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Xun Xu

Publications and source records attributed to Xun Xu.

At least 19 recordsLinked to original sources
PubMed2026

A Molecularly Anchored Spatial Transcriptomic Framework for Precise CA1-Subiculum Parcellation and Region-Resolved Analysis in Alzheimer's Disease.

BACKGROUND: The precise molecular delineation of the interface between the Subiculum (Sub) and cornu ammonis 1 (CA1) is a challenge in hippocampal research, as conventional cytoarchitectural boundaries are often ambiguous and limit reproducible regional annotation. Here, we developed a molecularly anchored spatial transcriptomic framework to define CA1-Sub regional identities using high-definition spatial transcriptomics (Stereo-seq) and single-nucleus RNA sequencing (snRNA-seq) references. FINDINGS: Using a human hippocampal Stereo-seq dataset from 12 donors, we established a data-driven parcellation framework that defines reproducible molecular features distinguishing CA1 and Sub while capturing the transition between these regions. FN1 was identified as a Sub-enriched marker in a subset of EX_Sub and, together with ETV1 and additional regional markers, enabled molecular assignment of CA1 and Sub identities across datasets. The Sub association of FN1 and ETV1 was further supported by human 10X Genomics spatial transcriptomics, mouse in situ hybridization data, and a mouse spatial transcriptomic dataset. Applying this framework to Alzheimer's disease (AD) tissues revealed region-specific transcriptional alterations across CA1 and Sub, including enrichment of mitochondrial energy metabolism-related transcripts in the Sub, suggesting exploratory transcriptional associations of altered metabolic function. CONCLUSIONS: This study provides a molecularly anchored framework for human CA1-Sub parcellation that complements conventional annotation. By defining regional molecular states while preserving the biological continuum across CA1-Sub interface, this approach enables more consistent regional analysis of human hippocampus tissue across donors, datasets, and disease conditions.

Journal Article↗
PubMed2026

Spatially resolved single-cell atlas reveals the macroevolutionary trajectory of animal hearts.

Animal hearts display diverse anatomical structures during adaptive evolution. Here, we present a multiomics atlas of adult hearts from 27 species across chordates, arthropods, and mollusks. Joint analysis indicates that Bilateria hearts share a core gene repertoire, taking a stepwise "add-on" approach as a universal evolutionary strategy. The "proto-heart" is populated by key cell types, including cardiomyocytes, fibroblasts, endothelial cells, and neural cells, which maintained core signatures while evolving with shifts in living environments and corresponding adaptations in the cardiovascular system. Additionally, we reveal an evolutionarily conserved cardiomyocyte state dynamic potentially linked to cardiac development and stress responses. Finally, we identify a common molecular program underpinning chamber evolution from a ventricular foundation. This work establishes a resource for understanding the intrinsic mechanisms of heart evolution.

Animals↗
PubMed2026

Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.

Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4+ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.

TCR/BCR↗
PubMed2026

Magnetic nanoparticle-mediated genetic transformation and gene editing system in loquat (Eriobotrya japonica).

Loquat (Eriobotrya japonica Lindl.) is a valuable subtropical fruit tree whose genetic improvement has been significantly constrained by the absence of an efficient genetic transformation system. Although Agrobacterium-mediated transformation is the most widely used method, it proves ineffective in loquat due to the species' recalcitrance to in vitro regeneration. Pollen-based transformation offers a promising alternative by bypassing the need for tissue culture. However, the pollen wall poses a major physical barrier to the uptake of exogenous DNA. In this study, we investigated magnetic nanoparticle (MNP)-mediated transformation as a novel strategy for loquat. We confirmed that loquat pollen contains tricolporate apertures with diameters ranging from 3.0 to 5.0 μm, which are structurally suitable for the entry of MNPs-DNA. Based on this finding, we developed and optimized a transformation protocol using polyethyleneimine-coated Fe3O4 nanoparticles to deliver genetic material into loquat pollen grains. Using this approach, we successfully generated stable transgenic loquat lines, including both overexpression and gene-edited mutants. To our knowledge, this is the first report of successful MNP-mediated pollen transformation in a woody plant species. This work establishes a robust and efficient genetic transformation platform for loquat, providing a valuable tool for functional genomics and molecular breeding, as well as a potentially applicable strategy for other recalcitrant woody plants.

Eriobotrya↗
PubMed2026

Exploring the substrate promiscuity and functional residues of UGT73 family enzymes in Entada phaseoloides.

Flavonoid glycosides and triterpenoid saponins are bioactive plant metabolites with broad applications in food, medicine, and agriculture. These compounds are typically synthesized through glycosylation catalyzed by uridine diphosphate-dependent glycosyltransferases (UGTs). In this study, phylogenetic analysis across multiple species revealed a lineage-specific expansion of the UGT73 family in legumes such as Entada phaseoloides and Glycine max. The genome of the medicinal legume E. phaseoloides was re-annotated using integrated Oxford Nanopore Technologies and Illumina transcriptomic data to identify target genes. Four expanded UGT73 family genes were selected and functionally characterized. UGT73AA6 specifically glycosylates flavonoids, while UGT73CG48 and UGT73CG49 catalyze glycosylation of both flavonoids and pentacyclic triterpenoids. UGT73CG49 exhibits higher catalytic activity for the glucosylation of flavonoids and pentacyclic triterpenes compared to its xylosylation activity. Structural modeling and molecular docking identified key active sites, and site-directed mutagenesis revealed Gly194 as a critical residue enhancing catalytic activity in UGT73CG49. This study provides new insights into the functional evolution and metabolic versatility of the UGT73 family in legumes. The identification and engineering of UGT73 genes from E. phaseoloides lay a foundation for future applications in biosynthetic pathway engineering and the industrial production of high-value glycosides.

Substrate Specificity↗
PubMed2025

Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays.

Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.

Animals↗
PubMed2025

Inferring cell trajectories of spatial transcriptomics via optimal transport analysis.

The integration of cell transcriptomics and spatial position to organize differentiation trajectories remains a challenge. Here, we introduce SpaTrack, which leverages optimal transport to reconcile both gene expression and spatial position from spatial transcriptomics into the transition costs, thereby reconstructing cell differentiation. SpaTrack can construct detailed spatial trajectories that reflect the differentiation topology and trace cell dynamics across multiple samples over temporal intervals. To capture the dynamic drivers of differentiation, SpaTrack models cell fate as a function of expression profiles influenced by transcription factors over time. By applying SpaTrack, we successfully disentangle spatiotemporal trajectories of axolotl telencephalon regeneration and mouse midbrain development. Diverse malignant lineages expanding within a primary tumor are uncovered. One lineage, characterized by upregulated epithelial mesenchymal transition, implants at the metastatic site and subsequently colonizes to form a secondary tumor. Overall, SpaTrack efficiently advances trajectory inference from spatial transcriptomics, providing valuable insights into differentiation processes.

Animals↗
PubMed2024

Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption.

Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.

Inositol↗
PubMed2006

Genomic organization, promoter characterization and expression profiles of an antiviral gene PmAV from the shrimp Penaeus monodon.

Diseases caused by viruses are the greatest challenge to worldwide shrimp aquaculture. PmAV is the first antiviral gene identified from the shrimp and its mRNA level is up-regulated in response to viral infection (Luo et al., 2003). The transcriptional regulation of PmAV is critical since the expression of this gene is regulated in response to viral stimuli. In this study, we show that the Penaeus monodon PmAV gene contains four exons, separated by three introns. The 5'-flanking sequence of PmAV gene consists of a typical TATA box, several potential regulatory elements, and a compound microsatellite repeat as well. Interestingly, a TATA box and several regulatory elements also exist in the first intron (intron 1). Both intron 1 and the microsatellite are involved in transcriptional regulation of the PmAV gene. PmAV promoter activity depends on the existence of intron 1 while the microsatellite in 5'-flanking sequence acts as a negative regulative element. In addition, using Real-time PCR, we found that PmAV was highly expressed in the hepatopancreas and was up-regulated from the second day post-infection with the increase of viral load. These results extend our previous findings and provide insights into the molecular regulation of PmAV gene expression, which will be helpful for shrimp viral disease control.

Animals↗
PubMed2006

Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: the role of reactive oxygen species in diabetic retinopathy.

Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria. They belong to the family of anion mitochondrial carriers. UCPs could act as proton carriers activated by metabolites and create a shunt between complexes of the respiratory chain and ATP synthase. The increased leakiness of the mitochondrial inner membrane to protons may be to minimize superoxide production by limiting the maximum Deltamu(H+). The purpose of this study was to detect UCP expression in retinal capillary cells and their modification in high levels of glucose. The role of reactive oxygen species (ROS) of mitochondria and UCPs in pathogenesis of diabetic retinopathy was investigated. Bovine retinal capillary endothelial cells and pericytes were cultured with selective culture media, respectively. Passage cells were cultured in three different glucose concentrations (5, 23, 30 mM) until passage four. ROS changes in mitochondria of these cells in different glucose concentrations were detected with scanning laser confocal microscopy (SLCM). The mitochondria membrane potential (Deltapsi), cell death rate and apoptosis rate were measured with flowing cytometry. UCP expression in retinal capillary cells was detected by immunocytochemistry. Expression and modification of MnSOD and uncoupling proteins (UCPs) in different concentrations of glucose were detected by means of semi-quantitative RT-PCR. ROS in mitochondria of both endothelial cells and pericytes increased as the glucose concentration of media increased. Deltapsi and cell death rate of endothelial cells increased also. ROS was correlated to Deltapsi and cell death rate positively in endothelial cells. No difference in Deltapsi and cell death rate among different glucose levels was found in pericytes. Apoptosis rate of endothelial cells and pericytes in high glucose levels was higher than that in lower glucose levels. UCP1 and UCP2 were expressed in cultured retinal capillary cells whereas UCP3 was not. At high levels of glucose, expression of UCP1, UCP2 and MnSOD increased to accommodate ROS production compensatively. The compensative mechanism disappeared when glucose concentration was too high (30 mM). The results of this study showed that increasing mitochondrial ROS could be induced by high glucose concentration. Those proteins related to antioxidation mechanism, such as MnSOD and UCPs, could exert compensative action to a certain extent. This compensative action was insufficient when the glucose concentration was too high.

Animals↗
PubMed2006

Cell autonomous requirement for Tgfbr2 in the disappearance of medial edge epithelium during palatal fusion.

Palatal fusion is a complex, multi-step developmental process; the consequence of failure in this process is cleft palate, one of the most common birth defects in humans. Previous studies have shown that regression of the medial edge epithelium (MEE) upon palatal fusion is required for this process, and TGF-beta signaling plays an important role in regulating palatal fusion. However, the fate of the MEE and the mechanisms underlying its disappearance are still unclear. By using the Cre/lox system, we are able to label the MEE genetically and to ablate Tgfbr2 specifically in the palatal epithelial cells. Our results indicate that epithelial-mesenchymal transformation does not occur in the regression of MEE cells. Ablation of Tgfbr2 in the palatal epithelial cells causes soft palate cleft, submucosal cleft and failure of the primary palate to fuse with the secondary palate. Whereas wild-type MEE cells disappear, the mutant MEE cells continue to proliferate and form cysts and epithelial bridges in the midline of the palate. Our study provides for the first time an animal model for soft palate cleft and submucous cleft. At the molecular level, Tgfb3 and Irf6 have similar expression patterns in the MEE. Mutations in IRF6 disrupt orofacial development and cause cleft palate in humans. We show here that Irf6 expression is downregulated in the MEE of the Tgfbr2 mutant. As a recent study shows that heterozygous mutations in TGFBR1 or TGFBR2 cause multiple human congenital malformations, including soft palate cleft, we propose that TGF-beta mediated Irf6 expression plays an important, cell-autonomous role in regulating the fate of MEE cells during palatogenesis in both mice and humans.

Animals↗
PubMed2006

Purification and characterisation of a calcium-independent lectin (PjLec) from the haemolymph of the shrimp Penaeus japonicus.

A natural lectin (nominated PjLec) was isolated from haemolymph of the shrimp Penaeus japonicus by affinity chromatography with fetuin-Sepharose. The result of SDS-PAGE showed that the purified PjLec protein consisted of 37kDa subunits. The native PjLec behaved as a 452kDa protein in gel filtration chromatography. Those data suggest that PjLec is composed of 12 subunits of similar molecular weight. PjLec has a broad spectrum of bacterial-agglutination activities against both Gram-positive and Gram-negative bacteria, including two Vibrio species and two other strains pathogenic for shrimp. In addition, PjLec could agglutinate all the vertebrate erythrocytes tested, and the haemagglutination was calcium-independent. The haemagglutination of PjLec was inhibited by ManNAc, Neu5A and lipopolysaccharide. Bovine submaxillary mucin, which contains mainly Neu5A, was the most potent inhibitor of PjLec (MIC of 0.0006mgml(-1)). The haemagglutination activity of PjLec was stable between pH 6 and pH 8, and was temperature-dependent. Our results suggested that PjLec may be an important humoral defence factor against bacterial infection in P. japonicus.

Agglutination Tests↗
PubMed2006

Binocular status after surgery for constant and intermittent exotropia.

PURPOSE: To investigate whether constant exotropia patients with a previous history of intermittent exotropia X(T), like X(T) patients, can achieve postoperative bifixation, and whether they have a better postoperative sensory outcome than those without previous history of X(T). DESIGN: Prospective comparative clinical study. METHODS: Sixty-three consecutive patients with intermittent or constant exotropia were divided into three groups: X(T) (group 1), constant exotropia with a previous history of X(T) (group 2), and constant exotropia without previous history of X(T) (group 3). The surgical outcomes were assessed and compared in motor and sensory terms separately between the three groups. Successful motor alignment was defined as within 8 prism diopters (PD) (exo or eso). A stereoacuity < or =60 seconds of arc was considered as bifixation, and a stereoacuity < or =800 seconds of arc was considered as gross stereopsis. RESULTS: The successful motor alignment rates of group 1, group 2, and group 3 were 79%, 71%, and 67%, respectively (group 1 vs group 2, P = .826; group 1 vs group 3, P = .551; group 2 vs group 3, P = 1.000). Twenty-five (74%) patients in group 1 achieved bifixation and none achieved in group 2 or group 3 (group 1 vs group 2, P = .001; group 1 vs group 3, P = .001). Meanwhile, 34 patients (100%) in group 1, 11 (79%) in group 2, and 5 (33%) in group 3 achieved gross stereopsis (group 1 vs group 2, P = .021; group 2 vs group 3, P = .025; group 1 vs group 3, P = .001). Compared with patients in the two constant exotropia groups, patients in X(T) group had a significantly better sensory outcome in both bifixation and gross stereopsis. Patients in group 2 had a better sensory outcome than those in group 3 in gross stereopsis. CONCLUSIONS: Constant exotropia patients with a previous history of X(T) have a better postoperative sensory outcome in gross stereopsis than those without previous history of X(T), but a worse surgical sensory outcome when compared with X(T) patients in both bifixation and gross stereopsis. Constant exotropia patients decompensated from X(T) may have missed the best time for treatment.

Adolescent↗
PubMed2006

Effects of intravitreal dispase on vitreoretinal interface in rabbits.

OBJECTIVE: To explore the efficacy and safety of dispase on the production of posterior vitreous detachment (PVD) following intravitreal injection at various concentrations for different exposure times in the rabbit eyes. METHODS: Sixty-four pigmented rabbits were assigned to two groups according to different combinations of concentrations of dispase and exposure times, namely group 1 (10, 5, or 1 U/ml for 30 min) and group 2 (0.25, 0.1, or 0.05 U/ml for one week). The control was established in both groups. One eye of each experimental rabbit was injected with dispase, and one eye of each control rabbit was injected with phosphate buffered saline. The presence of PVD and intraocular toxicity were observed by biomicroscope, macroexamination, and histology. RESULTS: None of the control eyes showed PVD. In group 1, PVD was present in 6 of 7 eyes in each sub-group. In group 2, all 7 eyes of 0.25 U/ml or 0.1 U/ml and 6 of 7 eyes of 0.05 U/ml showed PVD. Intraocular toxicity including inflammation in anterior chamber, vitreous haze, epiretinal membrane, and retinal damage were found in the experimental eyes with relatively higher concentrations of dispase. CONCLUSIONS: Although dispase has a definite effect on the induction of PVD in rabbits, its toxicity to retina also alerts us to the application in clinic. The intravitreal injection of dispase of 1 U/ml for 30 min may be acceptable.

Animals↗
PubMed2006

Quantitative in vivo retinal thickness measurement in chinese healthy subjects with retinal thickness analyzer.

PURPOSE: To measure the retinal thickness of the posterior pole in healthy Chinese subjects using a retinal thickness analyzer and to compare the retinal thicknesses between different age, gender, and refractive error groups. METHODS: Between February 2002 and September 2004, healthy Chinese subjects (age range, 21-50 years), underwent measurements of visual acuity, refractive error, intraocular pressure, and posterior pole retinal thickness with the RTA, as well as ophthalmoscopy and slit lamp examinations. Eleven retinal thickness parameters were directly derived from the reports of the RTA measurement. The average value of each parameter was compared between the male and female groups, the emmetropia and low-myopia groups, and the three age groups (21-30, 31-40, and 41-50 years). Linear regression analysis was also applied to determine the effect of age on 11 parameters. Some participants were also enrolled in the reproducibility assessment procedure. RESULTS: The 272 eyes of 272 subjects (mean age, 34.4 years) were included. The intraclass correlation coefficients of intravisit and intervisit reproducibility were 0.95 and 0.88, respectively. The average retinal thicknesses at the foveola and fovea are 147.6 and 160.0 microm, respectively. No significant difference was found in any of the parameters between the different gender groups, emmetropia and low-myopia groups, or age groups. Regression analysis revealed no significant negative linear correlation between any of the parameter values and age. CONCLUSIONS: The retinal thickness of macular region in the Chinese is a little lower than in Westerners, but not statistically significant. The Chinese retinal thickness was not gender or refractive error related.

Adult↗
PubMed2006

[Changes of reactive oxygen species in mitochondria of retinal endothelial cells and pericytes induced by high glucose].

OBJECTIVE: To study changes of reactive oxygen species (ROS) in mitochondria of bovine retinal endothelial cells and pericytes cultured in high-glucose and its relevance with the pathogenesis of diabetic retinopathy. METHODS: Bovine retinal endothelial cells and pericytes were cultured with selective culture media. ROS changes in mitochondria of retinal endothelial cells and pericytes in response to different concentrations of glucose were detected with scanning laser confocal microscope. The mitochondria membrane potential (MMP) and cell death ratio (CDR) were measured with flow cytometry. Expression of MnSOD and uncoupling protein (UCP) were detected with reverse-transcriptase PCR (RT-PCR). RESULTS: In high-glucose, increased ROS was seen in mitochondria of retinal endothelial cells and pericytes. However MMP and CDR only increased in endothelial cells, no change was found in pericytes. UCP1, 2 mRNA expressed in cultured cells whereas UCP3 was negative. The expression of UCP1, 2, MnSOD mRNA changed with the variation of glucose concentrations. CONCLUSIONS: Increasing of ROS production in mitochondria of retinal endothelial cells and pericytes can be induced by high glucose. There is feedback accommodation mechanism between ROS increasing and MMP elevation in endothelial cells. The different features of endothelial cells and pericytes in high glucose demonstrate their roles in pathogenesis of diabetic retinopathy are different.

Animals↗
PubMed2006

[Recent advances in the studies of genetic polymorphisms in diabetic retinopathy].

Diabetic retinopathy is one of the most serious complications of diabetes mellitus, which affects the health and life quality seriously. The development of procedures for prevention and treatment of diabetic retinopathy is one of the most important problems that should be solved. Epidemiological studies indicate that the development of diabetic retinopathy is not only determined by duration of diabetes and blood glucose control; individual diversities also play an important role. Some patients have a long course of disease and poor control of blood glucose, but they do not have diabetic retinopathy or only show slight pathological changes after a long term follow-up. Other patients only have a short term disease and well control of blood glucose, but they develop serious proliferative diabetic retinopathy. These patients usually have a positive family history. This phenomenon may relate to various genetic liabilities. This review introduce the recent advances in the studies of genetic polymorphisms in diabetic retinopathy.

Diabetic Retinopathy↗