PubMed HealthSearch

Biomedical subjects

Haiyang Zhang

Publications and source records attributed to Haiyang Zhang.

5 recordsLinked to original sources

Enrichment Performance Assessment of Extracellular Vesicles Using Different Functionalized Magnetic Materials and Application in Urinary Proteomics of Prostate Cancer.

Extracellular vesicles (EVs) are lipid bilayer nanovesicles that mediate intercellular communication and hold significant potential for clinical applications. Although material-based isolation strategies offer promising alternatives to conventional methods, their relative performances have not been systematically evaluated. In this study, we conducted a comparative assessment of magnetic nanomaterials with distinct surface functionalities, including metal oxides (TiO2), metal-organic frameworks (UiO-66), biopolymeric materials (chitosan), and lipid probes (DSPE-PEG, DOPE-PEG, and CLS-PEG). A comprehensive evaluation across multiple dimensions including capture capacity, capture rate, sample volume, and product purity reveals that the bifunctional magnetic nanomaterial Fe3O4@UiO-66@DSPE material exhibits superior EV capture performance. This material enables the efficient and stable enrichment of high-purity EVs by synergizing Zr4+-phosphate coordination with lipid bilayer anchoring, and preserves EV biological integrity and activity. Meanwhile, this method could be highly compatible with proteomics, and over 1000 proteins are identified by proteomic analysis of urinary EVs, while 34 proteins are upregulated and 25 proteins are downregulated in prostate cancer patients relative to healthy donors. Notably, the differentially expressed proteins, such as AGT, ITIH4, and PGLYRP2, are associated with disease progression. Overall, this work highlights the superior performance of the Fe3O4@UiO-66@DSPE material for efficient and selective EV isolation. It provides a powerful tool for clinical liquid biopsy and proteomic biomarker discovery, enabling early diagnosis, prognostic evaluation, and precision therapy.

Humans

Bifunctional covalent organic framework for rapid isolation of extracellular vesicles and proteomics-based biomarker discovery.

Extracellular vesicles (EVs), serving as crucial carriers of biomarkers for tumor diagnosis and prognostic evaluation, as well as drug delivery vehicles and therapeutic targets, making it a research hotspot. The isolation methods represent a key aspect of EV-associated research. In this work, an alkynyl-functionalized covalent organic framework (COF) was synthesized under acidic conditions at room temperature and further modified by photo-initiated thiol-yne click reaction, yielding a bifunctionalized COF material decorated with distearoyl phosphatidylethanolamine (DSPE) and Ti4+. This bifunctional COF material (COF-DSPE-Ti) can leverage the bifunctional synergistic effect between DSPE and Ti4+ sites, thereby facilitating the efficient isolation of EVs. This synergistic effect enables the efficient isolation of EVs within 3 min. Proteomic analysis reveals that this isolation method significantly outperforms ultracentrifugation, and an effective EV isolation and analysis can be completed using only 10 μL of plasma sample. For clinical liquid biopsy, the integration of the COF-DSPE-Ti method with proteomics lead to the identification of 64 upregulated proteins in plasma samples from colorectal cancer (CRC) patients, among which S100A9 emerged as a potential EV biomarker. In addition, KLK2, KLK3, and FOLH1, which have been established as diagnostic markers for prostate cancer (PCa), are successfully identified in EVs isolated from the urine of PCa patients. These findings demonstrate the reliability of this approach for screening EV-associated biomarkers and provide a novel strategy for the early diagnosis and prognostic assessment of CRC and PCa.

Proteomics

Thyroid-stimulating hormone receptor mediates peripheral-central neuroimmune crosstalk in autoimmune thyroid diseases.

BACKGROUND: Organ-specific autoimmune diseases, particularly Graves' disease (GD) and its extrathyroidal manifestation, Graves' orbitopathy (GO), are characterized by systemic autoimmunity that may extend its impact to the central nervous system (CNS). While thyroid-stimulating hormone receptor (TSHR) is the primary driver of pathological remodeling in the thyroid and orbital tissues, emerging evidence suggests it is also expressed in the brain and may participate in neuroimmune signaling. However, the molecular mechanisms linking peripheral TSHR-driven autoimmunity to these extended systemic features remain unclear. Thus, GD and GO provide a unique window to investigate how peripheral autoantibodies influence CNS involvement as part of its broader pathological spectrum. METHODS: Genome-wide association studies (GWAS) and post-GWAS analyses were integrated with bulk RNA sequencing, single-cell and spatial transcriptomics, and brain imaging phenotypes to comprehensively characterize peripheral and central alterations in GD and GO. Mendelian randomization was applied to test causal relationships between genetic variants and brain signatures. Structural biology analyses were further conducted including protein-protein docking, small-molecule docking, and normal mode dynamics to identify prospective modulators of TSHR. Immunofluorescence staining was performed in a GO mouse model to validate the colocalization of potential interacted proteins in the specific brain region. RESULTS: Brain imaging-derived phenotypes (IDPs) alterations in GO and GO were systematically analyzed to identify neuroanatomical and functional alterations. TSHR was further identified as a shared genetic driver across peripheral and central compartments. TSHR was expressed in spiny projection neurons, microglia, and peripheral T cells, with cell-cell communication analyses highlighting TSHR-mediated interactions among neurons, endothelial cells, and microglia. Immunofluorescence staining in a GO mouse model confirmed the colocalization of TSHR with FN1 and GNAS in the basal ganglia, providing tissue-level validation of the computationally predicted ligand-receptor interactions. Immune profiling further showed immune alterations in GD and GO. Structural modeling supported plausible physical interfaces between TSHR and interacting proteins, and small-molecule screening identified three repurposable compounds - venetoclax, irinotecan, and dutasteride - with predicted favorable docking scores and stable binding poses in our simulations. CONCLUSIONS: These findings demonstrate that TSHR acts as a molecular hub mediating peripheral-central neuroimmune crosstalk in GD and GO. The results support a broader "disease-molecule axis" framework that links genetic susceptibility with multi-level immune and neural mechanisms. This work provides mechanistic insights relevant to the development of TSHR-targeted therapies, with implications for both peripheral immune modulation and central regulation. However, the limited sample size, lack of longitudinal follow-up, and absence of in vivo validation warrant cautious interpretation and further investigation.

Receptors, Thyrotropin

Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene