Tandem mass spectral (MS/MS) data in liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis are often contaminated as the selection of precursor ions is based on a low-resolution quadrupole mass filter. In this work, we developed a strategy to differentiate contamination fragment ions (CFIs) from true fragment ions (TFIs) in an MS/MS spectrum. The rationale is that TFIs should coelute with their parent ions, but CFIs should not. To assess coelution, we performed a parallel LC-MS/MS analysis in data-independent acquisition (DIA) with all-ion-fragmentation (AIF) mode. Using the DIA (AIF) data, peak–peak correlation (PPC) score is calculated between the extracted ion chromatogram (EIC) of the fragment ion using the MS/MS scans and the EIC of the precursor ion using the MS1 scans. A high PPC score is an indication of TFIs, and a low PPC score is an indication of CFIs. Tested using metabolomics data generated by high resolution QTOF and Orbitrap MS from various vendors in different LC-MS configurations, we found that more than 70% of the fragment ions have PPC scores < 0.8 and identified three common sources of CFIs, including (1) solvent contamination, (2) adjacent chemical contamination, and (3) undetermined signals from artifacts and noise. Combining PPC scores with other precursor and fragment ion information, we further developed a machine learning model that can robustly and conservatively predict CFIs. Incorporating the machine learning model, we created an R program, MS2Purifier, to automatically recognize CFIs and clean MS/MS spectra of metabolic features in LC-MS/MS data with high sensitivity and specificity.

ShenKang injection is traditional Chinese medicine used to treat chronic renal failure in China. It is a compound preparation that consists of four herbs: Rhubarb, Salvia miltiorrhiza, Safflower and Radix Astragali. We developed an ultra high pressure liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high resolution accurate mass spectrometry tandem mass spectrometry method to analyze its chemical compositions, and a total of 90 compounds were identified from ShenKang injection. Among them, 19 major compounds were unambiguously detected by comparing with reference standards. Meanwhile, 13 representative compounds selected as quality control markers were simultaneously quantified in ShenKang injection samples. Chromatographic separation was accomplished on a Waters ACQUITY HPLC® HSS C column using gradient elution. The method was validated with respect to linearity, sensitivity, accuracy and precision, reproducibility and stability. And the validated method was successfully applied for simultaneous determination of 13 bioactive compounds in ShenKang injection from ten batches of samples by liquid chromatography with mass spectrometry. The results were analyzed by principal components analysis method, and three compounds had a significant relationship with the quality control of ShenKang injection. This research established a rapid and reliable method for the integrating quality control, including qualitation and quantification of ShenKang injection.

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Mutations in the isocitrate dehydrogenase (IDH) 1 gene, especially the R132H mutation, have been reported to be associated with a better prognosis in glioma patients. However, the underlying molecular mechanisms are not yet well understood. Many factors may contribute to differences in the survival of IDH1 wild‐type and IDH1 mutant glioma patients, in which immune components play a potentially important role. In this study, we analyzed The Cancer Genome Atlas (TCGA), and the Chinese Glioma Genome Atlas (CGGA) databases, as well as glioma patient‐derived tumor samples. We found that there was a higher infiltration of natural killer (NK) cells in IDH1 mutant glioma patients, and this was correlated with a better prognosis. We also showed that IDH1‐R132 tumor cells had higher expression levels of the chemokine CX3CL1. This arises as a result of the conversion of α‐ketoglutarate to R(‐)‐2‐hydroxyglutarate by the IDH1 mutant and the resultant phosphorylation of nuclear factor kappa B. Knockdown of CX3CL1 decreased the migration of NK cells. In addition, the high levels of expression of CX3CL1 were positively correlated with glioma patient survival in the TCGA and CGGA databases, and in the clinical samples. Overall, our data have identified a novel mechanism in which R132H mutation of the IDH1 gene serves as a tumor suppressor by promoting the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis.

ing the follow-up (HR: 4.90, 95% CI: 2.75-8.74, P < 0.001). Conclusion: Baseline concentration of misfolded a-Syn aggregates in CSF measured by the PMCA technique predicts risk of cognitive decline in PD.