Biomedical subjects

Xiao Han

Publications and source records attributed to Xiao Han.

At least 19 recordsLinked to original sources

PubMed2026

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↗

PubMed2026

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↗

PubMed2026

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↗

PubMed2026

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↗

PubMed2026

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↗

PubMed2026

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 × 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↗

PubMed2024

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↗

PubMed2023

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, PPARα 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↗

PubMed2006

The bcl-2 major breakpoint region (mbr) possesses transcriptional regulatory function.

The bcl-2 major breakpoint region (mbr), located within the 3'-UTR of the bcl-2 gene, is the site of the most common chromosomal translocation, t(14;18) (q32;q21), which occurs in follicular lymphoma. The mbr forms a triplex DNA structure under physiological conditions and the transcription factor special AT-rich sequence-binding protein 1 (SATB1) binds immediately downstream of the mbr. These observations raise the possibility that the mbr may be involved in regulation of bcl-2 gene expression. We investigated the role of the bcl-2 mbr on reporter gene activity and the relevance of SATB1 to this function in a variety of cell lines. We found that the mbr up-regulated reporter gene expression. Deletion of the 37-bp AT-rich SATB1 binding site abolished the bcl-2 mbr regulation of reporter gene expression. Overexpression of SATB1 enhanced bcl-2 mbr up-regulation of the reporter gene activity. Our data strongly demonstrated that the bcl-2 mbr possessed regulatory function that was related to SATB1.

3' Untranslated Regions↗

PubMed2006

Co-culture with fat cells induces cellular insulin resistance in primary hepatocytes.

Obesity is highly correlated with systemic insulin resistance. To assess the effect of fat cell on the development of hepatic insulin resistance, an in vitro system was developed in which primary hepatocytes were kept in co-culture with 3T3-L1 cells, then insulin signaling and glycogen production were subsequently analyzed in hepatocytes. The results showed that insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-2 was significantly blocked. Insulin-regulated activation of Akt kinase and glucose production in the hepatocytes were also reduced after co-culture. On the other hand, addition of TNF-alpha or IL-6 neutralizing antibodies to the supernatant of co-culture recovered both IRS-2 phosphorylation and Akt activation. In conclusion, fat cells may induce insulin resistance in liver cells, and this process appears to be mediated by TNF-alpha and IL-6. Our data present first the direct evidence of interaction for insulin signaling event between the adipocytes and hepatocytes.

3T3-L1 Cells↗

PubMed2006

Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer.

In vivo MRI-derived measurements of human cerebral cortex thickness are providing novel insights into normal and abnormal neuroanatomy, but little is known about their reliability. We investigated how the reliability of cortical thickness measurements is affected by MRI instrument-related factors, including scanner field strength, manufacturer, upgrade and pulse sequence. Several data processing factors were also studied. Two test-retest data sets were analyzed: 1) 15 healthy older subjects scanned four times at 2-week intervals on three scanners; 2) 5 subjects scanned before and after a major scanner upgrade. Within-scanner variability of global cortical thickness measurements was <0.03 mm, and the point-wise standard deviation of measurement error was approximately 0.12 mm. Variability was 0.15 mm and 0.17 mm in average, respectively, for cross-scanner (Siemens/GE) and cross-field strength (1.5 T/3 T) comparisons. Scanner upgrade did not increase variability nor introduce bias. Measurements across field strength, however, were slightly biased (thicker at 3 T). The number of (single vs. multiple averaged) acquisitions had a negligible effect on reliability, but the use of a different pulse sequence had a larger impact, as did different parameters employed in data processing. Sample size estimates indicate that regional cortical thickness difference of 0.2 mm between two different groups could be identified with as few as 7 subjects per group, and a difference of 0.1 mm could be detected with 26 subjects per group. These results demonstrate that MRI-derived cortical thickness measures are highly reliable when MRI instrument and data processing factors are controlled but that it is important to consider these factors in the design of multi-site or longitudinal studies, such as clinical drug trials.

Aged↗

PubMed2006

Role of peroxisome proliferator-activated receptor gamma in glucose-induced insulin secretion.

Peroxisome proliferator-activated receptor (PPAR) isoforms (alpha and gamma) are known to be expressed in pancreatic islets as well as in insulin-producing cell lines. Ligands of PPAR have been shown to enhance glucose-induced insulin secretion in rat pancreatic islets. However, their effect on insulin secretion is still unclear. To understand the molecular mechanism by which PPARgamma exerts its effect on glucose-induced insulin secretion, we examined the endogenous activity of PPAR isoforms, and studied the PPARgamma function and its target gene expression in INS-1 cells. We found that: (1) endogenous PPARg was activated in a ligand-dependent manner in INS-1 cells; (2) overexpression of PPARgamma in the absence of PPARgamma ligands enhanced glucose-induced insulin secretion, which indicates that the increased glucose-induced insulin secretion is a PPARgamma-mediated event; (3) the addition of both PPARgamma and retinoid X receptor (RXR) ligands showed a synergistic effect on the augmentation of reporter activity, suggesting that the hetero-dimerization of PPARgamma and RXR is required for the regulation of the target genes; (4) PPARs upregulated both the glucose transporter 2 (GLUT2) and Cb1-associated protein (CAP) genes in INS-1 cells. Our findings suggest an important mechanistic pathway in which PPARgamma enhances glucose-induced insulin secretion by activating the expression of GLUT2 and CAP genes in a ligand-dependent manner.

Animals↗

PubMed2006

[Mechanism of serum containing SSTG on calcium overload in cardiomyocytes injuryed by hypoxia and reoxygenation].

OBJECTIVE: To explore the effects and mechanism of Shuangshen Tongguan (SSTG) serum, a formula composed of the active fractions of Chinese medicine, on calcium overload in cultured cardiomyocytes injured by hypoxia and reoxygenation. METHOD: The cardiomyocytes were deprived of oxygen and glucose to producl hypoxia reoxygenation injuried models. The changes of intracellular calcium fluorescence intensity induced by K+ and Thapsigargin were measured by fluorospectrophotometry and laster scanning confocal microscope respectively. RESULT: Intracellular calcium concentration was low in normal cardiomyocytes and was enhanced after hypoxia/reoxygenation (P < 0.05); SSTC drug serum reduced the intracellular calcium concentration and depressed the increase of calcium fluorescence intensity in singular cardiomyocyte due to K+ and Thapsigargin stimulation. CONCLUSION: Hypoxia/reoxygenation injury, K+ and Thapsigargin could induce calcium overload in cardiomyocytes. The effects of calcium antagonism of SSTG drug serum were achieved by inhibiting calcium inflow, promoting calcium re-absorption of calcium.

Animals↗

PubMed2006

[Study on time-effect and dose-effect of serum containing Chinese herbal medicine].

OBJECTIVE: To study the time-effect, dose-effect of serum containing Shuangshentongguan (SSTG), a formula composed by active fraction of Chinese medicine. METHOD: Serum containing SSTG was obtained at different time after perorally administrated with different dose of SSTG. The cardiomyocytes were deprived of oxygen and glucose to mimic hypoxia reoxygenation injury and were treated by serum containing SSTG when reoxygenation. LDH content in supernatant was detected after reoxygenation. LDH release suppression rate was used to study the time-effect and dose-effect of serum containing SSTG. RESULT: The suppression rate of LDH release was not satisfied in serum containing high dose of SSTG. There was no significant dose-effect relationship between them. The suppression rate of LDH release was also different in drug serum taken at different time after SSTG treatment. CONCLUSION: It was not the case that the higher the dose given to animal, the better the pharmacological effects.

Animals↗

PubMed2005

The behavior of SATB1, a MAR-binding protein, in response to apoptosis stimulation.

As a MAR-binding protein, SATB1 regulates genes by folding chromatin into a loop domain. Apoptosis is known to be accompanied by a collapse of nuclear architecture and cleavage of condensing chromatin into oligonucleosomal fragments. To further understand the functional role of MAR-binding proteins during apoptosis we investigated the relationship of the behavior of SATB1 and the collapse of nuclear architecture in Jurkat cells with immunostaining and Western blot analysis. We demonstrated that SATB1 formed special three-dimensional network distributions during early apoptosis. The distribution change of SATB1 was associated with cleavage of the protein and accompanied by the nuclear architecture collapse. Cleavage of SATB1 was mediated by caspase-3 and was apoptosis specific. Our observations further support the notion that early proteolysis of MAR-binding proteins might represent a universal mechanism that renders these DNA sites vulnerable to endonucleolysis.

Apoptosis↗

PubMed2005

Blockade of L-type voltage-gated Ca channel inhibits ischemia-induced neurogenesis by down-regulating iNOS expression in adult mouse.

Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. The signals that regulate neurogenesis in the dentate gyrus following ischemic stroke insult are not well known. We have previously reported that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia-stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly increased the number of new neurons and up-regulated iNOS expression in the dentate gyrus. Blockade of the L-type voltage-gated Ca(2+) channel (L-VGCC) prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and down-regulated iNOS expression in the dentate gyrus after cerebral ischemia. This study suggests that Ca(2+) influx through L-VGCC is involved in ischemia-induced neurogenesis by up-regulating iNOS expression.

Animals↗

PubMed2005

Aryl ketones from Acronychia pedunculata with cyclooxygenase-2 inhibitory effects.

1-[2,4-Dihydroxy-6-methoxy-3,5-bis(3-methylbut-2-en-1-yl)phenyl]ethanone (1), and a new aryl ketone, named acrovestenol (2), were isolated as cyclooxygenase-2 (COX-2) inhibitory principles from a CH2Cl2 extract of the bark of Acronychia pedunculata by a bioassay-guided fractionation procedure. Compound 2 inhibited COX-2 with an IC50 value of 142.0+/-2.15 microM, compared to the COX-2 inhibitory reference compound NS-398 with an IC50 value of 11.3+/-1.12 microM. Compound 1 inhibited COX-2-catalyzed PG biosynthesis with 68% at a concentration of 500 microM. The structures were determined by UV, IR, and 1D- and 2D-NMR, including TOCSY, HSQC-DEPT, and HMBC, and MS investigations.

Acetophenones↗

PubMed2005

[Method for studying traditional Chinese compound prescription].

Treatment with traditional Chinese medicinal composite is one of the most important characteristics of traditional Chinese medicine (TCM). Studying material base of TCM composite and its mechanism is a key to modernizing the industry of Chinese medicinal herbs. The research for TCM composite can be carried out from many different angles, including multiple components, multiple actions, multiple levels and multiple targets. Such a way to study TCM composite will be beneficial to improving the theory of TCM composite, guiding clinical administration and developing new products.

Drug Combinations↗