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Biomedical subjects

Wei Zhang

Publications and source records attributed to Wei Zhang.

At least 19 recordsLinked to original sources

DDX21 Enhances Radiosensitivity in Head and Neck Squamous Cell Carcinoma by Suppressing MK2-Mediated DNA Damage Response.

Radioresistance remains a significant challenge in the radiotherapy (RT) of head and neck squamous cell carcinoma (HNSCC). However, the biological factors that govern sensitivity to this therapy are not well-understood. The DEAD-box family is known for its role in genome stability, and inextricably linked to the radiotherapy resistance of tumors. This study found the role of the RNA helicase DDX21 in regulating radiosensitivity through extensive data mining. High DDX21 expression predicted improved survival after postoperative radiotherapy. Overexpression of DDX21 increased radiosensitivity in vitro and in vivo, whereas depletion promoted radioresistance. In vitro, DDX21 enhanced radiation-induced DNA damage, genomic instability, and apoptosis by binding MK2 and suppressing MK2 phosphorylation independently of p38 activity. Meanwhile MK2 inhibition restored and further augmented radiosensitivity in DDX21-deficient cells and xenografts by increasing DNA damage and apoptosis. Overall, DDX21 regulates radiosensitivity in HNSCC by suppressing MK2 signaling and modulating the radiation-induced DNA damage response. Its expression may serve as a potential biomarker associated with radiosensitivity, and MK2 inhibition offers a promising approach to overcome radioresistance in tumors with low DDX21 expression.

DDX21

Integrated Genomic and Epigenomic Analysis Reveals Epigenetic Plasticity in Disease Progression and Multidrug Resistance in Multiple Myeloma.

UNLABELLED: Multiple myeloma is marked by recurrent cytogenetic abnormalities and mutations that accumulate as the disease progresses. In this study, we sought to elucidate the transitions driving tumorigenesis and therapy resistance in multiple myeloma using a unique cohort of nearly 900 patients spanning premalignant to late-stage refractory multiple myeloma, comprehensively characterized at molecular and clinical levels. Waves of epigenetic dysregulation drove these critical transitions. In this paradigm, genomic and cytogenetic events unlocked epigenetic plasticity, reshaping multiple myeloma cell biology to evade tumor microenvironment constraints and therapeutic pressures. Functional perturbation studies in an isogenic proteasome inhibitor-resistant cell line model demonstrated enhanced reliance on transcriptional cofactors, supporting a mechanistic link between chromatin plasticity and therapy adaptation. Collectively, these findings support a unifying framework in which genomic heterogeneity unlocks gene regulatory plasticity, enabling plasma cells (PC) to evade microenvironmental constraints and therapeutic pressure. These results provide a mechanistic explanation for sequential relapse without new genomic alterations and nominate epigenetic plasticity-mediated PC adaptation as a therapeutic vulnerability in the heterogeneous genetic background of multiple myeloma. SIGNIFICANCE: Assembly and analysis of a multiple myeloma cohort spanning the continuum from premalignant to late relapse that integrates bulk transcriptomics with single-cell multiomic data provides insights into disease progression and epigenetic plasticity.

Multiple Myeloma

Exploring the shared genetic architecture of sarcopenia using genomic structural equation modeling.

Sarcopenia is a common age-associated condition characterized by the progressive loss of skeletal muscle mass, strength, and physical functionality. While large-scale genome-wide association studies (GWAS) have previously addressed isolated traits of sarcopenia, the multifactorial genetic architecture underlying this condition remains largely undefined. To characterize the common genetic basis of sarcopenia-related traits, genomic structural equation modeling (Genomic-SEM) was implemented. Multiple post-GWAS analytic approaches were integrated to pinpoint susceptibility loci. These analyses encompassed identifying enriched genetic pathways and relevant genomic elements, as well as cell-type-specific enrichment in skeletal muscle satellite stem cells, mesenchymal stem cells, and skeletal muscle satellite cells in limb muscle. Furthermore, based on the integrated GWAS data of sarcopenia-related traits, polygenic risk score (PRS) analysis was conducted to evaluate risk associations at the chromosomal level. A well-fitted Genomic-SEM successfully integrated the GWAS data, revealing the shared genetic architecture of sarcopenia-related traits. We identified 110 single nucleotide polymorphisms (SNPs) reaching genome-wide significance (p&#x2009;<&#x2009;5&#x2009;&#xd7;&#x2009;10-8), of which 9 represent novel discoveries. Subsequent fine-mapping procedures and gene-set analyses identified 15 causal variants alongside 77 candidate susceptibility genes. This study provides a comprehensive genetic characterization of sarcopenia via Genomic-SEM, offering new insights into the etiological pathways underlying sarcopenia.

Sarcopenia

Computed tomography-guided precision biopsy combined with metagenomic next-generation sequencing for etiological diagnosis in patients with blood culture-negative systemic infections.

ObjectiveTo evaluate the diagnostic efficacy of computed tomography-guided percutaneous biopsy combined with metagenomic next-generation sequencing in patients with blood culture-negative systemic infections and to assess the clinical impact of using this combined strategy for etiological confirmation and guidance of targeted antimicrobial therapy.MethodsThis single-center retrospective observational cohort study enrolled 78 patients who met the Sepsis-3 consensus criteria for suspected systemic infection and had negative conventional microbiological work-ups (at least two sets of blood cultures) between April 2022 and March 2025. All patients underwent computed tomography-guided biopsy of radiologically identified infectious foci, with specimens processed concurrently for conventional culture and metagenomic next-generation sequencing. Diagnostic performance was benchmarked against the final comprehensive clinical diagnosis, and the influence of metagenomic next-generation sequencing findings on antimicrobial therapy modification was analyzed. Sample size calculation, based on a prior study estimating an metagenomic next-generation sequencing detection rate of 85% (&#x3b1;&#x2009;=&#x2009;0.05, &#x3b2;&#x2009;=&#x2009;0.2), indicated a minimum of 68 cases; accordingly, 78 patients were enrolled.ResultsComputed tomography-guided biopsy was technically successful in all 78 patients (100%). The pathogen detection rate of metagenomic next-generation sequencing (91.0%, 71/78) was significantly higher than that of conventional culture (55.1%, 43/78; p&#x2009;<&#x2009;0.001). Using the final clinical diagnosis as the reference standard, metagenomic next-generation sequencing achieved a sensitivity of 94.7% (95% confidence interval: 86.9-98.5), specificity of 100.0% (95% confidence interval: 29.2-100.0), positive predictive value of 100.0% (95% confidence interval: 94.9-100.0), and negative predictive value of 42.9% (95% confidence interval: 9.9-81.6). Among the 35 culture-negative specimens, metagenomic next-generation sequencing established a definitive microbiological diagnosis in 28 cases (80.0%) and detected polymicrobial infections in 11 cases (14.1% of the cohort). Antimicrobial therapy was rationally adjusted based on metagenomic next-generation sequencing results in 69.2% (54/78) of the patients.ConclusionsThe integration of computed tomography-guided precision biopsy with metagenomic next-generation sequencing offers a highly effective diagnostic approach for blood culture-negative systemic infections. This synergistic strategy improves etiological diagnosis by providing high-yield target specimens that enable comprehensive, unbiased pathogen screening, facilitates differentiation between infectious and non-infectious etiologies, and supplies critical evidence for guiding precision antimicrobial therapy. These findings highlight the growing role of interventional radiology in the contemporary framework of precision infectious disease management.

Humans

Chemoproteomics Prioritizes Mitochondrial ADP/ATP Translocase as a Candidate Target Associated with 6PPDQ-Induced Respiratory Toxicity in Rainbow Trout Gill.

6PPD quinone (6PPDQ) is an emerging contaminant that induces acute respiratory toxicity in rainbow trout (Oncorhynchus mykiss), yet its underlying molecular mechanisms remain poorly understood. In the present study, short-term in vivo exposure of rainbow trout to 6PPDQ resulted in substantial accumulation and limited biotransformation of 6PPDQ in the gill, accompanied by pronounced gill structural damage and increased whole-fish oxygen consumption. Taking advantage of the electrophilic reactivity of the quinone moiety of 6PPDQ toward cysteine residues, we applied activity-based protein profiling (ABPP) to gill tissue. ABPP revealed marked alterations in mitochondrial cysteine reactivity and highlighted ADP/ATP translocase (ANT) as a candidate 6PPDQ-interacting mitochondrial protein. A Cys-160-containing ANT peptide within the nucleotide-binding domain of ANT was pinpointed as the covalent binding site through ABPP, Peptide-centric Local Stability Assay (PELSA), and molecular docking. Functional assays using isolated gill mitochondria showed that 6PPDQ elicited an uncoupling-like mitochondrial respiratory response that was partially attenuated by the ANT inhibitor carboxyatractyloside (CATR), supporting the functional involvement of ANT in this gill-based model. Together, these findings nominate ANT as a candidate gill mitochondrial target associated with 6PPDQ-induced acute respiratory toxicity and demonstrate the utility of chemoproteomics for prioritizing mechanistically relevant protein interactions of emerging pollutants.

Animals

Non-invasive strategy for gastric cancer detection: Integration of cell-free DNA fragmentomics and protein biomarkers.

Gastric cancer (GC) ranks as the fifth most common cancer worldwide, however, accurate and non-invasive diagnostic modalities for GC remain limited. Cell-free DNA (cfDNA) fragmentomics has emerged as a promising tool for cancer cell detection. Here we develop a gastric cancer detection model, named GaFraD model. The GaFraD model uses four cfDNA fragmentomics features, including fragment size ratio (FSR), copy number variation (CNV), 9-bp end motif (Motif), and fragment size at transcription start sites (TF). This model achieves an area under the receiver-operating characteristic curve (AUC) of 0.970 (95% CI: 0.944 - 0.990), a sensitivity of 95.0% and a specificity of 80.9%. By combining the GaFraD model and conventional protein biomarkers CA19-9 and PG-I/PG-II, the CONFIRM model was generated. The CONFIRM model attained an AUC of 0.986 (95% CI: 0.966 - 1.000), a sensitivity of 95.0% and a specificity of 95.6% in detecting GC. Moreover, the CONFIRM model achieved remarkable performance (AUC&#x202f;=&#x202f;0.983, sensitivity 95.6%, specificity 94.2%) in distinguishing patients with early-stage GC from controls. Our work showed the high discriminatory power in distinguishing GC patients from controls, indicating the clinical potential of using cfDNA fragmentomics combined with protein biomarkers for non-invasive GC detection. The results of the study provide a new avenue for early, accurate, and non-invasive clinical diagnosis of GC.

Cell-free DNA

An immunoinformatics-based multi-epitope vaccine candidate confers cross-protection against two Actinobacillus pleuropneumoniae serovars.

Porcine contagious pleuropneumonia (PCP) is caused by Actinobacillus pleuropneumoniae (APP) and inflicts heavy economic losses on the swine industry. However, existing inactivated vaccines provide limited cross-protection, highlighting the need for improved vaccine strategies. In this study, we combined pangenome analysis with subtractive proteomics to screen the APP core genome and identified 11 potential antigens. Seven of them showed immunoreactivity by ELISA and Western blotting. These antigens, together with the ApxI-III toxins, were used for T and B cell epitope prediction. On this basis, a multi-epitope fusion protein MVAPP was constructed. In silico molecular docking with swine immune receptors and immune simulations suggested that MVAPP has the potential to induce immune responses. In the mouse model, that MVAPP elicited specific antibody responses, shifted the splenic T-cell subset distribution toward CD4+ T cells, and provided partial protection against challenge with strains from two serovars. In conclusion, MVAPP represents a potential multi-epitope vaccine candidate for further development against APP.

Animals

Development and evaluation of a multiplex PCR-based dual-platform targeted sequencing framework for precise differentiation of lumpy skin disease virus.

BACKGROUND: Lumpy skin disease virus (LSDV) shares over 96% genomic identity with goatpox and sheeppox viruses, presenting severe diagnostic challenges due to cross-reactivity. METHODS: To address this bottleneck, we established a targeted sequencing framework integrating multiplex PCR with short-read and long-read platforms. By sequentially screening target pathogens, identifying low-homology genes, and designing short and gradient long-fragment primer pools, we evaluated these dual-platform panels using highly homologous poxvirus samples. RESULTS: The short-read panel stably detected target viruses at inputs as low as 5.26 &#xd7;101 copies/&#x3bc;L. Under strict alignment criteria, LSDV mapping rates reached 42.91%, suppressing non-target signals to 3.05%. The Nanopore-Targeted Sequencing (NTS) long-amplicon strategy successfully eliminated homologous interference. By applying length-dependent diagnostic thresholds (&#x2265; 100 reads for short amplicons; &#x2265; 50 reads for long amplicons), precise species-level identification was achieved, maintaining near-zero cross-reads (0-5) in ultra-long regions. Crucially, the field-deployable NTS workflow enabled complete detection in approximately 4 h. CONCLUSION: This complementary strategy seamlessly meets both laboratory demands for high-sensitivity enrichment and frontline requirements for rapid typing, providing a reliable tool for LSDV surveillance, mutation tracking, and outbreak control.

Capripoxvirus differentiation

Integrated multi-omics profiling identifies aging-related molecular signatures and convergent interferon signaling in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by chronic immune activation and molecular alterations that overlap with aging-related biological processes. However, how these alterations are organized across molecular layers and whether they converge on shared regulatory networks remain incompletely understood. METHODS: We performed an integrative multi-omics analysis combining in-house proteomic and phosphoproteomic data from 130 patients with SLE and 90 healthy controls (HCs) and publicly available transcriptomic datasets comprising 1,461 SLE patients. Proteins and phosphorylation sites were annotated using established aging-related gene resources. Differential protein abundance and phosphorylation changes were analyzed across disease-status and disease-activity comparisons. Nominal P-value thresholds were used for exploratory feature selection, whereas FDR-adjusted P values were used to assess robustness after multiple-testing correction. Kinase-substrate enrichment, transcription factor annotation, and cell-type-resolved transcriptomic comparison were used to explore potential regulatory programs. RESULTS: We identified 128 nominally altered proteins annotated to aging-related biological processes, including genomic instability, mitochondrial dysfunction, and epigenetic alterations. Phosphoproteomic analysis revealed 36 nominally altered phosphorylation sites, including previously unreported sites in IFI16 (S153, S780) and PKC&#x3b4; (S507, S664). Clustering analysis demonstrated heterogeneous protein co-regulation patterns across disease states. Kinase activity inference suggested altered activity of TBK1 and IKK&#x3b2;. TF analysis further highlighted STAT1, RELA, and PML as potential central nodes within the inferred regulatory network. Notably, these multi-omic alterations were not randomly distributed but showed convergence toward shared signaling pathways, particularly those related to interferon responses. CONCLUSIONS: This integrative multi-omics study identifies inflammatory and interferon-dominated molecular alterations in SLE PBMCs that overlap with aging-related biological processes and converge on shared regulatory networks. These findings provide a hypothesis-generating framework for investigating the intersection between chronic immune activation and aging-related molecular remodeling in SLE.

Humans

Safeguarding biomedical AI: a critical scoping review of privacy-enhancing technologies, hybrid approaches, and deployment models.

BACKGROUND: Biomedical artificial intelligence (AI) requires the integration of privacy-enhancing technologies (PETs) to safeguard sensitive clinical, imaging, and genomic data while preserving analytical utility. OBJECTIVES: This review critically and systematically maps applications of PETs across the biomedical AI lifecycle in accordance with PRISMA-ScR guidelines and evaluates their technical trade-offs, deployment feasibility, and residual risks. METHODS: We systematically searched PubMed, IEEE Xplore, ACM Digital Library, and Scopus for studies published between 2015 and 2025. Eligible studies addressed differential privacy, federated learning, secure multiparty computation, homomorphic encryption, or hybrid approaches in biomedical AI. Data were charted on PET type, modality, lifecycle stage, utility metrics, privacy parameters, and deployment considerations. A critical appraisal rubric assessed threat-model adequacy, methodological clarity, reproducibility, privacy-utility transparency, and deployment realism. Additionally, we hand-searched major venues (USENIX Security, NeurIPS, AAAI) and screened Google Scholar for grey literature, applying de-duplication across sources. RESULTS: We identified 87 studies spanning clinical decision support, genomics, and medical imaging. From 25,761 initial records, 3,754 underwent title/abstract screening and 1,968 underwent full-text assessment. PETs demonstrated distinct strengths and limitations: differential privacy provided provable guarantees but reduced performance on imbalanced data; federated learning improved data access but remained vulnerable to gradient leakage; and cryptographic methods ensured confidentiality at high computational cost. Synthetic data generation supported privacy-conscious data sharing and benchmarking but remained sensitive to disclosure risk, fidelity loss, and subgroup representation. Hybrid and emerging approaches, including trusted execution environments, zero-knowledge proofs, and privacy-preserving transformer architectures, mitigated composability gaps yet lacked full end-to-end assurance. Case studies at hospital and biobank scale illustrated practical feasibility and infrastructure demands. CONCLUSIONS: Situating PETs within technical and operational contexts clarifies their capabilities, limitations, and deployment challenges. Residual risks persist, including fairness concerns, inference-time leakage, and overreliance on PETs as compliance proxies. Sustained technical innovation and institutional governance remain essential for the trustworthy integration of PETs in biomedical AI.

biomedical AI

Redox cycling of viral RNA polymerase controls picornavirus replication.

Picornaviruses, including foot-and-mouth disease virus (FMDV), enterovirus 71 (EV71) and encephalomyocarditis virus (EMCV), are important pathogens that cause fever, herpes, and myocarditis in humans and animals. The interplay between picornaviruses and their hosts remains enigmatic. Here we perform porcine genome-wide CRISPR/Cas9 screens and identify methionine sulfoxide reductase B3 (MSRB3) as an essential factor for FMDV. MSRB3 deficiency inhibits FMDV replication. Mechanistically, MSRB3 eliminates methionine oxidation of FMDV 3D polymerase and stabilizes its expression. Further studies show that radical SAM domain-containing protein 1 (RSAD1) catalyzes methionine oxidation of FMDV 3D polymerase and promotes its aggregation and subsequent degradation through the autophagy-lysosome pathway. Importantly, RSAD1-MSRB3-mediated redox modification also affects the stability of 3D polymerases of EV71 and EMCV, and regulates their infectivity and pathogenesis both in vitro and in vivo. Collectively, this study corroborates that RSAD1-MSRB3-mediated redox cycling of 3D polymerase plays a conserved function in modulating picornavirus infection, providing insights into viral pathogenesis and broad-spectrum antiviral development.

Animals

Blood and gut virome remodeling in gastric cancer: Anellovirus expansion and novel virus discovery.

Gastric cancer (GC) is a prevalent malignancy worldwide, yet effective early diagnostic tools remain lacking, and the role of the virome, a key component of the tumor microenvironment, in GC progression is largely unknown. This study aimed to characterize the virome landscapes in peripheral blood and feces of GC patients versus healthy controls, and to identify viral signatures associated with GC onset and metastasis. We performed viral metagenomic sequencing on pooled libraries from 100 GC patients (45 non-metastatic, 55 metastatic) and 50 healthy controls, followed by taxonomic annotation, diversity assessment, LEfSe differential abundance testing, and co-occurrence network analysis. In blood, the GC virome shifted from a bacteriophage-dominated profile in controls to one overwhelmingly dominated by Anelloviridae (> 80%), with significantly decreased alpha diversity. In contrast, the gut virome of GC patients showed increased alpha diversity and coexistence of diverse bacteriophages. LEfSe identified betatorquevirus in blood as a key discriminatory taxon for GC. Network analysis revealed negative correlations between Anelloviridae and multiple bacteriophage families, suggesting niche competition. We also discovered 67 provisional novel anellovirus species and one novel gemykibivirus in GC patient blood. Collectively, our findings indicate that GC is associated with compartment-specific virome remodeling in blood and gut, and that expansion of blood anelloviruses holds promise as a non-invasive biomarker. This study provides a foundational resource for understanding the virome's role in GC.

Humans

Psychological consequences of AI-assisted training and the buffering role of mindfulness.

The integration of artificial intelligence (AI) into athletic training is accelerating, yet its psychological implications for athletes remain insufficiently understood. Drawing on the transactional model of stress and the stress-buffering framework of mindfulness, this study examined whether mindfulness training can mitigate adverse psychological responses associated with AI-assisted training. Using a randomized controlled factorial design, 160 collegiate athletes were assigned to AI-assisted training or standard training, with or without concurrent mindfulness intervention, and assessed at baseline, week 4, and week 8. Athletes exposed to AI-assisted training without psychological support exhibited increases in perceived stress and AI dependence over time. In contrast, these stress increases were substantially attenuated when mindfulness training was implemented alongside AI-assisted training. A significant AI &#xd7; Mindfulness &#xd7; Time interaction emerged for perceived stress at post-intervention, and difference-in-differences analyses corroborated a robust buffering effect. Mediation analyses further indicated that mindfulness training reduced stress partially through enhancing mindful awareness; a three-wave cross-lagged analysis showed that mindful awareness and stress were reciprocally related over time, with the hypothesized awareness-to-stress pathway remaining robust. Together, these findings suggest that AI-assisted training introduces a distinct form of evaluative pressure, and that mindfulness training may serve as an effective psychological buffer during the adoption of continuous algorithmic performance evaluation systems.

Humans

Dynamic transcriptomic landscape from bulk RNA-seq reveals critical mmu-miR-181a-5p/hif1a and mmu-miR-101a-3p/col1a1 modules for deep second-degree burn wound healing.

Burn injuries constitute a significant global health challenge, with deep partial-thickness burns (deep second-degree) posing particular clinical concerns due to prolonged healing and high scarring risks stemming from reticular dermis damage. Current therapeutic strategies remain largely empirical, reflecting limited understanding of stage-specific regulatory mechanisms. This study systematically investigated the molecular basis of deep partial-thickness burn repair by establishing murine models and performing RNA-seq analysis across healing phases (0, 3, 7, 14&#xa0;days post-burn, dpb). Integrated bioinformatics revealed pivotal ceRNA and PPI networks, identifying hif1a (hypoxia-responsive immunomodulator) and col1a1 (ECM remodeling hub) as nodal regulators. Mechanistically, mmu-miR-101a-3p and mmu-miR-181a-5p were validated as post-transcriptional repressors of col1a1 and hif1a, respectively. Our work pioneers the discovery of the mmu-miR-181a-5p/hif1a and mmu-miR-101a-3p/col1a1 axes as master regulators of burn repair, offering novel therapeutic targets. The multi-omics dataset and molecular networks established herein provide a foundational resource for wound healing research.

MicroRNAs

Metagenomic insights into the mechanisms of heteroatom-doped, iron-loaded biochar in enhancing anaerobic digestion of waste activated sludge.

Anaerobic digestion is a crucial technology for resource recovery from waste activated sludge. Enhancing its methane production efficiency using conductive materials is a key research objective. This study aimed to elucidate the mechanisms by which conductive materials promote this process. Three types of biochar(FeS@BC300, FeP@BC600, and FeP@BC900) were prepared by doping bamboo powder with N, P, S and iron salts under pyrolysis conditions at 300-900&#xa0;&#xb0;C, and their physical and chemical properties were characterized, including surface functional groups, specific surface area, capacitance, electrical resistance, electron-accepting capacity (EAC), and electron-donating capacity (EDC). These analyses assessed the influence of synthesis parameters. These materials were subsequently introduced into the anaerobic digestion of thermally hydrolyzed sludge to evaluate their impacts on methanogenic performance, microbial community structure, and metabolic pathways. The results show that the FeP@BC600 material, which exhibited the highest EDC, substantially increased microbial cytochrome c production (by 29.2&#xa0;% compared to the control). This enhancement improved interspecies electron transfer, stimulated ATP synthesis (increased by 41.5&#xa0;%), and reinforced both hydrogenotrophic and acetoclastic methanogenic pathways, ultimately elevating methane production by 55&#xa0;%. Integrated analysis of metagenomic data, material properties, and performance metrics revealed that the key mechanism by which FeP@BC600 promotes methanogenesis is through the enrichment of cytochrome c-encoding genes, thereby facilitating direct interspecies electron transfer (DIET) and augmenting ATP synthesis. This study provides a foundation for the subsequent application of conductive materials to enhance anaerobic digestion and offers guidance for the optimized design of such materials.

Sewage

Urinary Small Extracellular Vesicle DNA as a Biomarker for the Non-Invasive Diagnosis of Bladder Cancer.

Existing diagnostic technologies for bladder cancer (BC) suffer from low sensitivity, low specificity, or a lack of validation. Therefore, validated, non-invasive diagnostic biomarkers with high sensitivity and specificity for early detection of BC are needed to complement and improve upon the limitations of existing diagnostic methods. We used low-pass whole genome sequencing (LP-WGS) technology to detect copy number variations (CNVs) in small extracellular vesicle (sEV) DNA isolated from urine samples of patients. Based on these results, we constructed and validated a diagnostic model to differentiate between benign and malignant bladder lesions. We conducted a receiver operating characteristic analysis and calculated the area under the curve (AUC) to evaluate the performance of the diagnostic model. The urine sEV-DNA LP-WGS data revealed CNV differences between benign and malignant samples. The diagnostic model achieved an AUC of 0.953, a sensitivity of 86.7%, and a specificity of 100% in the training cohort and an AUC of 0.985, a sensitivity of 90%, and a specificity of 100% in the validation cohort. Even at the lowest coverage depth of 0.01X, the performance of the diagnostic model remained relatively robust. Notably, the performance of this diagnostic model surpassed that of the biomarker neuron-specific enolase (sensitivity: 85.7% vs. 64.3%; specificity: 100% vs. 87.5%) and urinary cytology (sensitivity: 100% vs. 66.7%; specificity: 100% vs. 94.1%). Our study demonstrates that urine sEV-DNA exhibits high discriminatory power in distinguishing between benign and malignant bladder lesions, making it a promising tool for auxiliary diagnosis of BC.

Humans

A Network Pharmacology and Molecular Docking Study of TongBi Formula for Osteoarthritis.

This study applied network pharmacology combined with molecular docking to predict the potential therapeutic targets and molecular mechanisms of TongBi Formula (TBF) in osteoarthritis (OA). Active components and corresponding targets of TBF were retrieved from the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform, while OA-related targets were collected from Online Mendelian Inheritance in Man, GeneCards, DrugBank, and Therapeutic Target Database. A network visualization and analysis software was used to construct compound-target and protein-protein interaction (PPI) networks. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery platform. Molecular docking analysis was conducted using a molecular docking software to evaluate the predicted binding affinity between key active compounds and core target proteins. A total of 47 overlapping targets between TBF and OA were identified. PPI network analysis highlighted JUN, RELA, IL6, MAPK1, and IL10 as potential hub targets. Enrichment analysis suggested that TBF may regulate inflammation, lipid metabolism, and multiple intracellular signaling pathways associated with OA progression. Molecular docking results demonstrated favorable predicted binding affinities between core active compounds and key OA-related protein targets. These findings provide a computational framework for understanding the potential mechanisms of TBF against OA and support further experimental validation.

Molecular Docking Simulation

The utilization of Salmonella phage in milk and chicken: depolymerase identification and potential for anti-biofilm activity.

Bacteriophage (phage)-based biocontrol presents a promising strategy against foodborne pathogens. In this study, a novel phage, PH215, exhibited lytic activity against seven prevalent Salmonella serotypes, was isolated and characterized. PH215 demonstrated remarkable environmental stability, sustaining infectivity across a wide pH range (2-11) and at temperatures from 4 to 50&#xa0;&#xb0;C. The multiplicative potential of PH215 was evidenced by a low multiplicity of infection (MOI) of 10-6, a short latent period of 10&#xa0;min, and a substantial burst size of approximately 50 PFU per infected cell. Genomic analysis revealed a 43,505&#xa0;kb double-stranded DNA genome encoding 67 putative proteins. Notably, the product of the Peg38 gene, identified as a tail spike protein (termed PH215Depo), possessed depolymerase activity. We have shown that the cloned expression of PH215Depo exhibited enzymatic activity against various Salmonella serotypes and significantly impeded biofilm formation. Furthermore, in practical application models, PH215 application reduced Salmonella counts in milk and chicken by 2.04 to 5.37 log10 CFU/mL. Our findings highlight the potential of depolymerase-encoding phages like PH215 as effective and broad-spectrum biocontrol agents against Salmonella in the food industry.

Biofilms