative-to-reproductive phase transition. Nevertheless, the absence of a high-quality reference genome has severely hindered molecular insights into its developmental regulation. Here, we present the first telomere-to-telomere (T2T) genome assembly for P. chekiangensis, comprising two completely gap-free haplotypes with contig N50 values exceeding 65 Mb, base-level quality scores >36, and Long Terminal Repeat Assembly Index scores surpassing the gold standard threshold of 20. Approximately 29 000 genes were annotated per haplotype, supported by a BUSCO completeness score of >97%. Age-resolved transcriptomic landscapes identified two MADS-box transcription factors, PcMADS5 (AP1-like) and PcMADS19.1 (SOC1-like), as core activators of the floral transition. Both genes triggered precocious flowering when ectopically expressed in Arabidopsis thaliana. Whole-genome bisulfite sequencing revealed a progressive, age-dependent decline in CHG (where H is A, C, or T) DNA methylation, which was particularly pronounced at the PcMADS19.1 locus. Notably, DML1/2, which mediate active DNA demethylation, were coordinately upregulated during the onset of reproductive growth. Chemical demethylation using 5-azacytidine further diminished CHG methylation and selectively enhanced PcMADS19.1 expression, confirming a causal relationship between CHG hypomethylation and transcriptional activation. This work delivers the first chromosome-scale T2T genome within the genus Phoebe and uncovers CHG demethylation as a previously unrecognized epigenetic switch governing reproductive competence in woody perennials.

Journal Article

The Association of Allergic Rhinitis with Chronic Adenotonsillar Diseases and Chronic Rhinosinusitis: A Mendelian Randomization Study.

INTRODUCTION: Allergic rhinitis (AR) has long been considered to be associated with chronic adenotonsillar disease (CATD). However, their causal relationship remains unclear. This study aims to investigate the causal relationship between AR and CATD and to examine the mediating role of chronic rhinosinusitis (CRS) in this association. METHODS: This study employed a two-sample Mendelian randomization (MR) design using genetic instrumental variable analysis. Data for allergic rhinitis (AR) were obtained from the MRC IEU OpenGWAS data infrastructure, data for chronic adenotonsillar disease (CATD) from the FinnGen biobank, and data for chronic rhinosinusitis (CRS) from the GWAS Catalog. Several MR methods were applied. In addition, a two-step MR approach was used to investigate the mediating role of CRS in the relationship between AR and CATD. RESULTS: MR analysis identified a positive correlation between AR and CATD. IVW and weighted median analyses showed significant causal effects (beta = 0.55, 95% CI: 0.26 to 0.84); p <0.001). No causal association was found between CATD and AR. AR and CRS showed a positive correlation (beta = 1.38, 95% CI: 0.78 to 1.98; p = 6.5 &#xd7; 10-6). CRS had a beta value of 0.15 (95% CI: 0.06 to 0.24; p = 0.001) for CATD. CRS mediates 37.6% of the AR to CATD pathway (mediation effect = 0.20, 95% CI: 0.04 to 0.37; p = 0.013). DISCUSSION: These findings indicate that AR may contribute to CATD risk through CRS, highlighting the need for further research to explore underlying biological mechanisms and validate these findings. CONCLUSIONS: This study suggests a positive causal relationship between AR and CATD, with CRS acting as a mediator.

Mendelian Randomization Analysis

DKK1-SE recruits AP1 to activate the target gene DKK1 thereby promoting pancreatic cancer progression.

Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

Humans

Ypel5 regulates liver development and function in zebrafish.

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5-/- mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPAR&#x3b1; signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Animals