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Decoding bioactivity in pea proteins: optimised hydrolysis reveals antioxidant and ACE-inhibitory peptides
Pea proteins can be converted into health-promoting ingredients through enzymatic hydrolysis. This study systematically investigates the effect of different degrees of hydrolysis (DH), namely limited (DH 20 %), on the antioxidant properties (assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays.) and Angiotensin-Converting Enzyme (ACE)-inhibitory activities of pea protein hydrolysates (PPHs) obtained using Alcalase 2.4L. Moreover, the impact of a filtration step applied to isolate peptides below 3 kDa on biological properties was also studied. Enzymatic hydrolysis enhanced all bioactivities, but antioxidant properties peaked at intermediate hydrolysis, while ACE-inhibitory activity increased progressively with hydrolysis degree. In both cases, peptides with a molecular weight below 3 kDa were primarily responsible for the detected bioactivities. Distinct peptides, accurately sequenced by high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry (HPLC-ESI-MS/MS), were associated with each activity. Particularly, GFFC contributed to radical scavenging, while YDFXMF was linked to ACE inhibition. These findings highlight the importance of optimising hydrolysis conditions to maximise specific bioactivities. This approach supports the development of sustainable, functionally targeted pea-derived ingredients
I colori dei farmaci antichi: l’‘impiastro grigio Egizio’ nella letteratura medica e in un ricettario su papiro
L’articolo presenta un'analisi delle fonti letterarie e papirologiche per un particolare tipo di farmaco antico ad uso dermatologico, l’impiastro grigio Egizio. Vengono in particolare discusse le versioni tramandate da Galeno, insieme ad una nuova attestazione restituita da un papiro di recente pubblicazione (P.Egerton 13 verso)
Retrospective Case-Cohort Study on Risk Factors for Developing Distant Metastases in Women With Breast Cancer
OBJECTIVE: This study aimed to identify risk factors associated with the development of metastases in breast cancer patients, to investigate survival rates, and the relationship between local recurrences and distant metastases. METHODS: This retrospective case-cohort study included women with breast cancer who were treated at a certified Breast Unit between 2001 and 2015. Cases who developed distant metastases were compared to controls based on diagnosis year, stage, and age at diagnosis. Comprehensive information on patient characteristics, tumor biology, and treatment options was gathered. RESULTS: The study included 412 patients who developed distant metastases and 433 controls who remained metastasis-free over a median follow-up of 150 months (interquartile range 87-202). The 20-year overall survival was 99.23% for the control group and 23.62% for those with metastasis (p < 0.01). Significant risk factors for metastasis included lobular invasive carcinoma (odds ratio (OR) 2.26, p < 0.001), triple-negative subtype (OR 4.06, p = 0.002), high tumor grade (OR 2.62, p = 0.004), larger tumor size (OR 1.02, p < 0.001), lymph node involvement (p < 0.001), and loco-regional recurrence (OR 4.32, p < 0.001). Progesterone receptor (PR) expression was protective (OR 0.52, 95% confidence interval 0.34-0.81, p = 0.003). Machine learning models supported these findings, though their clinical significance was limited. CONCLUSIONS: Lobular invasive carcinoma, specific tumor subtypes, high grade, large tumor size, lymph node involvement, and loco-regional recurrence are all significant risk factors for distant metastasis, whereas PR expression is protective. The potential of machine learning in predicting metastasis was explored, showing promise for future personalized risk assessment
Ghost Villages and How to Inhabit Them
Alberto Cervesato's research has observed Italian marginal territories and then focused on those in Friuli. Marginal territories are understood to be those belonging to Apennine and Pre-alpine areas. They are characterised by high depopulation and environmental degradation resulting from a reduced anthropic presence, that has "deprived" environments and villages of the habitation and work that are necessary for the care and maintenance of cultivated and wooded open spaces. The subject is highly topical and, although not yet extensively studied, the available bibliography is beginning to be sufficiently articulate and varied. The focus on these "cold" territories makes it possible to more carefully read the "watermark" of those Italian contexts that, due to abandonment, today stand out as a social and environmental emergency
Cosmic-ray acceleration and escape from supernova remnant W44 as probed by Fermi -LAT and MAGIC
Context. The supernova remnant (SNR) W44 and its surroundings are a prime target for studying the acceleration of cosmic rays (CRs). Several previous studies established an extended gamma-ray emission that is set apart from the radio shell of W44. This emission is thought to originate from escaped high-energy CRs that interact with a surrounding dense molecular cloud complex. Aims. We present a detailed analysis of Fermi-LAT data with an emphasis on the spatial and spectral properties of W44 and its surroundings. We also report the results of the observations performed with the MAGIC telescopes of the northwestern region of W44. Finally, we present an interpretation model to explain the gamma-ray emission of the SNR and its surroundings. Methods. We first performed a detailed spatial analysis of 12 years of Fermi-LAT data at energies above 1 GeV, in order to exploit the better angular resolution, while we set a threshold of 100 MeV for the spectral analysis. We performed a likelihood analysis of 174 hours of MAGIC data above 130 GeV using the spatial information obtained with Fermi-LAT. Results. The combined spectra of Fermi-LAT and MAGIC, extending from 100 MeV to several TeV, were used to derive constraints on the escape of CRs. Using a time-dependent model to describe the particle acceleration and escape from the SNR, we show that the maximum energy of the accelerated particles has to be '40 GeV. However, our gamma-ray data suggest that a small number of lower-energy particles also needs to escape. We propose a novel model, the broken-shock scenario, to account for this effect and explain the gamma-ray emission
Proximity Strategies for Stakeholder Engagement in Business Models for Sustainability: A Conceptual Framework
Stakeholder engagement is a crucial part of business models for sustainability (BMfS), but companies struggle to implement it. One approach that could be leveraged is the concept of proximity, as it can enable sharing of knowledge and values. However, there is a lack of studies exploring proximity dimensions in BMfS and how they can be combined to facilitate the integration of stakeholder engagement in BMfS. Based on multiple case study research, this paper fills this gap by proposing the Stakeholder engagement in BMfS proximity framework, highlighting how five BMfS proximity dimensions (identity, production and supply chain, functional, inter-organizational and environmental proximity) can be combined in BMfS components through three distinctive strategies—adaptation, association, and identity strategy. These strategies facilitate stakeholder engagement by creating the perception of multiple localities, multiple communities, or a combination of those, providing an enhanced conceptual understanding of stakeholder engagement in BMfS for academics and practitioners
Improving the Quality of Mountain Facilities: A Novel Project in the Dolomites Area
In its broadest sense, the mountain environment represents a setting useful for promoting health. This Italian project, conceived and applied in the Dolomites, aims to encourage multi-sector preventive public health policies; improve refuge hygiene; strengthen safety requirements; and implement projects aimed at promoting health. With the support of healthcare workers (HCWs) of the Prevention Department and other professionals in this field, 27 establishments in the Alpine territory have joined the project, benefiting from being recognized as a “Healthy and Safe Refuge” at the end of the quality improvement process. This process consisted of a documentary assessment, an on-site evaluation, and an assessment of analytical evidence relating to parameters investigated by both HCWs and refuge managers according to specific protocols. Data were collected from a specific database via an application to join the project and from sampling reports of parameters investigated for evaluating the quality of water intended for human consumption. The outdoor Alpine environment has recently witnessed extraordinary development and must continue to meet all health and safety requirements, especially in view of a global event—the Olympic Games—that will be hosted in the Dolomites area in 2026
Adenine nucleotide translocator and ATP synthase cooperate in mediating the mitochondrial permeability transition
Abstract: The permeability transition (PT) is a permeability increase of the mitochondrial inner membrane causing mitochondrial swelling in response to matrix Ca2+. The PT is mediated by regulated channel(s), the PT pore(s) (PTP), which can be generated by at least two components, adenine nucleotide translocator (ANT) and ATP synthase. Whether these provide independent permeation pathways remains to be established. Here, we assessed the contribution of ANT to the PT based on the effects of the selective ANT inhibitors atractylate (ATR) and bongkrekate (BKA), which trigger and inhibit channel formation by ANT, respectively. BKA partially inhibited Ca2+-dependent PT and did not prevent the inducing effect of phenylarsine oxide, which was still present in mouse embryonic fibroblasts deleted for all ANT isoforms. The contribution of ANT to the PT emerged at pH 6.5 (a condition that inhibits ATP synthase channel opening) in the presence of ATR, which triggered mitochondrial swelling and elicited currents in patch-clamped mitoplasts. Unexpectedly, ANT-dependent PT at pH 6.5 could also be stimulated by benzodiazepine-423 [a selective ligand of the oligomycin sensitivity conferral protein (OSCP) subunit of ATP synthase], suggesting that the ANT channel is regulated by the peripheral stalk of ATP synthase. In keeping with docking simulations, ANT could be co-immunoprecipitated with ATP synthase subunits c and g, and oligomycin (which binds adjacent c subunits) decreased the association of ANT with subunit c. These results reveal a close cooperation between ANT and ATP synthase in the PT and open new perspectives in the study of this process. (Figure presented.). Key points: We have assessed the relative role of adenine nucleotide translocator (ANT) and ATP synthase in generating the mitochondrial permeability transition (PT). At pH 7.4, bongkrekate had little effect on Ca2+-dependent PT, and did not prevent the inducing effect of phenylarsine oxide, which was still present in mouse embryonic fibroblasts deleted for all ANT isoforms. The contribution of ANT emerged at pH 6.5 (which inhibits ATP synthase channel opening) in the presence of atractylate, which triggered mitochondrial swelling and elicited currents in patch-clamped mitoplasts. Benzodiazepine-423, a selective ligand of the oligomycin sensitivity conferral protein subunit of ATP synthase, stimulated ANT-dependent PT at pH 6.5, suggesting that the ANT channel is regulated by the peripheral stalk of ATP synthase. ANT could be co-immunoprecipitated with ATP synthase subunits c and g; oligomycin, which binds adjacent c subunits, decreased the association with subunit c, in keeping with docking simulations
Impact of pre-operative inflammatory markers on overall and disease-free survival of octogenarian patients undergoing video-assisted thoracoscopic lobectomy for early-stage lung cancer: a multicenter study
Background: The proportion of octogenarian patients who undergo surgery for lung cancer is growing over recent years. Elderly patients are characterized by age-related changes, such as inflammatory modifications of the lower respiratory tract, responsible for structural and functional alterations and tumor progression. Inflammatory markers (IMs) are a well-known prognostic factor in several tumor types, but they have not been analyzed extensively in octogenarian patients submitted to thoracoscopic lobectomy for early-stage lung cancer. The aim of our study is to assess the impact of the pre-operative IMs on the overall survival (OS), disease-free survival (DFS), and post-operative complications of this subset of patients. Methods: We conducted a retrospective and multi-institutional study. All octogenarian patients submitted to thoracoscopic lobectomy for early-stage lung cancer from January 2013 to April 2019 were enrolled. Preoperative cellular IMs were measured in peripheral blood samples and their cut-off values were set according to previous findings in literature. Cox regression model was used to analyze the relationship between IMs, and OS and DFS. Kaplan-Meier method was used to calculate the OS and DFS rates. The follow-up period was 36 months. All P values lower than 0.05 were considered statistically significant. Results: A total of 118 patients were included. At multivariate analysis adjusted by sex, age, and chronic obstructive pulmonary disease (COPD), neutrophils-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were strongly associated with higher risk of mortality [hazard ratio (HR) 2.89, 95% confidence interval (CI): 1.05–8.02, P=0.04, HR 2.74, 95% CI: 1.15–6.52, P=0.02, respectively]. NLR >2.5 and CRP >3 were associated with worse survival (respectively P=0.02 and P=0.02). Higher levels of monocyte-to-lymphocyte ratio (MLR) were still associated with a higher mortality rate, although more weakly (P=0.056). Conclusions: Elevated pre-operative NLR and CRP can be considered as a prognostic indicator in patients with non-small cell lung cancer (NSCLC) undergoing surgery with minimally invasive approach. Post-operative course and DFS is not influenced by pre-operative IMs levels
Da Werther ai Werther. «La storia di una malattia» nello specchio delle traduzioni
The numerous translations that have followed one another since the novel was first published have told the story of Werther’s ‘illness’ in different ways; in the translation choices as in the critical apparatus, from the covers to the introductions and comments, Werther’s suicide has been judged from time to time, condemned, concealed or exalted; each translation takes the form of a story of the protagonist’s fate that is different from the original version. Retracing some of the stages of the novel’s reception, the article focuses on several of these translations, from the earliest to the 20th century (Deyverdun, Seckendorf, Grassi, Salom, Ludger, Ceroni, Graziani, Borgese, Spaini/Baioni), trying to identify in each one the particular vision and interpretation of Werther’s destiny