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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.

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.

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.