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The aim of this research is to propose simple and scalable processes to obtain bioactive peptides extensively hydrolyzed starting from a tuna mixed biomass. The upcycling of this powdered biomass is challenging since it comes from the unsorted industrial side streams of the tuna canning process (cooked residues from fillet trimming) after a patented mild dehydration useful for preventing its degradation until its exploitation. Two different protocols were proposed, with and without the inclusion of an exogenous enzyme (Enzymatic-Assisted Extraction, EAE), with no relevant differences in yields (24% vs. 22%) and a comparable amino acid composition. Nevertheless, the former protocol (with EAE) provided peptides with an average molecular weight of 1.3 kDa, and the second one (without EAE) provided peptides with an average molecular weight of 2.2 kDa. The two corresponding types of tuna protein hydrolysates (Enzymatic Hydrolysates (EH) and Non-Enzymatic Hydrolysates (NEH)) were characterized by proximate compositions, pH, color profile, amino acid analysis, FTIR spectra, and molecular weight distribution. In addition, several biological analyses were performed to assess their potential use as nutraceutical supplements: special attention has been paid to antioxidant activity using three different methods to quantify it. EH showed the most promising antioxidant activity which could be exploited also in other fields (e.g., biomaterials, cosmetics). [ABSTRACT FROM AUTHOR]

Background: Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents. Case presentation: An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial weight loss. Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs. Conclusions: Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out. [ABSTRACT FROM AUTHOR]

Aging is characterized by increased oxidation and reduced efficiency of cytoprotective mechanisms. Nuclear factor erythroid-2-related factor (Nrf2) is a key transcription factor, controlling the expression of multiple antioxidant proteins. Here, we show that Nrf2−/− mice displayed an age-dependent anemia, due to the combined contributions of reduced red cell lifespan and ineffective erythropoiesis, suggesting a role of Nrf2 in erythroid biology during aging. Mechanistically, we found that the expression of antioxidants during aging is mediated by activation of Nrf2 function by peroxiredoxin-2. The absence of Nrf2 resulted in persistent oxidation and overactivation of adaptive systems such as the unfolded protein response (UPR) system and autophagy in Nrf2−/− mouse erythroblasts. As Nrf2 is involved in the expression of autophagy-related proteins such as autophagy-related protein (Atg) 4-5 and p62, we found impairment of late phase of autophagy in Nrf2−/− mouse erythroblasts. The overactivation of the UPR system and impaired autophagy drove apoptosis of Nrf2−/− mouse erythroblasts via caspase-3 activation. As a proof of concept for the role of oxidation, we treated Nrf2−/− mice with astaxanthin, an antioxidant, in the form of poly (lactic-co-glycolic acid) (PLGA)-loaded nanoparticles (ATS-NPs) to improve its bioavailability. ATS-NPs ameliorated the age-dependent anemia and decreased ineffective erythropoiesis in Nrf2−/− mice. In summary, we propose that Nrf2 plays a key role in limiting age-related oxidation, ensuring erythroid maturation and growth during aging. [ABSTRACT FROM AUTHOR]

DNA data storage based on synthetic oligonucleotides is a major attraction due to the possibility of storage over long periods. Nowadays, the quantity of data generated has been growing exponentially, and the storage capacity needs to keep pace with the growth caused by new technologies and globalization. Since DNA can hold a large amount of information with a high density and remains stable for hundreds of years, this technology offers a solution for current long-term data centers by reducing energy consumption and physical storage space. Currently, research institutes, technology companies, and universities are making significant efforts to meet the growing need for data storage. DNA data storage is a promising field, especially with the advancement of sequencing techniques and equipment, which now make it possible to read genomes (i.e., to retrieve the information) and process this data easily. To overcome the challenges associated with developing new technologies for DNA data storage, a message encoding and decoding exercise was conducted at a Brazilian research center. The exercise performed consisted of synthesizing oligonucleotides by the phosphoramidite route. An encoded message, using a coding scheme that adheres to DNA sequence constraints, was synthesized. After synthesis, the oligonucleotide was sequenced and decoded, and the information was fully recovered. [ABSTRACT FROM AUTHOR]

The enzymatic extraction of proteins from fish biomasses is being widely investigated. However, little or almost no research has paid attention to the exploitation of unsorted fishery biomasses. This work is part of a larger study, Part I of which has already been published, and focuses on an extensive characterization of two collagenous samples, namely gelatin (G) and hydrolyzed gelatin peptides (HGPs), extracted from a dehydrated fish biomass coming from unsorted canned yellowfin tuna side streams. The results indicate crude protein fractions of 90–93%, pH values between 3 and 5, white–yellow colors, collagen-like FTIR spectra, and 17% in terms of total amino acid content. Viscosity and the study of dynamic viscous–elastic behavior were analyzed. Thermo-gravimetric analysis was performed to assess the residual ashes. Both samples were investigated to determine their molecular weight distribution via size-exclusion chromatography, with a higher total average molecular weight for G compared to HGPs, with values of 17,265.5 Da and 2637.5 Da, respectively. G demonstrated technological properties similar to analogous marine gelatins. HGPs demonstrated antioxidant activity as per FRAP assay. All the results open up new perspectives for the potential use of these substances in biodegradable packaging, dietary supplements, and skin care cosmetics. [ABSTRACT FROM AUTHOR]

Estimating the habitual food and nutrient intakes of a population is based on dietary assessment methods that collect detailed information on food consumption. Establishing the list of foods to be used for collecting data in dietary surveys is central to standardizing data collection. Comparing foods across different data sources is always challenging. Nomenclatures, detail, and classification into broad food groups and sub-groups can vary considerably. The use of a common system for classifying and describing foods is an important prerequisite for analyzing data from different sources. At the European level, EFSA has addressed this need through the development and maintenance of the FoodEx2 classification system. The aim of this work is to present the FoodEx2 harmonization of foods, beverages, and food supplements consumed in the IV SCAI children's survey carried out in Italy. Classifying foods into representative food categories predefined at European level for intake and exposure assessment may lead to a loss of information. On the other hand, a major advantage is the comparability of data from different national databases. The FoodEx2 classification of the national food consumption database represented a step forward in the standardization of the data collection and registration. The large use of FoodEx2 categories at a high level of detail (core and extended terms) combined with the use of descriptors (facets) has minimized information loss and made the reference food categories at country level comparable with different food databases at national and international level. [ABSTRACT FROM AUTHOR]

Chestnut processing has increasingly grown in recent years. All the processes involved in the chestnut supply chain are characterized by the production of high levels of by-products that cause several environmental and disposal issues. The Castanea spp. fruit production is related to a high number of chestnut episperm. This underutilized agricultural by-product may be evaluated as a good resource for the extraction of health-promoting natural molecules, such as phenolics. This preliminary study aimed to develop and optimize, using a multivariate statistical approach, a sustainable protocol for the ultrasound-assisted extraction (UAE) of the main phenolics from chestnut episperm (cv Marsol, C. sativa × C. crenata). A design of experiment (DoE) approach was employed. This approach focused on the two quantitative UAE process factors: the extraction time (X1), within a timeframe ranging from 10 to 30 min, and the sample-to-solvent (w/v) ratio (X2), ranging from 1/30 to 1/10. These variables were investigated to determine their impact on phenol extraction yield. Exploratory analysis, in particular principal component analysis (PCA) and multiple linear regression (MLR), were carried out on the studied responses. The phenolic characterization of ten different extracts was also performed using high-performance liquid chromatography (HPLC), both to define the levels of specific phenolics selected for their health-promoting properties and to evaluate some important features, such as the total antioxidant capacity. The values of total polyphenolic content (TPC) obtained in the different experiments ranged between 97 (extract 4) and 142 (extract 6) mg GAE/g of dried weight (DW). Moreover, results from the ferric reducing antioxidant power (FRAP) test confirmed the high TPC values, highlighting that all the ultrasound extracts contained excellent levels of molecules with good antioxidant properties. In particular, extracts 2 and 3 showed the highest AOC values (about 490–505 mmol Fe2+/Kg of dried weight). The proposed optimized protocol allowed for obtaining formulations characterized by high levels of tannins, phenolic acids, and catechins. Indeed, episperm extracts contained high levels of chlorogenic acid (15–25 mg/100 g DW), ferulic acid (80–120 mg/100 g DW), castalagin (20–80 mg/100 g DW), and vescalagin (40–75 mg/100 g). Finally, in this research study, the potential of chestnut episperm as a source of polyphenolic molecules to be extracted by green technologies and used in several food and/or pharmaceutical applications was evaluated to valorize a sustainable reuse strategy of agri-food processing by-products, also reducing the environmental impact of this waste derived from chestnut processing. [ABSTRACT FROM AUTHOR]

Simple Summary: In older AML patients, their clinical fitness is of utmost importance for choosing the most appropriate therapy. Therefore, treatment-specific fitness criteria were devised in 2013 by SIE/SIES/GITMO to select patients deemed unfit for intensive chemotherapy (ICT) or even hypomethylating agents (HMAs). Since then, the therapeutic armamentarium for patients unfit for ICT has been enriched. In the present analysis of over 500 patients treated in REL centres, venetoclax/HMAs emerged as the most frequently used treatment. Considering its unique toxicity profile, an update of treatment-specific fitness criteria for selecting candidates for venetoclax/HMAs would be desirable. REL hematologists, who have gained experience with the combination over the last years, were asked if they actually restrict SIE/SIES/GITMO fitness criteria for HMAs when candidating patients to venetoclax/HMAs. A broad consensus emerged on limiting its choice to patients younger than 80–85, with a cardiac EF > 40%, without significant pulmonary comorbidities, and with an adequate caregiver. A retrospective survey was conducted in hematologic centres of the Rete Ematologica Lombarda (REL) on 529 older AML patients seen between 2020–2022. Compared to 2008–2016, the use of intensive chemotherapy (ICT) decreased from 40% to 18.1% and of hypomethylating agents (HMAs) from 19.5% to 13%, whereas the combination of Venetoclax/HMA, initially not available, increased from 0% to 36.7%. Objective treatment-specific fitness criteria proposed by SIE/SIES/GITMO in 2013 allow an appropriate choice between ICT and HMAs by balancing their efficacy and toxicity. Venetoclax/HMA, registered for patients unfit to ICT, has a unique toxicity profile because of prolonged granulocytopenia and increased infectious risk. Aiming at defining specific fitness criteria for the safe use of Venetoclax/HMA, a preliminary investigation was conducted among expert REL hematologists, asking for modifications of SIE/SIES/GITMO criteria they used to select candidates for Venetoclax/HMA. While opinions among experts varied, a general consensus emerged on restricting SIE/SIES/GITMO criteria for ICT-unfit patients to an age limit of 80–85, cardiac function > 40%, and absence of recurrent lung infections, bronchiectasis, or exacerbating COPD. Also, the presence of an adequate caregiver was considered mandatory. Such expert opinions may be clinically useful and may be considered when treatment-specific fitness criteria are updated to include Venetoclax/HMA. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) and joint hypermobility (JH) are considered two different etiological and clinical entities that most often appear in childhood. Despite growing increased research showing a co-occurrence for both conditions, a link between them is rarely established in clinical settings, and the relationship between ASD and JH has not so far been completely investigated in all age groups of ASD children. This preliminary study examined a cohort of 67 non-syndromic ASD children aged 2–18 years (sex ratio M:F = 12:1) showing different degrees of cognitive impairment and autism severity, using the Beighton scale and its revised version. A total of 63% of ASD patients aged 2–4 years and 73% of ASD patients aged ≥5 years presented significant scores of hypermobility. No significant correlation was found comparing total laxity score and cognitive assessments and severity of autistic symptomatology (p > 0.05). The results suggest that JH could be considered as a clinical characteristic of ASD patients and it needs to be assessed in order to schedule a better rehabilitation program. [ABSTRACT FROM AUTHOR]

Digital devices have gained popularity in the last 10 years as a tool for exercise prescription, the monitoring of daily physical activity, and nutrition for the management of a health-related parameter. Therefore, the aim of this study was to assess the effectiveness of the use of digital devices to monitor exercise data in sedentary persons with HIV who exercise following an individualized activity pacing (AP) protocol on cardiorespiratory fitness body composition, blood lipid profile, and psychological parameters. Twenty-four PLWH were enrolled in an 18-week randomized, open-label, pilot AP exercise protocol. All participants were monitored by a Health Band connected to a mobile app that transmitted the data to a server. At week 3, they were randomized either in an experimental group (EG), in which an open device configuration enabled them to receive training data feedback (n = 12), or continued with no data feedback (control group, n = 12). The primary endpoint was improvement from the baseline of 15% of steady-state oxygen consumption ( V ˙ O2) during a 6-min walking test. Technical issues occurred when pairing the health band with the app, which prevented EG participants from regularly receiving data feedback, and with data transmission to the server, which enabled only 40% monitoring of the total training days. Consequently, the study outcomes could not be compared between the two groups, and participants also lost confidence in the study. However, 19 out of 24 participants completed the AP program. Overall, only 6 (32%) improved steady-state V ˙ O2, with no significant changes at W18 from the baseline. Significant reductions were observed of BMI (p = 0.040), hip circumference (p = 0.027), and total-(p = 0.049) and HDL-cholesterol (p = 0.045). The failure of digital device performance substantially affected study procedures, monitoring, and participants' engagement, and likely limited the potential benefits of the AP exercise program. [ABSTRACT FROM AUTHOR]

Considering the global increase in fish consumption, the growing side-streams coming from the fish supply chain (e.g., skin, fins, tail, heads...), also including undersized or "unwanted catches", have been recently proposed as source of high-value bioactive compounds (e.g., peptides and fatty acids). In this case study, hydrolyzed collagen peptides (HCPs) were extracted from different parts of Mugil cephalus L. using environmentally friendly techniques such as ultrasounds and enzymatic treatments. Both a mixed biomass derived from the skin, fins, and tail, and a whole fish, were considered as starting biomass, simulating the unsorted processing side-streams and an undersized/unwanted catch, respectively. The extracted HCPs were purified in fractions (<3 KDa and >3 KDa) whose yields (about 5% and 0.04–0.3%, respectively) demonstrated the efficiency of the hydrolysis process. The extraction protocol proposed allowed us to also isolate the intermediate products, namely the lipids (about 8–10%) and the non-collagenous proteins (NCs, 16–23%), whose exploitation could be considered. Each sample was characterized using Sircol, UltraViolet-Spectra, and hydroxyproline assay, and the viability of their collagen fractions was tested on human endothelial cells. Significant effects were obtained at a fraction of <3 KDa, in particular at a concentration of 0.13 µg/mL. The T-scratch test was also performed, with positive results in all fractions tested. [ABSTRACT FROM AUTHOR]

Simple Summary: No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results. No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p < 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results. [ABSTRACT FROM AUTHOR]

This study presents for the first time a scalable process for the extraction of valuable proteins starting from samples of unsorted mixed tuna scraps which were previously dehydrated by an industrial patented process. The aims of this work were both to avoid the onerous sorting step of tuna leftovers, which generally consists of isolating skin and bones for collagen/gelatin extraction, and to improve the logistic of managing highly perishable biomass thanks to the reduction in its volume and to its microbiological stabilization. In view of a zero-waste economy, all the protein fractions (namely, non-collagenous proteins NCs and ALKs, gelatin, and hydrolyzed gelatin peptides, HGPs) isolated in the proposed single cascade flowchart were stabilized and preliminarily characterized. The extraction flowchart proposed allows one to obtain the following most promising compounds: 1.7 g of gelatin, 3.2 g of HGPs, and 14.6 g of NCs per 100 g of dehydrated starting material. A focus on oven-dried gelatin was reported in terms of proximate analysis, amino acid composition, color parameters, FT-IR spectrum, pH, and viscoelastic properties (5 mPa·s of viscosity and 14.3 °C of gelling temperature). All the obtained extracts are intended to be exploited in food supplements, feed, fertilizers/plant bio-stimulants, packaging, and the cosmetic industry. [ABSTRACT FROM AUTHOR]

Bud derivatives (BDs) represent a category of botanicals obtained by macerating the meristematic tissues (buds or young sprouts) of plants; widely used since ancient times in complementary medicine, they remain poorly investigated to date. In this study, a contribution is made toward the identification of the correct "a posteriori" attribution of the botanical species in commercial BDs, which is very important for ensuring the quality and safety of these natural products. Excitation–emission matrix (EEM) fluorescence spectroscopy proved to be a rapid, non-destructive and low-cost analytical instrument for providing a preliminary qualitative characterization of the BDs, allowing for the identification of specific spectral regions related to flavonol compounds and cinnamic and benzoic acids, in agreement with the targeted chromatographic analysis (HPLC-DAD), which completely defined a phytochemical profile for each BD considered. This information will be implemented in the first web application for the recognition of vegetable buds, named GEMMAPP, which was designed by the Authors and is proposed as a tool and future scientific data repository for providing information about the main, typical BDs of the France–Italy Alcotra territory. [ABSTRACT FROM AUTHOR]

Introduction: Specific Learning Disorder (SLD) is a neurodevelopmental disorder characterized by difficulties in perceiving and processing verbal and non-verbal information. It is usually accompanied by impaired academic skills leading to school dropout and emotional disturbances, resulting in significant distress and behavioral problems. Methods: A cognitive, academic, and emotional-behavioral assessment was performed at T0 and T1 in children and adolescents with SLD. Participants received psychotherapy and speech therapy treatment from T0 to T1. Results: In SLD, the most compromised cognitive functions were working memory and writing skills. An impact on academic abilities was found. Children and adolescents with SLD experience greater anxiety and depression levels compared to their control peers. Conclusions: SLD may adversely influence psychological well-being. To counteract such a consequence, more specific cognitive and academic skill-oriented strategies should be taken into consideration. [ABSTRACT FROM AUTHOR]

Zebrafish has become an essential model organism in modern biomedical research. Owing to its distinctive features and high grade of genomic homology with humans, it is increasingly employed to model diverse neurological disorders, both through genetic and pharmacological intervention. The use of this vertebrate model has recently enhanced research efforts, both in the optical technology and in the bioengineering fields, aiming at developing novel tools for high spatiotemporal resolution imaging. Indeed, the ever-increasing use of imaging methods, often combined with fluorescent reporters or tags, enable a unique chance for translational neuroscience research at different levels, ranging from behavior (whole-organism) to functional aspects (whole-brain) and down to structural features (cellular and subcellular). In this work, we present a review of the imaging approaches employed to investigate pathophysiological mechanisms underlying functional, structural, and behavioral alterations of human neurological diseases modeled in zebrafish. [ABSTRACT FROM AUTHOR]

We study the strategic similarity of game positions in two-player extensive games of perfect information by looking at the structure of their local game trees, with the aim of improving the performance of game-playing agents in detecting forcing continuations. We present a range of measures over the induced game trees and compare them against benchmark problems in chess, observing a promising level of accuracy in matching up trap states. Our results can be applied to chess-like interactions where forcing moves play a role, such as those arising in bargaining and negotiation. [ABSTRACT FROM AUTHOR]

In transportation networks, incomplete information is ubiquitous, and users often delegate their route choice to distributed route planners. To model and study these systems, we introduce network control games, consisting of multiple actors seeking to optimise the social welfare of their assigned subpopulations through resource allocation in an underlying nonatomic congestion game. We first analyse the inefficiency of the routing equilibria by calculating the Price of Anarchy for polynomial cost functions, and then, using an Asynchronous Advantage Actor–Critic algorithm implementation, we show that reinforcement learning agents are vulnerable to choosing suboptimal routing as predicted by the theory. Finally, we extend the analysis to allow vehicles to choose their route planner and study the associated equilibria. Our results can be applied to mitigate inefficiency issues arising in large transport networks with route controlled autonomous vehicles. [ABSTRACT FROM AUTHOR]

Angiogenesis and metastasis represent two challenging targets to combat cancer development in the later stages of its progression. Numerous studies have indicated the important role of natural products in blocking tumor angiogenesis signaling pathways in several advanced tumors. In recent years, the marine polysaccharides fucoidans emerged as promising anticancer compounds showing potent antitumor activity in both in vitro and in vivo models of different types of cancers. The objective of this review is to focus on the antiangiogenic and antimetastatic activities of fucoidans with special emphasis on preclinical studies. Independently from their source, fucoidans inhibit several angiogenic regulators, primarily vascular endothelial growth factor (VEGF). A glance towards fucoidans' ongoing clinical trials and pharmacokinetic profile is provided to present the main challenges that still need to be addressed for their bench-to-bedside translation. [ABSTRACT FROM AUTHOR]

Aging is commonly associated with a decline in motor control and neural plasticity. Tuning cortico–cortical interactions between premotor and motor areas is essential for controlling fine manual movements. However, whether plasticity in premotor–motor circuits predicts hand motor abilities in young and elderly humans remains unclear. Here, we administered transcranial magnetic stimulation (TMS) over the ventral premotor cortex (PMv) and primary motor cortex (M1) using the cortico–cortical paired-associative stimulation (ccPAS) protocol to manipulate the strength of PMv-to-M1 connectivity in 14 young and 14 elderly healthy adults. We assessed changes in motor-evoked potentials (MEPs) during ccPAS as an index of PMv-M1 network plasticity. We tested whether the magnitude of MEP changes might predict interindividual differences in performance in two motor tasks that rely on premotor-motor circuits, i.e., the nine-hole pegboard test and a choice reaction task. Results show lower motor performance and decreased PMv-M1 network plasticity in elderly adults. Critically, the slope of MEP changes during ccPAS accurately predicted performance at the two tasks across age groups, with larger slopes (i.e., MEP increase) predicting better motor performance at baseline in both young and elderly participants. These findings suggest that physiological indices of PMv-M1 plasticity could provide a neurophysiological marker of fine motor control across age-groups. [ABSTRACT FROM AUTHOR]

Despite being a common issue in people with multiple sclerosis (pwMS), sexual dysfunction is still underinvestigated. This work aims to assess the potential determinants of sexual dysfunction in pwMS by considering its relationship with disease severity (in terms of global disability), illness perception, and depressive symptoms. In this multicenter study, 1010 pwMS responded to an online survey. A serial mediation model considering negative illness perception and depressive symptoms as mediators of the relationship between disease severity and sexual dysfunction was conducted using the SPSS PROCESS Macro with bias-corrected bootstrapping (5000 samples). Disease severity exerts an indirect effect on sexual dysfunction via illness perception, both independently and through depressive symptoms. However, the results indicated that illness perception plays a more crucial role in sexual dysfunction in pwMS with mild disability than in pwMS with moderate-severe disability. This study suggests that higher disability increases its magnitude by enhancing negative illness perception, that, in turn, affects sexual dysfunction both directly and through depressive symptoms, especially in pwMS with mild disability. Modulating the effect of illness perception by favoring adaptive coping strategies might represent a valid approach to mitigate sexual dysfunction symptoms in MS. [ABSTRACT FROM AUTHOR]

Temoporfin (mTHPC) is one of the most promising photosensitizers used in photodynamic therapy (PDT). Despite its clinical use, the lipophilic character of mTHPC still hampers the full exploitation of its potential. Low solubility in water, high tendency to aggregate, and low biocompatibility are the main limitations because they cause poor stability in physiological environments, dark toxicity, and ultimately reduce the generation of reactive oxygen species (ROS). Applying a reverse docking approach, here, we identified a number of blood transport proteins able to bind and disperse monomolecularly mTHPC, namely apohemoglobin, apomyoglobin, hemopexin, and afamin. We validated the computational results synthesizing the mTHPC-apomyoglobin complex (mTHPC@apoMb) and demonstrated that the protein monodisperses mTHPC in a physiological environment. The mTHPC@apoMb complex preserves the imaging properties of the molecule and improves its ability to produce ROS via both type I and type II mechanisms. The effectiveness of photodynamic treatment using the mTHPC@apoMb complex was then demonstrated in vitro. Blood transport proteins can be used as molecular "Trojan horses" in cancer cells by conferring mTHPC (i) water solubility, (ii) monodispersity, and (iii) biocompatibility, ultimately bypassing the current limitations of mTHPC. [ABSTRACT FROM AUTHOR]

In this work, quantum chemical calculations based on density functional theory (DFT) were performed to predict the antioxidant potential of four bioactive gut microbiota metabolites of the natural polyphenols ellagitannins (ETs) and ellagic acid (EA), also known as urolithins (UROs). In order to evaluate their ability to counter the effect of oxidative stress caused by reactive oxygen species (ROS), such as the hydroperoxyl radical (•OOH), different reaction mechanisms were investigated, considering water and lipid-like environments. Through our in silico results, it emerged that at physiological pH, the scavenging activity of all urolithins, except urolithin B, are higher than that of trolox and other potent antioxidants existing in nature, such as EA, α-mangostin, allicin, caffeine and melatonin. These findings were confirmed by experimental assays. [ABSTRACT FROM AUTHOR]

The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range, making it a potential PS. Here, we exploited the intrinsic photosensitizing properties of doxorubicin to enhance its anticancer activity in leukemia, breast, and epidermoid carcinoma cells, upon irradiation. Light can selectively trigger the local generation of reactive oxygen species (ROS), following photophysical pathways. Doxorubicin showed a concentration-dependent ability to generate peroxides and singlet oxygen upon irradiation. The underlying mechanisms leading to the increase in its cytotoxic activity were intracellular ROS generation and the induction of necrotic cell death. The nuclear localization of doxorubicin represents an added value for its use as a PS. The use of doxorubicin in PCT, simultaneously acting as a chemotherapeutic agent and a PS, may allow (i) an increase in the anticancer effects of the drug, and (ii) a decrease in its dose, and thus, its dose-related adverse effects. [ABSTRACT FROM AUTHOR]

Marine sponges represent one of the richest sources of natural marine compounds with anticancer potential. Plocabulin (PM060184), a polyketide originally isolated from the sponge Lithoplocamia lithistoides, elicits its main anticancer properties binding tubulin, which still represents one of the most important targets for anticancer drugs. Plocabulin showed potent antitumor activity, in both in vitro and in vivo models of different types of cancers, mediated not only by its antitubulin activity, but also by its ability to block endothelial cell migration and invasion. The objective of this review is to offer a description of plocabulin's mechanisms of action, with special emphasis on the antiangiogenic signals and the latest progress on its development as an anticancer agent. [ABSTRACT FROM AUTHOR]

Temoporfin (mTHPC) is approved in Europe for the photodynamic treatment of head and neck squamous cell carcinoma (HNSCC). Although it has a promising profile, its lipophilic character hampers the full exploitation of its potential due to high tendency of aggregation and a reduced ROS generation that compromise photodynamic therapy (PDT) efficacy. Moreover, for its clinical administration, mTHPC requires the presence of ethanol and propylene glycol as solvents, often causing adverse effects in the site of injection. In this paper we explored the efficiency of a new mTHPC formulation that uses human serum albumin (HSA) to disperse the photosensitizer in solution (mTHPC@HSA), investigating its anticancer potential in two HNSCC cell lines. Through a comprehensive characterization, we demonstrated that mTHPC@HSA is stable in physiological environment, does not aggregate, and is extremely efficient in PDT performance, due to its high singlet oxygen generation and the high dispersion as monomolecular form in HSA. This is supported by the computational identification of the specific binding pocket of mTHPC in HSA. Moreover, mTHPC@HSA-PDT induces cytotoxicity in both HNSCC cell lines, increasing intracellular ROS generation and the number of γ-H2AX foci, a cellular event involved in the global response to cellular stress. Taken together these results highlight the promising phototoxic profile of the complex, prompting further studies to assess its clinical potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Arbuscular mycorrhizal fungi (AMF), as well as ultraviolet-B radiation (UV-B), could act as key factors affecting plant–insect interactions. The stress related to one of these two factors could be balanced by the positive effects of the other. In the present work, the feeding preferences of Myzus persicae aphids for lettuce plants exposed to two abiotic factors, i.e., AMF and UV-B, singly or in combination, was evaluated. Results showed that lettuce plants treated with UV-B increased in callose and oxidative stress indicators, signalling an alteration in the volatile organic compounds (VOCs) emitted. On the other hand, the negative effects of UV-B were partially mitigated in lettuces inoculated with AMF. Differently treated lettuces did not affect the feeding preferences of the M. persicae aphid population. Overall, this study shed light on how UV-B and AMF impact lettuce VOCs emission and defence mechanisms, but not the feeding behaviour of a polyphagous aphid species. Arbuscular mycorrhizal fungi (AMF) and ultraviolet-B radiation (UV-B) play important roles in plant–insect interactions by altering plant physiology and histology. We hypothesized that UV-B-induced oxidative stress was mitigated by AMF symbiosis. In this study, we conducted a multifactorial experiment to explore lettuce plant response to AMF inoculation and UV-B exposure (0.4 W m−2; 16 h d−1; 2 weeks), either together or individually, as well as the interaction with the polyphagous insect pest Myzus persicae (Sulzer). Lettuce plants subjected to UV-B radiation showed an increase in callose and oxidative stress indicators, as well as a decrease in stomatal density. Mycorrhizal colonization cancelled out the effect of UV-B on stomatal density, while the symbiosis was not affected by UV-B treatment. The plant volatile emission was significantly altered by UV-B treatment. Specifically, the non-terpene 1-undecene abundance (+M/+UVB: 48.0 ± 7.78%; −M/+UVB: 56.6 ± 14.90%) was increased, whereas the content of the non-terpene aldehydes decanal (+M/+UVB: 8.50 ± 3.90%; −M/+UVB: 8.0 ± 4.87%) and undecanal (+M/+UVB: 2.1 ± 0.65%; −M/+UVB: 1.20 ± 1.18%) and the sesquiterpene hydrocarbons (+M/+UVB: 18.0 ± 9.62 %; −M/+UVB: 19.2 ± 5.90%) was decreased. Mycorrhization, on the other hand, had no significant effect on the plant volatilome, regardless of UV-B treatment. Aphid population was unaffected by any of the treatments, implying a neutral plant response. Overall, this study provides new insights about the interactions among plants, UV-B, and AMF, outlining their limited impact on a polyphagous insect pest. [ABSTRACT FROM AUTHOR]

Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. leucotrichus fruits and R-perillaldehyde, a monoterpenoid isolated from A. leucotrichus fruits, are able to affect different processes involved in different phases of cancer development. In particular, we explored their genoprotective, proapoptotic, antiproliferative, and cytodifferentiating potential on different human cell models. We analyzed the genoprotective and proapoptotic activity on human lymphoblast cells (TK6) using the micronucleus test, and the cytodifferentiation effects on human promyelocytic cells (HL60) through the evaluation of different markers of differentiation forward granulocytes or monocytes. The results showed that the extract and perillaldehyde were able to induce apoptosis and protect from clastogen-induced DNA damage. To our best knowledge, this is the first report on the ability of A. leucotrichus and perillaldehyde to induce apoptosis and protect DNA from the toxicity of different compounds. Data reported in this work are the starting point for their pharmacological use. Going forward, efforts to determine their effects on other events associated with cancer development, such as angiogenesis and metastasization, will provide important information and improve our understanding of their potential in cancer therapy. [ABSTRACT FROM AUTHOR]

Lettuce is widely used for its healthy properties, and it is of interest to increase them with minimal environmental impact. The purpose of this work was to evaluate the effect of the arbuscular mycorrhizal fungus (AMF) Funneliformis mosseae in lettuce plants (Lactuca sativa L. cv. Salinas) cultivated in a soilless system with sub-optimal phosphorus (P) compared with non-inoculated controls at two different P concentrations. Results show that lettuce inoculation with the selected AMF can improve the growth and the nutritional quality of lettuce even at sub-optimal P. Leaf content of chlorophylls, carotenoids, and phenols, known as important bioactive compounds for human health, was higher in mycorrhizal lettuce plants compared with non-mycorrhizal plants. The antioxidant capacity in AMF plants showed higher values compared with control plants grown at optimal P nutrition level. Moreover, leaf gas exchanges were higher in inoculated plants than in non-inoculated ones. Nitrogen, P, and magnesium leaf content was significantly higher in mycorrhizal plants compared with non-mycorrhizal plants grown with the same P level. These findings suggest that F. mosseae can stimulate plants growth, improving the nutritional quality of lettuce leaves even when grown with sub-optimal P concentration. [ABSTRACT FROM AUTHOR]

Epilepsy accounts for a significant proportion of the world's disease burden. Indeed, many research efforts are produced both to investigate the basic mechanism ruling its genesis and to find more effective therapies. In this framework, the use of zebrafish larvae, owing to their peculiar features, offers a great opportunity. Here, we employ transgenic zebrafish larvae expressing GCaMP6s in all neurons to characterize functional alterations occurring during seizures induced by pentylenetetrazole. Using a custom two-photon light-sheet microscope, we perform fast volumetric functional imaging of the entire larval brain, investigating how different brain regions contribute to seizure onset and propagation. Moreover, employing a custom behavioral tracking system, we outline the progressive alteration of larval swim kinematics, resulting from different grades of seizures. Collectively, our results show that the epileptic larval brain undergoes transitions between diverse neuronal activity regimes. Moreover, we observe that different brain regions are progressively recruited into the generation of seizures of diverse severity. We demonstrate that midbrain regions exhibit highest susceptibility to the convulsant effects and that, during periods preceding abrupt hypersynchronous paroxysmal activity, they show a consistent increase in functional connectivity. These aspects, coupled with the hub-like role that these regions exert, represent important cues in their identification as epileptogenic hubs. [ABSTRACT FROM AUTHOR]

Basil-based semi-finished products, which are mainly used as an intermediate to produce the typical pesto sauce, are prepared and exported all over the world. Color is a fundamental organoleptic requirement for the acceptability of these semi-finished products by the manufacturers of the pesto sauce. Some alternative formulations, which adjust the typical industrial recipe by both changing the preservative agent (ascorbic acid, citric acid, or a mixture of both) and introducing a preliminary thermic treatment (blast chilling), were evaluated. In this work, a fast and non-destructive spectrophotometric analysis, to monitor the color variations in these food products during their shelf-life, was proposed. The raw diffuse reflectance spectra (380–900 nm) obtained by a UV–visible spectrophotometer, endowed with an integrating sphere, together with the CIELab parameters (L*, a*, b*) automatically obtained from these, were considered, and elaborated using multivariate statistical analysis (principal component analysis). From this preliminary study, blast chilling, together with the use of ascorbic acid, proved to be the best solution to better preserve the color of these products during their shelf-life. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i.e., abscopal effect) in addition to local effects. Thus, the incorporation of additional therapies could be key to improving immunotherapy's clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy. Various immunotherapies have been used in combination with IRE, such as NK cell- or γδ T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC. [ABSTRACT FROM AUTHOR]

Model checking is a well-established and widely adopted framework used to verify whether a given system satisfies the desired properties. Properties are usually given by means of formulas from a specific logic; there are several logics that can be used, such as CTL and LTL, which permit the expression of different types of properties on the branching-time or on the linear-time evolution of the system. In this paper, we will consider the problem of model checking quantum systems and present the solutions given in literature for solving such a problem with respect to different types of properties. [ABSTRACT FROM AUTHOR]