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Abstract Biallelic mutations in PIGK cause GPI biosynthesis defect 22 (GPIBD22), characterized with developmental delay, hypotonia, and cerebellar atrophy. The understanding of the underlying causes is limited due to the lack of suitable disease models. To address this gap, we generated a mouse model with PIGK deficits, specifically in Purkinje cells (Pcp2-cko) and an induced pluripotent stem cell (iPSC) model using the c.87dupT mutant (KI) found in GPIBD22 patients. Pcp2-cko mice demonstrated cerebellar atrophy, ataxia and progressive Purkinje cells loss which were accompanied by increased apoptosis and neuroinflammation. Similarly, KI iPSCs exhibited increased apoptosis and accelerated neural rosette formation, indicating that PIGK defects could impact early neural differentiation that confirmed by the RNA-Seq results of neural progenitor cells (NPCs). The increased apoptosis and accelerated NPC differentiation in KI iPSCs are associated with excessive unfolded protein response (UPR) pathway activation, and can be rescued by UPR pathway inhibitor. Our study reveals potential pathogenic mechanism of GPIBD22 and providing new insights into the therapeutic strategy for GPIBD.

Abstract Purpose Uveal melanoma (UM) is adults’ most common primary intraocular malignant tumor. It has been observed that 40% of patients experience distant metastasis during subsequent treatment. While there exist multigene models developed using machine learning methods to assess metastasis and prognosis, the immune microenvironment’s specific mechanisms influencing the tumor microenvironment have not been clarified. Single-cell transcriptome sequencing can accurately identify different types of cells in a tissue for precise analysis. This study aims to develop a model with fewer genes to evaluate metastasis risk in UM patients and provide a theoretical basis for UM immunotherapy. Methods RNA-seq data and clinical information from 79 μm patients from TCGA were used to construct prognostic models. Mechanisms were probed using two single-cell datasets derived from the GEO database. After screening for metastasis-related genes, enrichment analysis was performed using GO and KEGG. Prognostic genes were screened using log-rank test and one-way Cox regression, and prognostic models were established using LASSO regression analysis and multifactor Cox regression analysis. The TCGA-UVM dataset was used as internal validation and dataset GSE22138 as external validation data. A time-dependent subject work characteristic curve (time-ROC) was established to assess the predictive ability of the model. Subsequently, dimensionality reduction, clustering, pseudo-temporal analysis and cellular communication analysis were performed on GSE138665 and GSE139829 to explore the underlying mechanisms involved. Cellular experiments were also used to validate the relevant findings. Results Based on clinical characteristics and RNA-seq transcriptomic data from 79 samples in the TCGA-UVM cohort, 247 metastasis-related genes were identified. Survival models for three genes (SLC25A38, EDNRB, and LURAP1) were then constructed using lasso regression and multifactorial cox regression. Kaplan-Meier survival analysis showed that the high-risk group was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Time-dependent ROC curves demonstrated high predictive performance in 6 m, 18 m, and 30 m prognostic models. Cell scratch assay showed that the 24 h and 48 h migration rates of cells with reduced expression of the three genes were significantly higher than those of the si-NC group. CD8 + T cells may play an important role in tumour metastasis as revealed by immune infiltration analysis. An increase in the percentage of cytotoxic CD8 + T cells in the metastatic high-risk group was found in the exploration of single-cell transcriptome data. The communication intensity of cytotoxic CD8 was significantly enhanced. It was also found that the CD8 + T cells in the two groups were in different states, although the number of CD8 + T cells in the high-risk group increased, they were mostly in the exhausted and undifferentiated state, while in the low-risk group, the CD8 + T cells were mostly in the functional state. Conclusions We developed a precise and stable 3-gene model to predict the metastatic risk and prognosis of patients. CD8 + T cells exhaustion in the tumor microenvironment play a crucial role in UM metastasis.

Abstract Background We evaluated the diagnostic value of homocysteine (Hcy) levels combined with the Wells score and established a prediction model for venous thromboembolism (VTE) occurrence in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on the Hcy level and the Wells score. Patients and methods Clinical information from 914 patients with AECOPD was retrospectively collected in our hospital from June 2020 to October 2023. Receiver operating characteristic curves were plotted to evaluate the diagnostic ability of Hcy concentrations combined with Wells scores and the prediction ability of the model. Univariate and multivariate logistic regressions were used to explore the effects of Hcy levels and the Wells score on VTE occurrence. A nomogram was established for individual risk evaluation. Results Hcy levels and Wells scores were significantly greater in the VTE group than in the non-VTE group (P

Abstract Graphitic carbon nitride (g-C3N4) has gained increasing attention in artificial photosynthesis of H2O2, yet its performance is hindered by sluggish oxygen reduction reaction (ORR) kinetics and short excited-state electron lifetimes. Here we show a B-doped g-C3N4 (BCN) tailored with coordinatively unsaturated FeOOH and CoO x clusters for H2O2 photosynthesis from water and oxygen without sacrificial agents. The optimal material delivers a 30-fold activity enhancement compared with g-C3N4 under visible light, with a solar-to-chemical conversion efficiency of 0.75%, ranking among the forefront of reported g-C3N4-based photocatalysts. Additionally, an electron transfer efficiency reaches 34.1% for the oxygen reduction reaction as revealed by in situ microsecond transient absorption spectroscopy. Experimental and theoretical results reveal that CoO x initiates hole–water oxidation and prolongs the electron lifetime, whereas FeOOH accepts electrons and promotes oxygen activation. Intriguingly, the key to the direct one-step two-electron reaction pathway for H2O2 production lies in coordinatively unsaturated FeOOH to adjust the Pauling-type adsorption configuration of O2 to stabilize peroxide species and restrain the formation of superoxide radicals.

Abstract Background This study aimed to screen southern and southwestern Chinese individuals using expanded carrier screening (ECS), which explores the carrier status of recessively inherited diseases in southern and southwestern China, evaluates the clinical effectiveness of ECS application, and helps recognize high-risk fetuses that may have genetic disorders early in pregnancy, to provide better reproductive guidance. Methods ECS for 220 diseases based on next-generation sequencing was performed on 3024 southern and southwestern Chinese individuals (1512 couples). Carrier status was analyzed; genes and loci with high frequencies of variants and on high-risk couples (ARCs) were focused to evaluate the clinical utility of our ECS technology and provide them precise fertility guidance. Results In total, Pathogenic/likely pathogenic(P/LP) variants were found in 1885 individuals, so the carrier frequency was 62.3%, and 23.2% of the individuals were carriers of multiple diseases. furthermore, 2837 variants were detected, and the average number of P/LP variants carried per subject was 0.938. Additionally, 128 ARCs carried P/LP variants of the same gene, and the theoretical incidence rate in their offspring was as high as 2.12%. Conclusion This study validated the application of our ECS technique for carrier screening in southern China, identifying carrier status and providing accurate carrier frequencies for hundreds of genetic diseases.

Objective The role of hypoalbuminemia throughout the course of chronic periprosthetic joint infection (PJI) remains poorly understood. This study aimed to determine the prevalence and risk factors of hypoalbuminemia in periprosthetic joint infection (PJI) patients and to explore the association between hypoalbuminemia and treatment outcomes. Methods This retrospective cohort study included 387 PJI cases who underwent two‐stage exchange arthroplasty between January 2007 and August 2020, of which 342 were reimplanted. The mean follow‐up period was 7.9 years. Multivariate logistic regression analyses were performed to identify risk factors for hypoalbuminemia and to assess the effect of hypoalbuminemia at 1st‐ and 2nd‐stage exchange on the treatment outcome. Furthermore, the impact of dynamic changes in hypoalbuminemia was investigated. Results The prevalence of hypoalbuminemia at 1st‐ and 2nd‐stage exchange was 22.2% and 4.7%, respectively. Patients with age ≥ 68 years and those with isolation of Staphylococcus aureus, Streptococcus, or Gram‐negative bacteria exhibited a higher risk of hypoalbuminemia. Hypoalbuminemia at 1st‐stage was significantly related to treatment failure (OR = 3.3), while hypoalbuminemia at 2nd‐stage raised the OR to 10.0. Patients with persistent hypoalbuminemia at both the 1st‐ and 2nd‐stage exchanges had a significantly higher rate of treatment failure than patients with hypoalbuminemia at the 1st‐stage but normal albumin levels at the 2nd‐stage exchange (55.6% vs 20.0%, p = 0.036). Conclusion One in five patients with chronic PJI exhibits hypoalbuminemia. Hypoalbuminemia is more likely to develop in patients of advanced age and those infected by specific highly virulent organisms. Also, our results highlight the close association between hypoalbuminemia and treatment outcomes.

Li metal batteries (LMBs) with LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes could release a specific energy of >500 Wh kg−1 by increasing the charge voltage. However, high-nickel cathodes working at high voltages accelerate degradations in bulk and at interfaces, thus significantly degrading the cycling lifespan and decreasing the specific capacity. Here, we rationally design an all-fluorinated electrolyte with addictive tri(2,2,2-trifluoroethyl) borate (TFEB), based on 3, 3, 3-fluoroethylmethylcarbonate (FEMC) and fluoroethylene carbonate (FEC), which enables stable cycling of high nickel cathode (LiNi0.8Co0.1Mn0.1O2, NMC811) under a cut-off voltage of 4.7 V in Li metal batteries. The electrolyte not only shows the fire-extinguishing properties, but also inhibits the transition metal dissolution, the gas production, side reactions on the cathode side. Therefore, the NMC811||Li cell demonstrates excellent performance by using limited Li and high-loading cathode, delivering a specific capacity >220 mA h g−1, an average Coulombic efficiency >99.6% and capacity retention >99.7% over 100 cycles.

Abstract Background Protein–protein interactions are the primary means through which proteins carry out their functions. These interactions thus have crucial roles in life activities. The wide availability of fully sequenced animal and plant genomes has facilitated establishment of relatively complete global protein interaction networks for some model species. The genomes of cultivated and wild peanut (Arachis hypogaea L.) have also been sequenced, but the functions of most of the encoded proteins remain unclear. Results We here used homologous mapping of validated protein interaction data from model species to generate complete peanut protein interaction networks for A. hypogaea cv. ‘Tifrunner’ (282,619 pairs), A. hypogaea cv. ‘Shitouqi’ (256,441 pairs), A. monticola (440,470 pairs), A. duranensis (136,363 pairs), and A. ipaensis (172,813 pairs). A detailed analysis was conducted for a putative disease-resistance subnetwork in the Tifrunner network to identify candidate genes and validate functional interactions. The network suggested that DX2UEH and its interacting partners may participate in peanut resistance to bacterial wilt; this was preliminarily validated with overexpression experiments in peanut. Conclusion Our results provide valuable new information for future analyses of gene and protein functions and regulatory networks in peanut.

Abstract Background Hepatocellular carcinoma (HCC) is a highly malignant tumor known for its hypoxic environment, which contributes to resistance against the anticancer drug Sorafenib (SF). Addressing SF resistance in HCC requires innovative strategies to improve tumor oxygenation and effectively deliver therapeutics. Results In our study, we explored the role of KPNA4 in mediating hypoxia-induced SF resistance in HCC. We developed hemoglobin nanoclusters (Hb-NCs) capable of carrying oxygen, loaded with indocyanine green (ICG) and SF, named HPRG@SF. In vitro, HPRG@SF targeted HCC cells, alleviated hypoxia, suppressed KPNA4 expression, and enhanced the cytotoxicity of PDT against hypoxic, SF-resistant HCC cells. In vivo experiments supported these findings, showing that HPRG@SF effectively improved the oxygenation within the tumor microenvironment and countered SF resistance through combined photodynamic therapy (PDT). Conclusion The combination of Hb-NCs with ICG and SF, forming HPRG@SF, presents a potent strategy to overcome drug resistance in hepatocellular carcinoma by improving hypoxia and employing PDT. This approach not only targets the hypoxic conditions that underlie resistance but also provides a synergistic anticancer effect, highlighting its potential for clinical applications in treating resistant HCC.

Over the past decades, Na0.5Bi0.5TiO3 (NBT)-based ceramics have received increasing attention in energy storage applications due to their high power density and relatively large maximum polarization. However, their high remnant polarization (Pr) and low breakdown field strength are detrimental for their practical applications. In this paper, a new solid solution (1−x)Na0.5Bi0.5TiO3–xCaHfO3 (x = 0.04, 0.08, 0.12, 0.16) was constructed by introducing CaHfO3 into NBT, and thus was prepared using a conventional solid-state reaction. With the addition of CaHfO3, the disorder of the structure increased, A-site vacancies formed, and thus oxygen vacancies were suppressed due to the replacement of the Na+ by Ca2+, resulting in the enhanced relaxation behavior and the reduced Pr, the refined grain, and improved breakdown strength. Furthermore, an optimal recoverable energy storage density (Wrec) of 1.2 J/cm3 was achieved in 0.92Na0.5Bi0.5TiO3–0.08CaHfO3 ceramics under the breakdown strength of 140 kV/cm, which is mainly attributed to the resultant defect of Na+ vacancy.

Abstract Introduction To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. Methods Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0 mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0 mg. Patients were evaluated monthly for 48 weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. Results Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0 mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8 μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48 weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48 weeks. Conclusion RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

Abstract Introduction COVID-19 has demonstrated the importance of competent staff with expertise in public health emergency preparedness and response in the civil aviation system. The civil aviation system is a critical sentinel and checkpoint to prevent imported cases and slow the spread of communicable diseases. Understanding the current competencies of staff to deal with public health emergencies will help government agencies develop targeted training and evidence-based policies to improve their public health preparedness and response capabilities. Methods This cross-sectional pilot study was conducted from November 2022 to October 2023, involving 118 staff members from various positions within China’s civil aviation system. A 59-item questionnaire was translated and developed according to a competency profile. Data were collected using the self-report questionnaire to measure the workforce’s self-perceptions of knowledge and skills associated with public health emergency proficiency, categorized into (1) general competency, (2) preparedness competency, (3) response competency, and (4) recovery competency. KMO & Bartlett test and Cronbach’s α reliability analysis were used to test the reliability and validity of the questionnaire. Descriptive statistics, independent sample T-test, ANOVA, and linear regression models were performed to analyze the competencies. Results A total of 107 staff members from the aviation system were surveyed in this study. The KMO & Bartlett test, (KMO = 0.919, P

The Association of Southeast Asian Nations (ASEAN) is one of the regions where China has the closest exchanges and cooperation with foreign countries. Universal health coverage （UHC）is an important pillar for achieving the health-related targets of the United Nations Sustainable Development Goals, and it is also a strategic focus of common concern for China and ASEAN. How to implement cooperation with ASEAN on UHC and enhance China′s participation in regional health governance is an urgent task for deepening the China-ASEAN strategic partnership. This article summarizes the development opportunities and challenges of China-ASEAN cooperation on UHC by reviewing ASEAN policies and cooperation measures in this field. It provides strategic suggestions for China to strengthen cooperation with ASEAN on UHC in the future.

Noncontact optical thermometers have attracted widespread attention, but existing problems such as single-mode and low-sensitivity thermometers still urgently need to be solved. Herein, a novel multiple-mode thermometer was designed for the polymorphism LaSc3(BO3)4:Eu2+/3+,Li+. X-ray diffraction (XRD) patterns revealed a slight transition between α- and β-phases with the concentrations of the dopants, which is further proved by structure refinements and first-principles calculations. The coexistence of Eu2+ and Eu3+ in the phosphors and their relative percentages were confirmed by X-ray absorption near-edge structure (XANES) spectra. Benefiting from appropriate emissions from Eu2+ and Eu3+ without obvious energy transfer and their opposite changing trends with temperatures under 307 nm excitation, a triple-mode optical thermometer is obtained for this material within the temperature range of 150–450 K. The highest sensitivities of 27.65, 14.05, and 7.68 %·K−1 are achieved based on two fluorescence intensity ratio (FIR) modes of Eu2+ and Eu3+ (5d–4f/5D0–7F2,4) and the fluorescence lifetime (FL) mode of Eu2+, respectively. To the best of our knowledge, the former is almost the highest in Eu2+ and Eu3+ co-doped thermometers. These results indicate that this material may be used as an excellent multiple-mode optical thermometer.

Abstract Traditional quarter‐wavelength parallel‐line couplers (QWPLC) in microstrip form suffer heavily in low directivity because of unbalanced even‐mode and odd‐mode phase velocities. Related schemes to improve directivity lead to complex structures and large dimensions. This study derives and validates an iterative synthesis method to design a high‐directivity microstrip coupler adopting a symmetric stepped‐impedance microstrip coupled line (SSIMCL). Given that the even‐mode and odd‐mode effective dielectric constants (EDCs) vary with the characteristic impedances, the authors take the EDCs of traditional QWPLC as the initial values for an SSIMCL, and the characteristic impedances and EDCs can be computed and converged in several iterations, resulting in good phase delay balance and high coupler directivity. A 20‐dB microstrip coupler working at 1 GHz with high directivity is designed, fabricated, and measured. The obtained maximum directivity is 47 dB and approximately 1 GHz, while the relative bandwidth with a directivity higher than 20 dB and a return loss better than 20 dB is larger than 70%. The novel microstrip coupler also features a compact, simple structure shorter than λg/4.

Plant hyperspectral images (HSIs) contain valuable information for agricultural disaster prediction, biomass estimation, and other applications. However, they also include a lot of irrelevant background information, which wastes storage resources. In this paper, we propose a novel recursive sub-tensor hyperspectral compressive sensing method for plant leaves. This method uses recursive sub-tensor compressive sensing to compress and reconstruct each arbitrary-shape leaf region, discarding a large amount of background information to achieve the best possible reconstruction performance of the leaf region and significantly reduce storage space. The proposed method involves several key steps. Firstly, the optimal band is determined using the spatial spectral decorrelation criterion, and its corresponding mask image is used to extract the leaf regions from the background. Secondly, the recursive maximum inscribed rectangle algorithm is applied to obtain rectangular sub-tensors of leaves recursively. Each sub-tensor is then individually compressed and reconstructed. Finally, all sub-tensors can be reconstructed to form complete leaf HSIs without background information. Experimental results demonstrate that the proposed method achieves superior image reconstruction quality at extremely low sampling rates compared to other methods. The proposed method can improve average Peak Signal-to-Noise Ratio (PSNR) values by about 3.04% and 0.74% compared to Tensor Compressive Sensing (TCS) at the sampling rate of 2%. In the spectral domain, the proposed method can achieve significantly smaller Spectral Angle Mapper (SAM) values and relatively lower spectral indices errors for Double Difference, Triangular Vegetation Index, Leaf Chlorophyll Index, and Modified Normalized Difference 680 than those of TCS. Therefore, the proposed method achieves better compression performance for reconstructed plant leaf HSIs than the other methods.

BackgroundMany patients experience persistent symptoms after COVID-19, a syndrome referred to as Long COVID (LC). The goal of this study was to identify novel new or worsening comorbidities self-reported in patients with LC.MethodsPatients diagnosed with LC (n = 732) at the Mayo Long COVID Care Clinic in Rochester, Minnesota and Jacksonville, Florida were sent questionnaires to assess the development of new or worsening comorbidities following COVID-19 compared to patients with SARS-CoV-2 that did not develop LC (controls). Both groups were also asked questions screening for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), generalized joint hypermobility (GJH) and orthostatic intolerance. 247 people with LC (33.7%) and 40 controls (50%) responded to the surveys.ResultsIn this study LC patients averaged 53 years of age and were predominantly White (95%) women (75%). The greatest prevalence of new or worsening comorbidities following SARS-CoV-2 infection in patients with LC vs. controls reported in this study were pain (94.4% vs. 0%, p

To better realize direction control of the single-pump double-motor hydraulic system and simplify the system, structure and principle of a six-position six-way direction control valve was proposed, which the valve spool has two motion modes: sliding and rotating. Using this valve, the inner and outer motors can work independently and simultaneously. The pressure loss of the valve was tested by building a transmission system, and the experiment results were compared with theoretical analysis. The results show that the performance of the valve working in left and right positions is better than that in meso-position, and the maximum pressure loss occurred in meso-position. Under the rated flow, the maximum pressure loss is 0.331 MPa. Then the characteristic curve of flow-pressure loss and the relationship of pressure loss among oil ports are obtained. In the same conditions, except that the oil inlet pressure loss in the meso-position is greater than the oil outlet pressure loss, the oil inlet pressure loss in the left and right positions are less than the oil outlet pressure loss, the pressure loss in the forward position is less than the pressure loss in the reverse position. The experiment verifies the correctness and feasibility of the structure and principle.

Background: Cerebral ischemia is characterized by its rapid onset and high rates of recurrence, morbidity, and mortality, with blood-brain barrier (BBB) permeability playing a vital role in brain injury. Therefore, it is important to understand the molecular mechanism which regulates the BBB during cerebral ischemia. Materials and methods: An in vitro model of oxygen-glucose deprivation (OGD) and an in vivo model of cerebral ischemia/reperfusion (I/R) were constructed. PD-1 overexpression vectors and vectors containing si-RNA were transfected and injected into in vitro and in vivo models. Western blotting, real-time quantitative PCR (qPCR), immunofluorescence (IF) analysis, and immunohistochemical staining were employed to evaluate the expression levels of programmed cell death-1 (PD-1), microglia M1 and M2 biomarkers, and tight junction proteins. Flow cytometry and ELISA were used to measure the levels of pro-inflammatory cytokines. The BBB permeability of brain tissues was evaluated by Evans blue dye (EBD) extravasation and transendothelial electrical resistance (TEER). Brain water content was measured to assess the extent of inflammatory exudation. The infarct volume and neurological severity score (NSS) were used to assess the severity of brain injury. Brain cell apoptosis was assessed by the TUNEL assay and hematoxylin-eosin (H&E) staining. Results: PD-1 helped to convert the microglia M1 phenotype to the M2 phenotype and to reduce BBB permeability both in vitro and in vivo. Overexpression of PD-1 promoted a shift of the M1 phenotype to the M2 phenotype and reduced BBB permeability via the ERK and p38 MAPK signaling pathways. PD-1 reduced inflammatory exudation, BBB permeability, cell apoptosis, and brain injury in vivo. Conclusion: Our present study verified that PD-1 exerts an anti-inflammatory effect by converting the microglia M1 phenotype to the M2 phenotype, reducing BBB permeability, and thereby relieves brain injury caused by cerebral ischemia. PD-1 is potential therapeutic target for brain injury caused by cerebral ischemia.

Abstract Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS‐based magnetic beads (Mag‐CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV‐HCC patients. Leveraging data‐independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV‐HCC from CHB, LC, and non‐HCC conditions. Collectively, our findings highlight the utility of Mag‐CS‐based sEV isolation for identifying early detection biomarkers in HBV‐HCC.