Optical Nanobiosensor Based on Surface-Enhanced Raman Spectroscopy and Catalytic Hairpin Assembly for Early-Stage Lung Cancer Detection via Blood Circular RNA.

Lung cancer has become the leading cause of cancer-related deaths globally. However, early detection of lung cancer remains challenging, resulting in poor outcomes for the patients. Herein, we developed an optical biosensor integrating surface-enhanced Raman spectroscopy (SERS) with a catalyzed hairpin assembly (CHA) to detect circular RNA (circRNA) associated with tumor formation and progression (circSATB2). The signals of the Raman reporter were considerably enhanced by generating abundant SERS "hot spots" with a core-shell nanoprobe and 2D SERS substrate with calibration capabilities. This approach enabled the sensitive (limit of detection: 0.766 fM) and reliable quantitative detection of the target circRNA. Further, we used the developed biosensor to detect the circRNA in human serum samples, revealing that patients with lung cancer had higher circRNA concentrations than healthy subjects. Moreover, we characterized the unique circRNA concentration profiles of the early stages (IA and IB) and subtypes (IA1, IA2, and IA3) of lung cancer. These results demonstrate the potential of the proposed optical sensing nanoplatform as a liquid biopsy and prognostic tool for the early screening of lung cancer.

Tunable positions of Weyl nodes via magnetism and pressure in the ferromagnetic Weyl semimetal CeAlSi.

The noncentrosymmetric ferromagnetic Weyl semimetal CeAlSi with simultaneous space-inversion and time-reversal symmetry breaking provides a unique platform for exploring novel topological states. Here, by employing multiple experimental techniques, we demonstrate that ferromagnetism and pressure can serve as efficient parameters to tune the positions of Weyl nodes in CeAlSi. At ambient pressure, a magnetism-facilitated anomalous Hall/Nernst effect (AHE/ANE) is uncovered. Angle-resolved photoemission spectroscopy (ARPES) measurements demonstrated that the Weyl nodes with opposite chirality are moving away from each other upon entering the ferromagnetic phase. Under pressure, by tracing the pressure evolution of AHE and band structure, we demonstrate that pressure could also serve as a pivotal knob to tune the positions of Weyl nodes. Moreover, multiple pressure-induced phase transitions are also revealed. These findings indicate that CeAlSi provides a unique and tunable platform for exploring exotic topological physics and electron correlations, as well as catering to potential applications, such as spintronics.

High-density, spontaneous magnetic biskyrmions induced by negative thermal expansion in ferrimagnets.

Magnetic skyrmions are topologically protected quasiparticles that are promising for applications in spintronics. However, the low stability of most magnetic skyrmions leads to either a narrow temperature range in which they can exist, a low density of skyrmions, or the need for an external magnetic field, which greatly limits their wide application. In this study, high-density, spontaneous magnetic biskyrmions existing within a wide temperature range and without the need for a magnetic field were formed in ferrimagnets owing to the existence of a negative thermal expansion of the lattice. Moreover, a strong connection between the atomic-scale ferrimagnetic structure and nanoscale magnetic domains in Ho(Co,Fe)3 was revealed via in situ neutron powder diffraction and Lorentz transmission electron microscopy measurements. The critical role of the negative thermal expansion in generating biskyrmions in HoCo3 based on the magnetoelastic coupling effect is further demonstrated by comparing the behavior of HoCo2.8Fe0.2 with a positive thermal expansion.

Identification and validation of a prognostic signature of cuproptosis-related genes for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly lethal form of cancer. Cuproptosis is a recently discovered form of regulated cell death. However, its significance in ESCC remains largely unknown. In this study, we observed significant expression differences in most of the 12 cuproptosis-related genes (CRGs) in the TCGA-ESCC dataset, which was validated using GSE20347, GSE38129, and individual ESCC datasets. We were able to divide patients in the TCGA-ESCC cohort into two subgroups based on disease, and found significant differences in survivor outcomes and biological functions between these subgroups. Additionally, we identified 11 prognosis-related genes from the 12 CRGs using LASSO COX regression analysis and constructed a CRGs signature for ESCC. Patients were categorized into high- and low-risk subgroups based on their median risk score, with those in the high-risk subgroup having significantly worse overall survival than those in the low-risk subgroup. The CRGs signature was also highly accurate in predicting prognosis and survival outcomes. Univariate and multivariate Cox regression analyses revealed that 8 of the 11 CRGs were independent prognostic factors for predicting survival in ESCC patients. Furthermore, our nomogram performed well and could serve as a useful tool for predicting prognosis. Finally, our risk model was found to be relevant to the sensitivity of targeted agents and immune infiltration. Functional enrichment analysis demonstrated that the risk model was associated with biological pathways of tumor migration and invasion. In summary, our study may provide a promising prognostic signature based on CRGs and offers potential targets for personalized therapy.

Observation of Mott instability at the valence transition of f-electron system.

Mott physics plays a critical role in materials with strong electronic correlations. Mott insulator-to-metal transition can be driven by chemical doping, external pressure, temperature and gate voltage, which is often seen in transition metal oxides with 3d electrons near the Fermi energy (e.g. cuprate superconductor). In 4f-electron systems, however, the insulator-to-metal transition is mostly driven by Kondo hybridization and the Mott physics has rarely been explored in experiments. Here, by combining the angle-resolved photoemission spectroscopy and strongly correlated band structure calculations, we show that an unusual Mott instability exists in YbInCu4 accompanying its mysterious first-order valence transition. This contrasts with the prevalent Kondo picture and demonstrates that YbInCu4 is a unique platform to explore the Mott physics in Kondo lattice systems. Our work provides important insight for the understanding and manipulation of correlated quantum phenomena in the f-electron system.

Giant uniaxial negative thermal expansion in FeZr2 alloy over a wide temperature range.

Negative thermal expansion (NTE) alloys possess great practical merit as thermal offsets for positive thermal expansion due to its metallic properties. However, achieving a large NTE with a wide temperature range remains a great challenge. Herein, a metallic framework-like material FeZr2 is found to exhibit a giant uniaxial (1D) NTE with a wide temperature range (93-1078 K, [Formula: see text]). Such uniaxial NTE is the strongest in all metal-based NTE materials. The direct experimental evidence and DFT calculations reveal that the origin of giant NTE is the couple with phonons, flexible framework-like structure, and soft bonds. Interestingly, the present metallic FeZr2 excites giant 1D NTE mainly driven by high-frequency optical branches. It is unlike the NTE in traditional framework materials, which are generally dominated by low energy acoustic branches. In the present study, a giant uniaxial NTE alloy is reported, and the complex mechanism has been revealed. It is of great significance for understanding the nature of thermal expansion and guiding the regulation of thermal expansion.

The Prognostic Significance of Nomogram-Based Pretreatment Inflammatory Indicators in Patients With Esophageal Squamous Cell Carcinoma Receiving Intensity-Modulated Radiotherapy.

BACKGROUND: At present, there is no objective prognostic index available for patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiotherapy (IMRT). This study is to develop a nomogram based on hematologic inflammatory indices for ESCC patients treated with IMRT. METHODS: 581 patients with ESCC receiving definitive IMRT were enrolled in our retrospective study. Of which, 434 patients with treatment-naïve ESCC in Fujian Cancer Hospital were defined as the training cohort. Additional 147 newly diagnosed ESCC patients were used as the validation cohort. Independent predictors of overall survival (OS) were employed to establish a nomogram model. The predictive ability was evaluated by time-dependent receiver operating characteristic curves, the concordance index (C-index), net reclassification index (NRI), and integrated discrimination improvement (IDI). Decision curve analysis (DCA) was performed to assess the clinical benefits of the nomogram model. The entire series was divided into 3 risk subgroups stratified by the total nomogram scores. RESULTS: Clinical TNM staging, primary gross tumor volume, chemotherapy, neutrophil-to-lymphocyte ratio and platelet lymphocyte ratio were independent predictors of OS. Nomogram was developed incorporating these factors. Compared with the 8th American Joint Committee on Cancer (AJCC) staging, the C-index for 5-year OS (.627 and .629) and the AUC value of 5-year OS (.706 and .719) in the training and validation cohorts (respectively) were superior. Furthermore, the nomogram model presented higher NRI and IDI. DCA also demonstrated that the nomogram model provided greater clinical benefit. Finally, patients with <84.8, 84.8-151.4, and >151.4 points were categorized into low-risk, intermediate-risk, and high-risk groups. Their 5-year OS rates were 44.0%, 23.6%, and 8.9%, respectively. The C-index was .625, which was higher than the 8th AJCC staging. CONCLUSIONS: We have developed a nomogram model that enables risk-stratification of patients with ESCC receiving definitive IMRT. Our findings may serve as a reference for personalized treatment.

Development of a prognostic nomogram and risk stratification system for upper thoracic esophageal squamous cell carcinoma.

Background: The study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC). Methods: Newly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: In this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage. Conclusion: We built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians' abilities to predict individualized survival and facilitate to further stratify the management of patients at risk.

Influence of age as a continuous variable on survival outcomes and treatment options in patients with upper thoracic esophageal carcinoma.

Background: This retrospective review of patients with upper thoracic esophageal squamous cell carcinoma (ESCC) analyzed the prognostic value of age, as a continuous variable, and offered insight into treatment options. Methods: 568 upper ESCC patients underwent radical therapy between 2004 and 2016. Age as a continuous variable was entered into the Cox regression model with penalized spline (P-spline) analysis to investigate a correlation between age and survival outcomes. Results: Before adjustment, P-spline regression revealed U-shaped survival curves. Sixty years was the optimal cut-off age for differences in overall and progression-free survival (OS, PFS). The cohort was divided into age groups ≤ 50, 51-69, and ≥ 70 years. Multivariate analyses showed no significant differences in either PFS or OS for patients aged ≤ 50 and 51-69 years. After adjusting for covariates, P-spline regression showed that the risk of mortality and disease progression increased with age, and ≥ 70 years was an unfavorable independent prognostic factor. For age ≥ 70 years, the OS and PFS associated with non-surgery was comparable to that of surgery. For patients younger, the OS and PFS of patients given surgery was significantly better than that of patients given non-surgery. Conclusion: Age was an independent prognostic factor for upper ESCC. Patients ≥ 70 years achieved no significant survival benefit from surgery, but for those younger than 70 years surgery was the preferred treatment option.

Anchoring Filament Protein Ladinin-1 is an Immunosuppressive Microenvironment and Cold Tumor Correlated Prognosticator in Lung Adenocarcinoma.

Anchoring filament protein ladinin-1 (LAD1) codes for an anchor filament protein in the basement membrane. Here, we have aimed to determine its potential role in LUAD. According to the comprehensive analyses conducted in this study, we studied the expression, prognostic significance, function, methylation, copy number variations, and the immune cell infiltration of LAD1 in LUAD. A higher level of LAD1 gene expression was observed in the LUAD tumor tissues compared to the normal lung tissues (p < 0.001). Furthermore, the multivariate analysis indicated that a higher LAD1 gene expression level was the independent prognostic factor. Additionally, the DNA methylation level of the LAD1 was inversely linked to its expression (p < 0.001). We noted that the patients affected due to LAD1 hypomethylation showed a very low overall survival rate compared to the patients with a higher LAD1 methylation score (p < 0.05). Moreover, the results of the immunity analysis indicated that the LAD1 expression might be inversely linked to the immune cell infiltration degree, expression of the infiltrated immune cells, and the PD-L1 levels. Lastly, we supplemented some verification to increase the rigor of the study. The results suggested that high expression of LAD1 may be related to cold tumors. Hence, this indirectly reflects that the immunotherapy effect of LUAD patients with high LAD1 expression might be worse. Based on the role played by the LAD1 in the tumor immune microenvironment, it can be considered a potential biomarker for predicting the immunotherapy response to LUAD.

Comparative study of first-principles approaches for effective Coulomb interaction strength Ueff between localized f-electrons: Lanthanide metals as an example.

As correlation strength has a key influence on the simulation of strongly correlated materials, many approaches have been proposed to obtain the parameter using first-principles calculations. However, a comparison of the different Coulomb strengths obtained using these approaches and an investigation of the mechanisms behind them are still needed. Taking lanthanide metals as an example, we research the factors that affect the effective Coulomb interaction strength, Ueff, by local screened Coulomb correction (LSCC), linear response (LR), and constrained random-phase approximation (cRPA) in the Vienna Ab initio Simulation Package. The Ueff LSCC value increases from 4.75 to 7.78 eV, Ueff LR is almost stable at about 6.0 eV (except for Eu, Er, and Yb), and Ueff cRPA shows a two-stage decreasing trend in both light and heavy lanthanides. To investigate these differences, we establish a scheme to analyze the coexistence and competition between the orbital localization and the screening effect. We find that LSCC and cRPA are dominated by the orbital localization and the screening effect, respectively, whereas LR shows the balance of the competition between the two factors. Additionally, the performance of these approaches is influenced by different starting points from the Perdew-Burke-Ernzerhof (PBE) and PBE + U, especially for cRPA. Our results provide useful knowledge for understanding the Ueff of lanthanide materials, and similar analyses can also be used in the research of other correlation strength simulation approaches.

Shifted-excitation Raman difference spectroscopy for improving in vivo detection of nasopharyngeal carcinoma.

A strong fluorescence background is one of the common interference factors of Raman spectroscopic analysis in biological tissue. This study developed an endoscopic shifted-excitation Raman difference spectroscopy (SERDS) system for real-time in vivo detection of nasopharyngeal carcinoma (NPC) for the first time. Owing to the use of the SERDS method, the high-quality Raman signals of nasopharyngeal tissue could be well extracted and characterized from the complex raw spectra by removing the fluorescence interference signals. Significant spectral differences relating to proteins, phospholipids, glucose, and DNA were found between 42 NPC and 42 normal tissue sites. Using linear discriminant analysis, the diagnostic accuracy of SERDS for NPC detection was 100%, which was much higher than that of raw Raman spectroscopy (75.0%), showing the great potential of SERDS for improving the accurate in vivo detection of NPC.

Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer.

Immunotherapy is an effective treatment for esophageal cancer (ESCA) patients. However, there are no dependable markers for predicting prognosis and immunotherapy responses in ESCA. Our study aims to explore immune gene prognostic models and markers in ESCA as well as predictors for immunotherapy. The expression profiles of ESCA were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis was performed to construct an immune gene prognostic model. ESCA was grouped into three immune cell infiltration (ICI) clusters by CIBERSORT algorithm. The immunotherapy response of patients in different ICI score clusters was also compared. The copy number variations, somatic mutations, and single nucleotide polymorphisms were analyzed. Enrichment analyses were also performed. An immune gene prognostic model was successfully constructed. The ICI score may be used as a predictor independent of tumor mutation burden. Enrichment analyses showed that the differentially expressed genes were mostly enriched in microvillus and the KRAS and IL6/JAK/STAT3 pathways. The top eight genes with the highest mutation frequencies in ESCA were identified and all related to the prognosis of ESCA patients. Our study established an effective immune gene prognostic model and identified markers for predicting the prognosis and immunotherapy response of ESCA patients.

Prediction of Potential Biomarkers in Early-Stage Nasopharyngeal Carcinoma Based on Platelet RNA Sequencing.

Early diagnosis is essential for the treatment and prevention of nasopharyngeal cancer. However, there is a lack of effective biological indicators for nasopharyngeal carcinoma (NPC). Therefore, we explored the potential biomarkers in tumour-educated blood platelet (TEP) RNA in early NPC. Platelets were isolated from blood plasma and their RNA was extracted. High-throughput sequenced data from a total of 33 plasma samples were analysed using DESeq2 to identify the differentially expressed genes (DEGs). Subsequently, the DEGs were subjected to principal component analysis (PCA), gene ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis; and Cytoscape, TargetScan, and miRanda software were used for inferring the competing endogenous RNA network. We identified 19 long non-coding (lnc) RNAs (DElncRNAs) and 248 mRNAs (DEmRNAs) that were differentially expressed in the TEP RNA. In addition, SELP gene mRNA and lncRNAs AC092135.3, AC012358.2, AL021807.1, AP001972.5, and GPX1 were found to be down-regulated DEmRNA and DElncRNAs in the early stage of NPC. Bioinformatic analysis showed that these DEmRNAs and DElncRNAs may be involved in regulating the pathogenesis of NPC. Our research may provide new insights for exploring the biological mechanisms of NPC and early diagnosis using potential biomarkers.

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation.

This study comprehensively explored the clinical function of Aurora kinase A (AURKA) gene in nasopharyngeal carcinoma (NPC) and analyzed its potential as a therapeutic target in cancer. Data were downloaded from GEO, STRING, GTEx, and CellMiner databases, and subjected to multiple bioinformatic analyses, including differential expression analysis, WCGNA, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), miRNA-hub gene regulatory network analysis, immune cell infiltration, and drug sensitivity analysis. In-depth analysis of AURKA gene expression in NPC and its corresponding clinicopathological features was performed to explore its potential as a therapeutic target. Moreover, AURKA gene expression in NPC was validated by qRT-PCR in 21 NPC tissues and 17 normal nasopharyngeal epithelial tissues. AURKA was highly expressed in NPC tissues. Enrichment analysis of AURKA and its co-expressed hub genes indicated their oncogenic role in NPC and their potential involvement in cancer-promoting processes through histone kinase activity and microtubule motility activity, cell cycle, and p53 signaling pathways. AURKA high expression group had greater infiltration of neutrophils, macrophages M2, and dendritic cells resting and less infiltration of T cells CD4+ naïve and T cells γδ. Drug susceptibility analysis found that dacarbazine, R-306465, vorinostat, and other antitumor drugs that act on the cell cycle were closely related to AURKA. qRT-PCR verified the high expression of AURKA in NPC tissues (p < 0.05). We confirmed upregulation of AURKA in NPC tissues. Our results support an oncogenic role of AURKA in the context of NPC, and indicate its potential role as a novel therapeutic target.

Identification of clinical prognostic features of esophageal cancer based on m6A regulators.

Background: Esophageal cancer (ESCA) is a common malignancy with high morbidity and mortality. n6-methyladenosine (m6A) regulators have been widely recognized as one of the major causes of cancer development and progression. However, for ESCA, the role of regulators is unclear. The aim of this study was to investigate the role of m6A RNA methylation regulators in the immune regulation and prognosis of ESCA. Methods: RNA-seq data were downloaded using the Cancer Genome Atlas (TCGA) database, and the expression differences of m6A RNA methylation regulators in ESCA were analyzed. Further m6A methylation regulator markers were constructed, and prognostic and predictive values were assessed using survival analysis and nomograms. Patients were divided into low-risk and high-risk groups. The signature was evaluated in terms of survival, single nucleotide polymorphism (SNP), copy number variation (CNV), tumor mutation burden (TMB), and functional enrichment analysis (TMB). The m6A expression of key genes in clinical specimens was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: In ESCA tissues, most of the 23 regulators were significantly differentially expressed. LASSO regression analysis included 7 m6A-related factors (FMR1, RBMX, IGFBP1, IGFBP2, ALKBH5, RBM15B, METTL14). In addition, this study also identified that the risk model is associated with biological functions, including base metabolism, DNA repair, and mismatch repair. In this study, a nomogram was created to predict the prognosis of ESCA patients. Bioinformatics analysis of human ESCA and normal tissues was performed using qRT-PCR. Finally. Seven genetic features were found to be associated with m6A in ESCA patients. The results of this study suggest that three different clusters of m6A modifications are involved in the immune microenvironment of ESCA, providing important clues for clinical diagnosis and treatment.

Prognostic Value of SPOCD1 in Esophageal Squamous Cell Carcinoma: A Comprehensive Study Based on Bioinformatics and Validation.

In the study, we aimed to explore and analyze the potential function of SPOC Domain Containing 1 (SPOCD1) in esophageal squamous cell carcinoma (ESCC). We performed a comprehensive analysis of gene expression of SPOCD1 and its corresponding clinicopathological features in ESCC. In particular, the correlation between SPOCD1 and ESCC was evaluated using a wide range of analysis tools and databases, including TCGA, GTEx, GenePattern, CellMiner, GDSC, and STRING datasets. Different bioinformatics analyses, including differential expression analysis, mutation analysis, drug sensitivity analysis, function analysis, pathway analysis, co-expression network analysis, immune cell infiltration analysis, and survival analysis, were carried out to comprehensively explore the potential molecular mechanisms and functional effects of SPOCD1 on the initiation and progression of ESCC. The expression of SPOCD1 was upregulated in ESCC tissues compared to those in normal tissues. In the high SPOCD1 expression group, we found apparent mutations in TP53, TTN, and MUC16 genes, which were 92, 36, and 18%, respectively. GO and KEGG enrichment analysis of SPOCD1 and its co-expressed genes demonstrated that it may serve as an ESCC oncogene by regulating the genes expression in the essential functions and pathways of tumorigenesis, such as glycosaminoglycan binding, Cytokine-cytokine receptor interaction, and Ras signaling pathway. Besides, the immune cell infiltration results revealed that SPOCD1 expression was positively correlated with Macrophages M0 and Mast cells activated cells, and negatively correlated with plasma cells and T cells follicular helper cell infiltration. Finally, ESCC patients with high expression of SPOCD1 indicated poor overall survival. qRT-PCR demonstrated that the SPOCD1 expression in ESCC tissues was significantly higher than adjacent tissues (p < 0.001). Our study indicated that SPOCD1 was increased in ESCC tissues. The current data support the oncogenic role of SPOCD1 in the occurrence and development of ESCC. Most importantly, SPOCD1 might be an independent prognostic factor for ESCC patients.

Plasma Epstein-Barr Virus MicroRNA BART8-3p as a Diagnostic and Prognostic Biomarker in Nasopharyngeal Carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized. MATERIAL AND METHODS: We quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups. RESULTS: Plasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P = .001 or HR 2.74, 95% CI 1.27-5.91, P = .010), DMFS (HR 2.82, 95% CI 1.36-5.85, P = .005 or HR 3.27, 95% CI 1.57-6.81, P = .002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P = .018 or HR 2.03, 95% CI 1.14-3.62, P = .016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P = .070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis. CONCLUSION: Plasma BART8-3p is a promising biomarker for the detection and prognosis of NPC.

Activatable Nanoprobe with Aggregation-Induced Dual Fluorescence and Photoacoustic Signal Enhancement for Tumor Precision Imaging and Radiotherapy.

Owing to the high sensitivity and high spatial resolution, fluorescence (FL) imaging has been widely applied for visualizing biological processes. To gain insight into molecular events on deeper tissues, photoacoustic (PA) imaging with better deep-tissue imaging capability can be incorporated to provide complementary visualization and quantitative information on the pathological status. However, the development of activatable imaging probes to achieve both FL and PA signal amplification remains challenging because the enhancement of light absorption in PA imaging often caused the quenching of FL signal. Herein, we first developed a caspase-3 enzyme activatable nanoprobe of a nanogapped gold nanoparticle coated with AIE molecule INT20 and DEVD peptides (AuNNP@DEVD-INT20) for tumor FL and PA imaging and subsequent imaging-guided radiotherapy. The nanoprobe could interact with GSH and caspase-3 enzyme to liberate INT20 molecules, leading to AIE. Simultaneously, the in situ self-assembly of AuNPs was achieved through the cross-linking reaction between the sulfhydryl and the maleimide, resulting in ratiometric PA imaging in tumor. Remarkably, the nanoprobe can generate richful ROS for cancer radiotherapy under X-ray irradiation. The platform not only achieves the aggregation-induced FL and PA signal enhancement but also provides a general strategy for imaging of various biomarkers, eventually benefiting precise cancer therapy.