The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Editorial

Journal of Computer Virology and Hacking Techniques -     

Single chamber Solid Oxide Fuel Cells selective electrodes: A real chance with brownmillerite-based nanocomposites

In this contribution brownmillerite-based nanocomposite cathode for Single-Chamber Solid Oxide Fuel Cells is developed. These cells can be very attractive especially for small and cheap devices because of the absence of seals. The efficiency of SC-SOFCs is strictly connected to the selectivity of anode and cathode, the bottleneck for this technology. The development of a cathode inert in fuel oxidation is particularly challenging. Our strategy is to start from a catalytically un-active support (CFA = Ca₂FeAl_0.95Mg_0.05O₅) and induce the formation of iron oxide based nanoparticles, expected to activate oxygen. Symmetric (CFA + FeO_x/CGO/CFA + FeO_x) and complete cells (CFA + FeO_x/CGO/Ni-CGO) are studied in air and methane/oxygen 2:1 mixture. The Area Specific Resistance of CFA + FeO_x is less than 1/3 that of CFA. The high selectivity allows to reach an efficiency of 25%; power still needs to be increased but we demonstrated the possibility to develop selective low cost electrodes. The effect of air, methane/oxygen exposure and the heat treatments were carefully investigated.     

Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations

Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.     

From hospital to municipal cogeneration systems: an Italian case study

A mixed integer linear programming model combined with a more traditional design by scenarios is proposed to optimize facilities size and operation mode of a municipal energy system involving significant civil centres and a hospital. Moving from the need of a new heat and power station for the local hospital due to the construction of new pavilions, the opportunity of involving other centres in the neighbourhood in a distributed cogeneration system is analysed, increasing system complexity step by step. Smaller cogeneration units tailored to hospital needs are rewarding ventures with relatively low risks but, in a country whose traditional power generation systems heavily rely on fossil fuels and where energy policy and market conditions can make it profitable to sell surplus power, district heating systems foster the installation of larger cogenerators and lead thereby to higher profits and to better performance as for primary energy savings and greenhouse gases emission reduction. Copyright © 2006 John Wiley & Sons, Ltd.     

Waste-to-energy based greenhouse heating: exploring viability conditions through optimisation models

An optimisation approach is proposed in order to assess the technical and economic feasibility of a renewable-energy-based greenhouse in North-Eastern Italy. A floor heating system that can exploit a low-temperature heat flow coming from the condenser of a waste-to-energy plant is chosen for the greenhouse and designed developing a non-linear optimisation model, solved by a genetic algorithm. In order to determine under what conditions the combination of a floor-heating-based greenhouse with a waste-to-energy plant can be profitable, a mixed integer optimisation model is introduced to allow selection of the minimum cost fuel solution as a function of different design variables of the greenhouse, such as indoor temperature settings and floor area. The ranges within which the renewable energy solution can lead to significant savings in comparison to traditional fossil fuel are identified both from the point of view of costs and of environmental impact. Furthermore, the sales prices for waste heat that would make investment in the renewable energy solution attractive for potential entrepreneurs are given.     

Promoting the integration of technology in teaching: An analysis of the factors that increase the intention to use technologies among Italian teachers

Background: The rapid spread of COVID-19 forced many countries to adopt severe containment measures, transferring all didactic activities into virtual environments. However, the integration of technology in teaching may present difficulties, especially in some countries, such as Italy. Objectives: The present study analyzed how the two main factors of the Technology Acceptance Model (TAM), namely perceived usefulness and perceived ease of use, combined with online teaching self-efficacy, were associated with the intention to use technology to teach. We posited a moderated moderation model in which perceived usefulness represented the main predictor, with self-efficacy and perceived ease of use as moderators of intention to use technology to teach. Method: The model was tested through multiple regressions, using the PROCESS macro on SPSS 26 with a sample of 178 upper secondary school teachers in Italy. Results and conclusions: Regressions showed that each variable significantly predicted the intention to use technology. In addition, a moderation effect of self-efficacy on the perceived usefulness of using technology was found for medium and high-level of perceived ease of use of technology. Implications: The present study provides targeted implications for distance education policy and practice to promote its adoption (or the blended modality) in Italian upper schools.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.