TRIM26 restricts Epstein-Barr virus infection in nasopharyngeal epithelial cells through K48-linked ubiquitination of HSP-90ß.

The tripartite interaction motif (TRIM) family of proteins is known for their antiviral activity through different mechanisms, such as interfering with viral components, regulating immune responses, and participating in autophagy-mediated defense pathways. In this study, we investigated the role of tripartite interaction motif 26 (TRIM26), which is encoded by a major histocompatibility complex (MHC) gene, in regulating Epstein-Barr virus (EBV) infection of nasopharyngeal epithelial cells. We found that TRIM26 expression was induced upon EBV infection and that it indirectly targeted EphA2, a crucial epithelial receptor for EBV entry. Our results showed that TRIM26 interacted with heat shock protein 90-beta (HSP-90ß) and promoted its polyubiquitination, which led to its degradation via the proteasome pathway. This, in turn, affected EphA2 integrity and suppressed EBV infection. These findings suggest that TRIM26 could be a valuable target for developing therapeutic interventions against EBV infection and its associated pathogenesis.

Unmasking Bacterial Identities: Exploiting Silver Nanoparticle 'Masks' for Enhanced Raman Scattering in the Rapid Discrimination of Diverse Bacterial Species and Antibiotic-Resistant Strains.

Unraveling bacterial identity through Raman scattering techniques has been persistently challenging due to homogeneously amplified Raman signals across a wide variety of bacterial molecules, predominantly protein- or nucleic acid-mediated. In this study, we present an approach involving the use of silver nanoparticles to completely and uniformly "mask" adsorption on the surface of bacterial molecules through sodium borohydride and sodium chloride. This approach enables the acquisition of enhanced surface-enhanced Raman scattering (SERS) signals from all components on the bacterial surface, facilitating rapid, specific, and label-free bacterial identification. For the first time, we have characterized the identity of a bacterium, including its DNA, metabolites, and cell walls, enabling the accurate differentiation of various bacterial strains, even within the same species. In addition, we embarked on an exploration of the origin and variability patterns of the main characteristic peaks of Gram-positive and Gram-negative bacteria. Significantly, the SERS peak ratio was found to determine the inflection point of accelerated bacterial death upon treatment with antimicrobials. We further applied this platform to identify 15 unique clinical antibiotic-resistant bacterial strains, including five Escherichia coli strains in human urine, a first for Raman technology. This work has profound implications for prompt and accurate identification of bacteria, particularly antibiotic-resistant strains, thereby significantly enhancing clinical diagnostics and antimicrobial treatment strategies.

Long-term result of 125 I seed brachytherapy for pediatric desmoid tumor in the head and neck.

BACKGROUND: Desmoid tumor (DT) is rare and challenging, often affects the head and neck (HN) region in children, and its appropriate treatments are under-discussed. This study aimed to retrospectively evaluate the long-term effectiveness and safety of 125 I seed brachytherapy for pediatric DT in HN. PROCEDURE: Seven pediatric patients with a median age of three years who suffered from DT in HN treated with 125 I brachytherapy from January 2008 to June 2018 were included. Among these, five underwent sole brachytherapy and the others combined with surgery under prescription doses ranging from 10,000 to 12,000 cGy. The rate of local control (LC), complete response (CR), and partial response (PR) was calculated after evaluation by radiological and pathological means. Radiation-associated toxicities were also evaluated. RESULTS: The LC rate was 7/7 during the follow-up time ranging from 43 to 135 months and with a mean of 57 months. No recurrent lesion was found in the patients receiving surgery combined with brachytherapy. In patients treated with sole brachytherapy, the radiological PR rate and CR rate were 4/5 and 1/5, respectively. In those reaching radiological PR, 3/4 were pathological CR. Slight acute radiation-associated toxicities were observed in all patients, and no late or severe acute toxicity was observed. CONCLUSION: 125 I brachytherapy is effective and safe in the management of pediatric DT in HN as the sole modality or combined with surgery in the long term.

Label-free detection of vitamin B by two-step enhanced Raman technique using dynamic borohydride-reduced silver nanoparticles.

A creatively designed novel two-step enhancement technique is presented in which B vitamin molecules are dynamically adsorbed onto the surface of silver nanoparticles by sodium borohydride, followed by local plasmon resonance in the presence of cations (calcium ions), ultimately achieving synergistic chemical and physical enhancement on the same molecule and constructing a "surface hot spots" two-step enhancement platform for vitamin detection. The Raman signal of the promoted vitamin molecule is enhanced by nine orders of magnitude. In a subsequent study it was observed that the vitamin B2 molecules were in a near-vertical image on the surface of the silver nanoparticles, which may also contribute to the Raman signal enhancement. Combined with deep learning techniques, the method has been successfully applied to the detection of B vitamins in body fluids. As an accurate, rapid, reproducible, non-invasive, and versatile assay platform, it holds great promise for the intelligent identification of trace B molecules in food, pharmaceuticals, and the human body.

Correction: EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.

[This corrects the article DOI: 10.1371/journal.ppat.1007484.].

Rationally Driven Drug Nonradiative Decay via a Label-Free Polyprodrug Strategy to Renew Tumor Cascade Photothermal-Chemotherapy.

Drugs are frequently used for only chemotherapy that ignores their photophysical properties that potentially endow them with other therapeutic potency. Additionally, current photothermal-chemotherapy replies on the codelivery of drugs and photothermal agents, but their spatiotemporal delivery and precise release is unsatisfactory. Herein, label-free doxorubicin (DOX) polyprodrug nanoparticles (DPNs) are formulated from disulfide bonds-tethered DOX polyprodrug amphiphiles (PDMA-b-PDOXM). Benefiting from boosted nonradiative decay of high-density DOX, significant fluorescence quenching and photothermal effects are observed for DPNs without common photothermal agents. Upon cellular uptake and laser irradiation, the heat can promote lysosomal escape of DPNs into reductive cytosol, whereupon free DOX is released to activate chemotherapy and fluorescence, achieving rational cascade photothermal-chemotherapy. The current label-free polyprodrug strategy can make full use of drugs; it provides an alternative insight to extend the therapeutic domain of drugs.

A Modified Design of the Pectoralis Major Myocutaneous Flap for Reconstruction of Head and Neck Defect.

ABSTRACT: Even though the pectoralis major myocutaneous flap (PMMF) still has an important role in the free flaps ear, it is reported to have drawbacks such as the limited cephalad extension and high incidence of total or partial flap necrosis. Various modifications have been attempted to augment the limited cephalad extension and a stable blood supply.The aim of this study is to describe a modified design of the skin paddle and preparation of the PMMF, to achieve stable blood circulation and sufficient pedicle length. The priority skin paddle is the medial part for its stable blood supply, and the lateral margin should be adjusted as needed. During the harvesting, the lateral thoracic artery (LTA) is preserved to protect the perforating branches, and the anterior sheath of the rectus abdominis muscle is used as a suture margin to prevent damage of the thin muscle of the PMMF. The skin paddles in this study are larger than those previously reported. All of the 21 patients in our study, the skin paddles show complete survival with no partial necrosis of skin paddle, fistula, or wound dehiscence.It is worthwhile to consider and preserve the LTA as a major contributor to a lateral and distal PMMF. This study would be useful in future and preparation of the PMMF in head and neck reconstruction.

The special stemness functions of Tbx3 in stem cells and cancer development.

The T-box factors belong to an ancient protein family, which comprises a cluster of evolutionarily-conserved transcription factors that regulate gene expression and that are crucial to embryonic development. T-box transcription factor 3 (Tbx3) is a member of this family, is expressed in some tissues, and is a key regulator in many critical organs, including the heart, mammary gland, and limbs. Overexpression of Tbx3 is associated with a number of cancers, including head and neck squamous cell carcinoma, gastric, breast, ovary, cervical, pancreatic, bladder and liver cancers, as well as melanoma. Tbx3 promotes tumor development by modulating cell proliferation, tumor formation, metastasis, cell survival and drug resistance. Moreover, there is strong evidence that Tbx3 regulates stem cell maintenance by controlling stem cell self-renewal and differentiation. Verification of the upstream regulatory factors and potential molecular mechanism of Tbx3, being able to explain the function of Tbx3 in carcinogenic effects and stem cell maintenance, will make a valuable contribution to stem cell and cancer research. This review provides an insight into the current research on Tbx3 and explores the significance of Tbx3 in stem cells and tumorigenesis.

EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.

Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis. Here, we reported that one of the key miRNAs encoded by EBV, EBV-miR-Bart1-5P, can significantly promote nasopharyngeal carcinoma (NPC) cell glycolysis and induces angiogenesis in vitro and in vivo. Mechanistically, EBV-miR-Bart1-5P directly targets the α1 catalytic subunit of AMP-activated protein kinase (AMPKα1) and consequently regulates the AMPK/mTOR/HIF1 pathway which impelled NPC cell anomalous aerobic glycolysis and angiogenesis, ultimately leads to uncontrolled growth of NPC. Our findings provide new insights into metabolism and angiogenesis of NPC and new opportunities for the development of targeted NPC therapy in the future.

Efficacy of surgery combined with postoperative 125 I interstitial brachytherapy for treatment of acinic cell carcinoma of the parotid gland in children and adolescents.

BACKGROUND: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution. PROCEDURE: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated. RESULTS: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred. CONCLUSIONS: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT.

[Reference ranges of platelet and related parameters within 24 hours after birth in preterm infants with different gestational ages].

OBJECTIVE: To study the reference ranges of platelet and related parameters within 24 hours after birth in preterm infants with different gestational ages. METHODS: According to the inclusion and exclusion criteria, a retrospective analysis was performed for the chart review data of 1 070 preterm infants with a gestational age of 23-36+6 weeks who were admitted to the neonatal intensive care unit from January to December in 2018. The reference ranges of platelet parameters were calculated for the preterm infants within 24 hours after birth. RESULTS: There were no significant differences in platelet count (PLT) and plateletcrit (PCT) among the preterm infants with different gestational ages (P>0.05). The late preterm infants (34-36+6 weeks; n=667) had significantly lower mean platelet volume (MPV) and platelet distribution width (PDW) than the extremely preterm infants (23-27+6 weeks; n=36) and the early preterm infants (28-33+6 weeks; n=367) (P<0.05). There were no significant differences in these platelet parameters between the preterm infants with different sexes (P>0.05). The reference ranges of platelet parameters in preterm infants were calculated based on gestational age. The reference ranges of PLT and PCT were (92-376)×109/L and 0.1%-0.394% respectively, for the preterm infants with a gestational age of 23-36+6 weeks. The reference ranges of MPV and PDW were 9.208-12.172 fl and 8.390%-16.407% respectively, for the preterm infants with a gestational age of 23-36+6 weeks; the reference ranges of MPV and PDW were 9.19-11.95 fl and 9.046%-15.116% respectively, for the preterm infants with a gestational age of 34-36+6 weeks. CONCLUSIONS: The MPV and PDW of preterm infants with different gestational age are different within 24 hours after birth, and it is more helpful for clinical practice to formulate the reference range of MPV and PDW according to gestational age.

The expression of cysteine-rich secretory protein 2 (CRISP2) and its specific regulator miR-27b in the spermatozoa of patients with asthenozoospermia.

Cysteine-rich secretory protein 2 (CRISP2) is an important sperm protein and plays roles in spermatogenesis, modulation of flagellar motility, acrosome reaction, and gamete fusion. Clinical evidence shows a reduced CRISP2 expression in spermatozoa from asthenozoospermic patients, but the molecular mechanism underlying its reduction remains unknown. Herein, we carried out a study focusing on the CRISP2 reduction and its roles in asthenozoospermia. Initially, through analyzing CRISP2 expression and methylation on CRISP2 promoter activity in sperm, we observed a decreased expression of CRISP2 protein rather than its mRNA in the ejaculated spermatozoa from asthenozoospermic patients and no methylation in the CRISP2 promoter, suggesting CRISP2 expression may be regulated in the sperm at the posttranscriptional level. Subsequently, we found that microRNA 27b (miR-27b), predicted as a candidate regulator of CRISP2 using bioinformatics, was highly expressed in the ejaculated spermatozoa from asthenozoospermic patients. Luciferase reporter assay and transfection experiments disclosed that this microRNA could target CRISP2 by specifically binding its 3' untranslated region, suppressing CRISP2 expression. Extended clinical observation further confirmed a highly expressed miR-27b and its obviously negative correlation with CRISP2 protein expression in ejaculated spermatozoa samples from asthenozoospermic patients. Finally, we conducted a retrospective follow-up study to support that either high miR-27b expression or low CRISP2 protein expression was significantly associated with low sperm progressive motility, abnormal morphology, and infertility. Thus, this study provides the first preliminary insight into the mechanism leading to the reduced CRISP2 expression in asthenozoospermia, offering a potential therapeutic target for treating male infertility or for male contraception.

The expression of CXCL13 and its relation to unfavorable clinical characteristics in young breast cancer.

BACKGROUND: Young breast cancer occupies a higher and higher proportion of breast cancer, especially in Asia, and is associated with a more unfavorable prognosis compared with the disease arising in older women. However, the poor prognosis of young breast cancer cannot be fully explained by the clinical and molecular factors. METHODS: This study investigated 1125 Chinese breast cancer patients diagnosed from 2009 to 2013. A data mining of gene expression profiles was performed for the young and older breast cancer patients, identifying significantly differentially expressed genes. Quantitative RT-PCR, Western blotting and immunohistochemistry assay were carried out for the clinical sample validations. RESULTS: The investigation firstly displayed that young patients (≤45 years) accounted for 47.6 % (535/1125) of breast cancer, and clinically associated with some unfavorable factors related to poor prognosis, such as invasive pathological type, high tumor grade, lymph node positive, ER negative and triple-negative subtype. Subsequently, 553 significantly differentially expressed genes were identified by the data mining. Of them, a set of genes related to immune function were observed to be up-regulated in young patients with breast cancer. Impressively, the CXCL13 (C-X-C motif chemokine 13) expression level showed the most significant difference (FC = 2.64, P = 8.2 × 10(-4)). Furthermore, the validations with clinical samples and correlation analysis demonstrated that CXCL13 was indeed highly expressed in young breast cancer and closely associated with some prognostic factors including lymph node positive and ER negative. CONCLUSION: This is the first to indicate the clinical relevance of CXCL13 to young breast cancer and represents a potential therapeutic target for young breast cancer.

TGFßR2 is a major target of miR-93 in nasopharyngeal carcinoma aggressiveness.

BACKGROUND: MiR-17-92 cluster and its paralogues have emerged as crucial regulators of many oncogenes and tumor suppressors. Transforming growth factor-ß receptor II (TGFßR2), as an important tumor suppressor, is involved in various cancer types. However, it is in cancer that only two miRNAs of this cluster and its paralogues have been reported so far to regulate TGFßR2. MiR-93 is oncogenic, but its targetome in cancer has not been fully defined. The role of miR-93 in nasopharyngeal carcinoma (NPC) still remains largely unknown. METHODS: We firstly evaluated the clinical signature of TGFßR2 down-regulation in clinical samples, and next used a miRNA expression profiling analysis followed by multi-validations, including Luciferase reporter assay, to identify miRNAs targeting TGFßR2 in NPC. In vitro and in vivo studies were performed to further investigate the effects of miRNA-mediated TGFßR2 down-regulation on NPC aggressiveness. Finally, mechanism studies were conducted to explore the associated pathway and genes influenced by this miRNA-mediated TGFßR2 down-regulation. RESULTS: TGFßR2 was down-regulated in more than 50% of NPC patients. It is an unfavorable prognosis factor contributing to clinical NPC aggressiveness. A cluster set of 4 TGFßR2-associated miRNAs was identified; they are all from miR-17-92 cluster and its paralogues, of which miR-93 was one of the most significant miRNAs, directly targeting TGFßR2, promoting cell proliferation, invasion and metastasis in vitro and in vivo. Moreover, miR-93 resulted in the attenuation of Smad-dependent TGF-ß signaling and the activation of PI3K/Akt pathway by suppressing TGFßR2, further promoting NPC cell uncontrolled growth, invasion, metastasis and EMT-like process. Impressively, the knockdown of TGFßR2 by siRNA displayed a consentaneous phenocopy with the effect of miR-93 in NPC cells, supporting TGFßR2 is a major target of miR-93. Our findings were also substantiated by investigation of the clinical signatures of miR-93 and TGFßR2 in NPC. CONCLUSION: The present study reports an involvement of miR-93-mediated TGFßR2 down-regulation in NPC aggressiveness, thus giving extended insights into molecular mechanisms underlying cancer aggressiveness. Approaches aimed at blocking miR-93 may serve as a promising therapeutic strategy for treating NPC patients.

Clinical characteristics and risk factors for bacterial co-infections in COVID-19 patients: A retrospective study.

OBJECTIVE: This study aimed to analyse the bacterial composition, distribution, drug sensitivity, and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) who develop bacterial co-infections. METHODS: We conducted a retrospective study of 184 patients with COVID-19 admitted between December 2022 and January 2023. Data on gender, age, length of hospital stay, pneumonia classification, underlying diseases, invasive surgery, hormone therapy, inflammation indicators, and other relevant information were collected. Samples of sputum, bronchoscopy sputum, alveolar lavage fluid, middle urine, puncture fluid, wound secretions, and blood were collected for pathogen isolation, identification, and drug sensitivity testing. RESULTS: The majority of patients with COVID-19 with bacterial co-infection were elderly and had underlying diseases. Invasive surgery and hormone therapy were identified as risk factors for co-infections. Laboratory analysis showed reduced lymphocyte counts and elevated levels of C-reactive protein and procalcitonin. The most common pathogens in co-infections were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The detection rate of drug-resistant strains, including methicillin-resistant S. aureus, carbapenem-resistant K. pneumoniae, carbapenem-resistant A. baumannii, carbapenem-resistant P. aeruginosa, and carbapenem-resistant E. coli, increased with the severity of pneumonia. CONCLUSION: Respiratory tract infections were the most common site of bacterial co-infection in patients with COVID-19. Severe cases were more susceptible to multidrug-resistant pathogens, leading to a higher mortality rate. Timely control and prevention of co-infection are crucial for improving the prognosis of patients with COVID-19.

Accuracy of the modified tooth-supported 3D printing surgical guides based on CT, CBCT, and intraoral scanning in maxillofacial region: A comparison study.

BACKGROUND: Tooth-supported surgical guides have demonstrated superior accuracy compared with bone-supported guides. This study aimed to modify the fabrication of tooth-supported guides for compatibility with tumor resection procedures and investigate their accuracy. METHODS: Patients with tumors who underwent osteotomy with the assistance of modified tooth- or bone-supported surgical guides were included. Virtual surgical planning (VSP) was employed to align three dimensional (3D) models extracted from intraoperative computed tomography (CT) images. The distances and angular deviations between the actual osteotomy plane and preoperative plane were recorded. A comparative analysis of osteotomy discrepancies between tooth-supported and bone-supported guides, as well as among tooth-supported guides based on CT, cone-beam CT (CBCT), or intraoral scanner (IOS) was conducted. The factors influencing the precision of the guides were analyzed. RESULTS: Sixty patients with 81 resection planes were included in this study. In the tooth-supported group, the mean deviations in the osteotomy plane and angle were 1.39 mm and 4.30°, respectively, whereas those of the bone-supported group were 2.16 mm and 4.95°. In the tooth-supported isotype guide groups, the mean deviations of the osteotomy plane were 1.39 mm, 1.47 mm, 1.23 mm across CT, CBCT, and IOS, respectively. The accuracy of the modified tooth-supported guides remained consistent regardless of number and position of the teeth supporting the guide and location of the osteotomy lines. CONCLUSIONS: The findings indicate that the modified tooth-supported surgical guides demonstrated high accuracy in the maxillofacial region, contributing to a reduction in the amount of surgically detached soft tissue.

Sole brachytherapy for inoperable, recurrent, and irradiated salivary gland cancer.

BACKGROUND AND PURPOSE: Salivary gland cancers (SGCs) are hard to treat when inoperable, and sole brachytherapy appears to be a promising therapeutic strategy. This study aimed to evaluate the effectiveness, safety, and capability of pain palliation using sole brachytherapy for inoperable, recurrent, and irradiated SGCs. MATERIALS AND METHODS: Patients with inoperable SGCs treated using sole brachytherapy at Peking University School and Hospital of Stomatology were retrospectively included. Patients were divided into primary and recurrent groups and irradiated and non-irradiated groups. Local control (LC), overall survival (OS), radiation-relevant toxicities, and Visual Analogue Scale (VAS) score for pain, were recorded and evaluated. RESULTS: A total of 176 patients from 2006 to 2020 were included. The 5-year LC rate was 48.6 %; for the primary, recurrent, non-irradiated and irradiated groups, the rates were 72.6 %, 39.5 %, 56.8 %, and 34.5 %, respectively. The 5-year OS rates was 52.6 %; for the primary, recurrent, non-irradiated, and irradiated groups, the rates were 62.9 %, 48.6 %, 58.9 %, and 42.3 %, respectively. The mean ± standard deviation of posttreatment VAS score of pain was 2.154 ± 2.989, which was significantly decreased from the score of 6.923 ± 2.280 prior to brachytherapy. Skin hyperpigmentation, mucositis, and dysphagia were the most frequently reported adverse events. CONCLUSIONS: Brachytherapy as a sole modality, was retrospectively proven effective and safe in the management of inoperable SGCs and was beneficial in multiple irradiation and pain control.

Small extracellular vesicle CA1 as a promising diagnostic biomarker for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.

METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.

The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.

EBV-miR-BART1 is involved in regulating metabolism-associated genes in nasopharyngeal carcinoma.

EBV-miR-BART1 has been found to be highly expressed in some cancers including nasopharyngeal carcinoma (NPC), but its exact roles in the pathogenesis of NPC remain unclear. Here, we did RNA deep sequencing to compare the gene expression profile between EBV-miR-BART1-expressing CNE1 cells and the control cells to determine the possible effects of EBV-miR-BART1 in NPC. Gene expression profiling analysis unexpectedly showed a significant number of up- and down-modulated metabolism-associated genes, such as G6PD, SAT1, ASS1, PAST1, FUT1, SGPL1, DHRS3, B4GALT1, PHGDH, IDH2, PISD, UGT8, LDHB and GALNT1, in EBV-miR-BART1-expressing NPC cells, which were next confirmed by RT-qPCR. Moreover, of these metabolism-genes, PSAT1 and PHGDH expression levels were significantly upregulated and most of other genes were obviously up-expressed in NPC specimens compared with chronic nasopharyngitis (CNP) tissues. Collectively, we for the first time found the effects of EBV-miR-BART1 on the expression of mechanism-associated genes in NPC, suggesting a novel role of EBV-miR-BART1 in cancer metabolism, which remains to be fully elucidated.