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VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model. Antisera specific for the C-terminal end of the human and mouse VGF proteins, respectively, were used in immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), while gel chromatography and HPLC/ESI-MS/MS were used to identify the VGF peptides present. Immunoreactive VGF C-terminus peptides were reduced in both fibroblast and plasma samples from ALS patients in an advanced stage of the disease. In the G93A-SOD1 mice, the same VGF peptides were also decreased in plasma in the late-symptomatic stage, while showing an earlier down-regulation in the spinal cord. In immunohistochemistry, a large number of gray matter structures were VGF C-terminus immunoreactive in control mice (including nerve terminals, axons and a few perikarya identified as motoneurons), with a striking reduction already in the pre-symptomatic stage. Through gel chromatography and spectrometry analysis, we identified one form likely to be the VGF precursor as well as peptides containing the NAPP- sequence in all tissues studied, while in the mice and fibroblasts, we revealed also AQEE- and TLQP- peptides. Taken together, selective VGF fragment depletion may participate in disease onset and/or progression of ALS.

The present paper proposes an integrated method for modelling and designing Energy Storage Systems (ESSs) based on Sodium Metal Halide Batteries (SMHBs). The implementation of the proposed methodology for designing an SMHB-ESS used for supporting telecommunication DC microgrids is presented. The motivation concerning this specific case study is the role assumed by battery technology in improving the reliability and robustness of telecommunication DC microgrids. In this context, the SMHBs, due to their operative temperature, dynamic power response and robustness against cell breakdown, represent one of the most suitable technologies, mainly when challenging environmental conditions occur. The motivation for implementing an integrated design approach is the non-linear behaviour of SMHBs, which requires a high accuracy in battery modelling and in managing DC-DC interfacing for full SMHB capacity exploitation. To highlight the advantages of this novel approach, a comparison between the SMHB- ESS designs considering, as the DC-DC converter, a buck–boost topology actually implemented in the commercial systems and a Dual-Active-Bridge (DAB) converter, specifically developed for this kind of battery, was investigated. Considering different operating conditions in a specific DC telecommunication microgrid, the designed configurations of SMHB ESSs were simulated. Finally, a comparison of simulation results is presented and discussed, highlighting that DABs, despite their greater complexity compared to buck–boost converters, present advantages in terms of flexibility, dynamic performances and efficiency, increasing the available SMHB capacity by 10%.

In recent years, the demand for filter media has increased dramatically, driven by the need to manufacture personal protective equipment and for various applications in the industrial and civil sectors. Nanofiber‐based membranes are proposed as potential alternatives to commercial filtration devices. This study presents the design and implementation of an innovative pre‐industrial electrospinning setup, combining a negatively charged spinneret and a positively charged counter‐electrode, capable of producing polyvinylidene fluoride (PVDF) nanofibers with an average diameter of 410 nm and electrostatic surface potential values 3.7 times higher compared to a conventional electrospinning process, eliminating the need for further post‐treatment. These properties are essential for improving mechanical and electrostatic filtration of small particles, including infectious droplets. The surface potential of the membranes is also long‐lasting, as evidenced by tests one year after manufacture. As a case‐study, these filters are used to manufacture surgical masks, reporting excellent performance in terms of bacterial filtration efficiency (BFE) up to 99.9%, and breathability (29.8±4.5 Pa cm−2) when compared to commercially available meltblown polypropylene (PP) face masks, and also complied with the stringent European standard (EN14683:2019) for type‐II surgical masks. Furthermore, the pre‐industrial setup allows for increased production capacity of up to 42 000 m2 per year, suitable for large‐scale production. Herein, an innovative custom‐made pre‐industrial electrospinning setup is designed to produce filters made of nanofibers with small diameters and high surface potential, crucial features for fine particles filtration. As a case study, electrospun surgical masks are produced, demonstrating superior filtering and breathability performances, compared to traditional meltblown face masks, also complying with the European surgical mask standard (EN14683:2019).

Developing effective antibiotics against Gram-negative bacteria remains challenging due to their protective outer membrane. With this study, we investigated the relationship between antibiotic permeation through the OmpF porin of Escherichia coli and antimicrobial efficacy. We measured the relative permeability coefficients (RPCs) through the bacterial porin by liposome swelling assays, including non-antibacterial molecules, and the minimum inhibitory concentrations (MICs) against E. coli. We developed a machine learning (ML) approach by combining classification and regression models to correlate these data sets. Our strategy allowed us to quantify the negative correlation between RPC and MIC values, clearly indicating that increased permeability through OmpF generally leads to improved antimicrobial activity. Moreover, the correlation was remarkable only for compounds with significant permeability coefficients. Conversely, when permeation ability is low, other factors play the most significant role in antimicrobial potency. Importantly, the proposed ML-based approach was set by exploiting the available seminal information from previous investigations in order to keep the number of molecular descriptors to the minimum for greater interpretability. This provided valuable insights into the complex interplay between different molecular properties in defining the overall outer membrane permeation and, consequently, the antimicrobial efficacy. From a practical perspective, the presented approach does not aim at identifying the “golden rule” for boosting antibiotic potency. The automated protocol presented here could be used to inspect, in silico, many alternatives of a given molecular structure, with the output being the list of the best candidates to be then synthesized and tested. This could be a valuable in silico tool for researchers in both academia and industry to rapidly evaluate novel potential compounds and reduce costs and time during the early drug discovery stage.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M = 20/3) was compared before (T0) and after 3 months (T3) of nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, GM characterization confirmed typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction in body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, an increase in the abundance of several Bacteroidetes taxa (i.e., Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and a depletion of many Firmicutes taxa (i.e., Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas) were observed. In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of moderate caloric restriction in counteracting the gut dysbiosis.

Aqueous solutions of diammonium hydrogen phosphate (DAP) have been recently proposed for consolidation of archeological bones, as an alternative to traditional products. Here, we investigated several routes to improve the performance of the DAP-based treatment, namely increasing the DAP concentration, adding calcium ions and adding ethanol to the DAP solution. Archaeological bones dated to about 1–0.8 million years ago were used for the tests. After preliminary screening by FTIR microscopy and FEG-SEM among different formulations, confirming the formation of new hydroxyapatite phases, the most promising formulation was selected, namely a 3 M DAP solution. The strengthening ability of this formulation was systematically compared to that of the most widely used commercial consolidant, namely Paraloid B72. The performance of the two treatments was evaluated in terms of Knoop and Vickers microhardness, resistance to scratch and resistance to material loss by peeling off. The results of the study show that the DAP treatment was able to improve the bone surface properties and also the resistance to material loss by peeling off, which is more dependent on in-depth consolidation. Paraloid B72 led to the formation of a layer of acrylic resin on the bone surface, which influenced the mechanical tests. Nonetheless, Paraloid B72 was able to penetrate in depth and substantially decrease the material loss by peeling off, even more effectively than DAP. The results of this study indicate that the potential of the DAP treatment for bone consolidation is confirmed.

This study aims to evaluate the safety and efficacy of the Derivo peripher and Derivo 2 Embolization Device Flow Diverter Stents (DEDs, Acandis GmbH) in treating visceral aneurysms. This multicentric registry with core-lab evaluation involves 29 Italian Interventional Radiology and Vascular Surgery units, targeting 100 patients. Inclusion criteria include visceral artery aneurysms without signs of rupture and adherence to correct DED stent sizing and anticoagulant and antiplatelet protocols. Patients will undergo physical examination and computed tomography angiography (CTA) within 6-month and at 1-year post-procedure. A core laboratory will evaluate all pre- and post-procedure CTA and procedural angiographic images for procedural correctness (adherence to correct DED sizing, deployment accuracy, and technical issues), stent morphology during follow-up (patency and geometrical changes), and VAA morphological changes (volume variation, thrombosis grade, and number of patent branches). The primary objective is to evaluate the technical efficacy and safety of DEDs at 1-year follow-up. Efficacy will be assessed by patency of DEDs and side branches, aneurysm thrombosis (< 50%, > 50% or total volume of the aneurysm), and non-increase in aneurysm volume (percentage change relative to initial volume). Safety will be assessed by morbidity (adverse events during follow-up), mortality (any cause of death), and technical issues (adverse events during stent placement, based on CIRSE classification of complications). The DEDICATE registry will provide further information on the effectiveness of flow-diverting stents in treating visceral aneurysmal pathology. Trial Registration ClinicalTrials.gov identifier: NCT06325371.

PurposeTo evaluate the effects of wild trekking by examining, in postmenopausal women, the physiological adaptations to an intensive 5-day wild trek and comparing their responses to those displayed by a group of men of comparable age, training status and mountaineering skills.MethodsSix healthy, active postmenopausal women in their sixth decade of life participated in the study. Six men of comparable age and training status were also enrolled for gender-based comparisons. The participants traversed the Selvaggio Blu wild trek (Sardinia, Italy) completing a total of 56 km, for an overall height differential of 14,301 m. During all 5-day trek, subjects were supervised by two alpine guides. Changes in body composition, cardiorespiratory fitness, and metabolic patterns of energy expenditure were evaluated before and after the intervention.ResultsTotal energy expenditure during the trek was significantly higher (p = 0.03) in women (12.88 ± 3.37 kcal/h/kg) than men (9.27 ± 0.89 kcal/h/kg). Extracellular (ECW) and intracellular water (ICW) increased significantly following the trek only in women (ECW: − 3.8%; p = 0.01; ICW: + 3.4%; p = 0.01). The same applied to fat-free mass (+ 5.6%; p = 0.006), fat mass (− 20.4%; p = 0.006), skeletal muscle mass (+ 9.5%; p = 0.007), and appendicular muscle mass (+ 7.3%; p = 0.002). Peak VO2/kg (+ 9.4%; p = 0.05) and fat oxidation (at 80 W: + 26.96%; p = 0.04; at 100 W: + 40.95%; p = 0.02; at 120 W: + 83.02%; p = 0.01) were found increased only in women, although no concurrent changes in partial pressure of end-tidal CO2 (PETCO2) was observed.ConclusionsIn postmenopausal women, a 5-day, intensive and physically/technically demanding outdoor trekking activity led to significant and potentially relevant changes in body composition, energy balance and metabolism that are generally attained following quite longer periods of training.

A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays.

Phytoremediation and the use of suitable amendments are well-known technologies for the mitigation of petroleum hydrocarbon (PHC) contaminations in terrestrial ecosystems. Our study is aimed at combining these two approaches to maximize their favorable effects. To this purpose, Helichrysum microphyllum subsp. tyrrhenicum, a Mediterranean shrub growing on sandy and semiarid soils, was selected. The weathered PHC-polluted matrix (3.3 ± 0.8 g kg−1 dry weight) from a disused industrial site was employed as the cultivation substrate with (WCAM) or without (UNAM) the addition and mixing of wood chips. Under the greenhouse conditions, the species showed a survival rate higher than 90% in the UNAM while the amendment administration restored the totality of the plant survival. At the end of the greenhouse test (nine months), the treatment with the wood chips significantly increased the moisture, dehydrogenase activity and abundance of the microbial populations of the PHC degraders in the substrate. Cogently, the residual amount of PHCs was significantly lower in the UNAM (3–92% of the initial quantity) than in the WCAM (3–14% of the initial quantity). Moreover, the crown diameter was significantly higher in the WCAM plants. Overall, the results establish the combined technology as a novel approach for landscaping and the bioremediation of sites chronically injured by PHC-weathered contaminations.