What can we learn from ambient ionization techniques?

Ambient mass spectrometry—mass spectrometric analysis with no or minimal effort for sample preparation—has experienced a very rapid development during the last 5 years, with many different methods now available for ionization. Here, we review its range of applications, the hurdles encountered for its quantitative use, and the proposed mechanisms for ion formation. Clearly, more effort needs to be put into investigation of matrix effects, into defining representative sampling of heterogeneous materials, and into understanding and controlling the underlying ionization mechanisms. Finally, we propose a concept to reduce the number of different acronyms describing very similar embodiments of ambient mass spectrometr

Exploring fluorescence and fragmentation of ions produced by electrospray ionization in ultrahigh vacuum

Fluorescence spectroscopy and mass spectrometry have been extensively used for characterization of biomaterials, but usually separately. An instrument combining fluorescence spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS) has been developed to explore both fluorescence and mass spectrometric behavior of ions produced by electrospray ionization (ESI) in ultra high vacuum (<5 × 10−9 mbar). Using rhodamine 6G (R6G) as a sample, the instrument was systematically characterized. Gas-phase fluorescence and mass spectral signal of the same ion population are detected immediately after each other. Effects of gas pressure, ion density, and excitation laser power on the fluorescence signal intensity and mass spectral fragmentation patterns are discussed. Characteristic times of ion photodissociation in ultra high vacuum were recorded for different irradiation powers. Photofragmentation patterns of rhodamine 6G ions in the Penning trap of an FTICR spectrometer obtained by photoinduced dissociation (PID) with visible light and sustained off-resonance irradiation collision-induced dissociation (SORI-CID) were compared. The lowest energy dissociation fragment of rhodamine 6G ions was identified by relating PID patterns of rhodamine 6G and rhodamine 575 dyes at various irradiation powers. The unique instrument provides a powerful platform for probing the intramolecular relaxation mechanisms of nonsolvated ions when interacting with light, which is of great fundamental interest for better understanding of their physical and chemical propertie

Sequential Speciation Analysis of Metals in Geological Samples by Mass Spectrometry

Sequential analysis of metal speciation in geological samples has been demonstrated using mass spectrometry (MS). Various speciation for metal occurrences, such as water-soluble, exchangeable, oxidable, reducible, and crystalline, have been sequentially extracted from geological samples using a homemade device, followed by online ionized for MS analysis. The metal speciation in geological samples was not only useful for revealing the formation mechanism of geological samples but also beneficial for guiding the separation and exploitation of metals. Compared with the conventional methodology, the present approach takes the advantages of short analysis time (1 h), low sample consumption (1.0 mg), and high recovery (>95%), providing a useful platform for the efficient quantitative speciation analysis of metals in geological samples. This chapter introduces the mechanism and application of the MS approach for the analysis of rare earth minerals, dinosaur fossils, soil, etc

Sampling analytes from cheese products for fast detection using neutral desorption extractive electrospray ionization mass spectrometry

The development of analytical techniques suitable for sensitive, high-throughput, and nondestructive food analysis has been of increasing interest in recent years. In this study, mass-spectral fingerprints of various cheese products were rapidly recorded in the mass range of m/z 50-300Da without any sample pretreatment, using neutral desorption extractive electrospray ionization mass spectrometry (ND-EESI-MS) in negative ion mode. The results demonstrate that both volatile and nonvolatile analytes on greasy cheese surfaces can be directly sampled by a neutral desorption gas beam. The influence of the neutral desorption gas flow on the analyte signal was systematically investigated. Under optimized experimental conditions, reproducible results were obtained using ND-EESI-MS. Principal component analysis was applied to differentiate a total of 49 individual cheese samples (four different types), which were purchased from three different supermarkets. All samples were successfully classified according to their types; but distributors and sensory properties were not distinguishable from the spectra data. The principal components 2, 3, and 4 scores showed an excellent capacity of distinguishing types of cheese. Molecular markers of interest can be identified using tandem mass spectrometry and matching the data with those from reference compounds. The experimental data show that ND-EESI-MS is able to sensitively and directly detect analytes on greasy surfaces without chemical contamination, providing a convenient method for high-throughput food analysis with a high degree of safet

Some Rare Earth Elements Analysis by Microwave Plasma Torch Coupled with the Linear Ion Trap Mass Spectrometry

A sensitive mass spectrometric analysis method based on the microwave plasma technique is developed for the fast detection of trace rare earth elements (REEs) in aqueous solution. The plasma was produced from a microwave plasma torch (MPT) under atmospheric pressure and was used as ambient ion source of a linear ion trap mass spectrometer (LTQ). Water samples were directly pneumatically nebulized to flow into the plasma through the central tube of MPT. For some REEs, the generated composite ions were detected in both positive and negative ion modes and further characterized in tandem mass spectrometry. Under the optimized conditions, the limit of detection (LOD) was at the level 0.1 ng/mL using MS2 procedure in negative mode. A single REE analysis can be completed within 2~3 minutes with the relative standard deviation ranging between 2.4% and 21.2% (six repeated measurements) for the 5 experimental runs. Moreover, the recovery rates of these REEs are between the range of 97.6%–122.1%. Two real samples have also been analyzed, including well and orange juice. These experimental data demonstrated that this method is a useful tool for the field analysis of REEs in water and can be used as an alternative supplement of ICP-MS

Pan-cancer analysis of the prevalence and associated factors of lung metastasis and the construction of the lung metastatic classification system

This study first presents an analysis of the prevalence and associated factors of the lung metastasis (LM) database and then uses this analysis to construct an LM classification system. Using cancer patient data gathered from the surveillance, epidemiology, and end results (SEER) database, this study shows that the prevalence of LM is not consistent among different cancers; that is, the prevalence of LM ranges from 0.0013 [brain; 95% confidence interval (95% CI); 0.0010–0.0018] to 0.234 (“other digestive organs”; 95% CI; 0.221–0.249). This study finds that advanced age, poor grade, higher tumor or node stage, and metastases including bone, brain, and liver are positively related to LM occurrence, while female gender, income, marital status, and insured status are negatively related. Then, this study generates four categories from 58 cancer types based on prevalence and influence factors and satisfactorily validates these. This classification system reflects the LM risk of different cancers. It can guide individualized treatment and the management of these synchronous metastatic cancer patients and help clinicians better distribute medical resources

Simultaneous sampling of volatile and non-volatile analytes in beer for fast fingerprinting by extractive electrospray ionization mass spectrometry

By gently bubbling nitrogen gas through beer, an effervescent beverage, both volatile and non-volatile compounds can be simultaneously sampled in the form of aerosol. This allows for fast (within seconds) fingerprinting by extractive electrospray ionization mass spectrometry (EESI-MS) in both negative and positive ion mode, without the need for any sample pre-treatment such as degassing and dilution. Trace analytes such as volatile esters (e.g., ethyl acetate and isoamyl acetate), free fatty acids (e.g., caproic acid, caprylic acid, and capric acid), semi/non-volatile organic/inorganic acids (e.g., lactic acid), and various amino acids, commonly present in beer at the low parts per million or at sub-ppm levels, were detected and identified based on tandem MS data. Furthermore, the appearance of solvent cluster ions in the mass spectra gives insight into the sampling and ionization mechanisms: aerosol droplets containing semi/non-volatile substances are thought to be generated via bubble bursting at the surface of the liquid; these neutral aerosol droplets then collide with the charged primary electrospray ionization droplets, followed by analyte extraction, desolvation, ionization, and MS detection. With principal component analysis, several beer samples were successfully differentiated. Therefore, the present study successfully extends the applicability of EESI-MS to the direct analysis of complex liquid samples with high gas content. Figure By gently bubbling nitrogen gas through beer, both volatile and non-volatile compounds can be simultaneously sampled in the form of aerosol for further analysis, allowing fast chemically fingerprinting using extractive electrospray ionization mass spectrometry (EESI-MS

Relationship between occupational stress and job burnout among rural-to-urban migrant workers in Dongguan, China: a cross-sectional study

Objectives: In China, there have been an increasing number of migrant workers from rural to urban areas, and migrant workers have the highest incidence of occupational diseases. However, few studies have examined the impact of occupational stress on job burnout in these migrant workers. This study aimed to investigate the relationship between occupational stress and job burnout among migrant workers. Design: This study used a cross-sectional survey. Setting: This investigation was conducted in Dongguan city, Guangdong Province, China. Participants: 3806 migrant workers, aged 18–60 years, were randomly selected using multistage sampling procedures. Primary and secondary outcome measures: Multistage sampling procedures were used to examine demographic characteristics, behaviour customs and jobrelated data. Hierarchical linear regression and logistic regression models were constructed to explore the relationship between occupational stress and burnout. Results: Demographics, behaviour customs and jobrelated characteristics significantly affected on burnout. After adjusting for the control variable, a high level of emotional exhaustion was associated with high role overload, high role insufficiency, high role boundary, high physical environment, high psychological strain, high physical strain, low role ambiguity, low responsibility and low vocational strain. A high level of depersonalisation was associated with high role overload, high role ambiguity, high role boundary, high interpersonal strain, high recreation, low physical environment and low social support. A low level of personal accomplishment was associated with high role boundary, high role insufficiency, low responsibility, low social support, low physical environment, low self-care and low interpersonal strain. Compared to the personal resources, the job strain and personal strain were more likely to explain the burnout of rural-to-urban migrant workers in our study. Conclusions: The migrant workers have increased job burnouts in relation to occupational stress. Relieving occupational stress and maintaining an appropriate quantity and quality of work could be important measures for preventing job burnout among these workers

Prognostic value of various immune cells and Immunoscore in triple-negative breast cancer

BackgroundThis study aimed to evaluate the expression status and prognostic role of various immunoregulatory cells and test in triple-negative breast cancer (TNBC).MethodsThe expression of five markers (CD3/CD4/CD8/CD19/CD163) of tumor immune cells was evaluated retrospectively in tumor sections from 68 consecutive cases of TNBC by immunohistochemistry. Computational image analysis was used to quantify the density and distribution of each immune marker within the tumor region, tumor invasive margin, and expression hotspots. Immunoscores were calculated using an automated approach. Other clinical characteristics were also analyzed.ResultsFor all patients, Kaplan–Meier survival analysis showed that high CD3+ signals in the tumor region (disease-free survival (DFS), P=0.0014; overall survival (OS), P=0.0031) and total region (DFS, P=0.0014; OS, P=0.0031) were significantly associated with better survival. High CD4+ levels in the tumor region and total regions were significantly associated with better survival (P&lt;0.05). For Hotspot analysis, CD3+ was associated with significantly better survival for all Top1, Top2, and Top3 densities (DFS and OS, P&lt;0.05). High CD4+ levels were significantly associated with better prognosis for Top1 and Top3 densities (DFS and OS, P&lt;0.05). For stage IIB and IIIC patients, CD3+ in the tumor region and all Top hotspots was found to be significantly correlated with survival (DFS and OS, P&lt;0.05). CD4+ cells were significantly associated with survival in the tumor region, total region, and Top3 density (DFS, P=0.0213; OS, P=0.0728). CD8+ cells were significantly associated with survival in the invasive margin, Top2 density, and Top3 density. Spatial parameter analysis showed that high colocalization of tumor cells and immune cells (CD3+, CD4+, or CD8+) was significantly associated with patient survival.ConclusionComputational image analysis is a reliable tool for evaluating the density and distribution of immune regulatory cells and for calculating the Immunoscore in TNBC. The Immunoscore retains its prognostic significance in TNBC later than IIB stage breast cancer. Future studies are required to confirm its potential to predict tumor responses to chemotherapy and immune therapy

Constitutive Activation of NF-κB Pathway in Hematopoietic Stem Cells Causes Loss of Quiescence and Deregulated Transcription Factor Networks

Identifying physiological roles of specific signaling pathways that regulate hematopoietic stem cell (HSC) functions may lead to new treatment strategies and therapeutic interventions for hematologic disorders. Here, we provide genetic evidence that constitutive activation of NF-κB in HSCs results in reduced pool size, repopulation capacities, and quiescence of HSCs. Global transcriptional profiling and bioinformatics studies identified loss of ‘stemness’ and ‘quiescence’ signatures in HSCs with deregulated NF-κB activation. In particular, gene set enrichment analysis identified upregulation of cyclin dependent kinase- Ccnd1 and down regulation of cyclin dependent kinase inhibitor p57kip2. Interestingly, constitutive activation of NF-κB is sufficient to alter the regulatory circuits of transcription factors (TFs) that are critical to HSC self-renewal and functions. Molecular studies identified Junb, as one of the direct targets of NF-κB in hematopoietic cells. In essence, these studies demonstrate that aberrant activation of NF-κB signals impairs HSC quiescence and functions and alters the ‘TF networks’ in HSCs