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Abscisic acid (ABA) and gibberellic acid (GA3) are regulators of fruit color and sugar levels, and the application of these hormones is a common practice in commercial vineyards dedicated to the production of table grapes. However, the effects of exogenous ABA and GA3 on wine cultivars remain unclear. We investigated the impact of ABA and GA3 application on Malbec grapevine berries across three developmental stages. We found similar patterns of berry total anthocyanin accumulation induced by both treatments, closely associated with berry H2O2 levels. Quantitative proteomics from berry skins revealed that ABA and GA3 positively modulated antioxidant defense proteins, mitigating H2O2. Consequently, proteins involved in phenylpropanoid biosynthesis were downregulated, leading to decreased anthocyanin content at the almost ripe stage, particularly petunidin-3-G and peonidin-3-G. Additionally, we noted increased levels of the non-anthocyanins E-viniferin and quercetin in the treated berries, which may enhance H2O2 scavenging at the almost ripe stage. Using a linear mixed-effects model, we found statistical significance for fixed effects including the berry H2O2 and sugar contents, demonstrating their roles in anthocyanin accumulation. In conclusion, our findings suggest a common molecular mechanism by which ABA and GA3 influence berry H2O2 content, ultimately impacting anthocyanin dynamics during ripening.

Background: A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a disease-modifying drug for Friedreich ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted a pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Methods: Thirty-five patients were stratified into three severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Safety endpoints were the number and type of adverse events and number of dropouts. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T − 4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T + 4). Results: Etravirine was reasonably tolerated, and adverse events were generally mild. Four months of etravirine treatment did not significantly increase the peak oxygen uptake but was associated with a change in the progression of the SARA score (p value < 0.001), compared to the 4 months pre- and post-treatment. It also significantly increased peak workload (p value = 0.021). No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. Conclusions: In this open trial etravirine treatment was safe, reasonably well tolerated and appreciably improved neurological function and exercise performance. Even though a placebo effect cannot be ruled out, these results suggest that etravirine may represent a potential therapeutic agent in FRDA deserving testing in a randomized placebo-controlled clinical trial.

Prof. Dr. George Bakris was an Editorial Board Member of Kidney and Dialysis. His invaluable contributions were instrumental in guiding the journal’s direction and enhancing its success. We are deeply grateful for his unwavering dedication, commitment, and active involvement in the journal’s development.

Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses.

Chronic kidney disease (CKD) is linked to an elevated risk of malnutrition and sarcopenia, contributing to the intricate network of CKD-related metabolic disorders. Adipokines and myokines are markers and effectors of sarcopenia and nutritional status. The aim of this study was to assess whether the adipokine–myokine signature in patients on kidney replacement therapy could help identify malnutrition and sarcopenia. The study involved three groups: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, and 52 kidney transplant recipients (KTR). Mean age was 56.1 ± 16.3 years. Malnutrition was defined using the 7-Point Subjective Global Assessment (SGA) and the Malnutrition-Inflammation Score (MIS). Sarcopenia was diagnosed based on reduced handgrip strength (HGS) and diminished muscle mass. Concentrations of adipokines and myokines were determined using the enzyme-linked immunosorbent assay (ELISA). 32.8% of all study participants were identified as malnourished and 20.6% had sarcopenia. For malnutrition, assessed using the 7-Point SGA, in ROC analysis albumin (area under the curve (AUC) 0.67 was the best single biomarker identified. In dialysis patients, myostatin (AUC 0.79) and IL-6 (AUC 0.67) had a high discrimination value for sarcopenia, and we were able to develop a prediction model for sarcopenia, including age, albumin, adiponectin, and myostatin levels, with an AUC of 0.806 (95% CI: 0.721–0.891). Adipokines and myokines appear to be useful laboratory markers for assessing malnutrition and sarcopenia. The formula we propose could contribute to a better understanding of sarcopenia and potentially lead to more effective interventions and management strategies for dialysis patients.

Circadian oscillations of several physiological and behavioral processes are an established process in all the organisms anticipating the geophysical changes recurring during the day. The time-keeping mechanism is controlled by a transcription translation feedback loop involving a set of well-characterized transcription factors. The synchronization of cells, controlled at the organismal level by a brain central clock, can be mimicked in vitro, pointing to the notion that all the cells are endowed with an autonomous time-keeping system. Metabolism undergoes circadian control, including the mitochondrial terminal catabolic pathways, culminating under aerobic conditions in the electron transfer to oxygen through the respiratory chain coupled to the ATP synthesis according to the oxidative phosphorylation chemiosmotic mechanism. In this study, we expanded upon previous isolated observations by utilizing multiple cell types, employing various synchronization protocols and different methodologies to measure mitochondrial oxygen consumption rates under conditions simulating various metabolic stressors. The results obtained clearly demonstrate that mitochondrial respiratory activity undergoes rhythmic oscillations in all tested cell types, regardless of their individual respiratory proficiency, indicating a phenomenon that can be generalized. However, notably, while primary cell types exhibited similar rhythmic respiratory profiles, cancer-derived cell lines displayed highly heterogeneous rhythmic changes. This observation confirms on the one hand the dysregulation of the circadian control of the oxidative metabolism observed in cancer, likely contributing to its development, and on the other hand underscores the necessity of personalized chronotherapy, which necessitates a detailed characterization of the cancer chronotype.

Zinc is an important trace element for growth and health at pediatric ages. Zinc is fundamental in inflammatory pathways, oxidative balance, and immune function. Zinc exhibits anti-inflammatory properties by modulating Nuclear Factor-kappa (NF-κB) activity and reducing histamine release from basophils, leukocytes, and mast cells. Furthermore, its antioxidant activity protects against oxidative damage and chronic diseases. Finally, zinc improves the ability to trigger effective immune responses against pathogens by contributing to the maturation of lymphocytes, the production of cytokines, and the regulation of apoptosis. Given these properties, zinc can be considered an adjunctive therapy in treating and preventing respiratory, nephrological, and gastrointestinal diseases, both acute and chronic. This review aims to deepen the role and metabolism of zinc, focusing on the role of supplementation in developed countries in pediatric diseases.

Hyperspectral pansharpening is crucial for the improvement of the usability of images in various applications. However, it remains underexplored due to a scarcity of data. The primary goal of pansharpening is to enhance the spatial resolution of hyperspectral images by reconstructing missing spectral information without compromising consistency with the original data. This paper addresses the data gap by presenting a new hyperspectral dataset specifically designed for pansharpening and the evaluation of several deep learning strategies using this dataset. The new dataset has two crucial features that make it invaluable for deep learning hyperspectral pansharpening research. (1) It presents the highest cardinality of images in the state of the art, making it the first statistically relevant dataset for hyperspectral pansharpening evaluation, and (2) it includes a wide variety of scenes, ensuring robust generalization capabilities for various approaches. The data, collected by the ASI PRISMA satellite, cover about 262,200 km2 and their heterogeneity is ensured by a random sampling of the Earth’s surface. The analysis of the deep learning methods consists in the adaptation of these approaches to the PRISMA hyperspectral data and the quantitative and qualitative evaluation of their performance in this new scenario. The investigation included two settings: Reduced Resolution (RR) to evaluate the techniques in a controlled environment and Full Resolution (FR) for a real-world evaluation. In addition, for the sake of completeness, we have also included machine-learning-free approaches in both scenarios. Our comprehensive analysis reveals that data-driven neural network methods significantly outperform traditional approaches, demonstrating a superior adaptability and performance in hyperspectral pansharpening under both RR and FR protocols.

Duchenne muscular dystrophy (DMD) is one of the most frequent and severe childhood muscle diseases. Its pathophysiology is multifaceted and still incompletely understood, but we and others have previously shown that oxidative stress plays an important role. In particular, we have demonstrated that inhibition of mitochondrial monoamine oxidases could improve some functional and biohumoral markers of the pathology. In the present study we report the use of dystrophic mdx mice to evaluate the efficacy of a dual monoamine oxidase B (MAO-B)/semicarbazide-sensitive amine oxidase (SSAO) inhibitor, PXS-5131, in reducing inflammation and fibrosis and improving muscle function. We found that a one-month treatment starting at three months of age was able to decrease reactive oxygen species (ROS) production, fibrosis, and inflammatory infiltrate in the tibialis anterior (TA) and diaphragm muscles. Importantly, we also observed a marked improvement in the capacity of the gastrocnemius muscle to maintain its force when challenged with eccentric contractions. Upon performing a bulk RNA-seq analysis, PXS-5131 treatment affected the expression of genes involved in inflammatory processes and tissue remodeling. We also studied the effect of prolonged treatment in older dystrophic mice, and found that a three-month administration of PXS-5131 was able to greatly reduce the progression of fibrosis not only in the diaphragm but also in the heart. Taken together, these results suggest that PXS-5131 is an effective inhibitor of fibrosis and inflammation in dystrophic muscles, a finding that could open a new therapeutic avenue for DMD patients.

Glucosamine–chitosan synthesized by the Maillard reaction was combined with montmorillonite to obtain a nanohybrid composite to immobilize horseradish peroxidase. The material combines the advantageous properties of clay with those of the chitosan derivative; has improved water solubility and reduced molecular weight and viscosity; involves an eco-friendly synthesis; and exhibits ion exchange capacity, good adhesiveness, and a large specific surface area for enzyme adsorption. The physicochemical characteristics of the composite were analyzed by infrared spectroscopy and X-ray diffraction to determine clay–polycation interactions. The electrochemical response of the different polyphenols to glassy carbon electrodes modified with the composite was evaluated by cyclic voltammetry. The sensitivity and detection limit values obtained with the biosensor toward hydroquinone, chlorogenic acid, catechol, and resorcinol are (1.6 ± 0.2) × 102 µA mM−1 and (74 ± 8) nM; (1.2 ± 0.1) × 102 µA mM−1 and (26 ± 3) nM; (16 ± 2) µA mM−1 and (0.74 ± 0.09) μM; and (3.7± 0.3) µA mM−1 and (3.3 ± 0.2) μM, respectively. The biosensor was applied to quantify polyphenols in pennyroyal and lemon verbena extracts.

The impact of global warming on Argentine viticulture may result in a geographical shift, with wine-growing regions potentially moving towards the southwest, known as one of the windiest regions in the world. Deficit irrigation is a widely used strategy to control the shoot growth and improve fruit quality attributes, such as berry skin polyphenols. The present study aimed to assess the effects of different wind intensities and irrigation levels, as well as their interactions, on field-grown Vitis vinifera L. cvs. Malbec and Cabernet Sauvignon. The experiment was conducted during two growing seasons with two wind treatments (sheltered and exposed) and two irrigation treatments (well-watered and moderate deficit irrigation) in a multifactorial design. Vegetative growth, stomatal conductance, shoot biomass partition, fruit yield components and berry skin phenolics were evaluated. Our study found that, generally, wind exposure reduced vegetative growth, and deficit irrigation increased the proportion of smaller berries within the bunches. Meanwhile, deficit irrigation and wind exposure additively increased the concentration of berry skin phenolics. Combined stressful conditions enhance biomass partition across the shoot to fruits in Malbec, increasing the weight of bunches and the number of berries. Our findings offer practical implications for vineyard managers in windy regions, providing actionable insights to optimize grapevine cultivation and enhance wine quality.

The paracrine signaling pathways for the crosstalk between pericytes and endothelial cells are essential for the coordination of cell responses to challenges such as hypoxia in both healthy individuals and pathological conditions. Ischemia–reperfusion injury (IRI), one of the causes of cellular dysfunction and death, is associated with increased expression of genes involved in cellular adaptation to a hypoxic environment. Hypoxic inducible factors (HIFs) have a central role in the response to processes initiated by IRI not only linked to erythropoietin production but also because of their participation in inflammation, angiogenesis, metabolic adaptation, and fibrosis. While pericytes have an essential physiological function in erythropoietin production, a lesser-known role of HIF stabilization during IRI is that pericytes’ HIF expression could influence vascular remodeling, cell loss and organ fibrosis. Better knowledge of mechanisms that control functions and consequences of HIF stabilization in pericytes beyond erythropoietin production is advisable for the development of therapeutic strategies to influence disease progression and improve treatments. Thus, in this review, we discuss the dual roles—for good or bad—of HIF stabilization during IRI, focusing on pericytes, and consequences in particular for the kidneys.

Listeria monocytogenes is a foodborne pathogen that contaminates food-processing environments and persists within biofilms on equipment, thus reaching final products by cross-contamination. With the growing demand for clean-label products, the search for natural antimicrobials as biopreservants, such as bacteriocins, has shown promising potential. In this context, this study aimed to evaluate the anti-listerial action of bacteriocins produced by Enterococcus lactis LBM BT2 in an alternative medium containing sugarcane molasses (SCM). Molecular analyses were carried out to characterize the strain, including the presence of bacteriocin-related genes. In the kinetic study on SCM medium E. lactis, LBM BT2 showed biomass and bacteriocin productions similar to those observed on a sucrose-based medium (control), highlighting the potential of the sugarcane molasses as a low-cost substrate. Stability tests revealed that the molecule remained active in wide ranges of pH (4–10) and temperature (60–100 °C). Furthermore, the proteolytic treatment reduced the biomolecule’s antimicrobial activity, highlighting its proteinaceous nature. After primary purification by salting out and tangential flow filtration, the bacteriocin-like inhibitory substance (BLIS) showed bacteriostatic activity on suspended L. monocytogenes cells and against biofilm formation at a concentration of 0.625 mg/mL. These results demonstrate the potential of the produced BLIS as a biopreservative in the food industry.

Alzheimer’s disease (AD) is the most common form of dementia, characterized by the accumulation of β-amyloid plaques, tau tangles, neuroinflammation, and synaptic/neuronal loss, the latter being the strongest correlating factor with memory and cognitive impairment. Through an in vitro study on a neurons–astrocytes–microglia (NAM) co-culture system, we analyzed the effects of cerebrospinal fluid (CSF) samples from AD and non-AD patients (other neurodegenerative pathologies). Treatment with CSF from AD patients showed a loss of neurofilaments and spheroids, suggesting the presence of elements including CX3CL1 (soluble form), destabilizing the neurofilaments, cellular adhesion processes, and intercellular contacts. The NAM co-cultures were analyzed in immunofluorescence assays for several markers related to AD, such as through zymography, where the expression of proteolytic enzymes was quantified both in cell extracts and the co-cultures’ conditioned medium (CM). Through qRT-PCR assays, several genes involved in the formation of β-amyloid plaque, in phosphorylation of tau, and in inflammation pathways and MMP expression were investigated.

The potentiality of cv. Malbec grape pomace (GP) as a functional ingredient in the formulation of bakery foods (muffins, biscuits and cereal bars) was studied. The effect of GP addition on the phenolic compounds (PCs) composition, nutritional and sensory properties were evaluated. The addition of GP increased the content of dietary fiber, proteins, ash, total phenolic content (TPC), antiradical capacity (AC), anthocyanins and non-anthocyanin PCs while decreasing the carbohydrates content. The main PCs given by the GP to supplemented foods were quercetin-3-O-glucoside, rutin, caffeic acid, syringic acid and (+)-catechin. For anthocyanins, the acylated derivatives were more stable to heat treatment (baking) in food processing which was evidenced by a higher proportion of these PCs compounds when compared to the same derivatives quantified in GP. In general, when the TPC or individual concentrations of PCs were analyzed in a nutritional or functional context, one portion of the supplemented foods showed levels high enough to satisfy the recommended dose per day of these bioactive compounds. Additionally, the foods were well received by consumers during the sensory evaluation and supplemented biscuits received the highest acceptability. This study demonstrated that GP could be a viable functional ingredient in bakery foods to incorporate components like PCs and dietary fiber into traditional consumers’ diets.

The SI4CARE project is a transnational project which aims to develop both strategy and action plans to improve health and social care in the Adriatic–Ionian region. Starting from a survey of the status quo, each partner has developed some pilots to support the development and monitoring of the policy actions. In particular, partner number three, the Municipality of Miglierina, designed and developed a pilot related to the use of wearable devices for monitoring elderly patients in rural areas. With the collaboration of the complex unity of primary care (UCCP) of the Reventino area, the pilot is based on the use of smart wearable devices to monitor some parameters of older adults after their vaccinations for flu and covid. This paper focused on the design and implementation of the system. It describes its application in the Municipality of Miglierina. Presentation of the results and a discussion of the strengths and weaknesses will be presented, in detail, in future work. Finally, the possibility of extending the experiment to other Adriatic–Ionian regions is addressed.

The differential diagnosis between new occurrence or revelation of chronic kidney diseases in pregnancy and hypertensive disorders of pregnancy is not easy, and the presence of a hypertensive disorder superimposed on a glomerular disease is even more challenging, as this case exemplifies. A 29-year-old woman was referred with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome at the end of her pregnancy. Immediately after cesarean delivery, she developed anuria, unexplained by blood loss or hypotension, and in the absence of known nephrotoxic drugs. While the laboratory features of HELLP rapidly resolved, AKI persisted, and the finding of high-level proteinuria was the hint leading to diagnosis of a glomerular disease (focal segmental glomerulosclerosis, FSGS), later proven by kidney biopsy. This case, reporting on the rare association between HELLP and FSGS, offers the opportunity to discuss the role of proteinuria, hypertension, and in the differential diagnosis of pregnancy-related acute kidney injury (pAKI).

Mutations in the SARS-CoV-2 genome can alter the virus’ fitness, leading to the emergence of variants of concern (VOC). In Brazil, the Gamma variant dominated the pandemic in the first half of 2021, and from June onwards, the first cases of Delta infection were documented. Here, we investigate the introduction and dispersal of the Delta variant in the RS state by sequencing 1077 SARS-CoV-2-positive samples from June to October 2021. Of these samples, 34.7% were identified as Gamma and 65.3% as Delta. Notably, 99.2% of Delta sequences were clustered within the 21J lineage, forming a significant Brazilian clade. The estimated clock rate was 5.97 × 10−4 substitutions per site per year. The Delta variant was first reported on 17 June in the Vinhedos Basalto microregion and rapidly spread, accounting for over 70% of cases within nine weeks. Despite this, the number of cases and deaths remained stable, possibly due to vaccination, prior infections, and the continued mandatory mask use. In conclusion, our study provides insights into the Delta variant circulating in the RS state, highlighting the importance of genomic surveillance for monitoring viral evolution, even when the impact of new variants may be less severe in a given region.

Brugada Syndrome (BrS) is a genetic heart condition linked to sudden cardiac death. Though the SCN5A gene is primarily associated with BrS, there is a lack of comprehensive studies exploring the connection between SCN5A mutation locations and the clinical presentations of the syndrome. This study aimed to address this gap and gain further understanding of the syndrome. The investigation classified 36 high-risk BrS patients based on SCN5A mutations within the transmembrane/structured (TD) and intra-domain loops (IDLs) lacking a 3D structure. We characterized the intrinsically disordered regions (IDRs) abundant in IDLs, using bioinformatics tools to predict IDRs and post-translational modifications (PTMs) in NaV1.5. Interestingly, it was found that current predictive tools often underestimate the impacts of mutations in IDLs and disordered regions. Moreover, patients with SCN5A mutations confined to IDL regions—previously deemed ‘benign’—displayed clinical symptoms similar to those carrying ‘damaging’ variants. Our research illuminates the difficulty in stratifying patients based on SCN5A mutation locations, emphasizing the vital role of IDLs in the NaV1.5 channel’s functioning and protein interactions. We advocate for caution when using predictive tools for mutation evaluation in these regions and call for the development of improved strategies in accurately assessing BrS risk

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the occurrence of their assembly in supercomplexes, providing additional functional properties when compared with randomly colliding isolated complexes. According to the plasticity model, the two structural states of the respiratory chain may interconvert, influenced by the intracellular prevailing conditions. In previous studies, we suggested the mitochondrial membrane potential as a factor for controlling their dynamic balance. Here, we investigated if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. An analysis of the inhibitory titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The attained results, pharmacologically inhibiting either PKA or sAC, indicated that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influenced their assembly state in response to the membrane potential. This conclusion was supported by the scrutiny of the available structure of the CI/CIII2/CIV respirasome, enabling us to map several PKA-targeted serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

Background and Objectives: Bartter syndrome (BS) is a rare group of autosomal-recessive disorders that usually presents with hypokalemic metabolic alkalosis, occasionally with hyponatremia and hypochloremia. The clinical presentation of BS is heterogeneous, with a wide variety of genetic variants. The aim of this systematic review was to examine the available literature and provide an overview of the case reports and case series on BS. Materials and Methods: Case reports/series published from April 2012 to April 2022 were searched through Pubmed, JSTOR, Cochrane, ScienceDirect, and DOAJ. Subsequently, the information was extracted in order to characterize the clinical presentation, laboratory results, treatment options, and follow-up of the patients with BS. Results: Overall, 118 patients, 48 case reports, and 9 case series (n = 70) were identified. Out of these, the majority of patients were male (n = 68). A total of 21 patients were born from consanguineous marriages. Most cases were reported from Asia (73.72%) and Europe (15.25%). In total, 100 BS patients displayed the genetic variants, with most of these being reported as Type III (n = 59), followed by Type II (n = 19), Type I (n = 14), Type IV (n = 7), and only 1 as Type V. The most common symptoms included polyuria, polydipsia, vomiting, and dehydration. Some of the commonly used treatments were indomethacin, potassium chloride supplements, and spironolactone. The length of the follow-up time varied from 1 month to 14 years. Conclusions: Our systematic review was able to summarize the clinical characteristics, presentation, and treatment plans of BS patients. The findings from this review can be effectively applied in the diagnosis and patient management of individuals with BS, rendering it a valuable resource for nephrologists in their routine clinical practice.

Neuroblastoma is among the most common childhood cancers. Neuroblastoma in advanced stages is one of the most intractable pediatric cancers, notwithstanding the recent therapeutic advances. ALK mutations are among the leading cause of hereditary neuroblastoma and account for more than 14% of the somatically acquired alterations. ALK kinase activity is currently one of the main targets for pharmacological strategies. However, evidence from ALK fusion-positive lung cancer studies has shown that resistance to ALK inhibition arises during the therapy, causing a relapse within several years. IgLONs are membrane-bound proteins involved in cell-to-cell adhesion. The expression of the IgLON family results altered in different cancers. We found that the IgLON member Negr1 is downregulated in neuroblastoma. The ectopic overexpression of Negr1 impairs neuroblastoma growth in vitro and in vivo. Negr1 exists as a GPI-anchored membrane-bound protein and as a soluble protein released upon metalloprotease cleavage. We generated and characterized a panel of Negr1-derived peptides. The treatment with Negr1 protein and derived peptides induce ALK downregulation and halt neuroblastoma progression in vitro and in vivo.

In this paper, different machine learning methodologies have been evaluated for the estimation of the multiple soil characteristics of a continental-wide area corresponding to the European region, using multispectral Sentinel-3 satellite imagery and digital elevation model (DEM) derivatives. The results confirm the importance of multispectral imagery in the estimation of soil properties and specifically show that the use of DEM derivatives improves the quality of the estimates, in terms of R2, by about 19% on average. In particular, the estimation of soil texture increases by about 43%, and that of cation exchange capacity (CEC) by about 65%. The importance of each input source (multispectral and DEM) in predicting the soil properties using machine learning has been traced back. It has been found that, overall, the use of multispectral features is more important than the use of DEM derivatives with a ration, on average, of 60% versus 40%.

Nucleoporins (NUPs) are proteins that comprise the nuclear pore complexes (NPCs). The NPC spans the nuclear envelope of a cell and provides a channel through which RNA and proteins move between the nucleus and the cytoplasm and vice versa. NUP and NPC disruptions have a great impact on the pathophysiology of neurodegenerative diseases (NDDs). Although the downregulation of Nup358 leads to a reduction in the scaffold protein ankyrin-G at the axon initial segment (AIS) of mature neurons, the function of Nup358 in the cytoplasm of neurons remains elusive. To investigate whether Nup358 plays any role in neuronal activity, we downregulated Nup358 in non-pathological mouse cortical neurons and measured their active and passive bioelectrical properties. We identified that Nup358 downregulation is able to produce significant modifications of cell-membrane excitability via voltage-gated sodium channel kinetics. Our findings suggest that Nup358 contributes to neuronal excitability through a functional stabilization of the electrical properties of the neuronal membrane. Hypotheses will be discussed regarding the alteration of this active regulation as putatively occurring in the pathophysiology of NDDs.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of cellular tissues, and it is expressed through the vitamin D receptor (VDR) gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of BsmI single nucleotide polymorphism (SNP) of the VDR gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. After signing the informed consent form, individuals were invited to participate and answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p < 0.05. Results: 98 individuals with vitamin D ≤ 20 ng/dL were evaluated, and the BsmI SNP of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: BsmI SNP of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

The positive effects of youth civic engagement can be felt both at the individual level (e.g., better emotional regulation, a greater sense of empowerment) and at the community level (e.g., a greater likelihood of participation in civic and political activities). They may also be a protective factor for at-risk youth in the short and long term and a valuable element for positive identity development in general. The purpose of this longitudinal study was to assess the impact of an educational intervention implemented in secondary schools to promote youth civic engagement (N = 508 at Time 1, N = 116 at Time 2). The study is divided into two parts: first, it examines the changes stimulated by the project, and second, it uses a path analysis model to explain the intention to participate. Results show that after participation, hostile and benevolent sexism, classic and modern ethnic prejudice, and social dominance orientation decreased, while trust in institutions increased. In addition, the path analysis showed that policy control, social trust, and civic engagement increased the intention of civic engagement at time T1. Despite some limitations, this study may provide useful guidance for those designing and implementing civic education interventions for young people.

Nowadays, innovation in food technologies is fundamental and consumers are increasingly aware and demanding. To create a final product that is more and more appealing, health and safety guidelines are pushing towards new challenges. It is precisely due to the high quality required by the producers that the aim discussed in this project has been conceived. Until today, the controls on the entire production line have been slowed down by the limitations of the technologies involved, including the high cost of instrumentation for microbiological analysis, the need for qualified personnel to carry them out, the long execution times and the invasiveness of the techniques themselves. This project has, therefore, proposed a user-friendly solution that is minimally invasive, fast and at a lower cost. This system makes use of classical microbiological analysis and, in parallel, use of an innovative electronic-nose small sensor system (S3+), which can be trained to recognize the volatile fingerprint of a specific product and customized for a specific use. The aim of this project was to develop a system that is able to detect the mold contamination on fruit and vegetable jams and marmalades, using a new kind of innovative metal semiconductor gas sensor (MOS) device. The application of this technology has, therefore, made it possible to classify various samples of uncontaminated and contaminated fruit and vegetable preparations. Thanks to the classification implemented by a data-driven algorithm, it has been possible to build an anomaly detector that is able to recognize the occurrence of possible contamination, thus acting as an early alert system in the food chain. All this will occur in less than 1 min once the system is trained, in contrast with classical microbiological or chemical techniques that normally require longer timeframes to obtain a result and involve the use of reagents, increasing the costs.

Three-dimensional bioprinting is the process of manipulating cell-laden bioinks to fabricate living structures. Three-dimensional bioprinting techniques have brought considerable innovation in biomedicine, especially in the field of tissue engineering, allowing the production of 3D organ and tissue models for in vivo transplantation purposes or for in-depth and precise in vitro analyses. Naturally derived hydrogels, especially those obtained from the decellularization of biological tissues, are promising bioinks for 3D printing purposes, as they present the best biocompatibility characteristics. Despite this, many natural hydrogels do not possess the necessary mechanical properties to allow a simple and immediate application in the 3D printing process. In this review, we focus on the bioactive and mechanical characteristics that natural hydrogels may possess to allow efficient production of organs and tissues for biomedical applications, emphasizing the reinforcement techniques to improve their biomechanical properties.

Oxidative stress, a key mediator of cardiovascular disease, metabolic alterations, and cancer, is independently associated with menopause and obesity. Yet, among postmenopausal women, the correlation between obesity and oxidative stress is poorly examined. Thus, in this study, we compared oxidative stress states in postmenopausal women with or without obesity. Body composition was assessed via DXA, while lipid peroxidation and total hydroperoxides were measured in patient’s serum samples via thiobarbituric-acid-reactive substances (TBARS) and derivate-reactive oxygen metabolites (d-ROMs) assays, respectively. Accordingly, 31 postmenopausal women were enrolled: 12 with obesity and 19 of normal weight (mean (SD) age 71.0 (5.7) years). Doubled levels of serum markers of oxidative stress were observed in women with obesity in women with obesity compared to those of normal weight (H2O2: 32.35 (7.3) vs. 18.80 (3.4) mg H2O2/dL; malondialdehyde (MDA): 429.6 (138.1) vs. 155.9 (82.4) mM in women with or without obesity, respectively; p < 0.0001 for both). Correlation analysis showed that both markers of oxidative stress increased with an increasing body mass index (BMI), visceral fat mass, and trunk fat percentage, but not with fasting glucose levels. In conclusion, obesity and visceral fat are associated with a greater increase in oxidative stress in postmenopausal women, possibly increasing cardiometabolic and cancer risks.

The guidelines for the management of patients affected by propionic acidemia (PA) recommend standard cardiac therapy in the presence of cardiac complications. A recent revision questioned the impact of high doses of coenzyme Q10 on cardiac function in patients with cardiomyopathy (CM). Liver transplantation is a therapeutic option for several patients since it may stabilize or reverse CM. Both the patients waiting for liver transplantation and, even more, the ones not eligible for transplant programs urgently need therapies to improve cardiac function. To this aim, the identification of the pathogenetic mechanisms represents a key point. Aims: This review summarizes: (1) the current knowledge of the pathogenetic mechanisms underlying cardiac complications in PA and (2) the available and potential pharmacological options for the prevention or the treatment of cardiac complications in PA. To select articles, we searched the electronic database PubMed using the Mesh terms “propionic acidemia” OR “propionate” AND “cardiomyopathy” OR “Long QT syndrome”. We selected 77 studies, enlightening 12 potential disease-specific or non-disease-specific pathogenetic mechanisms, namely: impaired substrate delivery to TCA cycle and TCA dysfunction, secondary mitochondrial electron transport chain dysfunction and oxidative stress, coenzyme Q10 deficiency, metabolic reprogramming, carnitine deficiency, cardiac excitation–contraction coupling alteration, genetics, epigenetics, microRNAs, micronutrients deficiencies, renin–angiotensin–aldosterone system activation, and increased sympathetic activation. We provide a critical discussion of the related therapeutic options. Current literature supports the involvement of multiple cellular pathways in cardiac complications of PA, indicating the growing complexity of their pathophysiology. Elucidating the mechanisms responsible for such abnormalities is essential to identify therapeutic strategies going beyond the correction of the enzymatic defect rather than engaging the dysregulated mechanisms. Although these approaches are not expected to be resolutive, they may improve the quality of life and slow the disease progression. Available pharmacological options are limited and tested in small cohorts. Indeed, a multicenter approach is mandatory to strengthen the efficacy of therapeutic options.

A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and the lack of regeneration capacity of satellite cells. The physiologic decline in muscle mass and in motoneuron functionality associated with aging is exacerbated by the sedentary lifestyle that accompanies elderly people. Regular physical activity is beneficial to most people, but the elderly need well-designed and carefully administered training programs that improve muscle mass and, consequently, both functional ability and quality of life. Aging also causes alteration in the gut microbiota composition associated with sarcopenia, and some advances in research have elucidated that interventions via the gut microbiota–muscle axis have the potential to ameliorate the sarcopenic phenotype. Several mechanisms are involved in vitamin D muscle atrophy protection, as demonstrated by the decreased muscular function related to vitamin D deficiency. Malnutrition, chronic inflammation, vitamin deficiencies, and an imbalance in the muscle–gut axis are just a few of the factors that can lead to sarcopenia. Supplementing the diet with antioxidants, polyunsaturated fatty acids, vitamins, probiotics, prebiotics, proteins, kefir, and short-chain fatty acids could be potential nutritional therapies against sarcopenia. Finally, a personalized integrated strategy to counteract sarcopenia and maintain the health of skeletal muscles is suggested in this review.

Precision agriculture has emerged as a promising approach to improve crop productivity and reduce the environmental impact. However, effective decision making in precision agriculture relies on accurate and timely data acquisition, management, and analysis. The collection of multisource and heterogeneous data for soil characteristics estimation is a critical component of precision agriculture, as it provides insights into key factors, such as soil nutrient levels, moisture content, and texture. To address these challenges, this work proposes a software platform that facilitates the collection, visualization, management, and analysis of soil data. The platform is designed to handle data from various sources, including proximity, airborne, and spaceborne data, to enable precision agriculture. The proposed software allows for the integration of new data, including data that can be collected directly on-board the acquisition device, and it also allows for the incorporation of custom predictive systems for soil digital mapping. The usability experiments conducted on the proposed software platform demonstrate that it is easy to use and effective. Overall, this work highlights the importance of decision support systems in the field of precision agriculture and the potential benefits of using such systems for soil data management and analysis.

One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare facilities, especially for the older population. The aim of the current study was the exploration of the extent to which the healthcare systems responded to the healthcare needs of the older people with or without cognitive impairment and their caregivers in the Adrion/Ionian region. Data were collected through e-questionnaires regarding the adequacy of the healthcare system and were anonymously administered to older individuals and stakeholder providers in the following countries: Slovenia, Italy (Calabria), Croatia, Bosnia and Herzegovina, Greece, Montenegro, and Serbia. Overall, 722 older people and 267 healthcare stakeholders participated in the study. During the COVID-19 pandemic, both healthcare stakeholders and the older population claimed that the healthcare needs of the older people and their caregivers increased dramatically in all countries, especially in Italy (Calabria), Croatia and BiH. According to our results, countries from the Adrion/Ionian regions faced significant challenges to adjust to the special needs of the older people during the COVID-19 pandemic, which was possibly due to limited accessibility opportunities to healthcare facilities. These results highlight the need for the development of alternative ways of providing medical assistance and supervision when in-person care is not possible.

In this study, the antioxidant, antimicrobial, mechanical, optical, and barrier attributes of Solanum lycocarpum starch bio-based edible films incorporated with a phenolic extract from jaboticaba peel were investigated. Aiming to determine the effect of the polymers and the phenolic extract on the properties of the films, a three-factor simplex-lattice design was employed, and the formulation optimization was based on the produced films’ antioxidant potential. The optimized formulation of the starch-PEJP film showed a reddish-pink color with no cracks or bubbles and 91% antioxidant activity against DPPH radical. The optimized starch-PEJP film showed good transparency properties and a potent UV-blocking action, presenting color variation as a function of the pH values. The optimized film was also considerably resistant and highly flexible, showing a water vapor permeability of 3.28 × 10−6 g m−1 h−1 Pa−1. The microbial permeation test and antimicrobial evaluation demonstrated that the optimized starch-PEJP film avoided microbial contamination and was potent in reducing the growth of Escherichia coli, Staphylococcus aureus, and Salmonella spp. In summary, the active starch-PEJP film showed great potential as an environmentally friendly and halochromic material, presenting antioxidant and antimicrobial properties and high UV-protecting activity.

The COVID-19 pandemic has hampered the optimum management of retinal diseases. This study examined the impact of the pandemic on the intravitreal-injection practice in two academic centers in Italy along with the related medico-legal implications. A retrospective analysis of electronic medical records from 16 March 2020 to 14 March 2021 at the ophthalmological departments of University of Cagliari (SGD) and University Magna Græcia of Catanzaro (UMG) was conducted. The data collected between 16 March 2020 and 14 June 2020 (lockdown), 15 June 2020 and 13 September 2020 (unlock), and 14 September 2020 and 14 March 2021 (second wave) were compared with those of the same period of the previous year. Weekly data on the administered drug and the number and type of treated disease were collected and analyzed. During the lockdown, a drop of 59% at SGD (p < 0.00001) and 77% at UMG (p < 0.00001) in intravitreal injections was found. In the first year of the pandemic, the reduction in injections was approximately of 27% (p < 0.0008) and 38% (p < 0.0001) at SGD and UMG, respectively. The COVID-19-related containment measures and the health resources redistribution have led to a delay in the treatment of chronic diseases of the retina, prioritizing the undeferrable ones. The lack of management guidelines has conceived relevant ethical and medico-legal issues that need to be considered in future measures planning.

Sphingolipids are bioactive molecules that play either pro- and anti-atherogenic roles in the formation and maturation of atherosclerotic plaques. Among SLs, ceramide and sphingosine-1-phosphate showed antithetic properties in regulating various molecular mechanisms and have emerged as novel potential targets for regulating the development of atherosclerosis. In particular, maintaining the balance of the so-called ceramide/S1P rheostat is important to prevent the occurrence of endothelial dysfunction, which is the trigger for the entire atherosclerotic process and is strongly associated with increased oxidative stress. In addition, these two sphingolipids, together with many other sphingolipid mediators, are directly involved in the progression of atherogenesis and the formation of atherosclerotic plaques by promoting the oxidation of low-density lipoproteins (LDL) and influencing the vascular smooth muscle cell phenotype. The modulation of ceramide and S1P levels may therefore allow the development of new antioxidant therapies that can prevent or at least impair the onset of atherogenesis, which would ultimately improve the quality of life of patients with coronary artery disease and significantly reduce their mortality.

In the context of global warming, agriculture faces severe challenges such as water scarcity and soil erosion. Key to achieving soil sustainability is the choice of farming practices, the consequences of which are generally site-specific. In this study, the ability of Electrical Resistivity Tomography (ERT) and Electro Magnetic Induction (EMI) methods were assessed for monitoring the effects of conventional (CONV) and conservation (CONS) agricultural practices. The aim is to highlight differences in soil water distribution caused by both short- and long-term effects of the two different practices. Results demonstrated that both ERT and EMI provided sufficient information to distinguish between the effects of CONV and CONS, while traditional direct measurements, being punctual techniques, lacked sufficient spatial resolution. The ERT transects showed that the soil was much more homogeneous as a result of CONS practices, resulting in a higher sensitivity to changes in the water content. Conversely, due to the heterogeneous soil structure under CONV, water distribution was more irregular and difficult to predict. Similar patterns were also observed with the EMI surveys, with a strong link to spatial variability. Finally, we conclude that for CONV soil, the accessible water for the plant is clearly controlled by the soil heterogeneities rather than by the forcing atmospheric conditions. This study is a first step towards paving the way for more refined hydrology models to identify which soil parameters are key to controlling spatial and temporal changes in soil water content.

In recent years, the improvement in health and social conditions has led to an increase in the average lifespan. Since aging is the most important risk factor for the majority of chronic human diseases, the development of therapies and intervention to stop, lessen or even reverse various age-related morbidities is an important target to ameliorate the quality of life of the elderly. The gut microbiota, that is, the complex ecosystem of microorganisms living in the gastrointestinal tract, plays an important role, not yet fully understood, in maintaining the host’s health and homeostasis, influencing metabolic, oxidative and cognitive status; for this reason, it is also named “the forgotten endocrine organ” or “the second brain”. On the other hand, the gut microbiota diversity and richness are affected by unmodifiable factors, such as aging and sex, and modifiable ones, such as diet, pharmacological therapies and lifestyle. In this review, we discuss the changes, mostly disadvantageous, for human health, induced by aging, in microbiota composition and the effects of dietary intervention, of supplementation with probiotics, prebiotics, synbiotics, psychobiotics and antioxidants and of physical exercise. The development of an integrated strategy to implement microbiota health will help in the goal of healthy aging.

Orthotopic neobladder reconstruction is becoming an increasing option as a urinary diversion following cystectomy for bladder cancer. The purpose of the following article is to describe, step-by-step, our technique for the robotic intracorporeal neobladder, the Vesuvian Orthotopic Neobladder. The primary aim of this new surgical procedure is to simplify and speed up the reservoir reconstruction, while at the same time obtaining an appropriate reservoir capacity. The Vesuvian Orthotopic Neobladder was performed employing an intestinal tract of 36 cm which was successively shaped in order to form a reservoir with three horns (left, right, and caudal), formed via the use of a mechanical stapler. Both ureters were stented and anastomosed to the left and right horn while the urethral-neobladder anastomosis was performed with the caudal horn. In this initial experience, two male patients with non-metastatic muscle-invasive bladder cancer underwent radical cystectomy followed by Vesuvian Orthotopic Neobladder reconfiguration. The mean age was 58.5 ± 3.53 years while the mean overall operative time was 435 ± 35.35 min, with an average neobladder reconstruction time of 59 ± 4.24 min. No intraoperative or postoperative complications were reported. The new intracorporeal Vesuvian Orthotopic Neobladder technique is a feasible and good alternative to traditional robotic intracorporeal orthotopic bladder procedures, permitting us to reduce operative time and obtain a neobladder with a fair reservoir capacity.

Brugada Syndrome (BrS) is an inherited arrhythmogenic disorder with an increased risk of sudden cardiac death. Recent evidence suggests that BrS should be considered as an oligogenic or polygenic condition. Mutations in genes associated with BrS are found in about one-third of patients and they mainly disrupt the cardiac sodium channel NaV1.5, which is considered the main cause of the disease. However, voltage-gated channel’s activity could be impacted by post-translational modifications such as sialylation, but their role in BrS remains unknown. Thus, we analyzed high risk BrS patients (n = 42) and healthy controls (n = 42) to assess an involvement of sialylation in BrS. Significant alterations in gene expression and protein sialylation were detected in Peripheral Blood Mononuclear Cells (PBMCs) from BrS patients. These changes were significantly associated with the phenotypic expression of the disease, as the size of the arrhythmogenic substrate and the duration of epicardial electrical abnormalities. Moreover, protein desialylation caused a reduction in the sodium current in an in vitro NaV1.5-overexpressing model. Dysregulation of the sialylation machinery provides definitive evidence that BrS affects extracardiac tissues, suggesting an underlying cause of the disease. Moreover, detection of these changes at the systemic level and their correlation with the clinical phenotype hint at the existence of a biomarker signature for BrS.

Glucose impairment is common in preterm infants but the impact of early neonatal hyperglycemia on long term neurodevelopment is still highly controversial. This review reports current evidence of the effect of hyperglycemia on neurodevelopmental outcome. It was conducted according to the PRISMA guidelines. We searched MEDLINE via PubMed; EMBASE via Ovid; the Cochrane Central Register of Controlled Trials; the Cochrane Library; ClinicalTrials.gov; and the World Health Organization’s International Trials Registry and Platform. We included studies that investigated the association between hyperglycemia, defined as at least one episode of glycemia ≥8 mmol/L, and neurodevelopment outcome evaluated either through the Griffiths Mental Developmental Scales (GMDS) or the Bayley Scales of Infant Development (BSID) for the first 5 years of life, and the Wechsler Intelligence Scale for Children (WISC) and the Movement Assessment Battery for Children (MABC) for the following age category. We selected six studies, comprising 2226 infants in total and which included 1059 (48%) infants for whom neurodevelopment assessment was available. We found an association between hyperglycemia and neurological delay in the first two years of life, especially for motor functions; this result was confirmed in later childhood. The quality of evidence was poor; therefore, the negative influence of neonatal hyperglycemia on the neurological development of preterm infants must be investigated in further studies.

Reducing protein intake in patients with chronic kidney disease (CKD) limits glomerular stress induced by hyperfiltration and can prevent the progression of kidney disease; data in pregnancy are limited. The aim of this study is to analyze the results obtained in CKD patients who followed a plant-based moderately protein-restricted diet during pregnancy in comparison with a propensity-score-matched cohort of CKD pregnancies on unrestricted diets. A total of 52 CKD pregnancies followed up with a protein-restricted plant-based diet (Torino, Italy) were matched with a propensity score based on kidney function and proteinuria with CKD pregnancies with unrestricted protein intake (Cagliari Italy). Outcomes included preterm (2 with 13.46% of obese subjects. No statistical differences were found between women on a plant-based diet and women who were not in terms of age, parity, BMI, obesity, CKD stage, timing of referral, or cause of CKD. No differences were found between the two groups regarding the week of delivery. However, the combined negative outcome (birth before 37 completed gestational weeks or birth-weight centile p = 0.03). The lower risk was confirmed in a multivariable analysis adjusted for renal function and proteinuria (OR: 0.260 [Q1:0.093–Q3:0.724]; p = 0.010), in which the increase in proteinuria from the first to the last check-up before delivery was lower in patients on plant-based diets (median from 0.80 to 1.87 g/24 h; p: ns) than in controls (0.63 to 2.39 g/24 h p < 0.0001). Plant-based, moderately protein-restricted diets in pregnancy in patients with CKD are associated with a lower risk of preterm delivery and small-for-gestational-age babies; the effect may be mediated by better stabilization of proteinuria.

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aβ 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.

The marmalade and jam market is growing worldwide, with the European countries being the main producers in this sector. The market has ancient origins and the production is aimed at conserving the surplus fruits during some period of the year. Nowadays, the automatic production processes are wide-ranging but start with high-quality raw materials and follow an appropriate cooking process to conserve the main features of the final product. On the other hand, cases of overcooking may occur which lead to the production of hydroxy-methyl-furfural and derivatives with consequent browning and poor organoleptic characteristics of the final product. This study aimed to use chemical oxide nanowire gas sensors device S3 coupled with optical techniques and recognizing algorithms to create a multi-actor platform able to control the production process of jams and marmalades with a fast response time, to assist the production process and avoid economical losses in the sector. PCA shows that this innovative technology can recognize changes in the volatile fingerprint, distinguishing when the positive and more natural organoleptic characteristics of the fruit are still present from the appearance of the organoleptic defects due to a faulty production process.

Sarcopenia, an age-related decline in muscle mass and strength, is associated with metabolic disease and increased risk of cardiovascular morbidity and mortality. It is associated with decreased tissue vascularization and muscle atrophy. In this work, we investigated the role of the hypoxia inducible factor HIF-1α in sarcopenia. To this end, we obtained skeletal muscle biopsies from elderly sarcopenic patients and compared them with those from young individuals. We found a decrease in the expression of HIF-1α and its target genes in sarcopenia, as well as of PAX7, the major stem cell marker of satellite cells, whereas the atrophy marker MURF1 was increased. We also isolated satellite cells from muscle biopsies and cultured them in vitro. We found that a pharmacological activation of HIF-1α and its target genes caused a reduction in skeletal muscle atrophy and activation of PAX7 gene expression. In conclusion, in this work we found that HIF-1α plays a role in sarcopenia and is involved in satellite cell homeostasis. These results support further studies to test whether pharmacological reactivation of HIF-1α could prevent and counteract sarcopenia.

Platelets are emerging as a promising source of blood biomarkers for several pathologies, including cancer. New automated techniques for easier manipulation of platelets in the context of lab-on-a-chips could be of great support for liquid biopsy. Here, several polymeric materials were investigated for their behavior in terms of adhesion and activation of human platelets. Polymeric materials were selected among the most used in microfabrication (PDMS, PMMA and COC) and commercial and home-made resins for 3D printing technology with the aim to identify the most suitable for the realization of microdevices for human platelets isolation and analysis. To visualize adherent platelets and their activation state scanning, electron microscopy was used, while confocal microscopy was used for evaluating platelets’ features. In addition, atomic force microscopy was employed to further study platelets adherent to the polymeric materials. Polymers were divided in two main groups: the most prone to platelet adhesion and materials that cause few or no platelets to adhere. Therefore, different polymeric materials could be identified as suitable for the realization of microdevices aimed at capturing human platelets, while other materials could be employed for the fabrication of microdevices or parts of microdevices for the processing of platelets, without loss on surfaces during the process.

Soils form the basis for agricultural production and other ecosystem services, and soil management should aim at improving their quality and resilience. Within the SoilCare project, the concept of soil-improving cropping systems (SICS) was developed as a holistic approach to facilitate the adoption of soil management that is sustainable and profitable. SICS selected with stakeholders were monitored and evaluated for environmental, sociocultural, and economic effects to determine profitability and sustainability. Monitoring results were upscaled to European level using modelling and Europe-wide data, and a mapping tool was developed to assist in selection of appropriate SICS across Europe. Furthermore, biophysical, sociocultural, economic, and policy reasons for (non)adoption were studied. Results at the plot/farm scale showed a small positive impact of SICS on environment and soil, no effect on sustainability, and small negative impacts on economic and sociocultural dimensions. Modelling showed that different SICS had different impacts across Europe—indicating the importance of understanding local dynamics in Europe-wide assessments. Work on adoption of SICS confirmed the role economic considerations play in the uptake of SICS, but also highlighted social factors such as trust. The project’s results underlined the need for policies that support and enable a transition to more sustainable agricultural practices in a coherent way.

Coronary reperfusion strategies are life-saving approaches to restore blood flow to cardiac tissue after acute myocardial infarction (AMI). However, the sudden restoration of normal blood flow leads to ischemia and reperfusion injury (IRI), which results in cardiomyoblast death, irreversible tissue degeneration, and heart failure. The molecular mechanism of IRI is not fully understood, and there are no effective cardioprotective strategies to prevent it. In this study, we show that activation of sialidase-3, a glycohydrolytic enzyme that cleaves sialic acid residues from glycoconjugates, is cardioprotective by triggering RISK pro-survival signaling pathways. We found that overexpression of Neu3 significantly increased cardiomyoblast resistance to IRI through activation of HIF-1α and Akt/Erk signaling pathways. This raises the possibility of using Sialidase-3 activation as a cardioprotective reperfusion strategy after myocardial infarction.

Background: Early in-vivo diagnosis of Alzheimer’s disease (AD) is crucial for accurate management of patients, in particular, to select subjects with mild cognitive impairment (MCI) that may evolve into AD, and to define other types of MCI non-AD patients. The application of artificial intelligence to functional brain [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography(CT) aiming to increase diagnostic accuracy in the diagnosis of AD is still undetermined. In this field, we propose a radiomics analysis on advanced imaging segmentation method Statistical Parametric Mapping (SPM)-based completed with a Machine-Learning (ML) application to predict the diagnosis of AD, also by comparing the results with following Amyloid-PET and final clinical diagnosis. Methods: From July 2016 to September 2017, 43 patients underwent PET/CT scans with FDG and Florbetaben brain PET/CT and at least 24 months of clinical/instrumental follow-up. Patients were retrospectively evaluated by a multidisciplinary team (MDT = Neurologist, Psychologist, Radiologist, Nuclear Medicine Physician, Laboratory Clinic) at the G. Giglio Institute in Cefalù, Italy. Starting from the cerebral segmentations applied by SPM on the main cortical macro-areas of each patient, Pyradiomics was used for the feature extraction process; subsequently, an innovative descriptive-inferential mixed sequential approach and a machine learning algorithm (i.e., discriminant analysis) were used to obtain the best diagnostic performance in prediction of amyloid deposition and the final diagnosis of AD. Results: A total of 11 radiomics features significantly predictive of cortical beta-amyloid deposition (n = 6) and AD (n = 5) were found. Among them, two higher-order features (original_glcm_Idmn and original_glcm_Id), extracted from the limbic enthorinal cortical area (ROI-1) in the FDG-PET/CT images, predicted the positivity of Amyloid-PET/CT scans with maximum values of sensitivity (SS), specificity (SP), precision (PR) and accuracy (AC) of 84.92%, 75.13%, 73.75%, and 79.56%, respectively. Conversely, for the prediction of the clinical-instrumental final diagnosis of AD, the best performance was obtained by two higher-order features (original_glcm_MCC and original_glcm_Maximum Probability) extracted from ROI-2 (frontal cortex) with a SS, SP, PR and AC of 75.16%, 80.50%, 77.68%, and 78.05%, respectively, and by one higher-order feature (original_glcm_Idmn) extracted from ROI-3 (medial Temporal cortex; SS = 80.88%, SP = 76.85%, PR = 75.63%, AC = 78.76%. Conclusions: The results obtained in this preliminary study support advanced segmentation of cortical areas typically involved in early AD on FDG PET/CT brain images, and radiomics analysis for the identification of specific high-order features to predict Amyloid deposition and final diagnosis of AD.

The disaccharide trehalose is a well-established autophagy inducer, but its therapeutic application is severely hampered by its low potency and poor pharmacokinetic profile. Thus, we targeted the rational design and synthesis of trehalose-based small molecules and nano objects to overcome such issues. Among several rationally designed trehalose-centered putative autophagy inducers, we coupled trehalose via suitable spacers with known self-assembly inducer squalene to yield two nanolipid-trehalose conjugates. Squalene is known for its propensity, once linked to a bioactive compound, to assemble in aqueous media in controlled conditions, internalizing its payload and forming nanoassemblies with better pharmacokinetics. We assembled squalene conjugates to produce the corresponding nanoassemblies, characterized by a hydrodynamic diameter of 188 and 184 nm and a high stability in aqueous media as demonstrated by the measured Z-potential. Moreover, the nanoassemblies were characterized for their toxicity and capability to induce autophagy in vitro.