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Kefiran is a heteropolysaccharide that is considered a postbiotic and is obtained by kefir grains fermented in cow’s milk, while little is known about the donkey milk (DM) variety. Postbiotics are recognised as having important human health benefits that are very similar to probiotics but without the negative effects associated with their ingestion. Donkey is a monogastric animal, as are humans, and when used as an alternative food for infants who suffer from cow milk protein allergies, DM could therefore display more biocompatibility. In this study, the DM kefiran was extracted by ultrasound from kefir grains cultured in donkey milk and fully characterized for its structural and physicochemical properties by Fourier-transform infrared spectroscopy (FT-IR), High-Performance Liquid Chromatography- Refractive Index (HPLC-RI), Scanning electron microscope (SEM), Differential Scanning Calorimeters (DSC) and rheological analyses. In addition, tests were conducted on keratinocytes cell lines and human red blood cells to assess the nontoxicity and haemolysis degree of the polymer. The extraction yield of the DM kefiran was 6.5 ± 0.15%. The FT-IR analysis confirmed the structure of the polysaccharide by showing that the stretching of the C-O-C and C-O bonds in the ring, which formed two bands at 1157 and 1071 cm−1, respectively, and the anomeric band at 896 cm−1 indicates the β configuration and vibrational modes of glucose and galactose. Results were confirmed by HPLC-RI analysis indicating that the ratio glucose/galactose was 1:0.87. Furthermore, the SEM analysis showed a porous and homogeneous structure. The rheological analysis confirmed the pseudoplastic nature of the polymer, while the DSC analysis highlighted excellent thermal resistance (324 °C). Finally, DM kefiran was revealed to have biologically acceptable toxicity, showing a haemolytic activity of less than 2% when using fresh human red blood cells and showing no cytotoxicity on human keratinocytes. Therefore, kefiran obtained by DM shows an excellent biocompatibility, establishing it as a promising polymer for bioengineering human tissue for regenerative applications.

Background: Stereotactic body radiotherapy (SBRT) targeted at metastatic sites of disease progression is emerging as a potential therapeutic approach for managing oligoprogressive prostate cancer. However, a definitive benefit has yet to be demonstrated. Herein, we present our institution’s experience with this treatment approach. Methods: From April 2018 to March 2023, 11 patients affected by oligoprogressive prostate cancer were treated with SBRT targeting the nodal or bone sites of progression while maintaining the ongoing systemic therapy. Three patients were undergoing single-agent ADT (Androgen Deprivation Therapy), while the remaining eight were receiving a subsequent line of systemic therapy. All patients were evaluated with a pre-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT, which demonstrated between one and five localizations of disease. All the active sites were treated with SBRT in one (15–24 Gy) or three (21–27 Gy) fractions, except for one patient, who was treated in five fractions (35 Gy). PSA serum levels were tested at baseline, one month after RT and at least every three months; all patients underwent a post-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. The evaluated endpoints were PSA response, defined as a post-treatment decrease >50% from baseline measured within 6 months, time to next-line systemic treatment (NEST), local control (LC), biochemical progression-free survival (bPFS), radiological progression-free survival (rPFS) and freedom from polymetastatic progression (FPP). Results: Nineteen lesions were treated (seven nodal and twelve bone). At a median follow-up of 19 months (7–63), 9 of the 11 patients had a PSA response; all patients had local control of the treated metastases. A total of six patients switched to a next-line systemic treatment, with a median NEST of 13 months. Six patients had polymetastatic progression with an FPP median time of 19 months. No patients died during the follow-up period. The SBRT-related toxicity was negligible. Conclusions: Our data support the use of SBRT targeting the sites of oligoprogressive disease before moving to a subsequent line of systemic treatment in patients with metastatic prostate cancer. Prospective studies to evaluate the potential impact of this approach on overall survival are warranted.

Excessive daytime sleepiness (EDS) and insomnia (IN) complaints represent the most common sleep/wake disorders. Currently, the specific needs of these patients and their relatives, as well as the overall socio-economic burden of IN and EDS remains widely unexplored. This pilot study to be carried out in Switzerland is a retro- and prospective, national, one-center cohort observational study for the systematic evaluation of the burden of EDS and IN and its evolution 12 months after the first assessment. Patient recruitment will be organized through 7–8 primary care providers (primary/general care practitioners and pharmacies). Primary outcomes are the prevalence of EDS/IN in the primary care setting and the association between EDS/IN with health-related quality of life (QOL) as assessed with the established instruments. Secondary outcomes are the association between EDS/IN with the presence of comorbidities, number of injuries/accidents, and number of sick/leave days for the subgroup of working subjects. Calculation of direct per-patient costs will be undertaken to analyze the economic implications of sleep/wake disorders, providing valuable insights into the financial burden experienced by affected individuals within the healthcare system. This research will provide information on the feasibility of such a study and inform on aspects of the QOL most associated with EDS/IN. Based on this pilot project, a European multicenter study on the burden of sleep/wake disorders will be conducted by the European Academy of Neurology.

The by-products of green coffee processing are rich in compounds that can be recycled for their possible use in the production of beverages, fertilizers and weed control in production areas. The objective of this work was to identify the organic and inorganic bioactive compounds of green coffee and the coffee by-products related to the production of origin, such as dried cascara (skin-pulp), parchment and silverskin (unroasted), in order to investigate the role their biomolecules may have in reuse through practices and local knowledge, not yet valued. The metabolomic profile by HPLC-ESI-HRMS of the aqueous extract of the dried cascara highlighted 93 non-volatile molecules, the highest number reported for dried cascara. They belong to groups of organic acids (12), alkaloids (5), sugars (5), fatty acids (2), diglycerides (1), amino acids (18), phospholipids (7), vitamins (5), phenolic acids (11), flavonoids (8), chlorogenic acids (17), flavones (1) and terpenes (1). For the first time, we report the use of direct analysis in real-time mass spectrometry (DART-MS) for the identification of metabolites in aqueous extracts of dried cascara, parchment, silverskin and green coffee. The DART analysis mainly showed the presence of caffeine and chlorogenic acids in all the extracts; additionally, sugar adducts and antioxidant compounds such as polyphenols were detected. The mineral content (K, Ca, P, S, Mg and Cl) by EDS spectrometry in the by-products and green coffee showed a relatively high content of K in the dried cascara and green coffee, while Ca was detected in double quantity in the silverskin. These metabolomic and mineral profile data allow enhancement of the link between the quality of green coffee and its by-products and the traditional local practices in the crop-growing area. This consolidates the community’s experience in reusing by-products, thereby minimizing the impact on the environment and generating additional income for coffee growers’ work, in accordance with the principles of circular economy and bioeconomy.

The six PCGF proteins (PCGF1-6) define the biochemical identity of Polycomb repressor complex 1 (PRC1) subcomplexes. While structural and functional studies of PRC1 subcomplexes have revealed their specialized roles in distinct aspects of epigenetic regulation, our understanding of the variation in the protein interaction networks of distinct PCGF subunits in different PRC1 complexes is incomplete. We carried out an affinity purification mass spectrometry (AP-MS) screening of three PCGF subunits, PCGF1 (NSPC1), PCGF2 (MEL18), and PCGF4 (BMI1), to define their interactome and potential cellular function in pluripotent human embryonal carcinoma cell “NT2”. The bioinformatic analysis revealed that these interacting proteins cover a range of functional pathways, often involved in cell biology and chromatin regulation. We also found evidence of mutual regulation (at mRNA and protein level) between three distinct PCGF subunits. Furthermore, we confirmed that the disruption of these subunits results in reduced cell proliferation ability. We reveal an interplay between the compositional diversity of the distinct PCGF containing PRC1 complex and the potential role of PCGF proteins within the wider cellular network.

Third-generation snacks were developed from a triad of flours made up of chestnut, spelt, and chickpea flour. Optimal snack formulations and processing parameters have been established to ensure acceptable workability of the raw dough while protecting the bioactive components of the raw materials. The parameters examined were mixing time, speed, and temperature. The properties of the snack were evaluated by analyzing the expansion ratio, hardness, moisture content, and phenolic and volatile compounds. The optimal mixing conditions that ensure maximum expansion were a temperature of 30 °C, a speed of 30 rpm, and a time of 6 min. The results showed that the proper percentage of water and sodium bicarbonate was 35% and 2%, respectively, and that the developed snacks had an alveolar and homogeneous structure. The proposed approach brings several advantages, including the preservation of bioactive compounds during the production process. Furthermore, the mild operating conditions prevented the development of unwanted or unpleasant compounds, as confirmed by the analysis of volatile compounds. Therefore, this study opens new perspectives in the food industry, satisfying the growing demand for functional products and healthy snacks.

Bitumen, a vital component in road pavement construction, exhibits complex chemo-mechanical properties that necessitate thorough characterization for enhanced understanding and potential modifications. Nuclear Magnetic Resonance (NMR) spectroscopy emerges as a valuable technique for probing the structural and compositional features of bitumen. This review presents an in-depth exploration of the role of NMR spectroscopy in bitumen characterization, highlighting its diverse applications in determining bitumen content, group composition, molecular dynamics, and interaction with additives. Various NMR techniques, including free induction decay (FID), Carr–Purcell–Meilboom–Gill (CPMG), and Pulsed Field Gradient Stimulated Echo (PFGSE), are discussed in the context of their utility in bitumen analysis. Case studies, challenges, and limitations associated with NMR-based bitumen characterization are critically evaluated, offering insights into potential future research directions. Overall, this review provides a comprehensive overview of the current state-of-the-art in NMR-based bitumen characterization and identifies avenues for further advancement in the field.

Keeping up with the fast evolution of mobile operating systems is challenging for developers, who have to frequently adapt their apps to the upgrades and behavioral changes of the underlying API framework. Those changes often break backward compatibility. The consequence is that apps, if not updated, may misbehave and suffer unexpected crashes if executed within an evolved environment. Being able to quickly identify the portion of the app that should be modified to provide compatibility with new API versions can be challenging. To facilitate the debugging activities of problems caused by backward incompatible upgrades of the operating system, this paper presents FILO, a technique that is able to recommend the method that should be modified to implement the fix by analyzing a single failing execution. FILO can also provide additional information and key symptomatic anomalous events that can help developers understand the reason for the failure, therefore facilitating the implementation of the fix. We evaluated FILO against 18 real compatibility problems related to Android upgrades and compared it with Spectrum-Based Localization approaches. Results show that FILO is able to efficiently and effectively identify the fix-locus in the apps.

Antimicrobial resistance affects all environments, endangering the health of numerous species, including wildlife. Increasing anthropic pressure promotes the acquisition and dissemination of antibiotic resistance by wild animals. Sea turtles, being particularly exposed, are considered sentinels and carriers of potential zoonotic pathogens and resistant strains. Therefore, this study examined the antibiotic resistance profiles of bacteria isolated from loggerhead sea turtles hospitalised in a rescue centre of Southern Italy over a 9-year period. Resistance to ceftazidime, doxycycline, enrofloxacin, flumequine, gentamicin, oxytetracycline and sulfamethoxazole-trimethoprim was evaluated for 138 strains isolated from the clinical samples or organs of 60 animals. Gram-negative families were the most isolated: Vibrionaceae were predominant, followed by Shewanellaceae, Pseudomonadaceae, Enterobacteriaceae and Morganellaceae. These last three families exhibited the highest proportion of resistance and multidrug-resistant strains. Among the three Gram-positive families isolated, Enterococcaceae were the most represented and resistant. The opportunistic behaviour of all the isolated species is particularly concerning for diseased sea turtles, especially considering their resistance to commonly utilised antibiotics. Actually, the multiple antibiotic resistance was higher when the sea turtles were previously treated. Taken together, these findings highlight the need to improve antimicrobial stewardship and monitor antibiotic resistance in wildlife, to preserve the health of endangered species, along with public and environmental health.

In order to understand the coordinated proteome changes associated with differentiation of a cultured cell pluripotency model, protein expression changes induced by treatment of NT2 embryonal carcinoma cells with retinoic acid were monitored by mass spectrometry. The relative levels of over 5000 proteins were mapped across distinct cell fractions. Analysis of the chromatin fraction revealed major abundance changes among chromatin proteins and epigenetic pathways between the pluripotent and differentiated states. Protein complexes associated with epigenetic regulation of gene expression, chromatin remodelling (e.g., SWI/SNF, NuRD) and histone-modifying enzymes (e.g., Polycomb, MLL) were found to be extensively regulated. We therefore investigated histone modifications before and after differentiation, observing changes in the global levels of lysine acetylation and methylation across the four canonical histone protein families, as well as among variant histones. We identified the set of proteins with affinity to peptides housing the histone marks H3K4me3 and H3K27me3, and found increased levels of chromatin-associated histone H3 tail trimming following differentiation that correlated with increased expression levels of cathepsin proteases. We further found that inhibition of cathepsins B and D reduces histone H3 clipping. Overall, the work reveals a global reorganization of the cell proteome congruent with differentiation, highlighting the key role of multiple epigenetic pathways, and demonstrating a direct link between cathepsin B and D activity and histone modification.

Introduction: Children born prematurely (5, children with RSD, and children with neither elevated PLMS index nor RSD. Results: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27–34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal–Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3–0.9) than in the PLMS (median 1.7, IQR 0.7–3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8–4.5) groups. Conclusions: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.

This study explores the impact of environmental pollutants on nuclear receptors (CAR, PXR, PPARα, PPARγ, FXR, and LXR) and their heterodimerization partner, the Retinoid X Receptor (RXR). Such interaction may contribute to the onset of non-alcoholic fatty liver disease (NAFLD), which is initially characterized by steatosis and potentially progresses to steatohepatitis and fibrosis. Epidemiological studies have linked NAFLD occurrence to the exposure to environmental contaminants like PFAS. This study aims to assess the simultaneous activation of nuclear receptors via perfluorooctanoic acid (PFOA) and RXR coactivation via Tributyltin (TBT), examining their combined effects on steatogenic mechanisms. Mice were exposed to PFOA (10 mg/kg/day), TBT (5 mg/kg/day) or a combination of them for three days. Mechanisms underlying hepatic steatosis were explored by measuring nuclear receptor target gene and lipid metabolism key gene expressions, by quantifying plasma lipids and hepatic damage markers. This study elucidated the involvement of the Liver X Receptor (LXR) in the combined effect on steatosis and highlighted the permissive nature of the LXR/RXR heterodimer. Antagonistic effects of TBT on the PFOA-induced activation of the Pregnane X Receptor (PXR) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) were also observed. Overall, this study revealed complex interactions between PFOA and TBT, shedding light on their combined impact on liver health.

This research has investigated Italian consumers’ preferences for and purchasing behaviors of strawberries utilizing the Best–Worst Scaling methodology (BWS). This approach enables the key factors that influence strawberry purchasing decisions to be identified and different choice groups to be characterized. To achieve this goal, a survey was conducted on a sample of 496 respondents living in the metropolitan area of Milan (North Italy). The declared preferences of the individuals for 12 strawberry characteristics, divided into intrinsic, extrinsic, and credence attributes, were first measured. A Latent Class Analysis (LCA) was then performed to identify different clusters of consumers according to the individuals’ preferences. Subsequently, the heterogeneity of the clusters was tested, using the Chi-square test, and sociodemographic characteristics and purchasing habits were considered. The results suggest that the most important attribute in the choice of strawberries was appearance, highlighting the importance of preserving it throughout the supply chain, followed by one of the increasingly important aspects of diets, which is health benefits. The attribute considered the least important was the brand. This study demonstrates, from a holistic point of view, that sociodemographic characteristics, food habits, and perceptions of different strawberry attributes influence consumers’ preferences and behaviors. Practical implications suggest a new prospective for communication marketing strategies for producers, creating a better brand identity and highlighting in their marketing all of the aspects that consumers would like to know about the fruits they choose as quality certifications.

In recent times, circular economy initiatives in addition to the need for sustainable biomaterials have brought about several attempts at the eco-friendly, eco-sustainable and cost-effective production of asphalt pavements. It is an increasingly common practice in the asphalt industry to improve road pavement performance using additives to enhance the physico-chemical properties of bitumen, which performs the role of the binder in the asphalt mix. This paper evaluated the potential of a bio-based additive derived from olive leaf residue as a modifier and antioxidant agent for bitumen. Samples of neat, aged and doped aged bitumen were analyzed. In this study, the two bio-based additives were characterized in terms of phenol, chlorophyll, lignin and cellulose content, which was correlated with the mechanical properties of the tested samples. The mechanical properties of the neat, modified, aged and unaged samples were evaluated via Dynamic Shear Rheology. The bio-based additives proved to be promising and can improve the properties of bitumen binder and the performance of asphalt pavements in general.

The B-factor, also known as the atomic displacement parameter, is a fundamental metric in crystallography for quantifying the positional flexibility of atoms within crystal lattices. In structural biology, various developments have expanded the use of B-factors beyond conventional crystallographic analysis, allowing for a deeper understanding of protein flexibility, enzyme manipulation, and an improved understanding of molecular dynamics. However, the interpretation of B-factors is complicated by their sensitivity to various experimental and computational factors, necessitating rigorous rescaling methods to ensure meaningful comparisons across different structures. This article provides an in-depth description of rescaling approaches used for B-factors. It includes an examination of several methods for managing conformational disorder and selecting the atom types required for the analysis.

Colloidal systems are peculiar mixtures formed by the uniform dispersion of sub-micro sized particles of one substance through another substance. In this framework, a particular colloidal system, known as sol, is a colloid in which the dispersed particles are solid, and the dispersing medium is fluid. Sols have extensive applications in industries ranging from material science to food to pharmaceuticals and cosmetics. The size and size distribution of colloidal particles within these systems play a pivotal role in determining their stability, rheological properties, and overall functionality (which in turn directly influence material quality, performance, and shelf life). As a result, this study is aimed at devising a new method to analyze the dimensions of the colloidal particles (dispersed phase) of a colloidal system (sol), like bitumen, by (i) a cheap and common technique, optical microscopy, and (ii) the more complex confocal laser scanning microscopy. To do so, a validation by comparison with a standard technique—in this case, atomic force microscopy is presented. Both optical and confocal microscopies turned out to be suitable, valid, and effective for particle size determination. Both techniques effectively revealed, upon bitumen aging, a shift of the size distribution to slightly larger sizes. Large particles, whose abundance did not increase significantly, appeared to be more inert than small ones. A huge advantage of optical microscopy is its popularity and cost-effectiveness as it is commonly featured in laboratories independently of the research topic. On the other hand, confocal microscopy can observe more particles, thus providing better statistics. It also appears to be more efficient for particles smaller than 1 µm2. These microscopy techniques were used to evaluate the dimensions of the asphaltenes present in a complex colloidal system; bitumen; the model colloidal system for this study, which was examined before and after an aging process which is expected to change the size distribution.

Listeria monocytogenes is a ubiquitous pathogen found both in the environment and food. It can cause listeriosis in a wide range of animals as well as in humans. Investigations on presence, spread and virulence are still limited to terrestrial and human environments. Embracing the One Health Approach, investigating the presence and spread of L. monocytogenes in marine ecosystems and among wildlife, would provide us with useful information for human health. This study investigated the presence of L. monocytogenes and Listeria spp. in two species of sea turtles common in the Mediterranean Sea (Caretta caretta and Chelonia mydas). A total of one hundred and sixty-four carcasses of sea turtles (C. caretta n = 161 and C. mydas n = 3) stranded along the Abruzzo, Molise, Campania, and Calabria coasts, were collected. Brain and fecal samples were taken, enriched, and cultured for the detection of Listeria spp. From the specimens collected, strains of L. monocytogenes (brain n = 1, brain and feces n = 1, multiorgan n = 1 and feces n = 1), L. innocua (feces n = 1 and brain n = 1), and L. ivanovii (brain n = 1) were isolated. Typical colonies were isolated for Whole Genome Sequencing (WGS). Virulence genes, disinfectants/metal resistance, and antimicrobial resistance were also investigated. L. monocytogenes, L. innocua, and L. ivanovii were detected in C. caretta, whilst only L. monocytogenes and L. innocua in C. mydas. Notable among the results is the lack of significant differences in gene distribution between human and sea turtle strains. Furthermore, potentially pathogenic strains of L. monocytogenes were found in sea turtles.

Background: This study aims to evaluate the percutaneous permeation profiles of caffeic acid (CA) from the cubic and hexagonal liquid crystalline phases of Pluronic P123/water mixtures. Method: The resulting drug-loaded mesophases were subjected to characterisation through deuterium nuclear magnetic resonance spectroscopy and polarised optical microscopy observations. These analyses aimed to evaluate the structural changes that occurred in the mesophases loading with CA. Additionally, steady and dynamic rheology studies were conducted to further explore their mechanical properties and correlate them to the supramolecular structure. Finally, CA release experiments were carried out at two different temperatures to examine the behaviour of the structured systems in a physiological or hyperthermic state. Results: As the concentration of the polymer increases, an increase in the viscosity of the gel is noted; however, the addition of caffeic acid increases microstructure fluidity. It is observed that the temperature effect conforms to expectations. The increase in temperature causes a decrease in viscosity and, consequently, an increase in the rate of permeation of caffeic acid. Conclusions: The CA permeation profile from the prepared formulations is mostly dependent on the structural organisation and temperature. Cubic mesophase LLC 30/CA showed greater skin permeation with good accumulation in the skin at both tested temperatures.

Gout is caused by the deposition of monosodium urate crystals in the joint and represents the most common form of inflammatory arthritis in men. Its prevalence is rising worldwide mainly due to the increase of risk factors associated with the disease, in particular hyperuricemia. Besides gout, hyperuricemia leads to an increased inflammatory state of the body with consequent increased risk of comorbidities such as cardiovascular diseases. Increasing evidence shows that bioactive compounds have a significant role in fighting inflammatory and immune chronic conditions. In gout and hyperuricemia, these molecules can exert their effects at two levels. They can either decrease serum uric acid concentrations or fight inflammation associated with monosodium urate crystals deposits and hyperuricemia. In this view, they might be considered valuable support to the pharmacological therapy and prevention of the disease. This review aims to provide an overview of the beneficial role of bioactive compounds in hyperuricemia, gout development, and inflammatory pathways of the disease.

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent infiltrating type of pancreatic cancer. The poor prognosis associated with this cancer is due to the absence of specific biomarkers, aggressiveness, and treatment resistance. PDAC is a deadly malignancy bearing distinct genetic alterations, the most common being those that result in cancer-causing versions of the KRAS gene. Cannabigerol (CBG) is a non-psychomimetic cannabinoid with anti-inflammatory properties. Regarding the anticancer effect of CBG, up to now, there is only limited evidence in human cancers. To fill this gap, we investigated the effects of CBG on the PDAC cell lines, PANC-1 and MIAPaCa-2. The effect of CBG activity on cell viability, cell death, and EGFR-RAS-associated signaling was investigated. Moreover, the potential synergistic effect of CBG in combination with gemcitabine (GEM) and paclitaxel (PTX) was investigated. MTT was applied to investigate the effect of CBG on PDAC cell line viabilities. Annexin-V and Acridine orange staining, followed by cytofluorimetric analysis and Western blotting, were used to evaluate CBG’s effect on cell death. The modulation of EGFR-RAS-associated pathways was determined by Western blot analysis and a Milliplex multiplex assay. Moreover, by employing the MTT data and SynergyFinder Plus software analysis, the effect of the combination of CBG and chemotherapeutic drugs was determined.

In this work, the peels of red and blonde oranges as well as lemons were efficiently (5.75–9.65% yield) extracted by hydroalcoholic solution with ultrasound assistance and employed as active molecule sources in the preparation of functional gummies. Antioxidant performances of the hydroalcoholic extracts were characterized by colorimetric assays, whereas LC–HRMS analyses identified the main bioactive compounds (phenolic acids and flavonoids). The highest scavenging activity was recorded for lemon extract in an aqueous environment (IC50 = 0.081 mg mL−1). An ecofriendly grafting procedure was performed to anchor polyphenols to gelatin chains, providing macromolecular systems characterized by thermal analysis and antioxidant properties. Scavenger abilities (IC50 = 0.201–0.454 mg mL−1) allowed the employment of the conjugates as functional ingredients in the preparation of gummies with remarkable antioxidant and rheological properties over time (14 days). These findings confirmed the possible employment of highly polluting wastes as valuable sources of bioactive compounds for functional gummies preparation.

Enhanced oil recovery (EOR) processes are technologies used in the oil and gas industry to maximize the extraction of residual oil from reservoirs after primary and secondary recovery methods have been carried out. The injection into the reservoir of surface-active substances capable of reducing the surface tension between oil and the rock surface should favor its extraction with significant economic repercussions. However, the most commonly used surfactants in EOR are derived from petroleum, and their use can have negative environmental impacts, such as toxicity and persistence in the environment. Biosurfactants on the other hand, are derived from renewable resources and are biodegradable, making them potentially more sustainable and environmentally friendly. The present review intends to offer an updated overview of the most significant results available in scientific literature on the potential application of biosurfactants in the context of EOR processes. Aspects such as production strategies, techniques for characterizing the mechanisms of action and the pros and cons of the application of biosurfactants as a principal method for EOR will be illustrated and discussed in detail. Optimized concepts such as the HLD in biosurfactant choice and design for EOR are also discussed. The scientific findings that are illustrated and reviewed in this paper show why general emphasis needs to be placed on the development and adoption of biosurfactants in EOR as a substantial contribution to a more sustainable and environmentally friendly oil and gas industry.

Background. Transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has an analgesic effect superior to a placebo in chronic pain. Some years ago, tDCS was implemented at the Hospital Nacional of Paraplegics (Toledo, Spain) to treat patients with pharmacological resistance to chronic pain. Objective. The main objectives of this study with tDCS were (1) to confirm the safety of one-year treatment; (2) to estimate the number of patients after one year in treatment; (3) to describe the effects of tDCS on the pain intensity during one-year treatment; and (4) to identify factors related to treatment success. Methods. This was a retrospective study conducted at the National Hospital for Paraplegics with 155 patients with pharmacologically resistant chronic pain. Anodal tDCS was applied over the M1 for 20 min at 1.5 mA for 10 treatment sessions from Monday to Friday (Induction phase), followed by 2–3 sessions per month (Maintenance phase). Pain intensity was assessed using a Visual Analogue Scale (VAS). Results. Anodal tDCS on M1 confirmed the reduction in the pain intensity. Moreover, 58% of outpatients completed one year of treatment. Only the VAS values obtained during the baseline influenced the response to treatment. Patients with a very high VAS at the baseline were more likely to not respond adequately to tDCS treatment. Conclusions. Anodal tDCS over M1 is an adequate therapy (safe and efficient) to treat drug-resistant chronic pain. Moreover, pain intensity at the start of treatment could be a predictor of patients’ continuity with tDCS for at least one year.

The synthesis of core–shell magnetic mesoporous nanoparticles (MMSNs) through a phase transfer process is usually performed at the 100–250 mg scale. At the gram scale, nanoparticles without cores or with multicore systems are observed. Iron oxide core nanoparticles (IO) were synthesized through a thermal decomposition procedure of α-FeO(OH) in oleic acid. A phase transfer from chloroform to water was then performed in order to wrap the IO nanoparticles with a mesoporous silica shell through the sol–gel procedure. MMSNs were then functionalized with DTPA (diethylenetriaminepentacetic acid) and used for the separation of metal ions. Their toxicity was evaluated. The phase transfer procedure was crucial to obtaining MMSNs on a large scale. Three synthesis parameters were rigorously controlled: temperature, time and glassware. The homogeneous dispersion of MMSNs on the gram scale was successfully obtained. After functionalization with DTPA, the MMSN-DTPAs were shown to have a strong affinity for Ni ions. Furthermore, toxicity was evaluated in cells, zebrafish and seahorse cell metabolic assays, and the nanoparticles were found to be nontoxic. We developed a method of preparing MMSNs at the gram scale. After functionalization with DTPA, the nanoparticles were efficient in metal ion removal and separation; furthermore, no toxicity was noticed up to 125 µg mL−1 in zebrafish.

Road pavement characteristics can be improved by modifying bitumens through addition of fine particles. To avoid environmental issues, attention is recently being paid to bio-materials. In this study, a 50/70 bitumen was modified through the addition of char obtained from the pyrolysis of waste tires. Char addition causes an increase in transition (gel to sol) temperature of up to 4 °C and an increase in rigidity under working conditions (50 °C) of up to about one order of magnitude. The effect of the gas type flowing under the pyrolysis process (CO2, N2 and CO2 + N2) on the mechanical characteristics of the bitumen was also investigated. More marked effects on the rheological performances were found if char coming from pyrolysis under CO2 was used (the gel-to-sol transition temperature is increased by about 4.5 °C) compared to that coming from pyrolysis under N2 (gel-to-sol transition temperature is increased by about 3 °C). The effect is at a maximum for char from CO2 at 3% wt/wt, whereas regarding char from N, a lesser effect is seen with a more uniform (flat) effect as a function of char% and with an increase in gel-to-sol transition temperature of about 3 °C. Coherently, char obtained from pyrolysis under CO2 was found to possess a higher surface area constituted by smaller particles than that coming from pyrolysis under N2. In fact, the BET-specific surface passes 79 m2/g for N2-char to 174 m2/g for CO2-char and the micropore volume fraction increases from 2 to 9. The observed differences can be attributed to the oxidizing environment (CO2) that is more aggressive and reactive in the synthesis phase compared to an inert environment (N2). Char also showed an anti-aging effect, hindering the increase in rigidity typically associated with the aging process. This effect was explained in terms of the compatibility of char with bitumen’s organic nature, and presumably its more effective hosting in a bituminous structure, which is presumably higher when char is produced under CO2 rather than N2. This study quantitatively indicates how a residue derived from the pyrolysis of a waste material can be efficiently re-used to increase the mechanical characteristics of bitumen, accomplishing the recent circular-based needs for environmental protection.

Hepatitis C virus (HCV) has spread worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of the host’s immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct-acting antivirals (DAA) has created hope for the progressive elimination of chronic HCV infections; however, this approach requires a monumental global effort. HCV elicits a prompt innate immune response in the host, characterized by a robust production of interferon-α (IFN-α), although interference in IFN-α signaling by HCV proteins may curb this effect. The late appearance of largely ineffective neutralizing antibodies and the progressive exhaustion of T cells, particularly CD8 T cells, result in the inability to eradicate the virus in most infected patients. Moreover, an HCV cure resulting from DAA treatment does not completely restore the normal immunologic homeostasis. Here, we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind.

The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1β, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1β, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 β in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals.

Fmoc-diphenylalanine (Fmoc-FF) is a low-molecular-weight peptide hydrogelator. This simple all-aromatic peptide can generate self-supporting hydrogel materials, which have been proposed as novel materials for diagnostic and pharmaceutical applications. Our knowledge of the molecular determinants of Fmoc-FF aggregation is used as a guide to design new peptide-based gelators, with features for the development of improved tools. Here, we enlarge the plethora of Fmoc-FF-based hydrogelated matrices by studying the properties of the Fmoc-FFK tripeptide, alone or in combination with Fmoc-FF. For multicomponent matrices, the relative weight ratios between Fmoc-FFK and Fmoc-FF (specifically, 1/1, 1/5, 1/10, and 1/20 w/w) are evaluated. All the systems and their multiscale organization are studied using different experimental techniques, including rheology, circular dichroism, Fourier transform infrared spectroscopy, and scanning electron microscopy (SEM). Preliminary profiles of biocompatibility for the studied systems are also described by testing them in vitro on HaCaT and 3T3-L1 cell lines. Additionally, the lysine (K) residue at the C-terminus of the Fmoc-FF moiety introduces into the supramolecular material chemical functions (amino groups) which may be useful for modification/derivatization with bioactive molecules of interest, including diagnostic probes, chelating agents, active pharmaceutical ingredients, or peptide nucleic acids.

Muonic Atom X-ray Emission spectroscopy (µ-XES) is a novel elemental technique that exploits the high-energy X-rays emitted from the muonic atom cascade process to characterize materials. At the ISIS Neutron and Muon Source, the technique is performed at Port4 of the RIKEN-RAL facility, with a user demand that is increasing every year. To cope with this demand, it is necessary to continue to improve the method, either for the hardware (detectors, acquisition, etc.) or software (data analysis and interpretation). In both cases, Monte Carlo codes play an important role: with a simulation, it is possible to reproduce the experimental setup and provide a reliable quantitative analysis. In this work, we investigate the capabilities of GEANT4 for such applications. From the results, we observed that the generation of X-rays, especially the kα and kβ transition for high Z atoms, are not in agreement with the experimental ones. A solution to this issue, other than an attempt with a small modification of the GEANT4 cascade class, could be provided by a database of transition energy calculated by a Dirac equation software called MuDirac. The software, developed by the UKRI scientific computing department and the ISIS muon group, can compute all the transition energy for a given nuclide. Here, preliminary results of the implementation of the MuDirac database in GEANT4 are reported.

Two non-redundant, high-quality sets of protein X-ray crystal structures from the Protein Data Bank (room temperature, 288–298 K, and low temperature, 95–105 K) were compared to structural predictions conducted using ColabFold/AlphaFold2. In particular, the relationship between B-factors and pLDDT values, which estimate the degree of prediction confidence, was investigated. It was observed that there is basically no correlation between these two quantities and, consequently, that the level of confidence in predictions does not provide information about the degree of local structural flexibility of globular proteins.

Multicomponent hydrogels (HGs) based on ultrashort aromatic peptides have been exploited as biocompatible matrices for tissue engineering applications, the delivery of therapeutic and diagnostic agents, and the development of biosensors. Due to its capability to gel under physiological conditions of pH and ionic strength, the low molecular-weight Fmoc-FF (Nα-fluorenylmethoxycarbonyl-diphenylalanine) homodimer is one of the most studied hydrogelators. The introduction into the Fmoc-FF hydrogel of additional molecules like protein, organic compounds, or other peptide sequences often allows the generation of novel hydrogels with improved mechanical and functional properties. In this perspective, here we studied a library of novel multicomponent Fmoc-FF based hydrogels doped with different amounts of the tripeptide Fmoc-FFX (in which X= Cys, Ser, or Thr). The insertion of these tripeptides allows to obtain hydrogels functionalized with thiol or alcohol groups that can be used for their chemical post-derivatization with bioactive molecules of interest like diagnostic or biosensing agents. These novel multicomponent hydrogels share a similar peptide organization in their supramolecular matrix. The hydrogels’ biocompatibility, and their propensity to support adhesion, proliferation, and even cell differentiation, assessed in vitro on fibroblast cell lines, allows us to conclude that the hybrid hydrogels are not toxic and can potentially act as a scaffold and support for cell culture growth.

Alzheimer disease (AD) is one of the most common and disabling neuropathies in the ever-growing aged population around the world, that especially affects Western countries. We are in urgent need of finding an effective therapy but also a valid prophylactic means of preventing AD. There is a growing attention currently paid to DNA vaccination, a technology particularly used during the COVID-19 era, which can be used also to potentially prevent or modify the course of neurological diseases, including AD. This paper aims to discuss the main features and hurdles encountered in the immunization and therapy against AD using DNA vaccine technology. Ultimately, this work aims to effectively promote the efforts in research for the development of safe and effective DNA and RNA vaccines for AD.

The European eel, Anguilla anguilla (Linnaeus, 1758), is a species of high conservation and commercial value. Also, with a high aquacultural value, it was one of the most farmed species in Europe before its decline. Conservation measures for this species are currently being implemented, some of which are the release of adults to allow them to migrate to spawning grounds and artificial reproduction to minimise the impact of overfishing. Much progress has been made regarding the closing of the life cycle, but several problems remain to be solved, such as the weaning and growth of larvae. In this regard, the study of local populations and the identification of the best spawners could be a good way forward as it would help to identify spawners with high reproductive potential and good offspring quality. In this study, we compared the reproductive performance of female eels from migratory areas of the Northern Adriatic Sea at different maturation stages (10 pre-migrant stage; 10 migrant stage), treating both groups with the same hormonal protocol (weekly carp pituitary extract, injection of 17α,20β-Dihydroxy-4-pregnen-3-one at complete oocyte maturation). The research showed that eels at the beginning of metamorphosis (SI III), i.e., eels not yet ready to undertake migration, achieve reproductive performance equal to that of eels ready for migration (SI IV). Their performance was on par in both qualitative and quantitative terms. The optimal results in hatching (with values of 65.8 ± 3.2% for pre-migrant and 68.2 ± 4.1% for migrant) and survival rates (with value of 25.7 ± 5.4% pre-migrants; 27.2 ± 3.7% migrants), as well as the results about the time to reach full gonadal maturation, may have positive implications when considering release and restocking measures.

Before using basic oxygen furnace slag (BOFS) in any engineering application, it is important to determine its properties. The chemical composition, mineralogy, and physical properties of BOF slag are subject to large fluctuations as a result of different raw additives, different compositions of the molten iron used for producing the steel, oxygen stirring of a molten pool, uneven temperature fields, and other complex physical conditions. Thus, in this research, the engineering properties of BOF slag aggregates with different ages were identified, and then the feasibility of BOF slag aggregates in mortar application was investigated. It was found that stockpiled BOFS was harder than fresh BOF slag, which had lower aggregate crushing values and lower LA abrasion values. Also, stockpiled BOFS showed less expansion than fresh BOF slag regardless of water and 1 M NaOH solution immersion. The chemical reaction between f-CaO, f-MgO, and water due to weathering in the field extremely reduced the expansion of BOFS submerged in water. BOFS may contain reactive silica, which causes an alkali–silica reaction (ASR). Stockpiled BOFS (100%, 75%, 50%, 25%) used as a mineral filler in asphalt concrete mix brought about low tensile strength at break up (crack), low compressive strength at +50 °C, poor cohesion, and residual porosity. However, these parameters were partially improved with the use of a thermostable adhesive additive for road bitumen based on polyphosphoric acid esters. The comprehensive assessment in this study indicates that while some mixtures meet the specified criteria for certain properties, there are challenges, particularly regarding crack resistance and cohesion, that need to be addressed to fully align with the standard. Adjustments to the mixture proportions, the exploration of alternative additives, and the use of different types of fillers may be necessary to achieve the desired properties, especially in terms of crack resistance and cohesion.

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease worldwide, affecting 70–90% of obese individuals. In humans, a lower NAFLD incidence is reported in pre-menopausal women, although the mechanisms affording this protection remain under-investigated. Here, we tested the hypothesis that the constitutive androstane nuclear receptor (CAR) plays a role in the pathogenesis of experimental NAFLD. Male and female wild-type (WT) and CAR knock-out (CAR−/−) mice were subjected to a high-fat diet (HFD) for 16 weeks. We examined the metabolic phenotype of mice through body weight follow-up, glucose tolerance tests, analysis of plasmatic metabolic markers, hepatic lipid accumulation, and hepatic transcriptome. Finally, we examined the potential impact of HFD and CAR deletion on specific brain regions, focusing on glial cells. HFD-induced weight gain and hepatic steatosis are more pronounced in WT males than females. CAR−/− females present a NASH-like hepatic transcriptomic signature suggesting a potential NAFLD to NASH transition. Transcriptomic correlation analysis highlighted a possible cross-talk between CAR and ERα receptors. The peripheral effects of CAR deletion in female mice were associated with astrogliosis in the hypothalamus. These findings prove that nuclear receptor CAR may be a potential mechanism entry-point and a therapeutic target for treating NAFLD/NASH.

A baked gluten-free pastry was formulated using milk kefir, rice, and different amounts of carob pulp flour, i.e., 20% (B1) and 40% (B2). In all cases, B2 showed the most remarkable antioxidant properties in terms of total phenolic, phenolic acid, and flavonoid content, as well as scavenging activity both in aqueous and organic media. This trend was observed over a 6-day storage time. Lower cohesive interactions among dough aggregate domains were recorded as the carob pulp flour amount increased. At the same time, rigidity decreased in the order B0 > B1 > B2 as confirmed by lower textural properties shown by the carob-added samples. Sensory analysis recorded overall acceptability for both B1 and B2, with sweetness, cocoa, gingerbread, and rye aroma as predominant descriptors. The glycemic index determination confirmed a better score for B2 and revealed a medium GI value (62), in comparison with high GIs recorded for B1 and B0 (115 and 100, respectively).

The conjugation of polyphenols is a valuable strategy with which to confer tailored properties to polymeric materials of biomedical interest. Within this investigation, we aim to explore the possibility to use this synthetic approach to increase the viscosity of conjugates, thus allowing the release of a loaded therapeutic to be better controlled over time than in neat polyphenols. Curcumin (CUR) was conjugated to sodium alginate (CA) and chitosan (CS) with functionalisation degrees of 9.2 (SA-CUR) and 15.4 (CS-CUR) mg g−1. Calorimetric analyses showed higher degrees of chain rigidity upon conjugation, with a shift of the degradation peaks to higher temperatures (from 239 to 245 °C and from 296 to 303 °C for SA-CUR and CS-CUR, respectively). Rheological analyses were used to prove the enhanced interconnection between the polymer chains in the conjugates, confirmed by the weak gel parameters, A and z. Moreover, the typical non-Newtonian behaviour of the high-molecular-weight polysaccharides was recorded, together with an enhancement of the activation energy, Ea, in CS-CUR vs. CS (opposite behaviour recorded for SA-CUR vs. SA). The evaluation of the delivery performance (of Doxorubicin as a model drug) showed sustained release profiles, opening opportunities for the development of controlled delivery systems.

In the last few years, restless sleep has been described as the key element of many clinical issues in childhood, leading to the recognition of “restless sleep disorder” (RSD) as a new proposed diagnostic category. The essential aid of video-polysomnographic recordings enables detection and quantification of the “large muscle group movements” (such as limb movements and repositioning) frequently described by parents of children with RSD. Strong evidence links iron deficiency to the pathophysiology of sleep-related movement disorders such as RSD, restless legs syndrome, periodic limb movement disorder, and attention deficit hyperactivity disorder (ADHD) due to the important role played by the brain dopamine production system. Serum ferritin is the main parameter used to evaluate iron deficiency in patients with sleep-related movement disorders. Iron supplementation is recommended when the serum ferritin level is

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine that is involved in various innate and adaptive immune processes related to infection, inflammation, and autoimmunity. Therefore, it is described as a key mediator of autoinflammatory diseases associated with the development of macrophage activation syndrome (MAS), including systemic juvenile idiopathic arthritis and adult-onset Still’s disease. This review focuses on the role of IL-18 in inflammatory responses, placing emphasis on autoinflammatory diseases associated with chronic excess of serum IL-18, which correlate with clinical and biological signs of the disease. Therefore, it is useful for the diagnosis and monitoring of disease activity. Researchers are currently investigating IL-18’s role as a therapeutic target for the treatment of inflammatory diseases. The inhibition of IL-18 signaling through recombinant human IL-18BP (IL-18 binding protein) seems to be an effective therapeutic strategy, though further studies are necessary to clarify its importance as a therapeutic target.

The increased use of bioplastics in the market has led to their presence in municipal solid waste streams alongside traditional fossil-based polymers, particularly low-density polyethylene (LDPE), which bioplastics often end up mixed with. This study aimed to assess the impact of cellulose acetate plasticized with triacetin (CAT) on the mechanical recycling of LDPE. LDPE–CAT blends with varying CAT content (0%, 1%, 5%, 7.5%, and 10% by weight) were prepared by melt extrusion and analyzed using scanning electron microscopy, Fourier-transform infrared spectroscopy, thermal analysis (thermogravimetric and differential scanning calorimetry), dynamic rheological measurements, and tensile tests. The results indicate that the presence of CAT does not significantly affect the chemical, thermal, and rheological properties of LDPE, and the addition of CAT at different levels does not promote LDPE degradation under typical processing conditions. However, the addition of CAT negatively impacts the processability and mechanical behavior of LDPE, resulting in the reduced quality of the recycled material. Thus, the presence of cellulose-based bioplastics in LDPE recycling streams should be avoided, and a specific sorting stream for bioplastics should be established.

Octopus vulgaris is a commercially valuable species. It is overexploited in the natural environment and is considered to be an innovative species for aquaculture. However, large-scale farming is generally designed only based on economic requirements, disregarding any form of enrichment that induces the natural behavior of aquatic species. Although many studies have shown the influence of environmental enrichment on terrestrial vertebrates, fish, and cephalopod mollusks, information on the effect of environmental enrichment on the body patterns of O. vulgaris is limited. Therefore, in this study, we assessed how different environmental conditions (Basic vs. Enriched) affect sub-adults of O. vulgaris kept in recirculation systems, through qualitative–quantitative studies of the main body patterns and their potential application in the commercial production of this species. The results indicated that octopuses kept in the enriched environment showed several body patterns and gained a significantly higher weight than those kept in the basic environment. The body patterns displayed by the individuals kept in the basic environment were similar to those exhibited under situations of hostility and inter/intra-specific conflict. Hence, the environment of octopuses needs to be enriched, especially for the large-scale production of this species.

In audio transduction applications, virtualization can be defined as the task of digitally altering the acoustic behavior of an audio sensor or actuator with the aim of mimicking that of a target transducer. Recently, a digital signal preprocessing method for the virtualization of loudspeakers based on inverse equivalent circuit modeling has been proposed. The method applies Leuciuc’s inversion theorem to obtain the inverse circuital model of the physical actuator, which is then exploited to impose a target behavior through the so called Direct–Inverse–Direct Chain. The inverse model is designed by properly augmenting the direct model with a theoretical two-port circuit element called nullor. Drawing on this promising results, in this manuscript, we aim at describing the virtualization task in a broader sense, including both actuator and sensor virtualizations. We provide ready-to-use schemes and block diagrams which apply to all the possible combinations of input and output variables. We then analyze and formalize different versions of the Direct–Inverse–Direct Chain describing how the method changes when applied to sensors and actuators. Finally, we provide examples of applications considering the virtualization of a capacitive microphone and a nonlinear compression driver.

The sleep–wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin and GABA, that can be, in turn, regulated by different nutrients involved in their metabolic pathways. Although good sleep quality in children has been proven to be a key factor for optimal cognitive, physical and psychological development, a significant and ever-increasing percentage of the pediatric population suffers from sleep disorders. In children, behavioral interventions along with supplements are recommended as the first line treatment. This systematic review was conducted, according to the PRISMA guidelines, with the purpose of assessing the principal nutrients involved in the pathways of sleep-regulating neurotransmitters in children and adolescents. Our focus was the utilization of over the counter (OTC) products, specifically iron, hydroxytryptophan, theanine and antihistamines in the management of different pediatric sleep disorders with the intention of providing a practical guide for the clinician.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been responsible for a devastating pandemic since March 2020. Toll-like receptors (TLRs), crucial components in the initiation of innate immune responses to different pathogens, trigger the downstream production of pro-inflammatory cytokines, interferons, and other mediators. It has been demonstrated that they contribute to the dysregulated immune response observed in patients with severe COVID-19. TLR2, TLR3, TLR4 and TLR7 have been associated with COVID-19 severity. Here, we review the role of TLRs in the etiology and pathogenesis of COVID-19, including TLR7 and TLR3 rare variants, the L412F polymorphism in TLR3 that negatively regulates anti-SARS-CoV-2 immune responses, the TLR3-related cellular senescence, the interaction of TLR2 and TLR4 with SARS-CoV-2 proteins and implication of TLR2 in NET formation by SARS-CoV-2. The activation of TLRs contributes to viral clearance and disease resolution. However, TLRs may represent a double-edged sword which may elicit dysregulated immune signaling, leading to the production of proinflammatory mediators, resulting in severe disease. TLR-dependent excessive inflammation and TLR-dependent antiviral response may tip the balance towards the former or the latter, altering the equilibrium that drives the severity of disease.

The nuclear receptor, constitutive androstane receptor (CAR), which forms a heterodimer with the retinoid X receptor (RXR), was initially reported as a transcription factor that regulates hepatic genes involved in detoxication and energy metabolism. Different studies have shown that CAR activation results in metabolic disorders, including non-alcoholic fatty liver disease, by activating lipogenesis in the liver. Our objective was to determine whether synergistic activations of the CAR/RXR heterodimer could occur in vivo as described in vitro by other authors, and to assess the metabolic consequences. For this purpose, six pesticides, ligands of CAR, were selected, and Tri-butyl-tin (TBT) was used as an RXR agonist. In mice, CAR’s synergic activation was induced by dieldrin associated with TBT, and combined effects were induced by propiconazole, bifenox, boscalid, and bupirimate. Moreover, a steatosis, characterized by increased triglycerides, was observed when TBT was combined with dieldrin, propiconazole, bifenox, boscalid, and bupirimate. Metabolic disruption appeared in the form of increased cholesterol and lowered free fatty acid plasma levels. An in-depth analysis revealed increased expression of genes involved in lipid synthesis and lipid import. These results contribute to the growing understanding of how environmental contaminants can influence nuclear receptor activity and associated health risks.

Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH. Adult patients with AE-C1-INH, followed by Reference Centers belonging to the Italian Network for Hereditary and Acquired Angioedema (ITACA), were enrolled in this study. Patients received nucleoside-modified mRNA vaccines and vaccines with adenovirus vectors. Data on acute attacks developed in the 72 h following COVID-19 vaccinations were collected. The frequency of attacks in the 6 months after the COVID-19 vaccination was compared with the rate of attacks registered in the 6 months before the first vaccination. Between December 2020 and June 2022, 208 patients (118 females) with AE-C1-INH received COVID-19 vaccines. A total of 529 doses of the COVID-19 vaccine were administered, and the majority of patients received mRNA vaccines. Forty-eight attacks of angioedema (9%) occurred within 72 h following COVID-19 vaccinations. About half of the attacks were abdominal. Attacks were successfully treated with on-demand therapy. No hospitalizations were registered. There was no increase in the monthly attack rate following the vaccination. The most common adverse reactions were pain at the site of injection and fever. Our results show that adult patients with angioedema due to C1 inhibitor deficiency can be safely vaccinated against SARS-CoV-2 in a controlled medical setting and should always have available on-demand therapies.

Genome damage has been related to the induction of autoimmune processes, chronic inflammation, and apoptosis. Recent studies suggest that some rheumatological diseases are associated with overall genomic instability in the T cell compartment. However, no data regarding leucocyte abnormalities in synovial fluid (SF) and their relationship with inflammation are available. The aim of this study was to investigate cellular phenotypes in SF collected from patients with different inflammatory arthropathies, including rhematoid arthritis (RA), psoriatic arthritis (PsA), crystal-induced arthritis (CIA), and non-inflammatory arthropathies, such as osteoarthritis (OA). We found high percentage of micronuclei in SF from CIA compared to the other groups and a high frequency of pyknotic cell in RA and CIA patients. A correlation between pyknosis and immature polymorphonuclear cells with local inflammatory indices was observed. The study of the apoptosis process revealed an increased BAX expression in CIA and RA compared to OA and PsA, while Bcl-2 was higher in CIA. Caspase-3 activity was increased in SF from RA patients and correlates with inflammatory and anti-inflammatory cytokines. In conclusion, our results showed that inflammatory SF is associated with genomic instability and abnormal cell subsets.

This study investigates the potential of utilizing three food wastes: cheese whey (CW), beet molasses (BM), and corn steep liquor (CSL) as alternative nutrient sources for the cultivation of the diatom Phaeodactylum tricornutum, a promising source of polyunsaturated eicosapentaenoic acid (EPA) and the carotenoid fucoxanthin. The CW media tested did not significantly impact the growth rate of P. tricornutum; however, CW hydrolysate significantly enhances cell growth. BM in cultivation medium enhances biomass production and fucoxanthin yield. The optimization of the new food waste medium was conducted through the application of a response surface methodology (RSM) using hydrolyzed CW, BM, and CSL as factors. The results showed a significant positive impact of these factors (p < 0.005), with an optimized biomass yield of 2.35 g L−1 and a fucoxanthin yield of 3.64 mg L−1 using a medium composed of 33 mL L−1 of CW, 2.3 g L−1 of BM, and 2.24 g L−1 of CSL. The experimental results reported in this study showed that some food by-products from a biorefinery perspective could be utilized for the efficient production of fucoxanthin and other high-added-value products such as eicosapentaenoic acid (EPA).

Background: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a small-vessel necrotizing vasculitis. The anti-neutrophil cytoplasmic antibodies’ (ANCA) role in defining clinical EGPA phenotypes is well established. Although the role of eosinophils in disease pathogenesis has been clearly demonstrated, the value of blood eosinophil count (BEC) as a biomarker of disease phenotypes is currently uncertain. Methods: We retrospectively analyzed EGPA patients referred to our Immunology Clinic. Demographic, laboratory and clinical features were retrieved from clinical records, and a Logistic Regression was fitted to evaluate the predictive power of all baseline clinical and laboratory features to define EGPA phenotypes. Results: 168 patients were recruited. BEC ≤ 1500 cells/mL was predictive of a clinical involvement characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and lung opacities (OR 0.18, 95% CI 0.07–0.43; respiratory-limited phenotype); BEC > 3500/mL was predictive of extrapulmonary organ involvement (OR 3.5, 95% CI 1.7–7.1; systemic phenotype). BEC was also predictive of peripheral nervous system (PNS) involvement, with a positive trend with increasing BEC (3500/mL: OR 2.8, 95% CI, 1.5–5.28). ANCA positivity was also predictive of extrapulmonary involvement (OR 4.7, 95% CI 1.9–11.99). Conclusions: according to BEC and irrespective of the ANCA status, two EGPA phenotypes could be identified, named systemic and respiratory-limited phenotypes, with different organ involvement and possibly different prognoses.

In this study, we fabricated three different ZnO tetrapodal nanostructures (ZnO-Ts) by a combustion process and studied their physicochemical properties by different techniques to evaluate their potentiality for label-free biosensing purposes. Then, we explored the chemical reactivity of ZnO-Ts by quantifying the available functional hydroxyl groups (–OH) on the transducer surface necessary for biosensor development. The best ZnO-T sample was chemically modified and bioconjugated with biotin as a model bioprobe by a multi-step procedure based on silanization and carbodiimide chemistry. The results demonstrated that the ZnO-Ts could be easily and efficiently biomodified, and sensing experiments based on the streptavidin target detection confirmed these structures’ suitability for biosensing applications.