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Yan Xia

Publications and source records attributed to Yan Xia.

At least 19 recordsLinked to original sources
PubMed2026

Integrative multi-omics profiling of insomnia-related molecular features reveals microbiome, immune, and therapy-relevant heterogeneity in colorectal cancer.

Emerging evidence implicates insomnia as a potential risk factor in carcinogenesis, potentially involving systemic inflammation, circadian disruption, and microbiome alterations. However, the molecular associations linking insomnia-related features to colorectal cancer (CRC), particularly with respect to tumor biology, immune microenvironmental states, and therapy-relevant phenotypes, remain largely unexplored. Multi-omics integration of genomic, transcriptomic, and microbiome data from 3,026 CRC patients across seven independent cohorts, including a large, well-annotated Clinical Omics study of Colorectal Cancer in China (COCC) cohort, enabled insomnia-based molecular classification through unsupervised non-negative matrix factorization (NMF) clustering. The insomnia subtype (IS) was biologically characterized via pathway enrichment, immune deconvolution, microbial profiling, and single-cell transcriptomics. Furthermore, an insomnia score (ISscore) was developed and validated in multiple cohorts for risk stratification and assessment of treatment-response-related indicators in CRC. Unsupervised clustering revealed two distinct molecular subtypes (IS1/IS2), with IS2 demonstrating significantly poorer survival. IS2 exhibited marked activation of EMT/angiogenesis pathways versus cell cycle activation in IS1. The IS2 microenvironment showed increased immunosuppression-related infiltration and exhausted T cell signatures, together with intratumoral microbiome variation characterized by depletion of Ruminococcaceae UCG-002 and enrichment of Hungatella/Selenomonas. The ISscore system stratified survival risk and was associated with computational indicators of immunotherapy response. Single-cell analysis nominated PPIA-BSG as a potential cell-cell communication signal involving high-ISscore tumor cells, CXCL12+ endothelial cells, and CLEC9A+ dendritic cell subsets. This multi-omics characterization of insomnia-CRC interplay suggests that insomnia-related molecular features are associated with an immunologically distinct and microbiome-altered tumor ecosystem. The ISscore provides a reproducible framework for capturing insomnia-related molecular heterogeneity, supporting risk stratification and future evaluation of therapy-relevant phenotypes.IMPORTANCEChronic insomnia affects millions, but it is not typically considered a cancer risk factor. Our study, analyzing vast biological data from over 3,000 colorectal cancer patients, uncovers a potential link between a person's predisposition to insomnia and their risk of developing this disease. This suggests that the biological pathways related to sleep may play a role in cancer development. Understanding this connection opens up new avenues for identifying individuals at higher risk and developing novel prevention strategies for colorectal cancer.

colorectal cancer↗
PubMed2026

A Phosphoproteomic Platform Identifies Erythrocyte Membrane Protein Band 4.1-Like 3-Mediated Lipid Droplet Remodeling Linked to Liver Cancer Invasion and Migration.

Aberrant lipid metabolism is a hallmark of hepatocellular carcinoma (HCC), yet the regulatory mechanisms governing lipid droplet (LD) dynamics and their contribution to tumor progression remain poorly understood. Here, we developed an ultrasensitive phosphoproteomic platform using high-affinity HPDA@Ti4+ nanospheres to map LD-associated phosphorylation events across six HCC cell lines. By correlating phosphoproteomic signatures with LD morphology, we identified distinct regulatory signatures associated with LD size and abundance. Functional perturbation screens identified two distinct phosphoprotein modules controlling LD size: silencing SH3KBP1, SLK, EHD2, EPB41L3, and NEXN reduced LD size in Huh1 cells, whereas silencing CPD, BET1, UFL1, RRP1B, OGFR, and CD2BP2 enlarged LDs in Huh7 cells. Notably, we identified EPB41L3 as a critical metabolic-metastatic link; its loss decreased LD size and accelerated HCC migration and invasion, correlating with poor clinical prognosis. Crucially, we identified five key phosphorylation sites on EPB41L3 essential for its function; substituting these with alanine completely abolished its regulatory control over both LD size and HCC metastatic potential. Together, these findings delineate a phosphorylation-based regulatory network controlling the LD architecture and metastatic potential in HCC. Our study not only identifies potential therapeutic targets but also establishes a generalizable phosphoproteomic framework for interrogating lipid signaling in cancer metabolism.

Humans↗
PubMed2025

MetaflowX: a scalable and resource-efficient workflow for multi-strategy metagenomic analysis.

Microbiomes play crucial roles in diverse ecosystems, spanning environmental, agricultural, and human health domains. However, in-depth metagenomic data analysis presents significant technical and resource challenges, particularly at scale. Existing computational pipelines are typically limited to either reference-based or reference-free approaches and exhibit inefficiencies in process large datasets. Here, we introduce MetaflowX (https://github.com/01life/MetaflowX), an open-resource workflow integrating both analytical paradigms for enhanced metagenomic investigations. This modular framework encompasses short-read quality control, rapid microbial profiling, hybrid contig assembly and binning, high-quality metagenome-assembled genome (MAG) identification, as well as bin refinement and reassembly. Benchmarking tests showed that MetaflowX completed full metagenomic analyses up to 14-fold faster and with 38% less disk usage than existing workflows. It also recovered the highest number of high-quality and taxonomically diverse MAGs. A dedicated reassembly module further improved MAG quality, increasing completeness by 5.6% and reducing contamination by 53% on average. Functional annotation modules enable detection of key features, including virulence and antibiotic resistance genes. Designed for extensibility, MetaflowX provides an efficient solution addressing current and emerging demands in large-scale metagenomic research.

Metagenomics↗
PubMed2025

Network-based drug repurposing for psychiatric disorders using single-cell genomics.

Neuropsychiatric disorders lack effective treatments due to a limited understanding of the underlying cellular and molecular mechanisms. To address this, we integrated population-scale single-cell genomics data and analyzed 23 cell-type-level gene regulatory networks across schizophrenia, bipolar disorder, and autism. Our analysis revealed potential druggable transcription factors co-regulating known risk genes that converge into cell-type-specific co-regulated modules. We applied graph neural networks on those modules to prioritize novel risk genes and leveraged them in a network-based drug repurposing framework to identify 220 drug molecules with the potential for targeting specific cell types. We found evidence for 37 of these drugs in reversing disorder-associated transcriptional phenotypes. Additionally, we discovered 335 drug-cell quantitative trait loci (eQTLs), revealing genetic variation's influence on drug target expression at the cell-type level. Our results provide a single-cell network medicine resource that provides potential mechanistic insights for advancing treatment options for neuropsychiatric disorders.

Drug Repositioning↗
PubMed2007

Metabolism-based identification of a potent thrombin receptor antagonist.

The metabolism of our prototypical thrombin receptor antagonist 1, Ki = 2.7 nM, was studied and three major metabolites (2, 4, and 5) were found. The structures of the metabolites were verified independently by synthesis. Compound 4 was shown to be a potent antagonist of the thrombin receptor with a Ki = 11 nM. Additionally, compound 4 showed a 3-fold improvement in potency with respect to 1 in an agonist-induced ex-vivo platelet aggregation assay in cynomolgus monkeys after oral administration; this activity was sustained with 60% inhibition observed at 24 h post-dose. Compound 4 was highly active in functional assays and showed excellent oral bioavailability in rats and monkeys. Compound 4 showed a superior rat enzyme induction profile relative to compound 1, allowing it to replace compound 1 as a development candidate.

Animals↗
PubMed2006

MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress.

c-Jun, a major transcription factor in the activating protein 1 family of regulatory proteins, is activated by many physiologic and pathological stimuli. We show here that c-Jun was downregulated in response to osmotic stress via ubiquitination-dependent degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activity toward c-Jun in vitro and in vivo. The reduced c-Jun protein level resulting from exogenous expression of wild-type MEKK1 and the opposite effect induced by expression of a MEKK1 PHD/RING finger domain mutant were consistent with a higher level of c-Jun protein in MEKK1(-/-) cells than in corresponding wild-type cells. The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun in response to osmotic stress. Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis.

Animals↗
PubMed2006

F344 rat liver nonparenchymal cell transplantation can increase the number of albumin-positive hepatocytes in the liver following hematopoietic reconstitution in irradiated analbuminemic rats.

The adult liver contains hematopoietic stem cells that can reconstitute the bone marrow. We tested whether bone marrow cells (BMCs) derived from liver nonparenchymal cells (LNPCs) can increase the number of hepatocytes within livers. LNPCs from Fischer 344 rats (F344) were infused into the penile veins of F344 congenic Nagase's analbuminenic rats (F344alb) immediately after whole-body irradiation, and the recipients were sacrificed 8 weeks later. Eleven of 15 (73.3%) F344alb that received the LNPC transplantation after irradiation survived, while only 1 of 8 (12.5%) F344alb that received irradiation alone was alive after 8 weeks. Normal albumin gene sequences were detected by PCR in BMCs of the recipient F344alb that received LNPC transplantation after irradiation, indicating that F344alb bone marrow was reconstituted by F344 LNPCs. Although single or pairs of albumin-positive (Alb+) hepatocytes were seen in the liver of untreated F344alb and those with irradiation or LNPC transplantation alone, clusters consisting of >3 Alb+ hepatocytes were detected in the livers of F344alb with the LNPC or BMC transplantation after irradiation together with single or double Alb+ cells. Normal albumin gene sequences were detected by PCR in the DNA isolated from such Alb+ hepatocyte clusters microdissected from the immunostained sections. The data indicate that BMCs derived from F344 LNPCs could increase the number Alb+ hepatocytes within the F344alb liver.

Albumins↗
PubMed2006

Himbacine derived thrombin receptor (PAR-1) antagonists: structure-activity relationship of the lactone ring.

The structure-activity relationship (SAR) of the lactone ring of himbacine derived thrombin receptor (PAR-1) antagonists (e.g., 2-5) is described. The effect of the lactone carbonyl group on binding to PAR-1 is dependent on the substitution pattern of the pyridine ring. A stereoselective intramolecular Michael addition reaction to the vinyl pyridine group was observed for these pyridine analogs of himbacine in basic conditions at elevated temperature.

Alkaloids↗
PubMed2006

Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP.

XIAP-associated factor 1 (Xaf1) binds XIAP and re-localizes it to the nucleus, thus inhibiting XIAP activity and enhancing apoptosis [1]. Xaf1 expression is reduced or absent in tumor samples and cell lines suggesting it may function as a tumor suppressor [2-5]. To further study Xaf1 function we generated Xaf1 inducible cells in the osteosarcoma cell line Saos-2. Despite Xaf1 inducing apoptosis that is dramatically enhanced by TNFalpha we find no evidence for an interaction between Xaf1 and XIAP. Furthermore, Xaf1 expression sensitized XIAP-/- fibroblasts to TNFalpha, demonstrating the existence of a novel mechanism of Xaf1 induced apoptosis distinct from antagonizing XIAP. Xaf1 expression promotes cytochrome c release that cannot be blocked by inhibition of caspase activity. This implicates a role for the mitochondrial apoptotic pathway, consistent with the ability of Bcl2 to block Xaf1 induced apoptosis. The data indicate that in Saos2 cells Xaf1 activates the mitochondrial apoptotic pathway to facilitate cytochrome c release, thus amplifying apoptotic signals from death receptors.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Discovery of potent orally active thrombin receptor (protease activated receptor 1) antagonists as novel antithrombotic agents.

Structurally novel thrombin receptor (protease activated receptor 1, PAR-1) antagonists based on the natural product himbacine are described. The prototypical PAR-1 antagonist 55 showed a Ki of 2.7 nM in the binding assay, making it the most potent PAR-1 antagonist reported. 55 was highly active in several functional assays, showed excellent oral bioavailability in rat and monkey models, and showed complete inhibition of agonist-induced ex vivo platelet aggregation in cynomolgus monkeys after oral administration.

Administration, Oral↗
PubMed2005

Quantitative structure-retention relationships of benzoylphenylureas on polystyrene-octadecene-encapsulated zirconia stationary phase in reversed-phase high performance liquid chromatography.

Quantitative Structure-Retention Relationships of benzoylphenylureas and similar compounds have been studied on a new type of stationary phase (polystyrene-octadecene-encapsulated zirconia) in reversed-phase high performance liquid chromatography. Using stepwise regression analysis, the relationships between the structural descriptors of the compound and its chromatographic retention were examined. It was confirmed that the retention of the dihalogenobenzoylphenylureas is mainly governed by the dipole moment (DM), the calculated molar refractivity (CMR), and the hydrophobicity parameter (C log P) of the compounds. The predicting equations for the 18 dihalogenobenzoylphenylureas and similar compounds were also established; there is a good agreement between the observed k values and the predicted k values. In addition, a typical ODS (Kromasil-C18-SiO2) was compared with C18-PS-ZrO2. The results showed that there were some differences between the two stationary phase for the separation of the compounds investigated, which are certainly related to surface characteristics of the two different supports.

Journal Article↗
PubMed2005

Knowledge-based classification of neuronal fibers in entire brain.

This work presents a framework driven by parcellation of brain gray matter in standard normalized space to classify the neuronal fibers obtained from diffusion tensor imaging (DTI) in entire human brain. Classification of fiber bundles into groups is an important step for the interpretation of DTI data in terms of functional correlates of white matter structures. Connections between anatomically delineated brain regions that are considered to form functional units, such as a short-term memory network, are identified by first clustering fibers based on their terminations in anatomically defined zones of gray matter according to Talairach Atlas, and then refining these groups based on geometric similarity criteria. Fiber groups identified this way can then be interpreted in terms of their functional properties using knowledge of functional neuroanatomy of individual brain regions specified in standard anatomical space, as provided by functional neuroimaging and brain lesion studies.

Algorithms↗
PubMed2005

[Experimental study on the mechanism of the apoptosis of leukemic cells induced by valproic acid].

OBJECTIVE: To overcome the drug-resistance of tumor cells is one of the methods of improving the therapeutic results. Histone deacetylase inhibitors (HDACIs) is a novel class of chemotherapeutic agents which can induce apoptosis of tumor cells. Valproic acid (VPA) is a common drug used in the treatment of epilepsy. It has been shown that VPA has a marked HDACIs effect at the pharmaceutical level, and can induce the differentiation and apoptosis of transformed cells. But the mechanism of its effect has not been clarified. The aim of this study was to investigate the mechanism of VPA in inducing the apoptosis of leukemic cells at molecular level. METHODS: The cell lines U937, Jurkat clone E6 - 1 (Jurkat) and BALL-1 were cultured in RPMI 1640 medium containing 20% calf serum, then divided into three groups (control group, 1 mmol/L VPA group and 1 mmol/L VPA + 1 micromol/L Pan-caspase inhibitor zVAD-fmk group). At 72 hours after the treatment, the cells were double stained with Aunexin and PI (propidium iodide) and then were analyzed with the flow cytometry (FCM) to detect apoptosis. Before and after treatment with VPA the mean fluorescence index (MFI) of Bcl-2, Bax, Bcl-xl and the levels of caspase 8, 9 and 3 were also detected with the FCM. The changes of P(44/42) mitogen activating protein kinase (MAPK) and phosphorylated P(44/42) MAPK were determined by Western blotting. RESULTS: Seventy-two hours after the treatment, 1 mmol/L VPA induced apoptosis of U937 and Jurkat. The apoptotic rate of U937 was (75.78 +/- 4.20)% and that of Jurkat was (53.50 +/- 5.87)% (P < 0.01, vs. control group); zVAD-fmk could fully inhibit the apoptosis of U937, and the apoptotic rate was (2.89 +/- 0.36)%; while it could partly inhibit the apoptosis of Jurkat, and the apoptotic rate was (15.38 +/- 1.40)% (P < 0.01). 1 mmol/L VPA could not induce the apoptosis of BALL-1 which had a high expression level of Bcl-2. The MFI of Bcl-2, Bax and Bcl-xl in these three cell lines did not change significantly with VPA (P > 0.05). After treatment with VPA, the level of caspase 3 in U937 increased from (14.09 +/- 1.19)% to (32.30 +/- 2.47)%, and caspase 8 from (4.58 +/- 1.41)% to (86.47 +/- 3.26)% (P < 0.01), but there was no significant change in caspase 9 [(13.25 +/- 3.11)% and (10.95 +/- 1.30)%]. In Jurkat, the level of caspase 3 increased from (12.01 +/- 1.63)% to (35.56 +/- 0.27)%, and caspase 9 from (13.89 +/- 1.71)% to (75.89 +/- 4.08)% (P < 0.01 for both); no significant change was observed for caspase 8 [(5.94 +/- 1.38)% and (5.44 +/- 0.72)%]. In BALL-1, there was a slight decline in caspase 3 (P < 0.05). With the effect of VPA, levels of P(44/42) MAPK and phosphorylated P(44/42) MAPK decreased in all three cell lines (P < 0.01). CONCLUSION: VPA could induce apoptosis of U937 through the activation of caspase 3 and 8; and it induced the apoptosis of Jurkat involving the activation of caspase 3 and 9. P(44/42) MAPK pathway also plays an important role in this course. VPA induced apoptosis of these cell lines without the alteration of Bcl-2, Bax and Bcl-xl. High level of Bcl-2 could antagonize the effect of VPA.

Apoptosis↗
PubMed2004

Crust effect on multiscale pattern formations in drying micelle solution drops on solid substrates.

Spherical micelles of a polystyrene-b-poly(dimethylsiloxane) (PS-b-PDMS) diblock copolymer with the number-average molecular weight of 193 000 g/mol for PS and 39 000 g/mol for PDMS were obtained by using n-dodecane or n-octane as the selective solvent for the PDMS block. The drying process of micelle solution drops with relatively high polymer concentration on solid substrates and the resultant drying patterns were studied using optical microscopy and atomic force microscopy. The drying drops exhibited an inner solution "cap" connecting with an outer gelled "foot" through a transition zone. A crust was first formed on the surface of the transition zone and remained on the top of the foot region. An inhomogeneous stress perpendicular to the radial direction within the crust, which was due to the solvent evaporation accompanied by the receding of the solution cap, induced regular 45 degrees -tilted stripes (pleats) in the transition zone and main radial cracks in the foot region. The stripes and cracks have periods of a few and tens of microns, respectively. Concave micelle "bricks" were also observed between cracks. In addition to micelle close packing, these patterns demonstrate that drying micelle solution drops may provide a potential means to manipulate fine and multiscale structures for technological applications.

Journal Article↗
PubMed2004

A knowledge-driven algorithm for a rapid and automatic extraction of the human cerebral ventricular system from MR neuroimages.

A knowledge-driven algorithm for a rapid, robust, accurate, and automatic extraction of the human cerebral ventricular system from MR neuroimages is proposed. Its novelty is in combination of neuroanatomy, radiological properties, and variability of the ventricular system with image processing techniques. The ventricular system is divided into six 3D regions: bodies and inferior horns of the lateral ventricles, third ventricle, and fourth ventricle. Within each ventricular region, a 2D region of interest (ROI) is defined based on anatomy and variability. Each ventricular region is further subdivided into subregions, and conditions detecting and preventing leakage into the extra-ventricular space are specified for each subregion. The algorithm extracts the ventricular system by (1) processing each ROI (to calculate its local statistics, determine local intensity ranges of cerebrospinal fluid and gray and white matters, set a seed point within the ROI, grow region directionally in 3D, check anti-leakage conditions, and correct growing if leakage occurred) and (2) connecting all unconnected regions grown by relaxing growing conditions. The algorithm was validated qualitatively on 68 and quantitatively on 38 MRI normal and pathological cases (30 clinical, 20 MGH Brain Repository, and 18 MNI BrainWeb data sets). It runs successfully for normal and pathological cases provided that the slice thickness is less than 3.0 mm in axial and less than 2.0 mm in coronal directions, and the data do not have a high inter-slice intensity variability. The algorithm also works satisfactorily in the presence of up to 9% noise and up to 40% RF inhomogeneity for the BrainWeb data. The running time is less than 5 s on a Pentium 4, 2.0 GHz PC. The best overlap metric between the results of a radiology expert and the algorithm is 0.9879 and the worst 0.9527; the mean and standard deviation of the overlap metric are 0.9723 and 0.01087, respectively.

Adolescent↗