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Bridging the Gap Between HPLC and Direct MS: A Novel 2DμCFs System for High-Throughput and Solvent-Saving Complex Samples Fractionation.
No full textMolecular characterization of 41 known substances and 6 compounds never detected before in Abelmoschus manihot
flowers was performed by Two-Dimensional Microscale Carbon fiber fractionation combined with quadrupole time
of flight high-resolution mass spectrometry (2DμCFs-QTOF-HRMS) [1]. The comprehensive analysis was carried out
in a single run of only 5 minutes and with a solvent consumption of 1.5 mL. Improved detection sensitivity compared
with direct flow-injection MS analyses was achieved by the process of separations into fractions of different polarity
(weak, medium, and high) before entering the mass spectrometer. The METLIN database was used to match the
accurate experimental MS and MS/MS data. The main components of the flower extracts belong to flavonoids
(quercetin, myricetin, quercetin 7-o-glucoside, hyperin, isoquercetin, quercetin 3′-o-glucoside, etc.) amino acids
(γ-aminobutyric acid, serine, proline, valine, etc.), nucleosides (adenine, cytidine, 2′- deoxyadenosine, etc.),
organic acids (5-(hydroxymethyl)-2-furancarboxylic acid, chlorogenic acid, etc.) and fatty acids (linoleic acid, oleic
acid, etc.). The presence of 6 molecules (2-pyrrolidone-5-carboxylic acid, pipecolic acid, trigonelline, glucosamine,
1-aminocyclohexane-carboxylic acid, and 1,2-dioleoyl-sn-glycero-3-phosphocholine) not previously detected in A.
manihot flower extracts was observed and confirmed by a deeper investigation based on molecular polarity and
mass spectrum fragments.
From the dried flowers of Abelmoschus manihot, Huangkui capsule (HKC), a Chinese patent medicine, is prepared and
used for the treatment of chronic kidney diseases, including diabetic nephropathy, chronic glomerulonephritis, and
membranous nephropathy [2,3]. By 2DμCFs-QTOF-HRMS, a rapid, high-throughput, and comprehensive screening
of HKC metabolites in rat plasma was carried out, achieving high sensitivity and metabolite coverage. By excluding
the m/z values of blank plasma and HKC extracts, information on HKC plasma metabolites was derived. Most of
the metabolites come from the parent hyperoside, which is the main component in HKC. Finally, a comparison was
performed between different parts of the Abelmoschus manihot plant. Principal Component Analysis (PCA) was
performed using all the results obtained for flowers, buds, and stems, providing valuable insights into the active
ingredients of the plant and creating a bridge between phytochemistry and clinical applications
Can we enhance trust in the circular economy through referral marketing control?
No full textReferral marketing can be considered a promising tool to support the transition toward a circular economy, thanks to its capacity to raise consumer awareness, foster loyalty and encourage participation in sustainable practices. However, to strengthen public trust in new circular business models, it becomes essential to manage such campaigns carefully. In this paper, we apply the Z-control method to regulate the dynamics of a referral marketing model with self-information, through control actions capable of influencing a campaign’s persistence and preventing its risk of collapse. Our focus is on two types of direct interventions: increasing the engagement of broadcasters and reducing consumer inertia. The analysis highlights how these marketing strategies must be applied over time in order for circular products, practices and behaviors to gain stable traction among the population. Reducing inertia, in particular, emerges as the more difficult challenge, suggesting that companies may need to adopt stronger marketing efforts while being mindful of how and when such efforts are applied. In this context, a non-monotonic application of marketing interventions over time appears especially important to avoid overwhelming consumers early on and to better address the psychological resistance often linked to inertia
Minimum global tax: winners and losers in the race for mergers and acquisitions
No full textIn the context of the OECD’s reform of international taxation, the paper quantifies the impact of the global minimum corporate tax rate on large multinational crossborder mergers and acquisitions. Within a gravity model specification, it examines how differences in capital taxation may drive bilateral cross-border mergers and acquisitions, taking into account both the direct and indirect distortionary effects of taxes. The empirical exercise exploits a large purpose-built dataset comprising 13,562 investor-firm M&As data points from 2001 to 2020, in (at the 516 4-digit level) industries times 109 “source” countries, matched with 559 (also at the 4-digit) industries times 161 “target” countries. In line with a simple theoretical model underpinning the mechanisms of transmission, the empirical results suggest that M&As flows are higher when the source and target countries have closer tax rates. Next, whenever the target country’s corporate tax rate is lower than 15%, the gravity model estimates the impact of the 15% global minimum tax rate on cross-border
investments by firms whose revenue exceeds the €750 millions threshold. The simulation shows that the overall effect of the global minimum corporate tax on M&As flows would be negative, but small in magnitude. Less developed economies would be comparatively the most affected area. As a percentage of expected flows, developing countries would experience the largest decrease. In absolute terms, the biggest decrease in outflow investments would be among OECD countries, while the biggest drop in inflow investments would be among high-income non-OECD countries
Alteration of vasopressin-aquaporin system in hindlimb unloading mice
No full textMurine hindlimb unloading (HU) is considered a model of choice for simulating the physiological effects of microgravity on several functions, including fluid and electrolyte homeostasis. Microgravity causes changes in blood redistribution, modulating vasopressin secretion, a major hormone controlling water reabsorption through the vasopressin-sensitive water channel AQP2. In this study, mice were hindlimb suspended over 4 weeks or rested in the ground as controls, and vasopressin levels, along with renal aquaporins expression were investigated. Copeptin, a stable precursor of the hormone vasopressin, significantly increased as early as 1 week of unloading which correlated with a significant increase in AQP2 total protein expression and decrease in serum osmolality, suggesting early activation of the vasopressin/AQP2 axis in this model. Conversely, in 4 weeks HU suspended mice, copeptin decreased significantly and both AQP2 mRNA and AQP2 total protein expression were significantly reduced. Consistent with a downregulation of the vasopressin/AQP2 axis an increase in serum osmolality was observed at 4 weeks HU. The basolateral water channels AQP3 and AQP4 were, on the other hand, unaffected. Immunolocalization studies confirmed reduced expression of AQP2 in renal collecting ducts of HU mice at 4 weeks. A significantly increased amount of the expressed AQP2 was found phosphorylated at Ser261, a site regulating AQP2 protein stability and degradation. In line, p38-MAPK, committed to phosphorylate Ser261 and to increase miR137 expression, an AQP2 mRNA-targeted microRNA, was significantly increased in HU, suggesting that reduced AQP2 expression was mainly due to increased protein degradation and downregulation of AQP2-mRNA translation. Our results suggest that vasopressin/AQP2 axis is upregulated as early as 1 week and may be involved in the antidiuretic response also observed in early spaceflight period in astronauts. Contrariwise, the vasopressin-AQP2 system is downregulated after 4 weeks HU, likely to counteract the persistent central venous pressure due to cephalic shift of fluids
Elucidating the (lipo)Phenolic Composition of Olive Oil By‐Products and Biomass From Three Different Olea Europaea Cultivars by Liquid Chromatography Coupled to Photodiode Array and Mass Spectrometry
No full textThe olive oil industry is currently experiencing a period of significant growth, largely as a result of the high value placed on olive oil as a high-nutritional food product on a global scale. Industrial olive oil production generates significant quantities of solid waste and dark liquid effluents, involving olive leaves (OLs), olive pomace (OP), and olive mill wastewaters (OMWWs). Particular attention was given to the recycling and valorization of by-products and biomass from the olive oil industry due to their richness in bioactive compounds, including phenolic compounds with antioxidant properties. The aim of this study was the sustainable recovery and characterization of valuable biocompounds, notably phenols, with particular emphasis on lipophenols, from different matrices (OMWWs, OP, and OLs) of three different Olea europaea cultivars using LC coupled with photodiode array (PDA) and MS detection. Method validation demonstrated satisfactory linearity (R-2 > 0.9806), repeatability (lower than 9.82%) and recovery (over 79.07%) for all samples investigated. Before quantification, the matrix effect was also evaluated with values ranging from 71.99% to 139.70%.The results highlight that OLs, OP, and OMWWs might be employed for several applications, including nutraceuticals, cosmeceuticals, food, and animal feed
Neurofobia en estudiantes de medicina de Paraguay
No full textIntroduction: neurophobia, defined as the fear or aversion to neurology due to its perceived complexity, poses a challenge in medical education. This study examines the prevalence and associated factors of neurophobia among medical students in Paraguay. Objective: to explore perceptions, attitudes, and factors associated with neurophobia among medical students and identify educational strategies to enhance neurology teaching. Methodology: this was an observational, descriptive, and cross-sectional study conducted with a sample of 413 medical students from various Paraguayan universities. Data on sociodemographic characteristics, prior experiences in neurology, and knowledge perceptions were collected using a validated questionnaire. Descriptive and inferential statistical analyses were performed. Results: a total of 41.6 % of students reported a low likelihood of choosing neurology as a specialty, while 33.9 % expressed intermediate levels of fear toward this discipline. The main causes of neurophobia were theoretical teaching approaches (32.9 %) and the perceived difficulty of neuroanatomy (35.8 %). Additionally, 69.2 % considered neurology teaching to be insufficient, and 81.1 % reported a lack of extracurricular activities related to neurology. Conclusions: the findings highlight the need for a more practical and interactive curriculum, emphasizing clinical simulations and extracurricular activities to foster interest and confidence in neurology. These changes could mitigate neurophobia and encourage professional development in this specialty
Formazione letteraria nel teatro ateniese del V sec. a.C.: un caso di studio
No full textRiassunto: Nel presente contributo si intende mostrare come si sia formata la memoria letteraria degli antichi Greci e come sia stato, ad esempio, recepito dal pubblico ateniese il mito di Medea portato sulla scena da Euripide.
Abstract: This paper aims to show the formation of the literary memory of the Athenians who attended the performance of Euripides’ Medea
Fibrosis mechanisms in systemic sclerosis and new potential therapies
No full textSystemic sclerosis is a rare rheumatic disease characterized by immune cell activation, tissue fibrosis, and endothelial dysfunction. Extracellular matrix synthesis disorder causes widespread fibrosis, primarily in skin and internal organs. Various factors such as TGFβ, VEGF, Galectin-3, and signaling pathways like Wnt/β-catenin are involved in pathophysiological processes. Treatment lacks a unified approach but combines diverse modalities tailored to disease subtype and progression. Current therapeutic strategies include biologics, JAK inhibitors, and IL-6 pathway modulators. Monoclonal antibodies and hypomethylating agents demonstrate potential in fibrosis inhibition. This review focuses on emerging therapeutic evidence regarding drugs targeting collagen, cytokines, and cell surface molecules in systemic sclerosis, aiming to provide insight into potential innovative treatment strategies
Combination of Drugs in the Treatment of Alcohol Use Disorder: A Meta-Analysis and Meta-Regression Study
No full textBackground: Alcohol Use Disorder (AUD) is highly prevalent among substance use disorders worldwide and is characterized by a multifactorial pathophysiology. AUD treatment is mostly based on combined pharmacotherapy and multidisciplinary clinical approaches. Nonetheless, meta-analytical studies assessing the efficacy of combination therapy are scarcely available. Methods: We searched for randomized clinical trials through PubMed, ClinicalTrials.gov, Cochrane Library, SciELO, Biblioteca Virtual em Saúde, and Google Scholar databases. Original clinical trials published in English and Portuguese were selected. Data collection followed the PRISMA and MOOSE guidelines and was assessed using the Risk of Bias Tool (RoB 2). Heterogeneity was assessed using the Q test. Meta-regression was conducted using Egger’s regression method. Twelve articles were finally included in the analysis, and random-effects models were applied on aggregate trial results. Results: The meta-analysis found that combination therapies led to an average 4.045% increase in abstinence rates (95% CI: 0.415% to 7.675%) compared to monotherapies. Meta-regression showed a strong positive association between the use of naltrexone, acamprosate, and sertraline—either alone or in combination—and treatment success in AUD. The meta-regression also highlighted the impact of patients’ variables, such as gender, age, country, and psychiatric comorbidities, on their treatment outcomes. These findings may identify a potential therapeutic pathway promoting alcohol abstinence, further supported by a Number Needed to Treat (NNT) of 25, as an acceptable value for substance use disorder treatments. Conclusions: Combined pharmacotherapies are more effective than monotherapy in enhancing abstinence rates in AUD treatment, with naltrexone, acamprosate, and sertraline emerging as key adjunctive agents promoting these outcomes. These findings underscore the complexity of AUD as a multifactorial psychiatric condition and highlight the potential of combined pharmacotherapy as a promising strategy for achieving better treatment outcomes, particularly in terms of abstinence rates
Results of Mental Health Well-Being and Burnout Screening Among Medical Students: A Descriptive Study Comparing 2020 and 2024 Data
No full textObjective: Medical students frequently experience burnout, stress, anxiety, and depression. Research on this issue in Russia is scarce and challenging to compare due to the lack of studies on this topic in the country. The aim of the present study was to comparatively analyze the mental well-being and mental health needs of medical students in St. Petersburg, Russia, over time using the same methodology. Methods: An anonymous structured online survey was conducted among students of a medical institute in June–July 2024. The Short General Health Questionnaire (GHQ-12), Oldenburg Burnout Inventory (OLBI), and CAGE questionnaire were used in the study. Results were compared with the data of a survey conducted at the same institute in 2020. Results: The sample included responses from 152 students (76.3% women). The majority of respondents (95.4%) reported experiencing significant stress in their lives, with education-related factors (83.6%), uncertainty about the future (72.4%), and the current geopolitical situation (73.0%) being the leading sources of stress. According to the GHQ-12, screening was positive in 88.2% of students (cf 84.8% in 2020; p = 0.389). Screening for burnout using the OLBI showed positive results in 87.5% (cf 73.3% in 2020; p = 0.002) of students for disengagement and 90.1% (cf 80.0% in 2020; p = 0.012) of students for exhaustion. Screening with the CAGE tool identified a risk of problematic alcohol use in 20.4% of students (cf 20.0% in 2020; p = 0.930). Conclusions: The study showed increased burnout in students in 2024 compared to 2020 and stable rates of problematic alcohol use and positive screening for minor mental disorders