A Journey Around Boronic Acids: Sulfonyl Hydrazone-Containing Derivatives as Carbonic Anhydrase Inhibitors

Recently, a rising interest in boronic acids and their derivatives was recorded in the Medicinal Chemistry field due to their high versatility and broad applicability as bioactive compounds in several diseases, including cancer and microbial infections. The ability of boronic acid moieties to bind zinc ions was first hypothesized by the inhibitory activity of bortezomib, a boron-containing protease inhibitor, on different isoforms of the Carbonic Anhydrase (CA, EC: 4.2.1.1) enzyme family and then assessed through X-ray crystallographic studies on benzoxaboroles in complex with hCA II. These findings, along with the overexpression of isoforms IX and XII in hypoxic cancer and, in particular, breast cancer, drove us to explore the chemical space around the phenylboronic acids by generating a focused library of 16 derivatives (1–4a–d) decorated with alkyl sulfonyl hydrazones. The compounds were then subjected to stopped flow-based inhibition assays on a panel of hCAs, including the tumor-associated isoforms, revealing low micromolar inhibition constants (KIs) in some cases. However, antiproliferative assays conducted on a human triple-negative breast cancer cell line showed a lack of activity at the tested concentrations

Perceived coworkers' work addiction: Scale development and associations with one's own workaholism, job stress, and job satisfaction in 85 cultures

Background: While the empirical data on the role of environmental factors in work addiction (WA) is steadily growing, little is known about the extent to which the workaholic environment contributes to the increased risk of WA and what are the relative contributions of direct supervisor's and colleagues' WA to one's own workaholism. Methods: The Perceived Coworkers' Work Addiction Scale (PCWAS) assessing perceived direct supervisor's and colleagues' WA, defined as an addictive disorder, was administered alongside measures of WA, job stress, and job satisfaction in a total sample of 33,222 employees from 85 cultures across six continents (63.2% females, mean age 39.35 years). Results: The PCWAS showed scalar measurement invariance between genders and job positions, and approximate measurement invariance across cultures. In most cultures, the perceived supervisor's and colleagues' WA correlated with one's own WA, job stress (positively), and job satisfaction (negatively). In structural equation models, perceived colleagues' rather than supervisor's WA was more strongly related to one's own WA and job stress in most cultures. Discussion and conclusions: These findings suggest that the PCWAS is valid and reliable for assessing the workaholic environment, and it can be used globally to provide comparable and generalizable results. The present study is the first to show that WA may considerably depend on environmental factors in different cultures worldwide and that perceived colleagues' WA may play a particularly important role in this context. These findings may guide organizational interventions to decrease WA risks among employees and improve their well-being and productivity

L’intangibile spiritualità delle montagne d’Abruzzo

La spiritualità connaturata nelle montagne abruzzesi è stata rappresentata in diversi modi, riferita da artisti, letterati, pittori, musicisti che hanno fornito percezioni tangibili e intangibili, dei culti, delle tradizioni derivate dal fenomeno eremitico, originato principal- mente dalla figura di Celestino V, il Papa del rifiuto. La sacralità della Maiella, montagna madre, ha origini remote, leggende popolari testimoniano riti italici, migrazioni e cammini spirituali sulle ripide pareti rocciose, per raggiungere i ripari, le grotte in cui si ritiravano gli anacoreti ispirati dal fascino della ‘montagna santa’. Il contributo come richiesto, individua un’immagine per esprimere con i linguaggi della rappresentazione le valenze custodite nel patrimonio immateriale, nei luoghi celati sulle alture d’Abruzzo, l’humus da cui derivano memorie storiche, testimonianze visive e culturali che hanno portato ad avanzare un progetto di candidatura Unesco

From the Impersonal to Instituting Thought: Esposito’s Departure from Deleuze

Roberto Esposito’s relationship with Deleuzian thought is long-standing. The Italian philosopher begins to engage more intensely with Gilles Deleuze as early as Bios, where the themes of the political and the community were addressed from the perspective of life. Like all enduring relationships, it undergoes a major repositioning, from an initial adherence, albeit with a consistent critical distance, to then a slow distancing, due to the Italian philosopher’s increasing attention to the role of negation. If, therefore, Esposito stands on Deleuze’s side in the texts of the first decade of the new century, from Bios (2004) to A Philosophy for Europe: From the Outside (2016), starting from Politics and Negation (2018) and then even more markedly in the analyses on the institution, the distancing from the French philosopher acquires a clear-cut delineation

Life cycle impact assessment del blocco in calce e canapa per la bioedilizia

L’interferenza fra natura ed attività umane ha causato importanti problematiche che hanno innescato manovre per attuare uno sviluppo sostenibile. In questo ambito il settore delle costruzioni ha iniziato ad impiegare materiali bio-based, fra i quali anche la canapa. Lo scopo del presente studio è quello di valutare la sostenibilità, a livello di Life Cycle Assessment dei blocchi in calce e canapa in produzione presso un’Azienda italiana. L’analisi condotta è di tipo from cradle to gate, con ipotesi sugli scenari di smaltimento. Un’analisi, questa, che ha permesso di individuare il processo di approvvigionamento e prima trasformazione della calce come quello più impattante in fase A1, mentre la fase A3, di produzione del blocco, presenta valori di impatto contenuti

Assessment of Potential Landslide Scenarios Using Morphometry, Geomorphological Constraints, and Run-Out Analysis: A Case Study from Central Apennines (Italy)

Landslides are among the most damaging natural hazards, posing significant threats to human lives and infrastructures, especially in mountainous regions such as the Central Apennines (Italy). This study focuses on the Mt. Marsicano catchment (2245 m a.s.l.), characterized by peculiar morphometric features and geomorphological constraints that highlight the possibility of potential landslide scenarios. The methodological approach led to the identification of potential landslide propagation patterns. The RAMMS::DEBRIS FLOW module was used to model two potential landslide scenarios: a debris flow-like movement with a volume of 2.03 × 104 m3 and a rock avalanche-like movement with a volume of 1.2 × 106 m3. Findings from the latter scenario suggested river obstruction and potential lake formation upstream. Triggering mechanisms were partially explored, linking the debris flow scenario to heavy rainfall events (>50 mm/day) and the rock avalanche scenario to earthquakes with Mw > 5.0. Despite the absence of occurred landslides for back-calculation analysis and modeling based on geomorphic evidence rather than calibrating to a specific local past event, the study provides preliminary clues about the combination between morphometric analysis and geomorphological constraints in hypothesizing potential landslide scenarios. It provides a foundation for anticipating future landslide impacts in mountainous areas with limited historical data, offering valuable geomorphological insights for preventive hazard assessment and mitigation strategies in similar environments