Extensive generation and characterization of ion clusters by silicopolyoxometalate anions under matrix-assisted laser desorption/ionization conditions in the gas phase.

RATIONALE: The research area of ion clusters has helped to enrich the study of chemical bonding theory, clarify the crystal nucleation process and investigate the cluster ion-molecule reactions. The mass spectrometry (MS) technique, especially high-resolution MS, is an important method for investigating ion clusters in the gas phase. As polyoxometalates (POMs) have been attracting considerable interest in biochemistry, medicine and materials science due to their excellent structural and electronic features it is important to characterize these clusters by MS. METHODS: Singly negatively charged molybdenum-containing and tungsten-containing ion clusters with different matrices were produced by Keggin-type silicopolyoxometalate anions under matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) conditions. RESULTS: The matrices displayed an obvious influence on the formation of ion clusters. It was found that the molybdenum-containing ion species [(HSiO3 )(MoO3 )n ]- , [(SiO2 )m (MoO3 )n (H2 O)x ] -• , [(OH)(MoO3 )n ]-• , [(MoO3 )n ]-• , and [Hx SiMoy Oz ]- were the main ion series in the mass spectra. For the tungsten-containing ion clusters, [(HSiO3 )(WO3 )n ]- , [(C8 H5 Om )(WO3 )n (H2 O)x ]- , [(OH)(WO3 )n ]- , and [(WO3 )n ]-• were the main ion species in the mass spectra, and a series of organic-inorganic hybrid tungsten-containing ion clusters [(C8 H5 Om )(WO3 )n (H2 O)x ]- were generated by the interaction of DHAP and THAP matrices with tungstate anions. Furthermore, the most abundant species (magic number) in each ion series indicated that they might adopt more stable structures than other relevant clusters. CONCLUSIONS: Keggin-type silicopolyoxometalate anions can produce several series of singly charged molybdenum-containing/tungsten-containing ion clusters in negative-ion generating mode under MALDI conditions. It is proposed that the "Lucky Survivors" hypothesis may be used to illustrate the generation of ion clusters in the gas phase during the early stages of plume expansion. In addition, clear evidence of hydrogen transfer and electron capture to POMs was found in the obtained MALDI mass spectra. These results highlight the utility of the MALDI-FT method for obtaining novel ion clusters and also show the stability of these clusters.

Metal-ion-assisted structural and anomeric analysis of Amadori compounds by electrospray ionization mass spectrometry.

RATIONALE: The Maillard reaction plays an important role in food, physiology and traditional Chinese medicine, and its primary reaction products are formed through Amadori rearrangement by reducing sugars and amino acids. The analysis of the characteristic fragmentation and of the glycosidic bond configuration of Amadori compounds will promote their fast discovery and identification by mass spectrometry. METHODS: Four Amadori compounds that reduce disaccharides and proline/tryptophan were used to investigate the fragmentation mechanisms via tandem mass spectrometry (MS/MS) with different alkali metal ion adducts. Cu2+ could be used to distinguish glycosidic bond configurations of the reducing disaccharides in the full-scan mass spectra. Quantum calculations were also conducted for a single Amadori compound with Cu2+ for analysis of the most optimized configurations and binding energies of metal complexes. RESULTS: MS/MS analysis of Amadori-alkali metal complexes revealed that the radius of the alkali metal ions had profound effects on the degree of fragmentation of such compounds, among which lithium-cationized ions produced the most extensive fragmentation. Amadori compounds with different glycosidic bonds formed differently proportioned metal complexes with Cu2+ , and the complexity of the copper complexes containing tryptophan moieties was higher than that of those containing proline moieties in the mass spectra. Quantum calculations showed that Amadori compounds with ß-configurations can form more binding sites with Cu2+ than those with α-configurations, thus making the metal complex with a single ligand more stable. In addition, the chelation of tryptophan with copper ions increased the coordination binding energy, which showed that α-configured Amadori compounds were readily able to form multi-ligand copper complexes. CONCLUSIONS: Metal-ion-assisted analysis provides crucial information for structural and anomeric analysis of Amadori compounds by electrospray ionization mass spectrometry. Elucidation of binding sites and binding energies by quantum calculations has significantly improved the knowledge of metal complexes in the gas phase and provides background information for determining the glycosidic configuration of Amadori isomers.

Dynamic changes in PSA levels predict prognostic outcomes in prostate cancer patients undergoing androgen -deprivation therapy: A multicenter retrospective analysis.

Background: Androgen-deprivation therapy (ADT) is used for the treatment of prostate cancer. However, the specific risk factors for the development of castration-resistant disease are still unclear. The present study sought to identify predictors of patient prognostic outcomes through analyses of clinical findings in large numbers of prostate cancer patients following ADT treatment. Methods: Data pertaining to 163 prostate cancer patients treated at the Second Affiliated Hospital of Bengbu Medical University and Maoming People's Hospital from January 1, 2015, to December 30, 2020, were retrospectively analyzed. Dynamic changes in prostate-specific antigen (PSA) levels were regularly assessed, including both time to nadir (TTN) and nadir PSA (nPSA). Univariate and multivariate analyses were performed with Cox risk proportional regression models, while differences in biochemical progression-free survival (bPFS) were compared among groups with Kaplan-Meier curves and log-rank tests. Results: The bPFS values over the median 43.5-month follow-up period differed significantly between patients with nPSA levels < 0.2 ng/mL and ≥ 0.2 ng/mL, being 27.6 months and 13.5 months, respectively (log-rank P < 0.001). A significant difference in median bPFS was also observed when comparing patients with a TTN ≥ 9 months (27.8 months) to those with a TTN < 9 months (13.5 months) (log-rank P < 0.001). Conclusions: TTN and nPSA are valuable predictors of prognosis in prostate cancer patients after ADT treatment, with better outcomes evident in patients with nPSA < 0.2 ng/mL and TTN > 9 months.

Dextran-based micelles for combinational chemo-photodynamic therapy of tumors via in vivo chemiluminescence.

Natural polysaccharides, represented by dextran, chitosan, and hyaluronic acid, are widely approved for use as pharmaceutical excipients and are important carrier materials for the design of advanced drug delivery systems, particularly in the field of anticancer drug delivery. The combination of stimuli-activable prodrug based chemotherapy and photodynamic therapy (PDT) has attracted increasing attention. Recent studies have verified the effectiveness of this strategy in the treatment of multiple aggressive cancers. However, in such combination, the stimuli-responsive chemotherapy and PDT have their own problems that need to be overcome. The uneven distribution of endogenous stimuli within tumor tissues makes it difficult for prodrug to be completely activated. And the inadequate tissue penetration depth of external light results in low efficiency of PDT. Aiming at these two bottlenecks, we designed a biocompatible dextran based - multi-component nanomedicine (PCL-NPs) that integrate a chemiluminescence agent luminol, a photosensitizer chlorine e6 (Ce6), and a reactive oxygen species (ROS)-activable thioketal-based paclitaxel (PTX) prodrug. The presence of overexpressed hydrogen peroxide (H2O2) inside tumor oxidizes the luminol moiety to generate in-situ light for PDT through chemiluminescence resonance energy transfer (CRET). The singlet oxygen (1O2) produced in this process not only directly kills tumor cells but also amplifies oxidative stress to accelerate the activation of PTX prodrug. We propose that the PCL-NPs have great therapeutic potential by simultaneously enhancing chemotherapy and PDT in a combination therapy.

Identification of the key genes controlling stomach adenocarcinoma stem cell characteristics via an analysis of stemness indices.

Background: In-depth research on tumors has shown that cancer stem cells (CSCs) play a crucial role in tumorigenesis. However, the mechanisms underlying the growth and maintenance of CSCs in stomach adenocarcinoma (STAD) are unclear. This study sought to investigate the expression of stem cell-related genes in STAD. Methods: We identified key genes related to STAD stem cell characteristics by combining gene expression data obtained from The Cancer Genome Atlas to define a messenger ribonucleic acid expression-based stemness index (mRNAsi) based on mRNA expression. The correlations between the mRNAsi and STAD clinical characteristics, including age, tumor grade, pathological stage, and survival status, were explored. Additionally, a weighted gene co-expression network analysis was conducted to identify relevant modules and key genes. The expression verification and functional analysis of the key genes was carried out using multiple databases, including the TIMER (https://cistrome.shinyapps.io/timer/), and Gene Expression Profiling Integrative Analysis, and Gene Expression Omnibus databases. Results: The mRNAsi score was closely related to the clinical characteristics of STAD, including age, tumor grade, pathological stage, and survival status. Similarly, the mRNAsi score was significantly higher in STAD tissues than normal tissues, and the score decreased with tumor stage. The higher the mRNAsi score, the higher the overall survival rate. We screened a module of interest and found a strong correlation between 19 key genes. Among these 19 key genes, 16 had previously been shown to be closely related to STAD survival. The functional analysis showed that these key genes were linked to cell-cycle events, such as chromosome separation, mitosis, and microtubule movement. Conclusions: We identified 19 key genes that play an important role in the maintenance of STAD stem cells. Among these genes, 16 play a role in predicting the prognosis of STAD patients. The cell-cycle pathway was the most important signaling pathway for the key genes associated with STAD stem cells. These findings may provide a new rationale for screening therapeutic targets and the characterization of STAD stem cells.

Advances in the Current Understanding of the Mechanisms Governing the Acquisition of Castration-Resistant Prostate Cancer.

Despite aggressive treatment and androgen-deprivation therapy, most prostate cancer patients ultimately develop castration-resistant prostate cancer (CRPC), which is associated with high mortality rates. However, the mechanisms governing the development of CRPC are poorly understood, and androgen receptor (AR) signaling has been shown to be important in CRPC through AR gene mutations, gene overexpression, co-regulatory factors, AR shear variants, and androgen resynthesis. A growing number of non-AR pathways have also been shown to influence the CRPC progression, including the Wnt and Hh pathways. Moreover, non-coding RNAs have been identified as important regulators of the CRPC pathogenesis. The present review provides an overview of the relevant literature pertaining to the mechanisms governing the molecular acquisition of castration resistance in prostate cancer, providing a foundation for future, targeted therapeutic efforts.

Efficacy of antidepressant drugs in the treatment of depression in Alzheimer disease patients: A systematic review and network meta-analysis.

BACKGROUND: Depression is considered as one of the most common neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) patients. Prescription of antidepressants is a current clinical practice well-established as the first-line treatment for such patients. Our study was aimed at systematically examining the evidence on the efficacy of antidepressants in the treatment of depression in AD patients. METHODS: We conducted a network meta-analysis of randomized controlled trials retrieved by systematic search of the Cochrane Central Register of Controlled Trials, PubMed, Embase, and CNKI databases. Primary outcomes included mean depression score and safety. Secondary outcomes were cognition. The surface under the cumulative ranking curve was performed to estimate a ranking probability for different treatments. RESULTS: A total of 25 studies including 14 medications met the inclusion criteria. Compared with placebo, only mirtazapine (standard mean deviation [SMD], -1.94; 95% confidence interval [CI], -3.53 to -0.36; p < 0.05) and sertraline (SMD, -1.16; 95% CI, -2.17 to -0.15; p < 0.05) showed a slightly better effect in treating symptoms of depression. Clomipramine increased risk of adverse events than placebo (odds ratio, 3.01; 95% CI, 1.45 to 4.57; p < 0.05). In terms of cognitive function, there was no statistically significant difference between antidepressants and placebo. CONCLUSION: Overall, in the short-term treatment, these data suggest that commonly used antidepressants sertraline and mirtazapine should be considered as an alternative treatment for depression in AD patients. However, more high-quality trials with large samples and longer following-up are proposed.

Retrospective study of the clinicopathological characteristics and prognosis of elderly patients with oropharyngeal squamous cell carcinoma.

OBJECTIVE: Oropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of OPSCC have been performed in elderly patients. METHODS: Patients with human papilloma virus (HPV)-related OPSCC were extracted from the Head and Neck with HPV Status Database of the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. We identified 355 patients with HPV-positive status, and we retrospectively evaluated elderly (≥65 years) and younger (30-64 years) patient groups to compare the differences. RESULTS: Of the 355 patients who were diagnosed with HPV-related OPSCC, 113 constituted the elderly group. Comparing the elderly group with the younger group, the 3-year HPV-positive overall survival (OS) rates were 62.4% and 70.2%, respectively, and the 5-year OS rates were 50.4% and 59.2%, respectively. Cox regression analysis demonstrated that tumor (T) stage and chemotherapy were prognostic factors for OS. CONCLUSION: Elderly patients with OPSCC had different clinicopathological characteristics. T stage and chemotherapy should be priorities when evaluating the OS of elderly patients with OPSCC.