About

Professor Xun Zhao is an Assistant Professor in Mechanical and Aerospace Engineering and also serves as an Assistant Professor, by courtesy, in Electrical and Computer Engineering at the University of Virginia. He leads the AI for Medical Electronics (AIME) Lab, where his research focuses on developing unconventional bioelectronics assisted by artificial intelligence to advance precision health. His team designs intelligent sensors and robotics that aim to revolutionize the diagnosis, monitoring, and treatment of various diseases. Professor Zhao's work integrates cutting-edge AI technologies with innovative bioelectronic devices to create new approaches for healthcare applications, emphasizing the development of wearable devices and smart medical instruments that enhance the precision and effectiveness of health monitoring and disease management.

Research topics

• Immunology
• Biology
• Medicine
• Internal medicine
• Cancer research
• Oncology
• Cell biology
• Biochemistry
• Bioinformatics

Selected publications

• Lung-Targeting Cepharanthine Polymer Micelles Modified with Mannose: Effectiveness against Acute Lung Injury Evaluated Using in vitro and in vivo Analyses

  Current Drug Metabolism · 2025-11-12

  article

  Introduction: The currently available therapies for acute lung injury (ALI), including gluco-corticoids, protease inhibitors, and heparin, have limited clinical efficacy and are often associated with significant side effects. Cepharanthine (CEP) has demonstrated effectiveness in treating pulmonary dis-eases, but its clinical application is restricted by low solubility and poor bioavailability. This study aimed to develop mannosylated cepharanthine-loaded polymeric micelles (MA-CEP-PMs) to improve CEP bio-availability and enhance lung-targeted delivery for the treatment of ALI. Methods: The pharmacokinetics of MA-CEP-PMs in rats were assessed using Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS). Lung-targeting ability was evaluated through tissue distribution studies and near-infrared imaging. In a rat model of ALI induced by lipopolysaccharide (LPS), anti-ALI effects were assessed via general physiological indicators, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot analysis. Hematoxylin-eosin (HE) staining was used to examine hepatotoxicity and nephrotoxicity of MA-CEP-PMs in normal rats. Cyto-toxicity of the mannosylated polyethylene glycol-poly(lactic-co-glycolic acid) copolymer (MA-PEG-PLGA) on NR8383 cells was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake experiments were performed to determine the targeting ability of MA-PEG-PLGA in NR8383 cells, and the effects of MA-CEP-PMs on inflammatory cytokines were analyzed using ELISA. Results: MA-CEP-PMs significantly increased the AUC and exhibited better lung targeting ability com-pared to the unmodified micelles (P < 0.01). In the ALI model, MA-CEP-PMs improved the thymus and spleen indices, decreased the lung wet-to-dry weight ratio (P < 0.05), alleviated model animal damage, and inhibited inflammatory factor and nuclear factor-κB (NF-κB)-related protein levels (P < 0.05). MA-CEP-PMs exhibited no significant hepatotoxicity or nephrotoxicity. MA-PEG-PLGA exhibited low tox-icity against NR8383 cells and greater cell uptake, indicating stronger targeting of the lung. MA-CEP-PMs also exhibited more potent anti-inflammatory effects. Discussion: This study focused on the short-term therapeutic effects of ALI, whereas the clinical man-agement of lung injury often requires long-term intervention. Future research should therefore assess the long-term efficacy of this delivery system in chronic lung injury, along with determining its safety profile and potential impacts on extra-pulmonary organs. While the involvement of the NF-κB pathway in the anti-inflammatory effects has been confirmed, it remains to be deciphered whether mannose modification synergistically regulates other signaling pathways and what the specific intracellular targets of CEP are, which would require further exploration through detailed molecular biology experiments. Conclusion: The MA-CEP-PMs significantly improved CEP bioavailability and increased lung targeting. They exhibited good safety and had a significant effect on ALI management. .

  PublisherDOI

• Understanding the toxicity induced by radiation-triggered neuroinflammation and the on-demand design of targeted peptide nanodrugs

  Signal Transduction and Targeted Therapy · 2025-09-03 · 15 citations

  articleOpen access

  Abstract Radiation-induced brain injury (RIBI) represents a severe complication of cranial radiotherapy, substantially diminishing patients’ quality of life. Unlike conventional brain injuries, RIBI evokes a unique chronic neuroinflammatory response that notably aggravates neurodegenerative processes. Despite significant progress in understanding the molecular mechanisms related to neuroinflammation, the specific and precise mechanisms that regulate neuroinflammation in RIBI and its associated toxicological effects remain largely unclear. Additionally, targeted neuroprotective strategies for RIBI are currently lacking. In this study, we systematically characterized the pathophysiology of RIBI using zebrafish (larvae/adults) and murine models. We established direct associations between neuronal damage and cognitive-behavioral deficits. Mechanistically, we proposed a ROS-mitochondrial-immune axis. Specifically, radiation-induced ROS lead to mitochondrial dysfunction, resulting in the leakage of mitochondrial DNA into the cytosol. This, in turn, activated the cGAS-STING pathway, thereby driving persistent microglia-mediated neuroinflammation. Furthermore, we engineered a dual-function nanotherapeutic agent, Pep-Cu 5.4 O@H151. This agent integrates ultrasmall copper-based nanozymes (Cu 5.4 O) for ROS scavenging and H151 (a STING inhibitor) and is conjugated with peptides that can penetrate the blood-brain barrier and target microglia. This nanoplatform exhibited excellent synergistic therapeutic efficacy by simultaneously neutralizing oxidative stress and blocking inflammatory cascades. Our research provided an in-depth analysis of radiation-induced neurotoxicity, clarifying the crucial ROS-mitochondrial-immune axis. Moreover, we have developed a precise therapeutic strategy on the basis of this mechanism.

  PublisherOA PDFDOI

• KMO-driven metabolic reconfiguration and its impact on immune cell infiltration in nasopharyngeal carcinoma: a new avenue for immunotherapy

  Cancer Immunology Immunotherapy · 2025-02-01 · 7 citations

  articleOpen access

  BACKGROUND: Nasopharyngeal carcinoma (NPC), a malignant epithelial tumor, is characterized by a complex tumor microenvironment (TME) and closely associated with metabolic dysfunction. Mitochondrial metabolism plays a crucial role in supporting the rapid proliferation of tumor cells. However, the specific response of mitochondria to the NPC microenvironment and their role in regulating the metabolic heterogeneity of the tumor remain poorly understood. METHODS: Tissue samples and corresponding clinicopathological data were collected from 72 primary NPC patients and 36 non-tumor controls. Histological analysis, coupled with public transcriptomic database interrogation, was utilized to investigate mitochondrial dynamics and metabolism across different cell types. Characterizing the interactions within the tumor-immune microenvironment (TME), we identified mitochondrial genes associated with prognosis in NPC. Additionally, we explored the relationship between key mitochondrial genes, the TME, and the response to immunotherapy. RESULTS: Malignant epithelial cells in NPC exhibited altered mitochondrial metabolism, including dysregulation of amino acid and glucose metabolism, when compared to non-malignant cells. The mitochondrial-related hub gene KMO was significantly downregulated in NPC tissues relative to normal controls. Low expression of KMO was associated with poorer survival outcomes in patients. Furthermore, KMO expression was negatively correlated with DNA repair mechanisms and hypoxia. In addition, KMO levels were inversely associated with the upregulation of both oxidative phosphorylation (OXPHOS) and glycolysis pathways within the NPC tumor microenvironment (TME). Single-cell transcriptomic analysis revealed that KMO was primarily expressed in B cells, with some contribution from myeloid cells. Importantly, KMO levels positively correlated with the infiltration of various immune cell populations, including B cells, T cells, and macrophages, as well as inflammatory signatures. Further investigation indicated that individuals with elevated KMO expression may exhibit heightened sensitivity to immune checkpoint blockade (ICB) therapy compared to those with lower KMO expression. CONCLUSION: The mitochondrial hub gene KMO plays a pivotal role in regulating mitochondrial metabolism and modulating the immune microenvironment in NPC. As a potential prognostic biomarker, KMO may offer valuable predictive insights, and targeting KMO could represent a promising therapeutic strategy for NPC, potentially enhancing the efficacy of immunotherapies.

  PublisherDOI

• SH3BP5-driven metabolic-immune crosstalk in DLBCL: a prognostic biomarker and therapeutic target for reshaping immunosuppressive microenvironment

  Journal of Translational Medicine · 2025-09-24 · 1 citations

  articleOpen access

  BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous and aggressive hematologic malignancy, with the activated B-cell-like (ABC) subtype displaying particularly poor prognosis due to inherent treatment resistance and elevated recurrence rates. Despite advances in targeted therapies and immunotherapies, a significant proportion of patients experience relapse or refractory disease, highlighting the urgent need for novel biomarkers and innovative therapeutic strategies to improve clinical outcomes. METHODS: A multi-dimensional analysis of SH3BP5 expression was performed across DLBCL subtypes, integrating transcriptomic, proteomic, and clinical datasets to assess its correlation with immune infiltration, tumor metabolism, and patient prognosis. Single-cell RNA sequencing data were employed to examine the tumor microenvironment (TME) with higher resolution. Further analysis of the association between SH3BP5 and immune checkpoint gene expression was conducted to explore its potential role in immunotherapy response. Functional in vitro assays were carried out to assess the impact of SH3BP5 knockdown on DLBCL cell proliferation and apoptosis. RESULTS: The analysis revealed that SH3BP5 is preferentially overexpressed in the ABC subtype of DLBCL across multiple datasets and validated cohorts, and its high expression is significantly associated with poor overall survival. Single-cell transcriptomic profiling demonstrated that SH3BP5 is mainly expressed in malignant B cells and inversely correlated with immune cell infiltration, particularly CD8 + T cells. Mechanistically, pathway enrichment and metabolic assays indicated that SH3BP5 is linked to mitochondrial metabolic reprogramming, promoting oxidative phosphorylation (OXPHOS) and potentially contributing to reduced responsiveness to immune checkpoint inhibitors (ICIs). Functional studies showed that SH3BP5 knockdown significantly suppressed DLBCL cell proliferation, induced apoptosis, and reduced tumor cell viability in vitro. CONCLUSION: This study suggests that SH3BP5 may serve as a prognostic biomarker and a potential therapeutic target in DLBCL, particularly within the ABC subtype. By delineating its associations with immune evasion and metabolic reprogramming, these findings provide a mechanistic basis for further exploration of SH3BP5-targeted interventions to help overcome therapy resistance. Future studies in larger clinical cohorts and functional models are warranted to validate these results and assess the potential of integrating SH3BP5 expression profiling into precision medicine strategies for DLBCL. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2200060430; http://www.chictr.org.cn/ ) on June 1, 2022.

  PublisherOA PDFDOI

• Macrophage peroxisomes guide alveolar regeneration and limit SARS-CoV-2 tissue sequelae

  Science · 2025-03-06 · 39 citations

  articleOpen access

  Peroxisomes are vital but often overlooked metabolic organelles. We found that excessive interferon signaling remodeled macrophage peroxisomes. This loss of peroxisomes impaired inflammation resolution and lung repair during severe respiratory viral infections. Peroxisomes were found to modulate lipid metabolism and mitochondrial health in a macrophage type-specific manner and enhanced alveolar macrophage-mediated tissue repair and alveolar regeneration after viral infection. Peroxisomes also prevented excessive macrophage inflammasome activation and IL-1β release, limiting accumulation of KRT8 high dysplastic epithelial progenitors following viral injury. Pharmacologically enhancing peroxisome biogenesis mitigated both acute symptoms and post-acute sequelae of COVID-19 (PASC) in animal models. Thus, macrophage peroxisome dysfunction contributes to chronic lung pathology and fibrosis after severe acute respiratory syndrome coronavirus 2 infection.

  PublisherOA PDFDOI

• Chiral multilevel-structured hydroxyapatite nano-bacterial cellulose membrane with anti-inflammatory activity and regulation of immune microenvironment promotes wound healing in the elderly

  Chemical Engineering Journal · 2025-10-23 · 1 citations

  articleOpen access

  Cutaneous wound healing in the elderly is impaired by persistent inflammation and immune dysregulation. The chirality of materials has been shown to modulate wound healing efficacy. However, the translational potential of chiral-engineered biomaterials for wound dressing applications remains underexplored. In this study, we developed Chiral multilevel-structured hydroxyapatite nano-bacterial cellulose membrane (CMHAp@BC), a novel biomaterial, significantly modulates the innate immune response to accelerate aging skin full-thickness wound healing. Notably, levorotatory CMHAp@BC (L-CHB) demonstrated superior performance over other chiral forms (D-, rac-, and achiral variants) in comprehensively promoting wound healing by attenuating neutrophil infiltration and directing macrophage polarization toward regenerative phenotypes. Through evaluation in natural aging and severe combined immunodeficient murine models, we establish that L-CHB exerts multifunctional therapeutic effects by suppressing bacterial colonization, attenuating neutrophil recruitment through NF-κB pathway inhibition, and promoting a favorable shift toward M2 macrophage polarization. These findings underscore the potential of L-CHB to establish a regenerative immune microenvironment, thereby offering a promising strategy for advanced wound care. • First chiral dressing: L-CHB suppresses neutrophils via NF-κB inhibition and induces M2 macrophage polarization. • Targets geriatric immune dysregulation by attenuating neutrophil hyperactivation and controlling macrophage phenotypic polarization. • Efficacy confirmed in natural aging and severe combined immunodeficient models, proving innate immunity-dependent action.

  PublisherDOI

• Oxymatrine regulates microglia to produce IFN-β by activating the STING/TBK1/IRF3 pathway against experimental autoimmune encephalomyelitis

  European Journal of Pharmacology · 2025-11-20 · 1 citations

  article
  PublisherDOI

• Renin–angiotensin–aldosterone-system inhibitors increase the serum level of complement component 4 in patients with immunoglobulin A nephropathy

  International Immunopharmacology · 2024-02-21 · 2 citations

  articleOpen access

  OBJECTIVE: To investigate the impact of renin-angiotensin-aldosterone-system (RAAS) inhibitors on complement component 4 (C4) serum levels in patients with immunoglobulin A nephropathy (IgAN). METHODS: A total of 423 patients diagnosed with IgAN at Shanxi Provincial People's Hospital, China, between 1 January 2017 and 31 December 2021 were divided into two groups, a RAAS inhibitor group and a non-RAAS inhibitor group, for comparative analysis. RESULTS: The RAAS inhibitor group exhibited significantly increased C4 and eGFR levels and had a higher proportion of patients with hypertension compared with the non-RAAS inhibitor group. Serum C4 levels were positively correlated with 24-hour urine protein, serum C3 levels and blood uric acid levels but negatively correlated with eGFR levels. In addition, serum C4 levels were positively correlated with the severity of mesangial hypercellularity and interstitial/tubular injury. Through prognostic analysis, serum C4 was identified as an independent risk factor for the progression of IgAN. CONCLUSION: Renin-angiotensin-aldosterone-system inhibitors can increase serum C4 levels in patients with IgAN and may represent an independent risk factor for disease progression.

  PublisherDOI

• Lipomatous ependymoma with ZFTA: RELA fusion-positive: A case report

  World Journal of Clinical Cases · 2024-11-06 · 1 citations

  articleOpen access1st authorCorresponding

  BACKGROUND: Ependymoma with lipomatous differentiation is a rare type of ependymoma. The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system tumors. ZFTA fusion-positive lipomatous ependymoma has not been reported to date. CASE SUMMARY: We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six minutes. Magnetic resonance imaging showed a round cystic shadow of approximately 1.9 cm × 1.5 cm × 1.9 cm under the right parieto-occipital cortex. Microscopic examination showed characteristic perivascular pseudorosettes and adipose differentiation in the cytoplasm. Immunohistochemical staining showed that the tumor cells were negative for cytokeratin, NeuN, Syn and p53, but positive for GFAP, vimentin and S-100 protein. Significant punctate intracytoplasmic EMA immunoreactivity was observed. The level of Ki-67 was about 5%. Genetic analysis revealed ZFTA: RELA fusion. A craniotomy with total excision of the tumor was performed. The follow-up time was 36 months, no evidence of disease recurrence was found in magnetic resonance imaging. CONCLUSION: Based on these findings, the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous differentiation. This case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation, which can help pathologists to make a definitive diagnosis of this tumor.

  PublisherDOI

• Clinical features and risk factors for pyogenic liver abscess caused by multidrug-resistant organisms: A retrospective study

  Virulence · 2024-05-20 · 8 citations

  articleOpen access

  The incidence rate of pyogenic liver abscess caused by multidrug-resistant bacteria has increased in recent years.This study aimed to identify the clinical characteristics and risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria.We conducted a retrospective analysis of the clinical features, laboratory test results, and causes of pyogenic liver abscesses in 239 patients admitted to a tertiary hospital.Multivariable logistic regression was used to identify risk factors for multidrug resistance.Among patients with pyogenic liver abscesses, the rate of infection caused by multidrug-resistant organisms was observed to be 23.0%(55/239), with a polymicrobial infection rate of 14.6% (35/239).Additionally, 71 cases (29.7%) were associated with biliary tract disease.Patients with pyogenic liver abscesses caused by multidrug-resistant organisms had a significantly higher likelihood of polymicrobial infection and increased mortality (7/44 [15.9%] vs. 3/131 [2.3%]; p = .003).The Charlson Comorbidity Index (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.06-1.68),hospitalization (aOR: 10.34, 95% CI: 1.86-60.3)or an invasive procedure (aOR: 9.62; 95% CI: 1.66-71.7)within the past 6 months, and gas in the liver on imaging (aOR: 26.0; 95% CI: 3.29-261.3)were independent risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria.A nomogram was constructed based on the risk factors identified.The nomogram showed high diagnostic accuracy (specificity, 0.878; sensitivity 0.940).Multidrug-resistant organisms causing pyogenic liver abscesses have specific characteristics.Early identification of patients at high risk of infection with multidrug-resistant organisms could help improve their management and enable personalized treatment.

  PublisherOA PDFDOI

Frequent coauthors

• Sarah E. Ewald

  University of Virginia

  27 shared

• Fan Wang

  Second Affiliated Hospital of Dalian Medical University

  13 shared

• Nadia K. Holness

  University of Virginia

  12 shared

• Samantha L. Lempke

  Carter Center

  12 shared

• Bocheng Yin

  12 shared

• Beibei Feng

  Sixth Affiliated Hospital of Sun Yat-sen University

  12 shared

• Xiang‐Ming Lao

  10 shared

• Linqing Zhen

  10 shared

Labs

• AI for Medical ElectronicsPI

Education

• Ph.D., Bioengineering and Biomedical Engineering

  UCLA

Awards & honors

• Stephanie L. Kwolek Prize in 2024
• Harry M. Showman Prize