Schirmer Paper Noninvasive Microsampling for Direct Mass Spectrometry Analysis of Human Tears.

Rapid and sensitive detection of metabolites and chemical residues in human tears is highly beneficial for understanding eye health. In this study, Schirmer paper was used for noninvasive microsampling of human tears, and then paper spray mass spectrometry (PSMS) was performed for direct analysis of human tears. Schirmer PSMS was successfully used for rapid diagnosis of dry-eye syndrome by detecting the volume and metabolites of human tears. Drugs of abuse, therapeutic drugs, and pharmacodynamics in human tears were also investigated by Schirmer PSMS. Furthermore, specific markers of environmental exposures in the air to human eyes, including volatile organic compounds, aerosol, and smoke, were unambiguously sampled and detected in human tears using Schirmer PSMS. Excellent analytical performances were achieved, including single-use, low-sample consumption (1.0 µL), rapid analysis (the whole analytical procedure completed within 3 min), high sensitivity (absolute limit of detection less than or equal to 0.5 pg, signal-to-noise ratio greater than or equal to 3), good reproducibility (relative standard deviation less than 10%, n = 3), and accurate quantitation (average deviation less than 3%, n = 3). Overall, our results showed that Schirmer PSMS is a highly effective method for direct tear analysis and is expected to be a convenient tool for human tear analysis in significant clinical applications.

BaGeO3: A Mid-IR Transparent Crystal with Superstrong Raman Response.

Stimulated Raman scattering processes based on Raman crystals offer a simple and effective method to generate mid-IR lasers. However, currently available mid-IR Raman crystals are extremely scarce. Herein, a new type of mid-IR Raman crystal, BaGeO3, is reported. It crystallizes in the monoclinic space group C2/c with Ba2+ cations and [Ge3O9]6- rings as basic building units and features high transparency from 2.5 to 5.5 µm and a Raman response larger than that of diamond. The BaGeO3 crystal has 45 IR-active modes (22Au + 23Bu) and 42 Raman-active modes (20Ag + 22Bg). The wide mid-IR transparent window is attributed to the low phonon energy of the second-order IR-active Au ⊗ Bg mode. The strongest Raman band, located at 799 cm-1, arises from the symmetrically stretching vibration of the [Ge3O9]6- extra-ring Ge-O bonds. The findings provide new insights into the crystallographic and Raman spectroscopic characteristics of high-performance mid-IR Raman crystals.

Investigating distributions and changes of alkaloids in living Catharanthus roseus under low-phosphorus stress using wooden-tip electrospray ionisation mass spectrometry.

INTRODUCTION: Vinca alkaloids are important sources for producing anticancer drugs from Catharanthus roseus. The phosphorus of soil is one of crucial factors for planting C. roseus. OBJECTIVES: We aim to develop an in vivo sampling technique coupled with direct mass spectrometry with wooden tip for investigating distributions and changes of alkaloids in flowers, leaves, stems, veins and roots of living C. roseus under low-phosphorus stress. MATERIALS AND METHODS: Living C. roseus were prepared under low-phosphorus stress (n = 10) and control conditions (n = 10). Wooden-tip electrospray ionisation mass spectrometry and conventional liquid chromatography-mass spectrometry were applied to analyse living C. roseus and extracts of C. roseus, respectively. RESULTS: Distributions and changes of serpentine, vindoline, catharanthine, and anhydrovinblastine in living C. roseus under low-phosphorus stress and control conditions were successfully obtained. CONCLUSION: Compared to control soil conditions, low-phosphorus soil was found to induce C. roseus to generate more serpentine but less catharanthine and vindoline in leaves, veins, stems and roots, and to generate more anhydrovinblastine in flowers, leaves, stems and roots. Overall, our results showed a simple, rapid, and effective method for in vivo sampling and direct analysis of living plants.

Fast-switching high-voltage porous-tip electrospray ionization mass spectrometry for rapid detection of antirheumatic drugs in adulterated herbal dietary supplements.

RATIONALE: Herbal dietary supplements (HDSs) adulterated with undeclared synthetic drugs can lead to serious health problems METHODS: A fast-switching positive/negative high-voltage (+/- HV) was developed to apply on electrospray ionization mass spectrometry (ESI-MS) with porous tips for rapid screening of five antirheumatic drugs in antirheumatic HDSs. The fast-switching (switch-time: 100 ms) negative and positive ions were alternately generated to perform full-MS and tandem-MS analysis, providing an effective method for rapid detection of analytes in whichever mode of detection was most suitable (negative or positive ion mode). The use of different tips and solvents was also optimized in this work. RESULTS: The limits of detection of the five antirheumatic drugs were found to be less than 0.1 ng/g (S/N > 3). The reproducibility of the five drugs was measured to be 10.0-23.3% (n = 5). A single sample analysis could be completed within 1 min. Rapid screening of a total of 28 real HDS samples collected from the market was examined by the fast-switching HV substrate-tip ESI-MS method, and the screening result was further validated by conventional liquid chromatography/mass spectrometry. CONCLUSIONS: Overall, our results demonstrated that fast-switching HV substrate-tip ESI-MS is a rapid, reliable, and effective method for simultaneous screening of various analytes in complex samples.

Raman and Density Functional Theory Studies of Li2Mo4O13 Structures in Crystalline and Molten States.

The Li2Mo4O13 melt structure and its Raman spectral characteristics are the key for establishing the composition-structure relationship of lithium molybdate melts. In this work, Raman spectroscopy, factor group analysis, and density functional theory (DFT) were applied to investigate the structural and spectral details of the H-Li2Mo4O13 crystal and a Li2Mo4O13 melt. Factor group analysis shows that the crystal has 171 vibrational modes (84Ag + 87Au), including three acoustic modes (3Au), six librational modes (2Ag + 4Au), 21 translational modes (7Ag + 14Au), and 141 internal modes (75Ag + 66Au). All of the Ag modes are Raman-active and were assigned by the DFT method. The Li2Mo4O13 melt structure was deduced from the H-Li2Mo4O13 crystal structure and demonstrated by the DFT method. The results show that the Li2Mo4O13 melt is made up of Li+ ions and Mo4O132- groups, each of which is formed by four corner-sharing MoO3Ø/MoO2Ø2 tetrahedra (Ø = bridging oxygen). The melt has three acoustic modes (3A) and 54 optical modes (54A). All of the optical modes are Raman-active and were accurately assigned by the DFT method.

Investigation on the Structure of a LiB3O5-Li2Mo3O10 High-Temperature Solution for Understanding the Li2Mo3O10 Flux Behavior.

LiB3O5 is the most widely used nonlinear optical crystal. Li2Mo3O10 (a nominal composition) is a typical flux used to produce large-sized and high-quality LiB3O5 crystals. The structure of the LiB3O5-Li2Mo3O10 high-temperature solution is essential to understanding the flux behavior of Li2Mo3O10 but still remains unclear. In this work, high-temperature Raman spectroscopy combined with density functional theory (DFT) was applied to study the LiB3O5-Li2Mo3O10 solution structure. Raman spectra of a LiB3O5-Li4Mo5O17-Li2Mo4O13 polycrystalline mixture were recorded at different temperatures until the mixture melted completely. The solution structure was deduced from the spectral changes and verified by DFT calculations. When the mixture began to melt, its molybdate component first changed into the Li2Mo3O10 melt; meanwhile, the complicated molybdate groups existing in the crystalline state transformed into Mo3O102- groups, which are formed by three corner-sharing MoO3Ø-/MoO2Ø2 (Ø = bridging oxygen atom) tetrahedra. When LiB3O5 dissolved in the Li2Mo3O10 melt, the crystal structure collapsed into polymeric chains of [B3O4Ø2-]n. Its basic structural unit, the B3O4Ø2- ring, coordinated with the Mo3O102- group to form a MoO3·B3O4Ø2- complex and a Mo2O72- group. On the basis of the LiB3O5-Li2Mo3O10 solution structure, we discuss the LiB3O5 crystal growth mechanism and the compositional dependence of the solution viscosity.

Relatively low level of antigen-specific monocytes detected in blood from untreated tuberculosis patients using CD4+ T-cell receptor tetramers.

The in vivo kinetics of antigen-presenting cells (APCs) in patients with advanced and convalescent tuberculosis (TB) is not well characterized. In order to target Mycobacterium tuberculosis (MTB) peptides- and HLA-DR-holding monocytes and macrophages, 2 MTB peptide-specific CD4(+) T-cell receptor (TCR) tetramers eu and hu were successfully constructed. Peripheral blood (PBL) samples from inpatients with advanced pulmonary TB (PTB) were analyzed using flow cytometry, and the percentages of tetramer-bound CD14(+) monocytes ranged from 0.26-1.44% and 0.21-0.95%, respectively; significantly higher than those measured in PBL samples obtained from non-TB patients, healthy donors, and umbilical cords. These tetramers were also able to specifically detect macrophages in situ via immunofluorescent staining. The results of the continuous time-point tracking of the tetramer-positive rates in PBL samples from active PTB outpatients undergoing treatment show that the median percentages were at first low before treatment, increased to their highest levels during the first month, and then began to decrease during the second month until finally reaching and maintaining a relatively low level after 3-6 months. These results suggest that there is a relatively low level of MTB-specific monocytes in advanced and untreated patients. Further experiments show that MTB induces apoptosis in CD14(+) cells, and the percentage of apoptotic monocytes dramatically decreases after treatment. Therefore, the relatively low level of MTB-specific monocytes is probably related to the apoptosis or necrosis of APCs due to live bacteria and their growth. The bactericidal effects of anti-TB drugs, as well as other unknown factors, would induce a peak value during the first month of treatment, and a relatively low level would be subsequently reached and maintained until all of the involved factors reached equilibrium. These tetramers have diagnostic potential and can provide valuable insights into the mechanisms of antigen presentation and its relationship with TB infection and latent TB infection.

A review of sources, pathways, and toxic effects of human exposure to benzophenone ultraviolet light filters.

Benzophenone ultraviolet light filters (BPs) are high-production-volume chemicals extensively used in personal care products, leading to widespread human exposure. Given their estrogenic properties, the potential health risks associated with exposure to BPs have become a public health concern. This review aims to summarize sources and pathways of exposure to BPs and associated health risks. Dermal exposure, primarily through the use of sunscreens, constitutes a major pathway for BP exposure. At a recommended application rate, dermal exposure of BP-3 via the application of sunscreens may reach or exceed the suggested reference dose. Other exposure pathways to BPs, such as drinking water, seafood, and packaged foods, contribute minimal to the overall dose. Inhalation is a minor pathway of exposure; however, its contribution cannot be ignored. Human exposure to BPs is an order of magnitude higher in North America than in Asia and Europe. Studies conducted on laboratory animals and cells have consistently demonstrated the toxic effects of BP exposure. BPs are estrogenic and elicit reproductive and developmental toxicities. Furthermore, neurotoxicity, hepatotoxicity, nephrotoxicity, and carcinogenicity have been reported from chronic BP exposure. In addition to animal and cell studies, epidemiological investigations have identified associations between BPs and couples' fecundity and other reproductive disorders, as well as adverse birth outcomes. Further studies are urgently needed to understand the risks posed by BPs on human health.

[Detection of matrix metalloproteinase-11 in menstrual blood by enhanced chemiluminescence method].

OBJECTIVE: To explore the forensic application value of detection of matrix metalloproteinase-11 (MMP-11) in menstrual blood by enhanced chemiluminescence method. METHODS: Menstrual blood, vaginal swab, peripheral blood, saliva stain, urine stain and semen stain were collected to detect whether or not there were MMP-11 using enhanced chemiluminescence method. The specificity and reliability of the MMP-11 assay along with its sensitivity were evaluated. RESULTS: The positive detection rate of MMP-11 in menstrual blood was 89.47%, whereas no MMP-11 was found in vaginal swab, peripheral blood, saliva stain, urine stain and semen stain. When 25 microL sample was added, the mass concentration of protein was 1.329 microg/microL, then MMP-11 could be detected. A positive detection rate of 89.58% was observed in MMP-11 positive menstrual blood samples after stored at 4 degrees C for 20 months. CONCLUSION: Enhanced chemiluminescence method is sensitive and specific for detecting MMP-11, and can be applied to distinguish menstrual blood from common stain such as peripheral blood, vaginal fluid.

Temperature Distribution Simulation, Prediction and Sensitivity Analysis of Orthogonal Cutting of Cortical Bone.

Bone cutting plays an important role in spine surgical operations. The power devices with high speed employing in bone cutting usually leads to high cutting temperature of the bone tissue. This high temperature control is important in improving cutting surface quality and optimizing the cutting parameters. In this paper, the bone-cutting model was appropriately simplified for finite element (FE) based modeling of 2D orthogonal cutting to discuss the change law of cutting temperature of cortical bones for cervical vertebra, and to study the orthogonal cutting mechanism of the anisotropic cortical bone, a 3D FE simulation model had been also established in which longitudinal, vertical, and transversal cutting types were accomplished to investigate the effect of osteons orientation. Secondly, this response surface method was used to regress the simulation results, and establishes the prediction model of maximum temperature on cutting depth, cutting speed, and feed speed. Then, the Sobol method was used to analyze the sensitivity of the milling temperature prediction mathematical model parameters, in order to clarify and quantitatively analyze the influence of input milling parameters on the output milling temperature. Finally, the cutting temperatures obtained with the simulations were compared with the corresponding experimental results obtained from the bone milling tests. This study verifies the influence of key variables and the cutting parameters on thermo mechanical behavior of the bone cutting. The obtained cutting temperature distribution for the bone surfaces could be employed to establish a theoretical foundation for research on thermal damage control of bone tissues.

The association between rosacea and the condition of low tolerance to skincare of the facial skin: a case-control study in China.

BACKGROUND: Patients with rosacea often complained of low tolerance to skincare. AIM: To examine if the preexisted low tolerance to skincare is associated with rosacea the occurrence of the Chinese population. METHODS: A retrospective case-control survey of 997 rosacea cases and 1012 skin-healthy controls was carried out in China. Low tolerance to skincare was evaluated based on the history of facial skin allergic reactions related to skincare in the past 5 years before the onset of rosacea. A comparative analysis was performed between the case and control groups by the chi-square test and the logistic regression analysis. RESULTS: History of facial skin allergic reaction due to skin care products (OR = 5.110, 95% CI = 3.893-6.706) and skin care in beauty salons (OR = 3.002, 95% CI = 1.506-5.981) both presented a positive correlations with the occurrence of rosacea. Facial masks and cosmetics were two of the most common products causing facial allergic reaction. The OR values increased with the increased frequency of allergic reactions related to facial mask and cosmetics. In addition, the history of facial skin allergic reaction had a significantly associated with the severity of self-reported symptoms of rosacea including dryness, burning, stinging and itching. CONCLUSIONS: The condition of low tolerance of the facial skin to skincare was closely associated with the occurrence of rosacea.

Contactless electrospray ionization mass spectrometry for direct detection of analytes in living organisms.

In this study, we developed contactless electrospray ionization mass spectrometry (ESI-MS) for in vivo analysis of living organisms in different applications. The in vivo sampling and direct analysis processess of living organisms were integrated into an operation that only requires the organism close to MS inlet that was applied to a high voltage. Living plants and animals were directly induced to generate spray ionization. Direct detection and in vivo monitoring of metabolites and chemical residues in various living organisms were successfully demonstrated. Analysis of a single sample could be completed within 30 s. Overall, contactless ESI-MS provides an attractive in vivo method to straightforward investigation of living organisms.

Black phosphorus nanosheets and docetaxel micelles co-incorporated thermoreversible hydrogel for combination chemo-photodynamic therapy.

The platform of the combination chemo-photodynamic therapy has received widespread attention for enhancing anticancer efficacy and inhibiting tumor growth, which supports thermosensitive and controlled drug release. Here, an injectable thermoreversible hydrogel (BPNSs/DTX-M-hydrogel) co-encapsulating black phosphorus nanosheets (BPNSs) and docetaxel (DTX) micelles was prepared to increase drug accumulation in tumor tissue and improve anticancer efficacy. BPNSs were prepared by liquid exfoliation method with a simple and rapid preparation, and DTX micelles were prepared by the thin film dispersion method. Hydrogel was prepared with F127 as hydrogel matrix for intratumoral injection. BPNSs, DTX micelles, and BPNSs/DTX-M-hydrogel were characterized by particle size, morphology, stability and degradation, phase transition feature, and photodynamic performance. And the in vivo anticancer efficacy was evaluated in 4T1 tumor-bearing Balb/c mice. The results showed that the particle size of DTX micelles and BPNSs were about 16 and 180 nm, respectively. The hydrogel with the transformation temperature at near body exhibited great photodynamic efficacy and good biodegradability. Moreover, BPNSs/DTX-M-hydrogel with the combination of chemotherapy and photodynamic therapy exhibited unique anticancer efficacy with low toxicity. In conclusion, the combination platform of chemo-photodynamic therapy based on BPNSs could be a prospective strategy in antitumor research. Graphical abstract.

LncRNA LINC00974 Downregulates miR-122 to Upregulate RhoA in Oral Squamous Cell Carcinoma.

Background: LncRNA LINC00974 participates in oral fibrogenesis, indicating possible involvement in other oral diseases. Results: The authors found that LINC00974 was upregulated in oral squamous cell carcinoma (OSCC) and predicted poor survival. In OSCC tissues, LINC00974 was inversely correlated with miR-122 and positively correlated with RhoA. In OSCC cells, LINC00974 overexpression resulted in upregulated, whereas overexpression of miR-122 led to downregulated RhoA. Moreover, downregulated miR-122 was observed after LINC00974 overexpression, whereas LINC00974 expression was not significantly affected by miR-122 overexpression. In invasion and migration assay, miR-122 overexpression resulted in reduced, whereas LINC00974 and RhoA overexpression resulted in increased rate of cancer cell migration and invasion. In addition, miR-122 overexpression reduced the effects of LINC00974 overexpression. Conclusion: Therefore, LINC00974 can downregulate miR-122 to upregulate RhoA in OSCC, thereby promoting cell invasion and migration.

Direct Detection of Lysozyme in Viscous Raw Hen Egg White Binding to Sodium Dodecyl Sulfonate by Reactive Wooden-tip Electrospray Ionization Mass Spectrometry.

Direct characterization of native protein binding to ligands in raw biological samples is a challenging task, because the ligand solution might induce proteins to aggregation, flocculation and denaturation. In this work, we developed a reactive wooden-tip electrospray ionization mass spectrometry (ESI-MS) for formation and characterization of protein-ligand complexes upon rapid mixing in electrospray droplets. Raw viscous hen egg white (HEW) was directly loaded onto a wooden tip to induce spray ionization, and sodium dodecyl sulfonate (SDS) solution was directly loaded into the HEW spray by a pipette tip, and thus lysozyme-DS complexes were then formed in the electrospray droplets and were detected subsequently by mass spectrometry. The new approach was successfully applied to investigate interaction of SDS and native lysozyme in electrospray droplets of standard solution and raw egg white. Our results showed that wooden-tip ESI-MS is a promising method to form and characterize protein-ligand complexes.

[Application of ITO method and discriminant functions in full sibling and half sibling identification].

OBJECTIVE: To investigate the application of ITO method and discriminant functions method in full sibling and half sibling identification. METHODS: Five hundred pairs of full siblings (FS), 50 pairs of half siblings (HS) and 500 pairs of unrelated individuals (UR) were genotyped by PowerPlex 16 system. Full sibling index (FSI), half sibling index (HSI) and the FSI:HSI ratio were calculated with ITO method. Allelic matching of each pair of the three groups was compared. The locus numbers of no-allele sharing (x0), half-allele sharing (x1) and two-alleles sharing (x2) were calculated, respectively. The discriminant functions about full-siblings, half-siblings and unrelated individuals (UR) were established by SPSS 13.0 statistical software. RESULTS: (1) Regard FSI > or = 19 or FSI < 1 as the standard of distinguishing full sibling from unrelated individual, the alternate correct percentage was 96.4%. Regard HSI > or = 19 or HSI < 1 as the standard of distinguishing half sibling from unrelated individual, the alternate correct percentage was 85.3%. Regard FSI:HSI > or = 1 or FSI:HSI < 1 as the standard of distinguishing full sibling from half sibling, the alternate correct percentage was 87.5%. (2) Four groups of discriminant functions were established. The alternate correct percentage of these discriminant functions were 84.4%-97.7%, with the highest one in full sibship-unrelated individual group. CONCLUSION: Both ITO method and discriminant functions method are efficient in identification of full sibling or half sibling.

Detection and Seasonal Variations of Huanglongbing Disease in Navel Orange Trees Using Direct Ionization Mass Spectrometry.

Citrus greening disease [Huanglongbing (HLB)] is the most destructive disease of citrus. In this work, we have established a metabolite-based mass spectrometry (MS) method for rapid detection of HLB in navel orange trees. Without sample pretreatment, characteristic mass spectra can be directly obtained from the raw plant samples using the direct MS method. The whole detection process can be accomplished within 1 min. By monitoring and comparisons of the healthy and infected plants throughout a whole year, characteristic MS peaks of metabolites are found to be specific responses from infected plants and, thus, could be used as biomarkers for detection of HLB. Therefore, HLB could be directly detected in the asymptomatic samples, such as stems, using this metabolite-based direct MS method. In addition, principal component analysis and partial least squares discriminant analysis modes of metabolites from healthy and infected trees were established for investigating differentiation and seasonal variations of HLB in leaves, veins, and stems, providing valuable information for understanding the HLB in different seasons.

Analytical properties of electrospray ionization mass spectrometry with solid substrates and nonpolar solvents.

Electrospray ionization mass spectrometry (ESI-MS) is one of the most powerful ionization techniques for characterization of analytes in various areas. Polar solvents such as methanol, water and acetonitrile are commonly used for ESI-MS analysis, while nonpolar solvents such as hexane were usually considered as non-ESI-friendly solvents. Following our recent work on observation of ESI process from solid substrates using nonpolar solvents (Anal Chim Acta, 2018, 1004, 51-57), the analytical properties of ESI-MS with solid substrates and nonpolar solvents were further systematically investigated in this study. Compared to the uses of polar solvents, our results revealed that nonpolar solvents could serve as extractants for enhanced detection of low-polar analytes from complex samples, and could serve as refrigerants for rapid freezing of samples such as peptides, proteins and protein-ligand complexes. Furthermore, nonpolar solvents could be used for formation of ammonia-transition-metal acetylacetonates complexes under ambient conditions.

Comprehensive comparison of ambient mass spectrometry with desorption electrospray ionization and direct analysis in real time for direct sample analysis.

Ambient ionization mass spectrometry is a powerful analytical method for direct analysis of raw samples. Desorption electrospray ionization (DESI) and direct analysis in real time (DART) are two pioneer ambient ionization techniques and have been widely used in various fields. Despite it is a fact that the application and development of DESI and DART are gaining significant attention in analytical science, few comprehensive comparisons of DESI and DART have been made for in-depth understanding their characteristics for direct sample analysis. In this work, substituent effect on DESI and DART were systematically investigated using a serial of model molecules (i.e., tripeptides and fatty acids) that containing same molecular skeleton and different substituents, revealing that DESI response was determined by substituent hydrophilic effect and DART response of analyte was determined by substituent steric effect. Furthermore, matrix effects on DESI and DART were compared by detecting same analyte in different matrices, revealing respective characteristics of DESI and DART for direct sample analysis. Moreover, DESI and DART also were further compared for detecting same samples, including thermostable, thermally unstable, small and larger molecules, demonstrating complementation of DESI and DART to obtain comprehensive information of raw samples for different purposes in real-world applications. Overall, our results provided new insights into the mechanisms and applications of ambient MS with DESI and DART.

Vibrating tip spray ionization mass spectrometry for direct sample analysis.

In this work, a vibrating tip spray ionization source was developed for direct mass spectrometric analysis of raw samples under voltage-free condition. A solid tip was mounted on a vibrator, and the solid tip was placed on the front of MS inlet. Liquid, viscous, and bulk solid samples could be directly loaded on the tip-end surface, and then a drop of solvent at microliter level was subsequently loaded on the tip for dissolution and extraction of analytes, and a vibrator was then started to atomize and ionize the analytes under ambient condition. We demonstrated vibrating tip spray mass spectrometry in various applications, including food safety, pharmaceutical analysis, and forensic science. Furthermore, in situ analysis of biological tissues and in vivo analysis of living plants were conveniently performed, due to voltage-free. Different vibration frequencies and solvent compositions were investigated. The analytical performances, including sensitivity, reproducibility, and linear range, were investigated. The ionization process and mechanism were also discussed in this work.