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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.

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.

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.

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.