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Additional file 1: sTable 1. Clinical characteristics of patients in the development and validation cohorts. sTable 2. Distribution of pretreatment plasma EBV DNA by TNM stage (AJCC 8th edition). sTable 3. Distribution of postradiotherapy plasma EBV DNA by TNM stage (AJCC 8th edition). sTable 4. Comparison of AUC and OR of residue at different level of pretreatment EBV DNA in the development cohort (n=736). sTable 5. Comparison of AUC and OR of residue at different level of postradiotherapy EBV DNA in the development cohort (n=736). sTable 6. Pretreatment and postradiotherapy levels of EBV DNA in all patients (n=1050). sFigure 1. Kaplan-Meier curves for overall survival (A), progression-free survival (B), locoregional recurrence-free survival (C) and distant metastasis-free survival (D) in patients stratified by residual tumor type (n=190). sFigure 2. Pretreatment (A) and postradiotherapy (B) plasma EBV DNA levels by TNM stage (AJCC 8th edition) in the development cohort (n=736). sFigure 3. Kaplan-Meier curves for overall survival (A), progression-free survival (B), locoregional recurrence-free survival (C) and distant metastasis-free survival (D) in all patients stratified by pretreatment plasma EBV DNA level (n=1050). sFigure 4. Kaplan-Meier curves for overall survival (A), progression-free survival (B), locoregional recurrence-free survival (C) and distant metastasis-free survival (D) in all patients stratified by postradiotherapy plasma EBV DNA level (n=1050). sFigure 5. Comparison of six models using area under the receiver operating characteristic curve calculated for the development cohort (n=736). sFigure 6. Kaplan-Meier curves for locoregional recurrence-free survival (A) and distant metastasis-free survival (B) in development cohort stratified by predicted risk in tumor residue (n=736). sFigure 7. Kaplan-Meier curves for locoregional recurrence-free survival (A) and distant metastasis-free survival (B) in validation cohort stratified by predicted risk in tumor residue (n=314). sFigure 8. Kaplan-Meier curves for overall survival (A), progression free-survival (B), locoregional recurrence-free survival (C) and distant metastasis-free survival (D) in patients with residue from development cohort stratified by predicted risk in tumor residue (n=122). sFigure 9. Kaplan-Meier curves for overall survival (A), progression free-survival (B), locoregional recurrence-free survival (C) and distant metastasis-free survival (D) in patients with residue from validation cohort stratified by predicted risk in tumor residue (n=68).

Additional file 1: Supplementary Figure 1. Identification and distribution of lipid components. (A) Numbers of lipid species in lipid classes/subclasses detected by lipidomics analysis. Circular diagram of lipid subclass composition in non-metastatic group (B) and metastatic group (C). Supplementary Figure 2. The overlapped total ion chromatogram (TIC) of the plasma mixtures in negative and positive modes. Supplementary Table 1. Information of the instrument used in lipidomics analyses. Supplementary Table 2. Information of the reagents and internal standards used in lipidomics analyses. Supplementary Table 3. 655 unique lipids were identified and quantified. Supplementary Table 4. Baseline characteristics of patients in the training set and validation set. Supplementary Table 5. Associations of lipid species with distant metastasis-free survival (DMFS) of Nasopharyngeal carcinoma (NPC) by univariate Cox regression analysis. Only the lipid species with P value

Graphitic-phase carbon nitride (g-C

Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H

Nucleic acid nanoswitches have a status that cannot be ignored in the field of biosensing due to the excellent biocompatibility and flexibility of design. In our current research, we have constructed a new electrochemical platform based on self-assembled pH-sensitive continuous circular DNA nanoswitch for miRNA-21 detection. We elaborately designed an inside ring probe (IRP) which could form a circle when complemented with an outside ring probe (ORP). Under the weakly acidic condition, IRPs and ORPs are self-assembled into continuous annular DNA, meanwhile, the nanoswitch is activated. However, if it is not a weakly acidic environment with a pH equal to 6, these circles are separated and the nanoswitch cannot be triggered. Therefore, the biosensor doesn’t work. Only when the pH is 6, can the nanoswitch be activated. Consequently, a large number of RuHex will accumulate on the continuous annular DNA, which leads to highly sensitive detection of miRNA-21, with concentration ranged from 10–15 to 10-8 M and limit of detection down to 0.84 fM. More importantly, this nanoswitch-based biosensor can directly detect the target microRNA in human serum without pretreatment. Therefore, the proposed novel electrochemical DNA nanoswitch will have broad application prospects in biomarker detection and clinical diagnosis.

X-ray luminescence optical imaging has been recognized as a powerful technique for medical diagnosis due to its deep penetration and low auto-fluorescence in tissues. However, the low luminescence efficiency of current X-ray luminescence nanoprobes remains a major hurdle for sensitive bioimaging in practical medical applications. Here we present a new kind of energy transfer-sensitized X-ray luminescence nanoprobe (PEG-NaGd(WO

Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H

Three new mononuclear copper(II) complexes, [Cu(L2)](2+) (1), [Cu(acac)(L)](+) (2), and [Cu(acac-Cl)(L)](+) (3) (L = 2-(4-pyridine)oxazo[4,5-f]1,10-phenanthroline (4-PDOP); acac = acetylacetone; acac-Cl = 3-chloroacetylacetone), have been synthesized and characterized by elemental analysis, high resolution mass spectrometry (Q-TOF), and IR spectroscopy. Two of the complexes were structurally characterized by single-crystal X-ray diffraction techniques. Their interactions with DNA were studied by UV-vis absorption and emission spectra, viscosity, thermal melting, DNA unwinding assay and CD spectroscopy. The nucleolytic cleavage activity of the compounds was carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of an oxidant (H2O2). Active oxygen intermediates such as hydroxyl radicals and hydrogen peroxide generated in the presence of L and complexes 1-3 may act as active species for the DNA scission. The cytotoxicity of the complexes against HepG2 cancer cells was also studied.

The electrogenerated chemiluminescence (ECL) of two water-insoluble iridium(III) complexes (pq)2Ir(acac)(pq = 2-phenyl quinolone anion, acac = acetyl acetonate) and (ppy)2Ir(acac)(ppy = 2-phenylpyridine anion) in carbon nanotube (CNT)/Nafion composite films was investigated at a glassy carbon (GC) electrode. CNT and Nafion play significant roles in the iridium(III) complexes immobilization. The excellent chemical stability and electrical conductivity of CNT promote electron transfer. The experimental conditions, such as potential, pH, concentrations of CNT and various coreactants were investigated. The iridium(III) complexes modified electrode had good stability and reproducibility. In our work, the (pq)2Ir(acac)/DBAE (2-(dibutylamino)ethanol) system was used to detect the codeine, one of the many narcotics, and the detection limit was 0.05 μM (S/N = 3). This method enabled the two water-insoluble iridium(III) complexes to be used for the determination of the analyte in aqueous solution.

The photodynamic activities against Candida albicans have been evaluated for seven silicon (IV) phthalocyanines modified axially by different functional groups. The effects of the axial substituents on the spectroscopic, photochemical, cellular uptake, and photobiological properties of these silicon phthlaocyanines have been revealed. The dicationic compounds 2 and 4 , having two quaternary ammonium groups at the axial positions, exhibit the highest antifungal photocytotoxicity with an IC 90 of 61–66 μM, which can be ascribed to their high singlet oxygen quantum yield, non-aggregation nature, effective cellular uptake, and intracellular distribution pattern (localizing preferentially in the mitochondria). By comparison, compounds 2 and 4 show a higher photodynamic inactivation of C. albicans cells than methylene blue (MB), a known antifungal photosensitizer. The IC 90 values against C. albicans for 2 and 4 are ca. 8 times lower than that for MB. These results indicate that the dicationic silicon phthalocyanines 2 and 4 are interesting candidates as antifungal photosensitizers for future studies.

A sequential extraction procedure followed by HPLC–ICP-MS analysis was developed for the speciation and quantization of arsenic species in dry seafood products (DSPs). The extraction process involved three major steps, which produced respectively three As fractions: non-polar (Asnonpolar), polar (Aspolar) and inorganic arsenic species (Asinorganic). The extraction efficiency (EE%) is in the range of 87–115%. Asnonpolar is 0.6–10.2% of total arsenic in DSPs, which is served as the index of level of arsenolipid. For Aspolar and Asinorganic, a hyphenated HPLC–ICP-MS technique was established for the separation and quantification of six arsenic species including arsenobetaine (AsB), arsenocholine (AsC), arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The results indicate that AsB and AsV are the two dominate species in DSPs, while all other species are present in relatively low concentrations. The recovery efficiency of 77–02.8% could be obtained with spike recovery test in this two-steps extraction.

The effects of direct sampling and three digestion methods were investigated on the determination of arsenic in Chang liver hepatocytes after ultrasonic disintegration were investigated. The results showed that the efficiency of microwave digestion and obturator digestion was better than cold digestion and direct sampling. The day precision (present as RSD) of microwave digestion and obturator digestion were 2.1% and 1.2% the inter-day precision were 1.2% and 2.0%, respectively. The spike recovery for the total As in the sample is 95.7% - 108.1%. The As detection limits with these four sample treatment methods (including direct sampling) were 0.74 - 0.93 mu g/L. In addition, arsenic speciation in Chang liver hepatocytes was also analyzed using the hyphenated technique of high performance liquid chromatography coupled with inductively coupled plasma-mass spectrometry. The experimental results indicated that dimethylarsinic acid (DMA) and an intermediate metabolite of DMA were found lit Chang liver hepatocytes besides inorganic arsenic (As(III) and As(V)).

Inhibition and recovery of the catalytic activity of bovine serum albumin-capped gold nanoclusters (BSA-AuNCs) is observed for the first time by introduction of cysteine and Hg(2+). The prepared BSA-AuNCs possess highly intrinsic peroxidase-like activity. It can catalyze the oxidation of 3, 3, 5, 5-tetramethylbenzidine by H2O2 to produce a blue colored product. Based on this phenomenon, a new colorimetric assay for rapid, selective and sensitive detection of cysteine and Hg(2+) in aqueous solution has been demonstrated. The interaction process between target molecule and BSA-AuNCs is very fast, so that the whole test can be completed within ten minutes. Moreover, the fabricated colorimetric sensor is simple and cost-effective, without the need of nucleic acid based recognition element and complicated washing, separation and labeling process, thus holds great promise for routine analysis of cysteine and Hg(2+) in real samples.

Herein, a novel fluorescence sensor based on g-C3N4 nanosheet-MnO2 sandwich nanocomposite has been developed for rapid and selective sensing of glutathione (GSH) in aqueous solutions, as well as living cells. The graphitic-phase C3N4 (g-C3N4) nanosheet used here is a new type of carbon-based nanomaterial with high fluorescence quantum yield and high specific surface area. We demonstrate a facile one-step approach for the synthesis of a g-C3N4 nanosheet-MnO2 sandwich nanocomposite for the first time. The fluorescence of g-C3N4 nanosheet in this nanocomposite is quenched, which attributing to fluorescence resonance energy transfer (FRET) from a g-C3N4 nanosheet to the deposited MnO2. Upon the addition of GSH, MnO2 is reduced to Mn(2+), which leads to the elimination of FRET. As a result, the fluorescence of g-C3N4 nanosheet is restored. Importantly, the chemical response of the g-C3N4-MnO2 nanocomposite exhibits great selectivity toward GSH relative to other electrolytes and biomolecules. Under the optimal conditions, the detection limit of 0.2 μM for GSH in aqueous solutions can be reached. Furthermore, the g-C3N4-MnO2 nanocomposite is confirmed to be membrane-permeable and have low cytotoxicity. Moreover, we successfully apply this sensor for visualizing and monitoring change of the intracellular GSH in living cells. Moreover, the proposed sensor shows satisfying performance, such as low cost, easy preparation, rapid detection, good biocompatibility, and turn-on fluorescence response.

Multifunctional nanocomposites have the potential to integrate sensing, diagnostic, and therapeutic functions into a single nanostructure. Herein, we synthesize Fe3O4@polydopamine core-shell nanocomposites (Fe3O4@PDA NCs) through an in situ self-polymerization method. Dopamine, a melanin-like mimic of mussel adhesive proteins, can self-polymerize to form surface-adherent polydopamine (PDA) films onto a wide range of materials including Fe3O4 nanoparticles used here. In such nanocomposites, PDA provides a number of advantages, such as near-infrared absorption, high fluorescence quenching efficiency, and a surface for further functionalization with biomolecules. We demonstrate the ability of the Fe3O4@PDA NCs to act as theranostic agents for intracellular mRNA detection and multimodal imaging-guided photothermal therapy. This work would stimulate interest in the use of PDA as a useful material to construct multifunctional nanocomposites for biomedical applications.

In this work, the electrochemical catalytic properties of the topological insulator bismuth selenide (Bi₂Se₃) were first studied. In the presence of Bi₂Se₃ the reduction current of dissolved O₂ could be significantly enhanced. The electron transfer resistivity (Rct) was greatly reduced at the Bi₂Se₃-PVP modified electrode as evidenced by the electrochemical impedance spectrometry, implying that the topological insulator Bi₂Se₃ could facilitate the electron transfer at the interface due to the excellent surface conductivity. Based on the high electrochemical catalytic activity for the reduction of dissolved O₂, the Bi₂Se₃-PVP modified electrode was used to detect glucose with the modification of glucose oxidase, and applied for the detection of glucose in human blood serum.

A new method based on high performance liquid chromatography-electrospray ionization time of flight-mass spectrometry (HPLC-ESI-TOF/MS) was developed for the rapid identification of active compounds in Styela clava and the development of its specific chromatograms. Samples were extracted by ultrasonic-assisted extraction, and the extraction conditions were optimized. The developed HPLC-ESI-TOF/MS method was used to identify the components in Styela clava extract, and a specific chromatogram based on HPLC analysis was established. Ten compounds in Styela clava extract have been primary identified by HPLC-ESI-TOF/MS on-line detection combined with literature review. The result of similarity evaluation for specific chromatograms indicated that the quality of different Styela clava samples was not entirely consistent. This method has the advantages of simple operation, rapid measurement and it is a powerful tool for identification of active components in Styela clava and its quality control.

Excitation-emission matrix spectroscopy (EEMs) was applied to measure the fluorescence properties of dissolved organic matter (DOM) in seawater collected from Jiaozhou Bay in June, 2005. The study areas include central Bay area, receptor areas of Dagu River, Licun River and Haibo River. The aim was to investigate the influence of discharges from several typical rivers to the receiving seawater. Dagu River discharges mostly freshwater, while the other two rivers discharges include more wastewaters from factories and sewages treatments. The results indicate that there is a redshift of the position of humic-like fluorescence peaks due to the discharges from sewages and wastewaters from factories. The intensities of protein-like and humic-like peaks were the strongest in the samples from area near Haibo River and Licun River, while the weakest fluorescence intensities of both protein-like and humic-like were observed in the samples collected from central bay area. This suggests that river inputs are the mains sources of DOM in seawater of Jiaozhou Bay, while DOM produced by bioactivity in situ dominates those in central Bay area. The relationships of protein-like and humic-like fluorescence intensities vary depending on the water samples. The DOM in seawater of Jiaozhou Bay may be polluted by protein-like organic matter produced by human activity, as indicated by higher ratios of protein-like and humic-like fluorescence intensities. The results suggest the potential utility of EEMs technique for trace DOM and land-based pollution sources.

To develop a HPLC-DAD-ESI-TOF/MS analysis method for the determination of gentiopicroside and loganic acid in Radix gentianae samples and for the research of their fingerprints. The samples were extracted using ASE for 10 min under 100 degrees C and 9.65 MPa, and divided into water phase and chloroform phase and analyzed them with HPLC-DAD-ESI-TOF/MS method respectively. Based on this method, the HPLC fingerprints of Radix gentianae were established. Comparing the spectrogram and mass spectrum of the chromatogram peak with the reference value, three compounds in water phase were identified as gentiopicroside, asafetida acid and loganic acid. There is no report of the compounds in chloroform phase. The content of gentiopicroside and loganic acid in samples of different groups were determined, separately. The fingerprints were compared by the software of the similarity evaluation system for chromatographic fingerprint. The water phase fingerprint congruence coefficients of samples from six different areas were above 0.90, however, the chloroform phase fingerprint congruence coefficients were within 0.62 -0.99. This method can be used for determination of potent component in Radix gentianae and its quality control. Radix gentianae from different producing areas have the largest diversities, and the diversities embodied in the content of chloroform phase compounds.