N4BP1 specifically degrades a subset of mRNA targets through their coding sequences and functions as a negative regulator of inflammation; however, its role in cancer development remains undefined. N4BP1 exhibits the highest expression in head and neck squamous cell carcinoma among all analyzed cancer types. Unlike wild-type mice, N4bp1-/- mice did not develop visible tongue tumor masses in a 4-NQO-induced oral carcinogenesis model. Furthermore, N4bp1-/- mice (86% vs 0%) exhibited significantly prolonged survival compared to wild-type mice within 26 weeks in 4-NQO-induced oral carcinogenesis model. Single-cell profiling demonstrated that N4BP1-deficient epithelial cells arrest at an early stage of cancerous transformation, while wild-type epithelial cells efficiently progress to an advanced stage of cancer. In established human cancer cell lines, N4BP1 also plays a crucial role in proliferation, migration, colony formation, and in vivo growth. Transcriptome profiling identified CCL2 and GM-CSF as downstream targets of N4BP1 in oral cancer. Apart from its intrinsic role in cancer cells, N4BP1-deficient cancer cells induce the differentiation of macrophages into the M1 phenotype. In N4BP1-deficient tissues, CCL2 and GM-CSF were significantly increased, accompanied by the accumulation of M1 macrophages and neutrophils. Our results demonstrate that N4BP1 is an essential gene in tongue cancer development. N4BP1 not only drives cancer cell evolution but also establishes an immune-suppressive microenvironment. N4BP1 is an endoribonuclease that specifically regulates a subset of mRNA targets (including CCL2 and GM-CSF) and plays an essential role in oral cancer.

BACKGROUND:Tumor-associated neutrophils (TANs) play a crucial role in the tumor microenvironment of colorectal cancer (CRC). Although Annexin A11 (ANXA11) is highly expressed in CRC tissues, its prognostic value and its mechanism in mediating tumor-neutrophil crosstalk to drive CRC progression require further investigation. METHODS:The expression and prognostic value of ANXA11 were analyzed using bioinformatics databases, clinical CRC cohorts, and multiplex immunohistochemistry (mIHC). In vitro functional assays and in vivo subcutaneous xenograft mouse models were employed to evaluate its impact on tumor progression. Neutrophil recruitment and activation were assessed using in vivo orthotopic mouse models and in vitro co-culture systems comprising CRC cells and differentiated neutrophil-like cells (dHL-60). Potential molecular pathways and effector molecules were investigated through RT-qPCR, Western blotting, ELISA, and immunohistochemistry, combined with specific inhibitors and neutralizing antibodies. RESULTS:ANXA11 was significantly upregulated in CRC and served as an independent prognostic factor associated with poor patient survival. Functionally, ANXA11 promoted CRC cell proliferation, migration, invasion, and in vivo tumor growth. Notably, ANXA11 expression positively correlated with the abundance of infiltrating tumor-associated neutrophils in both clinical specimens and orthotopic mouse models. Mechanistically, ANXA11 activated the NF-κB signaling pathway in CRC cells to upregulate CXCL5 expression, which was effectively blocked by the NF-κB inhibitor BAY11-7082. Tumor-derived CXCL5 recruited neutrophils via the CXCR2 receptor and stimulated their secretion of matrix metalloproteinase-9 (MMP9). Subsequently, neutrophil-derived MMP9 triggered a malignant positive feedback loop by promoting epithelial-mesenchymal transition (EMT) and exacerbating tumor invasiveness. In vivo, blockade of this signaling axis using the CXCR2 antagonist SB225002 effectively reduced neutrophil infiltration, restored E-cadherin expression, and significantly inhibited ANXA11-driven tumor growth. CONCLUSIONS:ANXA11 establishes a pro-tumorigenic positive feedback loop in the CRC microenvironment by regulating the NF-κB/CXCL5/CXCR2 signaling axis. Targeting the ANXA11/CXCR2 axis represents a potential therapeutic strategy for CRC intervention.

BACKGROUND: Lenvatinib is a first-line therapeutic option for advanced hepatocellular carcinoma (HCC), while acquired resistance severely limits its clinical efficacy. The precise molecular targets reversing Lenvatinib resistance remain inadequately explored. This study aims to elucidate the role of ubiquitin-specific peptidase 1 (USP1) in mediating resistance and identify potential therapeutic targets to improve treatment outcomes in HCC. METHODS: Comprehensive analyses employing genetic modulation (USP1 knockdown and overexpression), pharmacological inhibition, and a series of in vitro and in vivo assays were conducted to assess the effects of USP1 on HCC cell sensitivity to Lenvatinib. Mass spectrometry-based proteomics, integrated bioinformatics analysis, and subsequent molecular validation techniques were utilized to systematically identify key USP1 substrates and interacting E3 ubiquitin ligases. Additionally, virtual screening was conducted using the ChemDiv library to identify potential inhibitors, followed by validation of candidate compounds through in vitro and in vivo experiments. RESULTS: Depletion of USP1 markedly enhanced sensitivity to Lenvatinib in HCC cells, while its overexpression induced resistance. Notably, USP1 knockdown led to obvious chromosome misalignment during metaphase in the presence of Lenvatinib. Mechanistically, Polo-like kinase 1 (PLK1) was identified as a critical substrate stabilized by USP1-mediated deubiquitination, essential for maintaining chromosome alignment and facilitating drug resistance. Additionally, we discovered that the E3 ubiquitin ligase STIP1 homology and U-box-containing protein 1 (STUB1) antagonized with USP1 to regulate PLK1 stability, further modulating resistance of HCC cells. c-Myc was identified as a transcriptional regulator of USP1, establishing a positive feedback loop as USP1/ PLK1/ c-Myc axis. Importantly, NTUZLB-001, a novel compound identified via in silico screening, effectively overcame resistance by promoting PLK1 destabilization. CONCLUSIONS: Our findings reveal a novel mechanism wherein USP1 promotes Lenvatinib resistance in HCC by regulating chromosome alignment through PLK1 deubiquitination. Targeting the USP1/PLK1 axis with NTUZLB-001 represents a promising therapeutic strategy to overcome drug resistance and enhance the clinical efficacy of Lenvatinib in HCC treatment.

Prostate cancer (PCa) is one of the most common malignant tumours in men and imposes a significant disease burden worldwide. Existing treatments have limitations such as drug resistance, and drug repurposing provides a new direction for drug management. Among the drugs explored, metformin has demonstrated certain preventive potential. Epidemiological evidence suggests that long-term use of metformin may be associated with reduced PCa incidence. This potential benefit is particularly evident in Asian and European populations. However, existing studies still exhibit heterogeneity, publication bias, and stage-specific variability. Its clinical efficacy varies by disease stage and individual patient characteristics: although it may reduce disease-specific mortality, evidence for consistent survival benefits remains limited and inconsistent. Notably, metformin possesses a favourable and controllable safety profile. Mechanistically, metformin exerts its antitumour effects through a coordinated network of metabolic and signalling pathways rather than a single dominant mechanism. In many prostate cancer contexts, inhibition of mitochondrial complex I likely represents a primary upstream event, leading to bioenergetic stress. This metabolic perturbation subsequently activates AMP-activated protein kinase (AMPK), suppresses mTOR signalling, and modulates androgen receptor (AR)-associated pathways. In parallel, metformin induces oxidative stress remodelling by increasing reactive oxygen species and disrupting redox homeostasis, which further contributes to tumour growth inhibition. Clinically, metformin does not yet show consistent survival benefits across unselected prostate cancer populations, but it may have potential value in specific disease stages and metabolically defined patient subgroups.

Background:Exosomes are the key mediators of intercellular communication within the tumor microenvironment. Pancreatic cancer (PC) exhibits an abnormal increase in exosome secretion, and this abnormal secretion is closely associated with the invasive migration and metastatic progression of PC. Although the role of exosomes in PC metastasis has been confirmed, the precise molecular mechanism regulating this process remains unclear. This study aims to explore the regulatory mechanism of the exosome secretion cascade and its correlation with malignant migration in PC. Methods:By comparing the serum miRNA profiles of PC patients with those of healthy controls, the key inhibitory factor microRNA-27b-5p (miR-27b-5p) was identified. After verifying its direct targeting of RAB27A, overexpression of miR-27b-5p and RAB27A rescue experiments were conducted in PC cells. Combined with the detection of intracellular multivesicular bodies (MVBs), the mechanism by which this axis regulates exosome secretion and PC metastasis was explored. Results:In vitro experiments demonstrated that miR-27b-5p, which plays a crucial regulatory role, was significantly downregulated in PC. Additionally, it significantly inhibited exosome secretion and migration ability of PC cells both in vivo and in vitro. Through biological analysis and luciferase reporter experiments, it was confirmed that miR-27b-5p directly targets RAB27A. Notably, functional experiments in PC cells indicated that overexpression of miR-27b-5p inhibited the expression level of RAB27A, exosome secretion ability, and the metastatic potential of cancer cells. Finally, a RAB27A rescue experiment was conducted to verify that overexpression of RAB27A counteracted the inhibitory effect of miR-27b-5p overexpression on PC exosome secretion. Conclusions:This study reveals a novel molecular mechanism: miR-27b-5p directly targets RAB27A to suppress PC cell migration. This regulatory axis may contribute to exosome-related metastatic phenotypes of PC.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a chronic metabolic liver disorder characterized by excessive hepatic fat accumulation in humans and is closely associated with metabolic dysfunction. MASLD has become a global public health issue that cannot be ignored. Currently, the global prevalence of MASLD has reached as high as 38%. It can evolve from simple fatty liver disease through liver fibrosis and cirrhosis, ultimately potentially leading to hepatocellular carcinoma. In 2019, approximately 134,000 people worldwide died from complications related to this disease. In China, the impact of this disease is even more pronounced, having surpassed that of viral hepatitis to become the leading cause of cirrhosis. Faced with this serious public health challenge, this review systematically organizes the core risk factors and major pathogenesis mechanisms of MASLD. This study aims to provide critical scientific evidence for advancing liver disease prevention and management strategies, reducing the disease burden, and realizing precise diagnosis and stratified treatment. Unlike conventional reviews that discuss risk factors and pathogenic mechanisms separately, this review integrates these elements into a unified pathophysiological framework, providing a more comprehensive understanding of MASLD.

The maternal microbiome influences child health. However, its impact on a given offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring’s stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients’ offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings’ stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings’ stem cells and represent a promising target for interventions.

Pancreatic cancer (PC) is an extremely deadly type of cancer, and the 5-year survival rate remains less than 10%. The tumour microenvironment (TME) affects the occurrence, progression and treatment outcomes of PC. MicroRNAs (miRNAs) are essential to regulate PC TME. This review delves into the different roles of miRNAs in the PC TME, including exosome communication, angiogenesis, interactions with cancer-associated fibroblasts, the immunological and neuronal microenvironments and metabolic reprogramming. However, research on the complex regulatory networks and synergistic effects of miRNAs in the TME is still insufficient, and their clinical translation and application face challenges. This review summarised the activities of miRNAs in the PC TME, guiding future research and therapeutic strategies involving miRNAs in PC. Future studies should integrate advanced technologies to decode the spatiotemporal dynamics of miRNA regulation within the TME and develop optimised nanodelivery systems for stable and targeted miRNA delivery, advancing clinical applications in PC treatment.

Lactylation is a novel post-translational modification of proteins, which has attracted extensive attention since its discovery. Lactylation takes lactate, a common metabolite, as its substrate and mediates the modification under the action of lactyltransferases. Although lactylation modification was initially found to undergo in histones, subsequent studies have shown that this novel modification is not limited to specific protein classes, and can undergo in both histone and non-histone proteins. Lactylation has been proved to play an important regulatory role in a variety of diseases, including tumors, metabolic disorders, cardiovascular diseases, and neurodegenerative diseases. Given the tumor properties of its substrate lactate, lactylation has been most extensively studied in tumors, and as a result, we have gained a deeper understanding of the potential molecular mechanisms and regulatory roles of lactylation in tumors. In this paper, we will summarize the regulatory and functional mechanisms of lactylation, explain the cellular processes in which lactylation is involved and its association with various diseases, and look forward to the future clinical application of lactylation.

ABSTRACT Background Gamma‐glutamyltransferase (GGT) is a membrane‐bound enzyme involved in glutathione metabolism and oxidative stress regulation. Although it is traditionally viewed as a liver function marker, emerging evidence suggests that its aberrant expression is closely associated with tumorigenesis, progression, and therapeutic resistance across multiple solid tumors. However, the comprehensive landscape of the GGT gene family and its clinical value in tumor diagnosis and prognosis remain unclear. Objective To systematically review the multidimensional roles of the GGT molecular family—including gene variants, mRNA isoforms, enzyme activity, and protein isoforms—in tumor biology and clinical oncology and to evaluate their potential as diagnostic and prognostic biomarkers. Methods We conducted a comprehensive literature review (PubMed, CNKI; inception–August 2025) focusing on (1) GGT family gene structure, expression patterns, and regulatory mechanisms; (2) GGT mRNA splice variants and isoforms; (3) GGT enzymatic activity and posttranslational modifications; and (4) clinical studies evaluating GGT as a biomarker in solid tumors. Data were synthesized narratively, emphasizing molecular mechanisms and clinical significance. Results The human GGT family comprises 13 homologous genes (e.g., GGT1‐7 and GGTLC1‐3) localized on chromosomes 20 and 22, which exhibit tissue‐specific expression and functional diversity. GGT1 (22q11.23), which is the most extensively studied gene, is highly expressed in renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), gastric cancer (GC), and breast cancer (BRC) and is correlated with poor prognosis and metastasis. GGT5 acts as a tumor suppressor in HCC but promotes progression in gastric cancer via PI3K/AKT pathway activation. GGT7 overexpression predicts poor survival in patients with HCC and glioblastoma. The GGT‐II isoform demonstrated 78.7% sensitivity and 92.3% specificity for HCC diagnosis, outperforming AFP (AUC: 0.89 vs. 0.67). Serum GGT activity ≥ 50 U/L independently predicts poor overall survival (OS) in patients with HCC (HR: 1.78, 95% CI: 1.26–2.50). GGT mRNA splice variants (e.g., the GGT‐I mRNA‐B subtype) enhance early HCC detection when combined with AFP (sensitivity: 98%). Conclusions The GGT molecular family plays pleiotropic roles in tumor biology via redox homeostasis, EMT, and immune modulation. The GGT1/5/7 and GGT‐II isoforms represent promising biomarkers for early diagnosis, prognosis, and therapeutic targeting in multiple cancers. Future multicenter studies should validate GGT‐based biomarker panels and elucidate the mechanisms underlying tissue‐specific GGT functions.

Sepsis-induced myocardial dysfunction (SIMD) is a severe complication of sepsis, characterized by impaired cardiac function and high mortality rates. Despite significant advances in understanding sepsis pathophysiology, the molecular mechanisms underlying SIMD remain incompletely elucidated. Ubiquitination and deubiquitination, critical post-translational modifications (PTMs) regulating protein stability, localization, and activity, play pivotal roles in cellular processes such as inflammation, apoptosis, mitochondrial function, and calcium handling. Dysregulation of these systems has been increasingly implicated in the pathogenesis of SIMD. This review provides a comprehensive overview of the pathological mechanisms driving SIMD, with a focus on the classification and functions of E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), their regulatory systems, and their involvement in SIMD. Dysfunction of the ubiquitin-proteasome system (UPS), often driven by altered activity of E3 ligases, accelerates the degradation of critical regulatory proteins, thereby exacerbating cardiac inflammation, oxidative stress, and apoptosis. Concurrently, imbalances in DUB activity disrupt protein homeostasis, further amplifying myocardial injury. Emerging research underscores the therapeutic potential of targeting these systems. Strategies aimed at modulating E3 ligase activity or restoring DUB balance have shown promise in preclinical studies. This review summarizes current findings on the roles of ubiquitination and deubiquitination in SIMD pathogenesis, highlights the key challenges in advancing this field, and proposes directions for future research.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. It is characterized by a high incidence, high mortality rate, and poor prognosis. With the increasing consumption of antibiotics and the growing prevalence of antimicrobial resistance, clinicians are in greater need of easily accessible and effective inflammatory markers to monitor the infection process, guide treatment, and assess patient prognosis. Numerous biomarkers have been studied for their potential value in the diagnosis of sepsis, and more than 250 different biomarkers have been proposed. However, many of these biomarkers are more useful for prognostic evaluation than for diagnosis. Biomarkers such as procalcitonin and C-reactive protein have been extensively studied, with procalcitonin being the only sepsis biomarker included in clinical guidelines. It can be used to guide antibiotic use but should not be used as a standalone diagnostic indicator. C-reactive protein has poor sensitivity and specificity for sepsis diagnosis. In recent years, new biomarkers, such as neutrophil extracellular traps, interleukin-6, histones, cell-free DNA and composite indicators, such as the systemic immune inflammation index,have been identified. This article provides a comprehensive review of the diagnostic value of traditional and recently popular novel biomarkers for sepsis.

Recently, deep eutectic solvents (DESs) have attracted considerable interest in analytical chemistry. This work described the enantioseparations of twenty amino alcohol drugs with several DESs based on lactobionic acid (LA) as the sole chiral selector in capillary electrophoresis (CE) firstly. Compared to the single LA system and the ionic liquid/LA synergistic system, the DES system exhibited considerably improved separations. The influences of some key parameters on separations were investigated in detail. This work also experimentally demonstrated that the carboxyl group was indispensable in the process of chiral recognition. The mechanisms of the improvements of DESs on enantioseparations were studied via ultraviolet spectroscopy. Furthermore, the proposed method was used to determine the enantiomeric purity of propranolol hydrochloride successfully. This is the first time that chiral DESs were utilized as the sole chiral selectors in CE, and this strategy has opened up a new prospect for the use of DESs in enantioseparation.

Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require to multiply, once thought to be a characteristic of tumor cells known as the “Warburg effect”. In fact, throughout the process of carcinogenesis, immune cells and stromal cells, two major cellular constituents of the tumor microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. In this review, we provide a full-scale review of the glycolytic remodeling of several types of TME cells and show how these TME cells behave in the acidic milieu created by glucose shortage and lactate accumulation as a result of increased tumor glycolysis. Notably, we provide an overview of putative targets and inhibitors of glycolysis along with the viability of using glycolysis inhibitors in combination with immunotherapy and chemotherapy. Understanding the glycolytic situations in diverse cells within the tumor immunological milieu will aid in the creation of subsequent treatment plans.

Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication primarily driven by inflammation, yet its molecular mechanisms remain unclear. In this study, we identified significant upregulation of the m6A methyltransferase METTL3 (methyltransferase-like 3), the m6A reader protein YTHDF1 (YTH N6-methyladenosine RNA binding protein 1), as well as increased expression levels of USP12 (ubiquitin-specific peptidase 12), FOXO3 (forkhead box O3), and key molecules in the intrinsic apoptotic pathway, PUMA (p53 upregulated modulator of apoptosis) and BAX (Bcl-2-associated X), through proteomic profiling in an LPS (Lipopolysaccharide)-induced SIMD mouse model. In vitro and in vivo experiments demonstrated that METTL3 and YTHDF1 regulated USP12 mRNA expression and stability through m6A modification. Elevated USP12 interacted with FOXO3, preventing its ubiquitin-mediated degradation, which enhanced FOXO3 binding to the PUMA promoter, leading to upregulation of PUMA. PUMA upregulation initiated the intrinsic apoptotic pathway, activating downstream BAX, Apaf1 (apoptotic protease-activating factor 1), and Caspases, ultimately driving SIMD. Inhibition of METTL3 (with STM2457), YTHDF1 (with Ebselen), or PUMA (with CLZ-8) significantly suppressed intrinsic apoptosis and alleviated SIMD symptoms. These findings underscore the critical role of METTL3/YTHDF1-dependent m6A modification in modulating the USP12-FOXO3-PUMA-BAX-Apaf1-Caspases signaling axis in SIMD, and suggest that targeting this pathway may offer a potential therapeutic strategy for SIMD.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. In this study, we aimed to investigate the role and regulatory mechanism of Annexin A2 (ANXA2) in the pathogenesis of NAFLD. Histological analyses and ELISA were used to illuminate the expression of ANXA2 in NAFLD and healthy subjects. The role of ANXA2 was evaluated using high-fat diet (HFD)-fed mice via vein injection of adeno-associated viruses (AAV) knocking down ANXA2 or non-targeting control (NC) shRNAs. Moreover, HepG2 and LO2 cells were employed as in vitro hepatocyte models to investigate the expression and function of ANXA2. ANXA2 was confirmed to be one of three hub genes in liver injury, and its expression was positively correlated with NAFLD activity score (NAS) and macrophage infiltration in NAFLD. Moreover, ANXA2 was significantly upregulated in NAFLD patients and HFD-fed mice. LPS/TLR4 pathway strongly upregulated ANXA2 expression, which is mediated by direct ANXA2 promoter binding by TLR4 downstream NF-κB p65 and c-Jun transcription factors. Increased ANXA2 expression was correlated with decreased autophagy flux and autophagy was activated by the depletion of ANXA2 in the models of NAFLD. Furthermore, ANXA2 interference led to the activation of AMPK/mTOR signaling axis, which may play a causal role in autophagy flux and the amelioration of steatosis. ANXA2 is a pathological predictor and promising therapeutic target for NAFLD. ANXA2 plays a crucial role in linking inflammation to hepatic metabolic disorder and injury, mainly through the blockage of AMPK/mTOR-mediated lipophagy.

衰弱会导致老年癌症患者出现多种不良健康结局,而准确识别衰弱有助于医护人员及时实施针对性干预方案.本文对国内外常用的老年癌症衰弱测评工具进行综述,包括测评工具的主要内容、特点、预测效能、优缺点等,以期为国内老年癌症患者衰弱工具的引进及开发提供参考.

目的 汉化简版老年综合评估问卷,并对其进行信效度检验.方法 根据量表跨文化研究指南对英文版简版老年综合评估问卷进行正译、回译和跨文化调适,最终形成中文版简版老年综合评估问卷.采用便利抽样法,选取2021年2-7月南通大学附属医院3个科室的275例老年癌症患者为研究对象,采用一般资料调查表、中文版简版老年综合评估问卷和衰弱身体表型量表对患者进行调查.运用SPSS 25.0和AMOS 24.0软件检验问卷的信效度.结果 中文版简版老年综合评估问卷共3个维度15个条目,问卷的Cronbach's α系数为0.806,抑郁、功能、认知维度的Cronbach's α系数分别为0.919,0.957,0.806,评分者间一致性的Kappa值为0.778.条目水平的内容效度指数为0.833～1.000,问卷水平的内容效度指数为0.943.探索性因子分析共析出3个公因子,累计方差贡献率为81.181％.该问卷测评结果与衰弱身体表型量表呈强相关(r=0.629,P＜0.01).结论 中文版简版老年综合评估问卷信效度良好且筛查性能较佳,适用于对老年癌症患者衰弱的初步筛查.

某三级综合医院以STEM评价指标为基础,通过制定切实有效的医院创新人才培养模式,提升医院创新人才培养的效果.文章通过对入选人才培养计划的医师在培养前后 3 年科研业绩进行对比分析,发现经过培养后的医学创新人才在科技产出方面业绩较为突出,差异具有统计学意义(P<0.05),成功助力医院登上中国医院科技量值百强榜.因此,该培养计划对医师科研水平的提升有一定的效果,有助于医院科研竞争力的进一步提升,助力医院高质量发展.

Mosquito‐borne flaviviruses including Zika virus (ZIKV) represent a public health problem in some parts of the world. Although ZIKV infection is predominantly asymptomatic or associated with mild symptoms, it can lead to neurological complications. ZIKV infection can also cause antibody‐dependent enhancement (ADE) of infection with similar viruses, warranting further studies of virion assembly and the function of envelope (E) protein‐specific antibodies. Although extracellular vesicles (EVs) from flavivirus‐infected cells have been reported to transmit infection, this interpretation is challenged by difficulties in separating EVs from flavivirions due to their similar biochemical composition and biophysical properties. In the present study, a rigorous EV‐virion separation method combining sequential ultracentrifugation and affinity capture was developed to study EVs from ZIKV‐infected cells. We find that these EVs do not transmit infection, but EVs display abundant E proteins which have an antigenic landscape similar to that of virions carrying E. ZIKV E‐coated EVs attenuate antibody‐dependent enhancement mediated by ZIKV E‐specific and DENV‐cross‐reactive antibodies in both cell culture and mouse models. We thus report an alternative route for Flavivirus E protein secretion. These results suggest that modulation of E protein release via virions and EVs may present a new approach to regulating flavivirus‐host interactions.