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Abstract Bioconjugation is one of the most promising strategies to improve drug delivery, especially in cancer therapy. Biomolecules such as bile acids (BAs) have been intensively explored as carriers, due to their peculiar physicochemical properties and biocompatibility. BAs trafficking is regulated by intracellular lipid-binding proteins and their transport in the liver can be studied using chicken liver Bile Acid-Binding Proteins (cL-BABPs) as a reference model. Therefore, we conceived the idea of developing a BA-conjugate with Mirin, an exonuclease inhibitor of Mre11 endowed with different anticancer activities, to direct its transport to the liver. Following computational analysis of various BAs in complex with cL-BABP, we identified cholic acid (CA) as the most promising candidate as carrier, leading to the synthesis of a novel bioconjugate named CA-M11. As predicted by computational data and confirmed by X-ray crystallographic studies, CA-M11 was able to accommodate into the binding pocket of BABP. Hence, it can enter BAs trafficking in the hepatic compartment and here release Mirin. The effect of CA-M11, evaluated in combination with varying concentrations of Doxorubicin on HepG2 cell line, demonstrated a significant increase in cell mortality compared to the use of the cytotoxic drug or Mirin alone, thus highlighting chemo-sensitizing properties. The promising results regarding plasma stability for CA-M11 validate its potential as a valuable agent or adjuvant for hepatic cancer therapy.

Following the severe impact of capitalist industrialization on the environment, the EU has funded several projects in the context of the European Green Deal to pursue climate neutrality by 2050. Some of these projects attempt to achieve zero emissions through political participation, while others by committing EU citizens to adopt sustainable habits in terms of both practical behavior and economic choices. The GreenSCENT project, funded by the European Union's Horizon 2020 research and innovation programme, aims to develop a Competence Framework compliant with the European Qualifications Framework and the European Green Deal. The present article documents the process of developing such a Competence Framework. Eight distinct research teams independently conducted a similar thorough literature review over an assigned topic (Climate Change; Clean Energy; Circular Economy; Green Building; Smart Mobility; From Farm to Fork; Biodiversity; Zero Pollution). The resulting documental corpora have then elicited to build the competence matrices and the corresponding European Qualification Framework levels. Once the information has been reorganized as a knowledge graph, the researchers discovered a large amount of novel interdomain connections, providing a more engaging way of interacting with the Competence Framework, and potentially apt to avoiding information overload issues while preserving the complexity, in line with the simplexity paradigm. The environmental education tools produced by this research could be useful in mitigating the repercussions of Capitalocene on the environment toward the adoption of more sustainable behaviors.

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H2O2-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST’s significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through “green” methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy.

Abstract Background There is no evidence in the current literature about the best treatment option in sacral fracture with or without neurological impairment. Materials and methods The Italian Pelvic Trauma Association (A.I.P.) decided to organize a consensus to define the best treatment for traumatic and insufficiency fractures according to neurological impairment. Results Consensus has been reached for the following statements: When complete neurological examination cannot be performed, pelvic X-rays, CT scan, hip and pelvis MRI, lumbosacral MRI, and lower extremities evoked potentials are useful. Lower extremities EMG should not be used in an acute setting; a patient with cauda equina syndrome associated with a sacral fracture represents an absolute indication for sacral reduction and the correct timing for reduction is “as early as possible”. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an indication for laminectomy after reduction in the case of a displaced sacral fracture in a high-energy trauma, while a worsening and progressive radicular neurological deficit represents an indication. In the case of a displaced sacral fracture and neurological deficit with imaging showing no evidence of nerve root compression, a laminectomy after reduction is not indicated. In a patient who was not initially investigated from a neurological point of view, if a clinical investigation conducted after 72 h identifies a neurological deficit in the presence of a displaced sacral fracture with nerve compression on MRI, a laminectomy after reduction may be indicated. In the case of an indication to perform a sacral decompression, a first attempt with closed reduction through external manoeuvres is not mandatory. Transcondylar traction does not represent a valid method for performing a closed decompression. Following a sacral decompression, a sacral fixation (e.g. sacroiliac screw, triangular osteosynthesis, lumbopelvic fixation) should be performed. An isolated and complete radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an absolute indication. A worsening and progressive radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. In the case of a displaced sacral fracture and neurological deficit in a low-energy trauma, sacral decompression followed by surgical fixation is indicated. Conclusions This consensus collects expert opinion about this topic and may guide the surgeon in choosing the best treatment for these patients. Level of Evidence: IV. Trial registration: not applicable (consensus paper).

The concept of a “circular bioeconomy” holds great promise for the health, cosmetic, and nutrition sectors by re-using Castanea sativa (Mill.) by-products. This sustainable resource is rich in bioactive secondary metabolites with antioxidant and anti-inflammatory properties. By transforming these by-products into high-value products for human health, we can promote sustainable economic growth and reduce the environmental impact of traditional waste disposal, adding value to previously underutilized resources. In the present study, we investigated the antioxidant capacity, phytochemical composition, and in vitro antioxidant and anti-inflammatory activity of C. sativa burr (CSB) aqueous extract. The spectrophotometric study revealed high total phenolic content (TPC) values with significant antioxidant and anti-radical properties. Using UPLC-MS/MS techniques, the phytochemical investigation identified 56 metabolites, confirming the presence of phenolic compounds in CSBs. In addition, CSBs significantly downregulated pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophage cells without significant cell toxicity. Lastly, in silico studies pinpointed three kinases from RAW 264.7 cells as binding partners with ellagic acid, the predominant compound found in our extract. These findings strongly advocate for the recycling and valorization of C. sativa by-products, challenging their conventional classification as mere “waste”.

Utilizing plant-based resources, particularly their by-products, aligns with sustainability principles and circular bioeconomy, contributing to environmental preservation. The therapeutic potential of plant extracts is garnering increasing interest, and this study aimed to demonstrate promising outcomes from an extract obtained from an underutilized plant waste. Chaetomorpha linum, an invasive macroalga found in the Orbetello Lagoon, thrives in eutrophic conditions, forming persistent mats covering approximately 400 hectares since 2005. The biomass of C. linum undergoes mechanical harvesting and is treated as waste, requiring significant human efforts and economic resources—A critical concern for municipalities. Despite posing challenges to local ecosystems, the study identified C. linum as a natural source of bioactive metabolites. Phytochemical characterization revealed lipids, amino acids, and other compounds with potential anti-inflammatory activity in C. linum extract. In vitro assays with LPS-stimulated RAW 264.7 and TNF-α/IFN-γ-stimulated HaCaT cells showed the extract inhibited reactive oxygen species (ROS), nitric oxide (NO), and prostaglandin E2 (PGE2) productions, and reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions via NF-κB nuclear translocation, in RAW 264.7 cells. It also reduced chemokines (TARC/CCL17, RANTES/CCL5, MCP-1/CCL2, and IL-8) and the cytokine IL-1β production in HaCaT cells, suggesting potential as a therapeutic candidate for chronic diseases like atopic dermatitis. Finally, in silico studies indicated palmitic acid as a significant contributor to the observed effect. This research not only uncovered the untapped potential of C. linum but also laid the foundation for its integration into the circular bioeconomy, promoting sustainable practices, and innovative applications across various industries.

Repurposing saffron (Crocus sativus) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste—350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H2O2-induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae. This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST's significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through "green" methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy. [ABSTRACT FROM AUTHOR]

Social media have become increasingly embedded in adolescents’ daily lives. Although these contexts have been widely studied, how trust in online relationships is built among adolescents is still an unexplored issue. By adopting the theoretical socio-cognitive model of trust, this study aims to explore the components of online trust as far as today’s teenagers are concerned. The study involved 10 adolescents aged between 12 and 18 (M = 15.5). The data were collected using individual semi-structured, audio-recorded, and faithfully transcribed interviews. A deductive-inductive content analysis carried out with the NVivo10 software was performed on the textual material. Results show that adolescents seem to be aware of online trust value in “selecting” peers to be trusted. To protect themselves from the risks they are exposed to, they choose to interact with peers/friends who are already known in real life or are similar to them in terms of interests, ways of thinking, passions, and age. Additionally, others’ competencies and willingness play an important role in adolescents’ evaluations and decisions to rely on others online. The results of this study could be useful for developing awareness-raising interventions on the risks that adolescents are exposed to in order to promote “safe” relationships of trust and emphasize the possible positive use of technologies (e.g., by building online trust relationships using peer “safe” models).

The concept of a "circular bioeconomy" holds great promise for the health, cosmetic, and nutrition sectors by re-using Castanea sativa (Mill.) by-products. This sustainable resource is rich in bioactive secondary metabolites with antioxidant and anti-inflammatory properties. By transforming these by-products into high-value products for human health, we can promote sustainable economic growth and reduce the environmental impact of traditional waste disposal, adding value to previously underutilized resources. In the present study, we investigated the antioxidant capacity, phytochemical composition, and in vitro antioxidant and anti-inflammatory activity of C. sativa burr (CSB) aqueous extract. The spectrophotometric study revealed high total phenolic content (TPC) values with significant antioxidant and anti-radical properties. Using UPLC-MS/MS techniques, the phytochemical investigation identified 56 metabolites, confirming the presence of phenolic compounds in CSBs. In addition, CSBs significantly downregulated pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophage cells without significant cell toxicity. Lastly, in silico studies pinpointed three kinases from RAW 264.7 cells as binding partners with ellagic acid, the predominant compound found in our extract. These findings strongly advocate for the recycling and valorization of C. sativa by-products, challenging their conventional classification as mere "waste". [ABSTRACT FROM AUTHOR]

We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood-brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity. Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol and behaves as a cannabinoid (CB1/CB2) receptor indirect agonist. Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner. Moreover, 4a produced analgesic effects in a rodent model of acute inflammatory pain, which was antagonized by CB1 and CB2 receptor antagonists/inverse agonists. 4a also relieves the neuropathic hypersensitivity induced by oxaliplatin. Given these evidence, 4a, as MGL selective inhibitor, could represent a valuable lead for the future development of therapeutic options for multiple sclerosis and chronic pain.

Biocompatible nanocarriers can be obtained by lipid extraction from natural sources such as algal biomasses, which accumulate different lipid classes depending on the employed culture media. Lipid aggregates can be distinguished according to supramolecular architecture into lamellar and nonlamellar structures. This distinction is mainly influenced by the lipid class and molecular packing parameter, which determine the possible values of interfacial curvature and thus the supramolecular symmetries that can be obtained. The nanosystems prepared from bio-sources are able to self-assemble into different compartmentalized structures due to their complex composition. They also present the advantage of increased carrier-target biocompatibility and are suitable to encapsulate and vehiculate poorly water-soluble compounds, e.g., natural antioxidants. Their functional properties stem from the interplay of several parameters. Following previous work, here the functionality of two series of structurally distinct lipid nanocarriers, namely liposomes and cubosomes deriving from algal biomasses with different lipid composition, is characterized. In the view of their possible use as pharmaceutical or nutraceutical formulations, both types of nanovectors were loaded with three well-known antioxidants, i.e., curcumin, α-tocopherol and piperine, and their carrier efficacy was compared considering their different structures. Firstly, carrier stability in biorelevant conditions was assessed by simulating a gastrointestinal tract model. Then, by using an integrated chemical and pharmacological approach, the functionality in terms of encapsulation efficiency, cargo bioaccessibility and kinetics of antioxidant capacity by UV-Visible spectroscopy was evaluated. Subsequently, in vitro cytotoxicity and viability tests after administration to model cell lines were performed. As a consequence of this investigation, it is possible to conclude that nanovectors from algal lipids, i.e., cubosomes and liposomes, can be efficient delivery agents for lipophilic antioxidants, being able to preserve and enhance their activity toward different targets while promoting sustained release.

Utilizing plant-based resources, particularly their by-products, aligns with sustainability principles and circular bioeconomy, contributing to environmental preservation. The therapeutic potential of plant extracts is garnering increasing interest, and this study aimed to demonstrate promising outcomes from an extract obtained from an underutilized plant waste. Chaetomorpha linum, an invasive macroalga found in the Orbetello Lagoon, thrives in eutrophic conditions, forming persistent mats covering approximately 400 hectares since 2005. The biomass of C. linum undergoes mechanical harvesting and is treated as waste, requiring significant human efforts and economic resources—A critical concern for municipalities. Despite posing challenges to local ecosystems, the study identified C. linum as a natural source of bioactive metabolites. Phytochemical characterization revealed lipids, amino acids, and other compounds with potential anti-inflammatory activity in C. linum extract. In vitro assays with LPS-stimulated RAW 264.7 and TNF-α/IFN-γ-stimulated HaCaT cells showed the extract inhibited reactive oxygen species (ROS), nitric oxide (NO), and prostaglandin E2 (PGE2) productions, and reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions via NF-κB nuclear translocation, in RAW 264.7 cells. It also reduced chemokines (TARC/CCL17, RANTES/CCL5, MCP-1/CCL2, and IL-8) and the cytokine IL-1β production in HaCaT cells, suggesting potential as a therapeutic candidate for chronic diseases like atopic dermatitis. Finally, in silico studies indicated palmitic acid as a significant contributor to the observed effect. This research not only uncovered the untapped potential of C. linum but also laid the foundation for its integration into the circular bioeconomy, promoting sustainable practices, and innovative applications across various industries. [ABSTRACT FROM AUTHOR]

Following the severe impact of capitalist industrialization on the environment, the EU has funded several projects in the context of the European Green Deal to pursue climate neutrality by 2050. Some of these projects attempt to achieve zero emissions through political participation, while others by committing EU citizens to adopt sustainable habits in terms of both practical behavior and economic choices. The GreenSCENT project, funded by the European Union's Horizon 2020 research and innovation programme, aims to develop a Competence Framework compliant with the European Qualifications Framework and the European Green Deal. The present article documents the process of developing such a Competence Framework. Eight distinct research teams independently conducted a similar thorough literature review over an assigned topic (Climate Change; Clean Energy; Circular Economy; Green Building; Smart Mobility; From Farm to Fork; Biodiversity; Zero Pollution). The resulting documental corpora have then elicited to build the competence matrices and the corresponding European Qualification Framework levels. Once the information has been reorganized as a knowledge graph, the researchers discovered a large amount of novel interdomain connections, providing a more engaging way of interacting with the Competence Framework, and potentially apt to avoiding information overload issues while preserving the complexity, in line with the simplexity paradigm. The environmental education tools produced by this research could be useful in mitigating the repercussions of Capitalocene on the environment toward the adoption of more sustainable behaviors. [ABSTRACT FROM AUTHOR]

BackgroundClinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina.MethodsMulticenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU).ResultsA total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27).ConclusionsThis cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

An easy and viable crosslinking procedure by click-chemistry (click-crosslinking) of hyaluronic acid (HA) was developed. In particular, the clickable propargyl groups of hyaluronane-based HA-FA-Pg graft copolymers showing low and medium molecular weight values were exploited in crosslinking by click-chemistry by using a hexa(ethylene glycol) spacer. The resulting HA-FA-HEG-CL materials showed an apparent lack of in vitro cytotoxic effects, tuneable water affinity, and rheological properties according to the crosslinking degree that suggests their applicability in different biomedical fields.

This study aimed to determine the in vitro cytotoxicity and mutagenicity of graphene flake (GF) and aqueous graphene paste (AGP) in order to evaluate their potential for application as biomaterials. Furthermore, their antitumor activity against adherent and suspended cells, namely, human breast adenocarcinoma cells (MDA-MB-231), and human monocytes from histiocytic lymphoma (U-937), was investigated. The results demonstrated that GF reduced the viability and proliferation of NIH3T3 immortalized murine fibroblasts for concentrations >0.8 µg/mL and incubation times of 48 and 72 h. AGP showed no toxic effects in any of the tested concentrations and incubation times. The same results were obtained for MDA-MB-231 cells. The viability of the U-937 cells was not affected by either GF or AGP. The Ames test showed that GF and AGP were not genotoxic against Salmonella typhimurium strains TA98 and TA100, with and without metabolic activation. The present study demonstrated good in vitro cellular compatibility of GF and AGP and. Among these, AGP was the best material as it did not interfere, at any of the tested concentrations, with cell viability and proliferation for up to 72 h of incubation. In any case, neither material induced alterations to cell morphology and were not mutagenic.

Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports an overview of the hemostatic process and thrombotic disorders together with data on plants, more and less common from around the world, containing bioactive compounds characterized by antiplatelet and anticoagulant activity. The reported literature was obtained from Medline, PubMed, Elsevier, Web of Science, Google Scholar considering only articles in the English language, published in peer-reviewed journals. The number of citations of the articles and the impact factor of the journals were other parameters used to select the scientific papers to be included in the review. The analysis of the literature data selected demonstrates that many plants’ bioactive compounds show antiplatelet and anticoagulant activity that make them potential candidates to be used as new natural compounds able to interfere with both primary and secondary hemostasis. Moreover, they could be used together with anticoagulants currently administered in clinical practice to increase their efficacy and to reduce complications in the treatment of thrombotic disorders.

Plants and their extracts have traditionally been used against various pathologies and in some regions are the only therapeutic source for the treatment and prevention of many chronic diseases [...]