Accurate and High-Resolution Particle Mass Measurement Using a Peak Filtering Algorithm.

Charge detection quadrupole ion trap mass spectrometry (CD-QIT MS) is an effective way of achieving the mass analysis of microparticles with ultrahigh mass. However, its mass accuracy and resolution are still poor. To enhance the performance of CD-QIT MS, the resolution Rpeak of each peak in the mass spectra resulting from an individual particle was assessed, and a peak filtering algorithm that can filter out particle adducts and clusters with a lower Rpeak was proposed. By using this strategy, more accurate mass information about the analyzed particles could be obtained, and the mass resolution of CD-QIT MS was improved by nearly 2-fold, which was demonstrated by using the polystyrene (PS) particle size standards and red blood cells (RBCs). Benefiting from these advantages of the peak filtering algorithm, the baseline separation and relative quantification of 3 and 4 µm PS particles were achieved. To prove the application value of this algorithm in a biological system, the mass of yeast cells harvested at different times was measured, and it was found that the mixed unbudded and budded yeast cells, which otherwise would not be differentiable, were distinguished and quantified with the algorithm.

Biofluid Metabolic Profiling for Lung Cancer Screening via Reactive Matrix-Assisted Laser Desorption Ionization Mass Spectrometry.

Lung cancer (LC) has the highest mortality rate among various cancer diseases. Developing an early screening method for LC with high classification accuracy is essential. Herein, 2-hydrazinoquinoline (2-HQ) is utilized as a dual-mode reactive matrix for metabolic fingerprint analysis and LC screening via matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Metabolites in both positive mode and negative mode can be detected using 2-HQ as the matrix, and derivative analysis of aldehyde and ketone compounds can be achieved simultaneously. Hundreds of serum and urine samples from LC patients and healthy volunteers were analyzed. Combined with machine learning, LC patients and healthy volunteers were successfully distinguished with a high area under the curve value (0.996 for blind serum samples and 0.938 for urine). The MS signal was identified for metabolic profiling, and dysregulated metabolites of the LC group were analyzed. The above results showed that this method has great potential for rapid screening of LC.

High Speed Mass Measurement of a Single Metal-Organic Framework Nanocrystal in a Paul Trap.

Mass spectrometry (MS) has emerged as an excellent tool for the characterization of metal-organic frameworks (MOFs) based on the characteristic metal ions and organic ligands. Mass measurement of intact MOF nanocrystals, however, remains a challenge for MS technology. Here, we reported the development of a probe particles based charge detection-quadrupole ion trap mass spectrometry (probe CD-QIT MS) method, where charge detection and mass measurement of a single MOF nanocrystal were achieved under the assistance of probe particles of micrometer size. As a validation of the method, the masses of a series of polystyrene (PS) size standards from 493 nm to 1.6 µm were measured with 3 µm PS particles as probes, and the measured masses were found to match well with their certified masses. Then, charge detections and mass analysis of single ZIF-8 and GOx@ZIF-8 with a size around 600 nm were achieved successfully. The method presented here demonstrates simplicity, high speed, and accuracy. Notably, it allows quantitative measurement of the amount of immobilized GOx enzyme by using the mass difference between ZIF-8 and GOx@ZIF-8. In addition, based on the determined mass, the size analysis of these MOF particles with irregular shape was carried out and demonstrated to be complementary to transmission electron microscopy (TEM).

N-Phenyl-2-naphthylamine as a Novel MALDI Matrix for Analysis and in Situ Imaging of Small Molecules.

Due to its strong ultraviolet absorption, low background interference in the small molecular range, and salt tolerance capacity, N-phenyl-2-naphthylamine (PNA) was developed as a novel matrix in the present study for analysis and imaging of small molecules by matrix-assisted laser desorption/ionization mass spectrometry time-of-fight (MALDI-TOF MS). The newly developed matrix displayed good performance in analysis of a wide range of small-molecule metabolites including free fatty acids, amino acids, peptides, antioxidants, and phospholipids. In addition, PNA-assisted LDI MS imaging of small molecules in brain tissue of rats subjected to middle cerebral artery occlusion (MCAO) revealed unique distributions and changes of 89 small-molecule metabolites including amino acids, antioxidants, free fatty acids, phospholipids, and sphingolipids in brain tissue 24 h postsurgery. Fifty-nine of the altered metabolites were identified, and all the changed metabolites were subject to relative quantitation and statistical analysis. The newly developed matrix has great potential application in the field of biomedical research.

Development of Visible-Wavelength MALDI Cell Mass Spectrometry for High-Efficiency Single-Cell Analysis.

Mass is a fundamental physical property of an individual cell, from which is revealed the cell growth, cycle, and activity. Taking advantage of cell mass spectrometry (CMS), accurate mass measurement of a charged single cell has been achieved. However, with the increasing demand for high-efficiency single-cell analysis in biology, the limited throughput and inefficient cell desorption/ionization of the CMS inevitably become important issues. To address the challenge, a state of the art visible-wavelength matrix assisted laser desorption/ionization (MALDI) CMS was developed. The employed transmission mode laser ablation and fast evaporation sample preparation enabled the visible-wavelength MALDI to be soft enough and to generate intact charged cells for mass measurement. By using resorufin as matrix, ten sorts of cells, viz., red blood cells (RBCs), Jurkat (JK), CCRF-CEM, SNU-5, BGC-803, MCF-7, L-O2, 293T, Hep G2, and A549 cells, have been successfully analyzed. It was found that the desorption/ionization efficiency of visible-wavelength MALDI was at least 3-fold higher than that of conventional laser-induced acoustic desorption (LIAD) and relevant to the suspension/adherent property of analyzed cells. Based on the measured mass, different cell types in either the individual or mixed state can be differentiated successfully.

MALDI-TOF MS imaging of metabolites with a N-(1-naphthyl) ethylenediamine dihydrochloride matrix and its application to colorectal cancer liver metastasis.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a label-free technique for identifying multiplex metabolites and determining both their distribution and relative abundance in situ. Our previous study showed that N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC) could act as a matrix for laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) detection of oligosaccharides in solution. In the present study, NEDC-assisted LDI-TOF MSI yielded many more endogenous compound peaks between m/z 60 and m/z 1600 than 9-aminoacridine (9-AA). Our results show that NEDC-assisted LDI-TOF MSI is especially well-suited for examining distributions of glycerophospholipids (GPs) in addition to low molecular weight metabolites below m/z 400. Particularly, NEDC matrix allowed the LDI-TOF MSI of glucose in animal tissue. Furthermore, NEDC-assisted LDI-TOF MSI was applied to a mouse model of colorectal cancer liver metastasis. We revealed the distinct spatio-molecular signatures of many detected compounds in tumor or tumor-bearing liver, and we found that taurine, glucose, and some GPs decreased in tumor-bearing liver as the tumor developed in liver. Importantly, we also found a glucose gradient in metastatic tumor foci for the first time, which further confirms the energy competition between tumors and liver remnant due to the Warburg effect. Our results suggest that NEDC-assisted LDI MSI provides an in situ label-free analysis of multiple glycerophospholipids and low molecular weight metabolites (including glucose) with abundant peaks and high spatial resolution. This will allow future application to in situ definition of biomarkers, signaling pathways, and disease mechanisms.

1,5-Diaminonaphthalene hydrochloride assisted laser desorption/ionization mass spectrometry imaging of small molecules in tissues following focal cerebral ischemia.

A sensitive analytical technique for visualizing small endogenous molecules simultaneously is of great significance for clearly elucidating metabolic mechanisms during pathological progression. In the present study, 1,5-naphthalenediamine (1,5-DAN) hydrochloride was prepared for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) of small molecules in liver, brain, and kidneys from mice. Furthermore, 1,5-DAN hydrochloride assisted LDI MSI of small molecules in brain tissue of rats subjected to middle cerebral artery occlusion (MCAO) was carried out to investigate the altered metabolic pathways and mechanisms underlying the development of ischemic brain damage. Our results suggested that the newly prepared matrix possessed brilliant features including low cost, strong ultraviolet absorption, high salt tolerance capacity, and fewer background signals especially in the low mass range (typically m/z < 500), which permitted us to visualize the spatial distribution of a broad range of small molecule metabolites including metal ions, amino acids, carboxylic acids, nucleotide derivatives, peptide, and lipids simultaneously. Nineteen endogenous metabolites involved in metabolic networks such as ATP metabolism, tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle, and malate-aspartate shuttle, together with metal ions and phospholipids as well as antioxidants underwent relatively obvious changes after 24 h of MCAO. The results were highly consistent with the data obtained by MRM MS analysis. These findings highlighted the promising potential of the organic salt matrix for application in the field of biomedical research.

Quantitative assessment of protein adsorption on microparticles with particle mass spectrometry.

In this paper, particle mass spectrometry (PMS), which consists of an aerodynamic desorption/ionization (AD) source, a quadrupole ion trap (QIT) mass analyzer, and a charge detector, was exploited to characterize the protein adsorption on microparticles based on the mass variations of microparticles before and after protein adsorption. This method is simple and has low sample cost. Importantly, its mass resolution is good enough to distinguish the microparticles with and without protein. For the adsorption of bovine serum albumin (BSA) on 3 µm porous poly styrene-divinylbenzene (poly S-DVB), the minimum mass increase that can be resolved by PMS corresponds to 128 fg (1.8 ng/cm(2)) or 1.17 × 10(6) BSA molecules on each poly S-DVB particle. With PMS, the adsorption process of BSA on poly S-DVB spheres was successfully characterized, and the obtained maximum adsorption capacity qm and dissociation constant Kd were consistent with that determined by the conventional depletion method. In addition, the influence of surface modification of silica particles on the enzyme immobilization was evaluated. Compared with C4 (propyldimethylsilane), C8 (octyldimethylsilane), and Ph (phenyldimethylchlorosilane), the CN (cyanoethyldimethylchlorosilane) functionalized silica particles were screened to be most beneficial for the immobilization of both lysozyme and trypsin.

Organic salt NEDC (N-naphthylethylenediamine dihydrochloride) assisted laser desorption ionization mass spectrometry for identification of metal ions in real samples.

The significance of metals in life and their epidemiological effects necessitate the development of a direct, efficient, and rapid method of analysis. The matrix assisted laser desorption/ionization technique is on the horns of a dilemma of metal analysis as the conventional matrixes have high background in the low mass range. An organic salt, NEDC (N-naphthylethylenediamine dihydrochloride), is applied as a matrix for identification of metal ions in the negative ion mode in the present work. Sixteen metal ions, Ba(2+), Ca(2+), Cd(2+), Ce(3+), Co(2+), Cu(2+), Fe(3+), Hg(2+), K(+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+), Sn(2+) and Zn(2+), in the form of their chloride-adducted clusters were systematically tested. Mass spectra can provide unambiguous identification through accurate mass-to-charge ratios and characteristic isotope patterns. Compared to ruthenium ICP standard solution, tris(2,2'-bipyridyl)dichlororuthenium(ii) (C30H24N6Cl2Ru) can form organometallic chloride adducts to discriminate from the inorganic ruthenium by this method. After evaluating the sensitivity for Ca, Cu, Mg, Mn, Pb and Zn and plotting their quantitation curves of signal intensity versus concentration, we determined magnesium concentration in lake water quantitatively to be 5.42 mg L(-1) using the standard addition method. There is no significant difference from the result obtained with ICP-OES, 5.8 mg L(-1). Human urine and blood were also detected to ascertain the multi-metal analysis ability of this strategy in complex samples. At last, we explored its applicability to tissue slice and visualized sodium and potassium distribution by mass spectrometry imaging in the normal Kunming mouse brain.

Differentiation of Chinese liquors by using ambient glow discharge ionization mass spectrometry.

Chinese liquors are often a very important part of social event in China. Driven by high profit, some illegal traders often use inferior liquors instead of the products with high quality to cheat the customer. Therefore, it is highly required to authenticate Chinese liquors. In this paper a novel method based on ambient glow discharge ionization mass spectrometry has been developed to differentiate Chinese liquors. Volatile components from liquor samples were ionized by the plasma generated by glow discharge and then detected by a commercial linear ion trap mass spectrometer. Consequently, the fingerprint mass spectra of several Chinese liquors were obtained. Combined with principal component analysis, this new method was successfully applied to differentiate different brands of Chinese liquors without any sample pretreatment. Compared with conventional methods, this novel method has the advantages of easy operation, high speed, and high efficiency, which make it a potential tool in the fields of food safety, atmosphere chemistry.

Maturity degree assessment of hospital ward system using integrated fuzzy AHP-TOPSIS model.

BACKGROUND: The hospital ward system is the core service unit of a hospital and an important aspect of hospital management. The maturity of the hospital ward system represents the level of development and improvement in ward management and services. In order to improve the quality of hospital services, it is significant to assess the maturity of the ward system. Although various assessment methods have been proposed in existing studies, there are some issues such as a single-dimensional factor system, subjectivity in qualitative factor values, and insufficient objectivity in the evaluation methods. METHODS: Therefore, based on the data collection of the factors used in the existing literature, this study made correlation analysis, determined the similarity of factors, and established a maturity assessment factor system satisfying distinctiveness and comprehensiveness. Furthermore, an evaluation method for the weights of each factor was proposed based on the fuzzy analytic hierarchy process, while taking account of the ambiguity of expert information. In addition, through the technique for order of preference by similarity to ideal solution method, an objective evaluation method for the maturity of the hospital ward system was established. Finally, a case study involving 6 hospitals in a specific location was conducted. RESULTS: There are a total of 16 factors used to assess the maturity of the hospital ward system, among which the most important is Doctor service. The maturity degree of the 6 researched hospitals are 0.4517, 0.0035, 0.4254, 0.8681, 0.6636, 0.1586, and the maturity degree of the 6 researched hospitals are II, I, II, IV, III, I. CONCLUSION: The factor system constructed in this study effectively reflected the importance of human-related factors in the development process of ward system. The evaluation results were consistent with the actual situation, demonstrating the effectiveness of the proposed method.

Nasal Alar and Scalp Metastases From Lung Carcinoma: A Case Report and Literature Review.

Both nasal alar and scalp metastases from lung carcinoma are exceedingly rare. Herein, we report a case of an elderly male smoker who had left lung carcinoma and underwent radical resection. Seven months later, masses began to appear on his nasal alar and parietal scalp which gradually increased in size. The nasal computed tomography and head magnetic resonance imaging scan revealed a dense soft tissue shadow in the right nasal alar and nasal cavity, as well as a soft tissue nodule in the middle of the parietal scalp. A biopsy was performed and immunohistochemistry suggested poorly differentiated metastatic carcinoma that was consistent with the characteristics of primary lung carcinoma and supported the diagnosis of nasal alar and scalp metastases. Then, he received a combined treatment of Albumin paclitaxel and Xindirizumab. However, he passed away 3 months later. In addition to this case, we also review the clinical features of nose and/or scalp metastases from lung carcinoma based on previously reported cases as well as this case.

Interfacial and rheological properties of long-lived foams stabilized by rice proteins complexed to transition metal ions in the presence of alkyl polyglycoside.

HYPOTHESIS: Transition-metal coordination complexes are hopeful to make advanced structural materials, since the metal-coordination bonds, unlike typical covalent bonds, can regenerate after rupture, allowing for dynamic, tunable, and reversible mechanical characteristics. Integration of metal-coordinate crosslinking in foam material has rarely been reported. EXPERIMENTS: We developed the hydrolyzed rice proteins (HRP) as the building block for amphiphilic transition-metal coordination complexes that could be used to make long-lived foams with high yield stress. Surface properties of the foaming solution were determined using equilibrium and dynamic tensiometers. Structural information of aggregates in the foaming solution was detected by small-angle X-ray scattering (SAXS) and Cryo-Tem. Visualization of liquid flow in the interfacial liquid film was studied by the reflective optical interference technique. Rheological response of liquid foam was characterized by a rheometer with amplitude-sweep and frequency-sweep modes. FINDINGS: In the presence of transition metal ions, HRP formed a mechanically strong rigid film. In the absence of transition metal ions or the addition of alkyl polyglycoside (APG), HRP was desorbed to produce a mobile film with a detergent state. The two interfacial states could be actively switched based on facile changes in bulk solution composition (metal ions or alkyl glycoside or chelating agent), and the switching between the two states led to the formation of extremely stable foam with high yield stress or the collapse of foam with a significant decrease in yield limit. The transition-metal coordination complexes adsorbed on the surface of the liquid film could increase the elastic modulus of liquid foam by more than an order of magnitude without increasing the viscosity of the foaming solution. We further revealed the origin of foam stability/instability and used other well-characterized proteins to prepare transition-metal coordination complexes to make long-lived foams. The cases described in this work illustrate the universal nature of the strategy, which in principle can be extended to many types of protein.

2,3,4,5-Tetrakis(3',4'-dihydroxylphenyl)thiophene: a new matrix for the selective analysis of low molecular weight amines and direct determination of creatinine in urine by MALDI-TOF MS.

Small organic matrixes are still the most commonly used ones in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) because of their advantages of high sensitivity, convenience, and cost-effectiveness. However, due to the matrix interference in the low mass region, the direct analysis of low molecular weight amines in complex surroundings with conventional organic matrixes remains a challenge. Here, a new Brønsted-Lowry acid compound 2,3,4,5-tetrakis(3',4'-dihydroxylphenyl)thiophene (DHPT) was designed, synthesized, and applied as a matrix for analysis of low molecular weight amines by MALDI-TOF MS. DHPT displays good selectivity in the analysis of amines without matrix-related interference and the low picomole/femtomole limit-of-detection was obtained in positive ion mode. With DHPT, the metabolites including creatinine, glycine, alloxan, allantoin, and 3-hydroxyhippuric acid in human urine were directly analyzed by MALDI-TOF MS. The identity of these metabolites was confirmed by tandem mass spectrometry. Furthermore, the urine creatinine was quantitatively determined using isotope-labeled internal standard. This DHPT-assisted LDI MS method provides a general approach for both qualitative and quantitative analysis of low molecular weight amines.

Structural characterization of synthetic polymers using thermal-assisted atmospheric pressure glow discharge mass spectrometry.

With the development of material science and the practical needs of the polymer industry, rapid characterization of synthetic polymers using mass spectrometry is of sustainable interest. Herein a new method for characterizing synthetic polymers using thermal-assisted atmospheric pressure glow discharge mass spectrometry (TA-APGD-MS) is established. After illustration of the mechanism of ion formation, typical polymer samples such as polystyrene (PS), polyoxymethylene (POM) and poly (butanediol succinate) (PBS) were directly characterized at the molecular level using TA-APGD-MS. The thermal degradation products of synthetic polymers including monomer units and/or other fragments were rapidly detected by tandem mass spectrometry, providing rich information about the chemical composition for the structural characterization of homo- and co-polymers. The result suggests that TA-APGD-MS allows direct and rapid analysis of both synthetic homo-polymers and co-polymers under ambient conditions without any sample pretreatment. This method features high throughput, high sensitivity and rich information, showing promising applications in polymer science.

Effect of static magnetic field extended supercooling preservation on beef quality.

Supercooling can preserve beef without freezing damage, whereas maintaining the supercooled state is difficult. An innovative method of static magnetic field extended supercooling (SM-ES) was proposed to maintain the non-frozen state of beef. Effect of SM-ES (-4 °C + SMF) compared with refrigerated (4 °C), slow-frozen (-4 °C) and frozen (-18 °C) treatment on beef quality was investigated. Results demonstrated that SM-ES successfully preserved beef at -4 °C without ice nucleation for 14 days. The SEM images revealed that the microstructure of slow-frozen/frozen samples was damaged due to crystallizing, while the ice nucleation was not observed in SM-ES treated beef. Compared with refrigerated, slow-frozen and frozen treatment, the drip loss of SM-ES decreased by 21.9%, 47.8% and 30.9%, respectively. The lipid oxidation degree of beef decreased following SM-ES treatment. SM-ES treatment extended the shelf-life of beef for more than 6 days compared with refrigeration while prevented its crystallizing.

[Sensitivity of new reagents for laboratory monitoring of low molecular weight heparin: an in vitro study].

OBJECTIVE: To explore the sensitivity of new activated clotting time (ACT) reagent for laboratory monitoring of low molecular weight heparin (LMWH). METHODS: Blood samples were collected from 30 healthy volunteers and different doses of LMWH (dalteparin) added. The dalteparin concentration of final blood samples was 0.1 - 1.8 U/ml. ACT and clot rate (CR) were measured with traditional reagent kaolin and new reagent magbar. Linear regression analysis was performed and a regression equation established between different dalteparin concentrations and their corresponding ACT and CR values. RESULTS: With rising dalteparin concentrations, the ACT values became gradually extended and the CR values were gradually reduced by both kaolin and magbar. Analysis of dose-response curves was obtained in vitro. And an excellent linear relationship was observed between the ACT and dalteparin concentrations for two reagents (P < 0.01). An exponential relationship was observed between the CR and dalteparin concentrations (P < 0.01). Differences in slope of regression curves of ACT were observed with the tested reagents (magbar 1097.6 s/U vs kaolin 59.3 s/U, P < 0.01). CONCLUSION: This in vitro study has shown that the sensitivity of new ACT test reagent (magbar) is good for laboratory monitoring of dalteparin. The new reagent magbar may be used for bedside monitoring of anticoagulant activity of LMWH.

[Clinical analysis and surgical discussion of juvenile ossifying fibroma in nasal root].

Objective:To analyze the clinical features of juvenile ossifying fibroma in nasal root and to compare different surgical methods. Methods:Seven cases of juvenile ossifying fibroma occurring in the nasal root were treated via surgery, 5 cases were resected under nasal endoscopy guided by Image Guidance System-based electromagnetic navigation, and 2 cases were resected by lateral nasal butterfly incision. Postoperative follow-up included endoscopy and CT scan of the sinuses. Results:The pathological results of 7 patients were consistent with juvenile ossifying fibroma. Follow-up period ranged from 6 to 45 months, and there were no recurrence or surgical complications. Conclusion:Surgery is the only effective treatment. Endoscopic sinus surgery with image navigation and lateral nasal butterfly incision resection has been deemed available. The external nasal butterfly incision has less bleeding and shorter operation time, but with mild nasal face swelling after surgery, and nasal endoscopy is a surgical method with less damage.

Collagen Family Genes Associated with Risk of Recurrence after Radiation Therapy for Vestibular Schwannoma and Pan-Cancer Analysis.

BACKGROUND: The safety of radiotherapy techniques in the treatment of vestibular schwannoma (VS) shows a high rate of tumor control with few side effects. Neuropeptide Y (NPY) may have a potential relevance to the recurrence of VS. Further research is still needed on the key genes that determine the sensitivity of VS to radiation therapy. MATERIALS AND METHODS: Transcriptional microarray data and clinical information data from VS patients were downloaded from GSE141801, and vascular-related genes associated with recurrence after radiation therapy for VS were obtained by combining information from MSigDB. Logistics regression was applied to construct a column line graph prediction model for recurrence status after radiation therapy. Pan-cancer analysis was also performed to investigate the cooccurrence of these genes in tumorigenesis. RESULTS: We identified eight VS recurrence-related genes from the GSE141801 dataset. All of these genes were highly expressed in the VS recurrence samples. Four collagen family genes (COL5A1, COL3A1, COL4A1, and COL15A1) were further screened, and a model was constructed to predict the risk of recurrence of VS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these four collagen family genes play important roles in a variety of biological functions and cellular pathways. Pan-cancer analysis further revealed that the expression of these genes was significantly heterogeneous across immune phenotypes and significantly associated with immune infiltration. Finally, Neuropeptide Y (NPY) was found to be significantly and negatively correlated with the expression of COL5A1, COL3A1, and COL4A1. CONCLUSIONS: Four collagen family genes have been identified as possible predictors of recurrence after radiation therapy for VS. Pan-cancer analysis reveals potential associations between the pathogenesis of VS and other tumorigenic factors. The relevance of NPY to VS was also revealed for the first time.