Marche Polytechnic University

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    Herbal terpenoids activate autophagy and mitophagy through modulation of bioenergetics and protect from metabolic stress, sarcopenia and epigenetic aging

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    : Small molecular food components contribute to the health benefits of diets rich in fruits, vegetables, herbs and spices. The cellular mechanisms by which noncaloric bioactives promote healthspan are not well understood, limiting their use in disease prevention. Here, we deploy a whole-organism, high-content screen in zebrafish to profile food-derived compounds for activation of autophagy, a cellular quality control mechanism that promotes healthy aging. We identify thymol and carvacrol as activators of autophagy and mitophagy through a transient dampening of the mitochondrial membrane potential. Chemical stabilization of thymol-induced mitochondrial depolarization blocks mitophagy activation, suggesting a mechanism originating from the mitochondrial membrane. Supplementation with thymol prevents excess liver fat accumulation in a mouse model of diet-induced obesity, improves pink-1-dependent heat stress resilience in Caenorhabditis elegans, and slows the decline of skeletal muscle performance while delaying epigenetic aging in SAMP8 mice. Thus, terpenoids from common herbs promote autophagy during aging and metabolic overload, making them attractive molecules for nutrition-based healthspan promotion

    Sustainable Biochar–Alumina Composites for Electroanalytical Sensing of Herbicide and Antibiotic

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    The problem of water pollution by various xenobiotics has gained a lot of interest due to their persistence, bioaccumulation potential, and toxic effects on ecosystems and humans. Electrochemical sensors offer a rapid, sensitive, and cost-effective method for on-site monitoring. In this research, an electrochemical sensor for xenobiotics based on a biochar–alumina composite is developed. The biochar–alumina composites were obtained by the air-limited pyrolysis of oak sawdust in the presence of alumina. Two types of alumina were mixed with oak sawdust in three ratios and subjected to thermal treatment. The resulting composites were characterized by SEM, N2 adsorption isotherm, XRD, and electrochemical characterization. The detection of the herbicide pendimethalin and the antibiotic ciprofloxacin was investigated, and the composite with the optimal biochar/alumina ratio was selected for each of the xenobiotics studied. A linear current response was obtained for pendimethalin in the concentration range 0.7 μM to 70.0 μM with an LOD of 0.5 μM. A linear current response was obtained for ciprofloxacin in the concentration range 1.6 μM to 55.4 μM with an LOD of 0.63 μM. A comparison of the characterization results with the electroanalytical performance implied the importance of the hydrophobic/hydrophilic nature of the electrode surface for detecting the analyte under investigation

    Genomic pathway alterations and their prognostic impact in biliary tract cancer: Insights from a multinational cohort treated with cisplatin, gemcitabine, and durvalumab

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    Background: Biliary tract cancers (BTC) are aggressive malignancies with limited therapeutic options. Recent advances have integrated immunotherapy into the standard of care, yet outcomes remain heterogeneous, emphasizing the need for molecular biomarkers to guide patient selection. This study aimed to assess the prognostic impact of pathway-level genomic alterations in patients with BTC treated with first-line cisplatin, gemcitabine, and durvalumab. Methods: This retrospective, multicenter study included 735 patients with advanced BTC, of whom 197 underwent comprehensive genomic profiling using the FoundationOne® CDx assay. Pathways were classified based on the presence of key gene alterations, and their association with overall survival (OS) and progression-free survival (PFS) was assessed through univariate and multivariate analyses. Tumor mutational burden (TMB) was also evaluated as a potential biomarker. Results: HRD/BRCAness pathway alterations were associated with significantly improved OS (23.3 vs. 13.8 months, HR 0.51, 95 % CI 0.27-0.93, p = 0.0295) and PFS (13.2 vs. 8.1 months, HR 0.53, 95 % CI 0.32-0.89, p = 0.0153). TGF-β pathway alterations were linked to longer PFS (16.0 vs. 8.1 months, HR 0.53, 95 % CI 0.28-0.99, p = 0.0473) but did not independently predict OS. High TMB (>10 mut/Mb) was associated with improved OS (NR vs. 11.0 months, HR 0.34, 95 % CI 0.14-0.85, p = 0.0206) and PFS (NR vs. 7.6 months, HR 0.40, 95 % CI 0.13-0.96, p = 0.043). However, no single pathway was significantly correlated with early treatment response. Conclusions: HRD/BRCAness and TGF-β pathway alterations, along with high TMB, emerged as potential prognostic biomarkers in patients with BTC treated with chemo-immunotherapy. These findings, if prospectively confirmed and validated, support the integration of molecular profiling into routine clinical practice to improve patient stratification and treatment outcomes in this challenging tumor type

    A Multidimensional Immunological Perspective on Long COVID

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    Long COVID is a chronic condition that arises after SARS-CoV-2 infection and is characterized by persistent and often debilitating symptoms, such as fatigue, cognitive dysfunction (“brain fog”), dyspnea, and autonomic disturbances. Increasing evidence suggests that Long COVID shares key immunopathological mechanisms with autoimmune diseases, primarily sustained immune dysregulation. In individuals with genetic or immunological susceptibility, SARS-CoV-2 infection can trigger the production of autoantibodies targeting cytokines, membrane receptors, and components of the autonomic nervous system (ANS), thereby disrupting neuroimmune homeostasis. This immune imbalance may impair anti-inflammatory regulatory pathways, such as the cholinergic anti-inflammatory pathway (CAP), and may contribute to a chronic state of inflammation and autoimmunity. One proposed contributor to this process is inflammaging – a chronic, low-grade inflammation associated with aging – which may not only predispose individuals to Long COVID but may also be amplified by the persistent immune activation seen in this condition. In this perspective, we propose a conceptual framework in which inflammaging, immune-tolerance breakdown, and autonomic dysfunctions interact to sustain the pathophysiology of Long COVID. We discuss emerging biomarkers across these axes, including inflammatory cytokines, circulating autoantibodies, immune cell phenotypes, epigenetic modifications, and heart rate variability. Advances in inflammaging-related biomarkers and biological clocks may support early identification of individuals at higher risk for persistent immune and autonomic dysregulation, ultimately informing more precise diagnostic and therapeutic strategies for Long COVID

    Digital interventions in sport psychology and psychiatry

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    Introduction: The increasing prevalence of mental health challenges among athletes and the general population has catalyzed a growing demand for digital interventions in sport psychology and psychiatry. This study aims to map the research landscape of digital interventions in sport psychology and psychiatry, highlighting key trends, influential contributions, and areas for future exploration. Methods: Bibliometric analysis of digital interventions in sport psychology and psychiatry was conducted to provide insights into the global research landscape, collaboration patterns, and thematic evolution. Using data from 2005 to 2024 indexed in the Scopus database, the analysis highlights key metrics, including publication growth, citation impact, and emerging trends. Results: A significant increase in research activity, with mental health, sport, and digital health identified as core themes, while topics like social media and virtual reality emerge as expanding areas of interest. Leading contributors include the United Kingdom, the United States, Australia, and China, with notable institutional and author-level collaborations driving innovation in the field. Discussion: The findings underscore the interdisciplinary and global nature of this domain, emphasizing the integration of digital technologies to address mental health and optimize performance in sport contexts. This study provides a foundation for future research, highlighting opportunities in underexplored areas such as virtual reality applications, algorithm-driven interventions, and culturally specific approaches to digital mental health care

    Inflation, inequality and financial vulnerability: Monetary vs. fiscal policy in the face of an energy shock

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    The energy shock caused by the conflict in Ukraine has exacerbated inflation, prompting central banks to respond by raising interest rates. This study uses an agent-based stock-flow consistent (AB-SFC) model to assess the impact of energy shocks, as well as monetary and fiscal policy, on inflation, inequality, and household financial vulnerability. The results show that energy shocks increase nominal spending for households and non-financial firms, leading to higher inflation, unemployment, inequality, household indebtedness and financial vulnerability. Furthermore, while monetary policy is effective in reducing inflation, it does so at the cost of exacerbating inequality and household financial vulnerability. In contrast, fiscal measures, such as energy price caps, can reduce inflation without exacerbating the economic crisis caused by the energy shock; indeed, compared to the monetary approach, fiscal policy reduces inflation and inequality and also improves household financial stability

    The impact of glyphosate at regulatory “safe” levels on reproductive health: cellular and molecular disruptions on male germ line

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    Glyphosate, a widely used herbicide in both agricultural and non-agricultural practices, has become pervasive in the environment, leading to significant human and animal exposure. Despite growing evidence of its potential endocrine-disrupting and reproductive toxicity, European regulatory agencies continue to affirm its safety. This study examines the effects of glyphosate on male reproductive health by exposing adult zebrafish to dietary glyphosate at doses within European safety thresholds. After 21 days of exposure, testicular samples were analysed using a combined approach involving transcript analysis, targeted metabolomics and proteomics, epigenetics, as well as immunohistochemistry. At 0.5 mg/kg body weight(bw)/day (the acceptable daily intake, ADI), glyphosate impaired germ cell differentiation and triggered cell-specific changes in histone acetylation within the male germline. Higher exposure levels of 50 mg/kg bw/day (the no observed adverse effect level, NOAEL) induced metabolomic and proteomic disruptions linked to impaired steroidogenesis, DNA damage in germ cells, and alterations in testicular architecture, culminating in reduced reproductive capacity. Interestingly, minimal testicular effects observed at 5 mg/kg bw/day highlighted the non-monotonic dose–response relationship to glyphosate. These findings unveil critical molecular and cellular disruptions caused by glyphosate and emphasize its potential reproductive risks, even at doses considered “safe” by regulatory standards. This research contributes to ongoing discussions surrounding sustainable agricultural practices and public health policies, calling for a re-evaluation of glyphosate safety thresholds

    Comparison of HRTF Interpolation Algorithms based on Neural Network

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    Head-related transfer functions (HRTFs) are used in immersive audio rendering applications. In many cases, these functions have to be calculated or measured in many relative positions between head and source requiring a large amount of time and significant computational resources. Therefore, the generation of HRTFs becomes crucial and interpolation procedures can solve this problem. An extensive analysis of an interpolation method based on neural network is presented taking into consideration the state of the art and the use of a real dataset filtered by a refinement procedure. The neural network interpolation approach is compared with conventional nearest-neighbor interpolation methods. The investigation based on differences between interpolated and measured HRTFs shows promising results of the proposed methodology that are in line with traditional interpolation techniques

    Enhanced growth and photosynthetic efficiency in wild rocket (Diplotaxis tenuifolia L.) following multi-species microalgal biostimulant application

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    Foliar spraying is a simple and efficient technique that enables targeted delivery of biostimulants directly onto plant surfaces, minimizing losses and environmental dispersion. Among biostimulant categories, microalgaebased formulations represent an eco-friendly solution to improve crop productivity, thanks to their richness in bioactive compounds and rapid growth in low-input systems. In this study, the crude extract of three green microalgae with high commercial value and broad biotechnological potential-Auxenochlorella protothecoides, Tetradesmus obliquus and Chlamydomonas reinhardtii-along with their consortium, was tested as foliar biostimulants for the first time on wild rocket (Diplotaxis tenuifolia L.) at an early vegetative stage. Plants received three sequential treatments, and physiological and biochemical responses were evaluated at 24, 48, and 72 h after the final application. Biostimulation led to up to 32 % increases in fresh biomass and significantly enhanced photosynthetic efficiency (Fv/Fm, PI), particularly in consortium-treated plants. The multi-step application also triggered a late and transient rise in antioxidant compounds (carotenoids and phenolics), potentially improving post-harvest quality. Remarkably, these effects were observed even in the absence of abiotic stress, highlighting the intrinsic biostimulant potential of the treatments. Notably, when the consortium crude extract was applied, higher chlorophyll content, nitrate accumulation, and enhanced nitrogen assimilation (indicated by lower delta 15N values) were also observed. These results suggest a compositional and functional uniqueness of the consortium, likely due to interspecies interactions. Overall, early-stage, multi-step foliar biostimulation with selected microalgal species or consortia represents a promising and sustainable strategy to improve crop performance and modulate quality traits in leafy vegetables

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