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Background. Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis. Telomeric repeat-binding factor 2 (TRF2) is a critical telomere protection protein. Emerging evidence indicates that TRF2 may be an essential treatment option for GC; however, the exact mechanism remains largely unknown. Objective. We aimed to explore the role of TRF2 in GC cells. The function and molecular mechanisms of TRF2 in the pathogenesis of GC were mainly discussed in this study. Methods. Relevant data from GEPIA and TCGA databases regarding TRF2 gene expression and its prognostic significance in GC samples were analyzed. Analysis of 53BP1 foci at telomeres by immunofluorescence, metaphase spreads, and telomere-specific FISH analysis was carried out to explore telomere damage and dysfunction after TRF2 depletion. CCK8 cell proliferation, trypan blue staining, and colony formation assay were performed to evaluate cell survival. Apoptosis and cell migration were determined with flow cytometry and scratch-wound healing assay, respectively. qRT-PCR and Western blotting were carried out to analyze the mRNA and protein expression levels after TRF2 depletion on apoptosis, autophagic death, and ferroptosis. Results. By searching with GEPIA and TCGA databases, the results showed that the expression levels of TRF2 were obviously elevated in the samples of GC patients, which was associated with adverse prognosis. Knockdown of TRF2 suppressed the cell growth, proliferation, and migration in GC cells, causing significant telomere dysfunction. Apoptosis, autophagic death, and ferroptosis were also triggered in this process. The pretreatment of chloroquine (autophagy inhibitor) and ferrostatin-1 (ferroptosis inhibitor) improved the survival phenotypes of GC cells. Conclusion. Our data suggest that TRF2 depletion can inhibit cell growth, proliferation, and migration through the combined action of ferroptosis, autophagic death, and apoptosis in GC cells. The results indicate that TRF2 might be used as a potential target to develop therapeutic strategies for treating GC.

Mycotoxin contamination is a globally concerned problem for food and agricultural products since it may directly or indirectly induce severe threats to human health. Sensitive and selective screening is an efficient strategy to prevent or reduce human and animal exposure to mycotoxins. However, enormous challenges exist in the determination of mycotoxins, arising from complex sample matrices, trace-level analytes, and the co-occurrence of diverse mycotoxins. Appropriate sample preparation is essential to isolate, purify, and enrich mycotoxins from complicated matrices, thus decreasing sample matrix effects and lowering detection limits. With the cross-disciplinary development, new solid-phase extraction strategies have been exploited and integrated with nanotechnology to meet the challenges of mycotoxin analysis. This review summarizes the advance and progress of solid-phase extraction techniques as the methodological solutions for mycotoxin analysis. Emphases are paid on nanomaterials fabricated as trapping media of solid-phase extraction techniques, including carbonaceous nanoparticles, metal/metal oxide-based nanoparticles, and nanoporous materials. Advantages and limitations are discussed, along with the potential prospects.

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Cell senescence is characterized by the irreversible arrest of cell proliferation and has been implicated as one of the critical causes of Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Telomere dysfunction, oxidative stress, DNA damage, senescence-associated secretory phenotype, and mitochondrial dysfunction contribute to the development of cellular senescence. Telomerase reverse transcriptase (TERT), which is the catalytic subunit of telomerase, can counteract cellular senescence with telomerase RNA template in a telomere-dependent manner. In addition, TERT has also been confirmed to exert extra-telomeric and neuroprotective roles in neurodegenerative diseases. In this review, we focus on the close relationship between cellular senescence and neurodegenerative diseases, and in particular, we elucidate the neuroprotective role of TERT in neurodegenerative diseases.

An infrared laser (808 nm) has been coupled with dielectric barrier discharge (DBD) for optical emission spectrometric determination of S and Cl in organic compounds. The use of a continuous wave IR laser with an output power of 1-2 W allows volatilization of analytes from condensed surfaces. Analytes thermally delivered to the gas phase are excited and atomized by the DBD plasma triggered by an alternative voltage of 10 kV at 25 kHz at atmospheric pressure. Direct analysis of S- and Cl-containing organics in manufactured tablets by measuring the S and Cl emissions resulted in a dynamic range of 0.5%-20% with linearities (R2) above 0.93 and limits of detection (LODs) in the μg/g level. Detection precision was examined by measuring inter-day and intra-day reproducibilities, leading to relative standard deviations (RSDs) ranging from 4.6% to 15.0%. The feasibility of LA-DBD-OES was further demonstrated with commercial pharmaceutical tablets of sulfadiazine (SDZ) and chloramphenicol (CAP). There is the potential for probing the tablet uniformity by monitoring elemental emissions of S and Cl. Quantitative results of the commercial tablets were consistent with the indication amounts and were verified by HPLC measurements. All these results suggest the proposed methodology as a promising tool for on-line analysis of solids and pharmaceutical tablets with minimal sample treatments and rapid detection respond.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with high morbidity and mortality. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, is overexpressed in most cancers including GBM. It is well known that hTERT can compensate telomere shortening to immortalize cells. However, in addition to the canonical function, hTERT has the roles beyond canonical telomere maintenance. To further understand the effects of hTERT on glioblastoma progression, we investigated the role of hTERT in regulating autophagy—a conserved pathway, by which cells deliver cellular organic material and impaired organelles to the lysosomes for degradation and recycle these cargos to produce energy under a stressful condition. Our results showed that downregulation of hTERT impaired autophagy levels by suppressing BECN1/beclin-1 and induced an increase of reactive oxygen species (ROS), which resulted in cell death ultimately. On the contrary, overexpression of BECN1 or treating cells with the antioxidant N-acetylcysteine (NAC) could restore the survival of hTERT knockdown cells. Our study will provide an additional basis of telomerase-targeting therapy for future clinical anticancer treatment.

Lasers have long been used in the field of mass spectrometric analysis for characterization of condensed matter. However, emission of neutrals upon laser irradiation surpasses the number of ions. Typically, only one in about one million analytes ejected by laser desorption/ablation is ionized, which has fueled the quest for postionization methods enabling ionization of desorbed neutrals to enhance mass spectrometric detection schemes. The development of postionization techniques can be an endeavor that integrates multiple disciplines involving photon energy transfer, electrochemistry, gas discharge, etc. The combination of lasers of different parameters and diverse ion sources has made laser desorption/ablation postionization (LD/API) a growing and lively research community, including two-step laser mass spectrometry, laser ablation atmospheric pressure photoionization mass spectrometry, and those coupled to ambient mass spectrometry. These hyphenated techniques have shown potentials in bioanalytical applications, with major inroads to be made in simultaneous location and quantification of pharmaceuticals, toxins, and metabolites in complex biomatrixes. This review is intended to provide a timely comprehensive view of the broadening bioanalytical applications of disparate LD/API techniques. We also have attempted to discuss these applications according to the classifications based on the postionization methods and to encapsulate the latest achievements in the field of LD/API by highlighting some of the very best reports in the 21st century. © 2020 John Wiley & Sons Ltd.

Background: Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2DM) have an increased incidence in modern society. Although increasing evidence has supported the close linkage between these two disorders, the inter-relational mechanisms remain to be fully elucidated. Objective: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and T2DM. Methods: We downloaded the microarray data of AD and T2DM from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis (WGCNA) to identify gene network modules related to AD and T2DM. Then, Gene Ontology (GO) and pathway enrichment analysis were performed on the common genes existing in the AD and T2DM related modules by clusterProfiler and DOSE package. Finally, we utilized the STRING database to construct the protein-protein interaction network and found out the hub genes in the network. Results: Our findings indicated that seven and four modules were the most significant with AD and T2DM, respectively. Functional enrichment analysis showed that AD and T2DM common genes were mainly enriched in signaling pathways such as circadian entrainment, phagosome, glutathione metabolism and synaptic vesicle cycle. Protein-protein interaction network construction identified 10 hub genes (CALM1, LRRK2, RBX1, SLC6A1, TXN, SNRPF, GJA1, VWF, LPL, AGT) in AD and T2DM shared genes. Conclusions: Our work identified common pathogenesis of AD and T2DM. These shared pathways might provide a novel idea for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosis and treatment of AD and T2DM.

We fabricate a high-efficient ion source for real time on-line monitoring of trace compounds in ambient air by introducing a weak longitudinal magnetic field to a micro-fabricated DC glow discharge. Mass spectrometric detection of various samples indicates that the signal intensity increases by an order of magnitude and the limit of detection can be lowered to 1/10 of the original level. This improvement results from the increasing ion transport efficiency through the magnetic confinement.

Background Emerging evidence shows the gastrointestinal microbiome might play an important role in the carcinogenesis of gastric cancer. While Helicobactor pylori has been reported to be a specific risk factor of gastric cancer, it is still controversial whether significant difference of non- H. pylori microbiota exists between gastric cancer patients and healthy control.Results In this study, we employed multiple bioinformatic databases to excavate the potential correlation between gastrointestinal microbiome and gastric cancer. The databases involved in this investigation include HMDB, STITCH, OMIM, GWAS Catalog, WebGestalt, Toppgene, GeneMANIA. In addition, the network diagrams were built by use of Cytoscape software. Notably, our results showed that 33 common genes participate in both gastrointestinal microbiome and gastric cancer. The further analysis of these common genes suggested that there was a wide array of interactions and pathways in which the correlation between gastrointestinal microbiome and gastric cancer is involved.Conclusions Our present study gives a bioinformatic insight into possible pathways in which the gastrointestinal microbiome play roles in gastric cancer. Future efforts are necessary to be paid to elicit the exact mechanisms as well as potential therapeutic targets of gastric cancer.

Aging is a biological process characterized by a progressive functional decline in tissues and organs, which eventually leads to mortality. Telomeres, the repetitive DNA repeat sequences at the end of linear eukaryotic chromosomes protecting chromosome ends from degradation and illegitimate recombination, play a crucial role in cell fate and aging. Due to the mechanism of replication, telomeres shorten as cells proliferate, which consequently contributes to cellular senescence and mitochondrial dysfunction. Cells are the basic unit of organismal structure and function, and mitochondria are the powerhouse and metabolic center of cells. Therefore, cellular senescence and mitochondrial dysfunction would result in tissue or organ degeneration and dysfunction followed by somatic aging through multiple pathways. In this review, we summarized the main mechanisms of cellular senescence, mitochondrial malfunction and aging triggered by telomere attrition. Understanding the molecular mechanisms involved in the aging process may elicit new strategies for improving health and extending lifespan.

RATIONALE Neurosteroids are important signalling molecules that modulate neuronal activity. Their low concentrations and low volatility make neurosteroid detection and quantification by ambient mass spectrometry challenging. Here we develop a reactive low-temperature plasma mass spectrometry (LTP-MS) method and demonstrate its potential for fast screening and quantification of neurosteroids in mouse brain. METHODS Ketone-based neurosteroids were analysed with the LTP-MS method. The plasma of the LTP was heated in order to improve the desorption efficiency of low-volatility neurosteroids. Methylamine with a concentration of 500 ppbv was employed as the reactive reagent. Neurosteroids in mouse brain tissue extracts were detected in 70 s with mass errors less than ±3 ppm due to coupling of the ion source with a high-performance mass spectrometer. RESULTS Reaction between neurosteroids and methylamine, seeded into the LTP gas stream, resulted in the formation of protonated methylamine-neurosteroid adducts with 5- to 100-fold abundances, compared to [M + H]+ ions detected in non-reactive LTP-MS. The lowest detectable concentrations of neurosteroid standards were in the range of ng/mL. Concentrations of neurosteroids in male and female mouse brain extracts as determined with reactive LTP-MS were on the level of ng/g, comparable to results obtained with high-performance liquid chromatography-tandem mass spectrometry. CONCLUSIONS The developed reactive LTP-MS is capable of providing sensitive identification and quantification of ketone-based neurosteroids in mouse brain extracts with minimal sample treatment, and showcases the potential of reactive LTP-MS as a tool for fast screening of neurosteroid levels in brain.

An innovative method for directly screening pesticide residues in foodstuffs was developed using ambient microfabricated glow discharge plasma (MFGDP) desorption/ionization mass spectrometry. The capability of qualitative and quantitative analysis with MFGDP–MS at atmospheric pressure on agrochemicals has been demonstrated. Nine multi-class compounds (ametryn, amitraz, buprofezin, dimethoate, diphenylamine, imazalil, isoproturon, malathion, parathion-ethyl) were examined in spiked solutions, in extracts of fruits and vegetables, and in unprocessed samples. In the standard solutions of the nine pesticides, the application of MFGDP-MS for the detection of organophosphorus, organochlorine and organonitrogen compounds was demonstrated. Limits of detection (LODs) at levels down to 0.13 ng g −1 mm −2 of the spiked extracts of tomato, green pepper, and orange (collected by “QuEChERS”) were obtained, with RSDs of 3.48–13.46%. In the direct analysis of unspiked peels and extracts of apple, celery and grapes, the residues of diphenylamine, dimethoate and malathion were successfully analyzed by tandem mass spectrometry (MS/MS). The distribution of diphenylamine in apples was obtained by scanning the various unprocessed parts of the apple piece-by-piece in depth directly. Thus, an MFGDP–MS, having a small size and operating at a low temperature, made it possible to directly and accurately screen for pesticide residues in fruits and vegetables in situ .

Microwave induced plasma desorption/ionization (MIPDI) mass spectrometry is a promising tool for on-line analysis of various samples without pre-treatment at atmospheric pressure. Since the first report of the MIPDI source by our group, a related instrument is emerging. Other than the advantages of any existing ambient ion source, this newly emerging ambient desorption/ionization source has unique characteristics when compared with traditional ambient pressure ionization (API) and plasma based desorption ion sources. In the work described herein, preservatives for cosmetics were chosen as sample molecules in a systematic study of the characteristics of the MIPDI source because of their variety. Description of the ionization process of the MIPDI source is given. The background spectra of reagent ions and interference ions were observed. The basic operational parameters including flow rate and microwave forward power were optimized. The mass spectrum specificities of the MIPDI source were exhibited and explained for their possible formation routes. Thermal effects were investigated by comparing the composition ratio of fragment ions in the spectra under different microwave forward powers. The desorption efficiency, related to the thermal effect, was explored. For the first time, a molecule having a quaternary ammonium functionality was successfully detected without any auxiliary agents or devices by using a desorption/ionization source. Also for the first time, a direct comparison of the fragmentation features of MIPDI spectra and EI spectra was made. It was concluded that MIPDI is a hard-soft ion source which provides a considerable population of fragment ions as well as relative stable molecular ions.

Organic UV filters in personal care products (PCPs) have been persistently reported as a potential threat to human health. In order to guarantee consumers ’ safety, the dose of these compounds in PCPs needs to be monitored. Here, a methodology based on reactive low temperature plasma ionization (LTP) mass spectrometry (MS) has been developed for the determination of common organic UV filters in PCPs including benzophenone-3, ethylhexyl dimethyl p-aminobenzoic acid, ethylhexyl methoxycinnamate, 4-methylbenzylidene camphor, octocrylene, and ethylhexyl salicylate. The experiments were carried out in transmission geometry where the LTP ion source, samples loaded on a stainless steel mesh, and the MS inlet were aligned coaxially. Four chemicals, ammonia, ammonium formate, aniline, and methylamine were considered as reactive additives allowing reactions with the UV filters through different mechanisms. Methylamine-induced reactive LTP-MS showed the most prominent improvement on the detection of UV filter compounds. Compared to direct LTP-MS, the developed method improved the detection limits of UV filters more than 10 fold. Moreover, the method enabled fast semi-quantitative screening of UV filters in authentic PCPs. Concentrations of active ingredients in eight authentic PCPs as determined with reactive LTP-MS were found comparable to values offered by the cosmetic companies and corresponding HPLC data. The methodology provides high throughput analysis (70 s per sample) and sensitive identification of organic UV filters. Lowest detectable concentrations ranged from 0.13 µg/g for 4-methylbenzylidene camphor to 7.67 µg/g for octocrylene in spiked cream. In addition, it shows the potential to be used as a screening tool for legal authentications of these chemicals in the future due to its semi-quantitative determination of UV filters in PCPs without tedious sample preparation and time-consuming chromatographic separation.

The development of ambient desorption/ionization mass spectrometry fuels the boom of mass spectrometry science. As an important branch of ambient MS, plasma-based ambient MS techniques have recently received much attention from fields of academy, instrument manufacturing, chemical and biological analysis, due to the features of non-sample pretreatment, solvent-free, high sensitivity, high throughput, real-time on-line detection, etc. In this review, the domestic research progress in plasma-based ambient mass spectrometry from the perspectives of types of the ion source, principles, and applications are summarized. Also discussed herein are the limits and developments of the plasma-based ambient MS ion sources. In this paper, we emphasis on sources based on microwave, micro-glow discharge and corona beam.

Plasma-based ambient mass spectrometry is emerging as a frontier technology for direct analysis of sample that employs low-energy plasma as the ionization reagent. The versatile sources of ambient mass spectrometry (MS) can be classified according to the plasma formation approaches; namely, corona discharge, glow discharge, dielectric barrier discharge, and microwave-induced discharge. These techniques allow pretreatment-free detection of samples, ranging from biological materials (e.g., flies, bacteria, plants, tissues, peptides, metabolites, and lipids) to pharmaceuticals, food-stuffs, polymers, chemical warfare reagents, and daily-use chemicals. In most cases, plasma-based ambient MS performs well as a qualitative tool and as an analyzer for semi-quantitation. Herein, we provide an overview of the key concepts, mechanisms, and applications of plasma-based ambient MS techniques, and discuss the challenges and outlook.

A novel ambient ionization technique for mass spectrometry, microfabricated glow discharge plasma (MFGDP), is reported. This device is made of a millimeter-sized ceramic cavity with two platinum electrodes positioned face-to-face. He or Ar plasma can be generated by a direct current voltage of several hundreds of volts requiring a total power below 4 W. The thermal plume temperature of the He plasma was measured and found to be between 25 and 80 °C at a normal discharge current. Gaseous, liquid, creamy, and solid samples with molecular weights up to 1.5 kDa could be examined in both positive and negative mode, giving limits of detection (LOD) at or below the fg/mm(2) level. The relative standard deviation (RSD) of manual sampling ranged from 10% to ~20%, while correlation coefficients of the working curve (R(2)) are all above 0.98 with the addition of internal standards. The ionization mechanisms are examed via both optical and mass spectrometry. Due to the low temperature characteristics of the microplasma, nonthermal momentum desorption is considered to dominate the desorption process.

A low power micro-plasma device was designed, constructed and evaluated for nonmetal detection, particularly for the direct measurement of phosphorus and sulfur. The device employed an open discharge chamber to generate an argon plasma discharge at atmospheric pressure of about 2 watts power and 150 nL volume for elemental excitation and molecular fragmentation. The emission light from the miroplasma source was collected and coupled to a palm-sized spectrometer through an optical fiber for spectral measurement. The characteristics of the low power micro-nano-plasma discharge, such as relationship of voltage–current, were studied to optimize discharge parameters. Two spectral lines of 253.6 nm and 469.4 nm were used for detection of phosphorus and sulfur, respectively. The stability of the low power micro-plasma device was quantitatively evaluated, and the analytical figures of merit for nonmetal detection were reported. The detection limits are 68 ppbv for phosphorus, and 1.0 ppmv for sulfur, respectively. The sensitivities of the device for nonmetal detection are comparable with those of conventional methods. However, our device provides significant advantages of small size, low power, low cost, and fieldable detection.

Plasma-based ambient mass spectrometry is emerging as a frontier technology for direct analysis of sample that employs low-energy plasma as the ionization reagent. The versatile sources of ambient mass spectrometry (MS) can be classified according to the plasma formation approaches; namely, corona discharge, glow discharge, dielectric barrier discharge, and microwave-induced discharge. These techniques allow pretreatment-free detection of samples, ranging from biological materials (e.g., flies, bacteria, plants, tissues, peptides, metabolites, and lipids) to pharmaceuticals, food-stuffs, polymers, chemical warfare reagents, and daily-use chemicals. In most cases, plasma-based ambient MS performs well as a qualitative tool and as an analyzer for semi-quantitation. Herein, we provide an overview of the key concepts, mechanisms, and applications of plasma-based ambient MS techniques, and discuss the challenges and outlook.

A low-power, portable dc microplasma source has been developed for use in molecular emission spectrometry. The device employs a 450 nL plasma chamber in which an atmospheric pressure dc glow discharge is generated with argon gas. The discharge ignites spontaneously when the system is operated at dc input power of 0.95–6.5 W and gas flows of 100–2500 mL min−1. Two sample introduction modes are used to enable direct analysis of gaseous and liquid samples. The detection of volatile organic compounds was achievable via the emissions from CN at 387.15 nm, CH at 431.41 nm and C2 at 516.53 nm. Under the optimized experimental conditions, the limit of detection (LOD) down to ppb (v/v) level can be achieved. These detection limits are competitive to or better than those of other microfabricated plasma devices. More importantly, the effect of organic compound structure on emission response is systematically studied. It was found for the first time that the ratio of C2/CH emission is closely associated with the ratio of hydrogen to carbon atoms (H/C) in a molecule, which might be potentially used for direct semi-qualitative analysis of organics. The dc microplasma detector possesses the advantages of simple construction, high sensitivity, low power consumption, long lifetime, and potential for portability in mass reduction and instrumentation.