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Background/Objectives: Chronic inflammatory diseases (CIDs) often present a preclinical phase influenced by genetic and environmental factors, including nutrition. Early dietary habits may modulate long-term health trajectories by shaping the intestinal microbiota. Previous work showed that weaning with fresh foods from the Mediterranean diet (MD) improved dietary habits and microbiota composition at 3 years of age. This study aimed to assess whether such benefits persist at 9 years. Methods: This long-term follow-up included 191 children (96 MD, 95 controls) from the original randomized cohort (ClinicalTrials.gov NCT05297357). The primary endpoint was adherence to MD (KidMed score ≥ 8). Secondary endpoints included BMI, incidence of CID, maternal dietary adherence, and intestinal microbiota composition in a subset of 36 children. Results: At 9 years, no difference was found in overall MD adherence (27.4% controls vs. 27.1% MD; p > 0.99) or BMI (17.7 vs. 18.1 kg/m2; p = 0.384). However, children from the MD group reported higher daily vegetable intake (71.9% vs. 51.6%; p = 0.005). Microbiota analyses revealed persistent differences between groups, with higher alpha diversity in the MD group. Although not statistically significant, the MD group showed lower prevalence of atopic dermatitis, allergic rhinitis, autism spectrum disorder, and ADHD. Maternal adherence to MD did not differ between groups. Conclusions: Early introduction of Mediterranean-style foods during weaning exerts lasting effects on dietary patterns and gut microbiota, with a potential protective trend against CID. While overall MD adherence converged between groups by 9 years, these findings suggest that early-life nutritional interventions may induce durable microbiome-mediated benefits and contribute to preventive strategies for chronic disease, warranting confirmation in larger, extended cohorts. Moreover, this study highlights the value of the collaboration between the Italian primary care pediatric system and the integration of the pediatric residency program, demonstrating a feasible and cost-effective methodology to generate large-scale prospective data within routine clinical practice. Larger studies and a longer follow-up period are necessary to confirm these results.

Mediterranean Diet (Med Diet) is one of the healthiest dietary patterns. We aimed to verify the effects of weaning (i.e., the introduction of solid foods in infants previously fed only with milk) using adult foods typical of Med Diet on children eating habits, and on the microbiota composition. A randomized controlled clinical trial on 394 healthy infants randomized in a 1:1 ratio in a Med Diet group weaned with fresh; seasonal and tasty foods of Med Diet and control group predominantly weaned with industrial baby foods. The primary end point was the percentage of children showing a good adherence to Med Diet at 36 months. Secondary end points were mother’s changes in adherence to Med Diet and differences in children gut microbiota. At 36 months, children showing a good adherence to Med Diet were 59.3% in the Med Diet group and 34.3% in the control group (p < 0.001). An increase in adherence to the Med Diet was observed in the mothers of the Med Diet group children (p < 0.001). At 4 years of age children in the Med Diet group had a higher gut microbial diversity and a higher abundance of beneficial taxa. A Mediterranean weaning with adult food may become a strategy for early nutritional education, to develop a healthy microbiota, to prevent inflammatory chronic diseases and to ameliorate eating habits in children and their families.

Propulsion systems for automotive applications are facing the issues related to the stringent noxious emission and CO 2 regulations which are driving the manufacturer and the researchers to the development of innovative powertrains. Among the different solutions, relevant efforts are being directed towards the decarbonisation of internal combustion engines (ICEs). In this scenario, the hydrogen, particularly the green one obtained through the water electrolysis using renewable energy sources, is emerging as a promising fuel for a future sustainable mobility. In this work, a multi-cylinder hydrogen Spark Ignition (SI) engine conceived for automotive applications is developed and optimized to operate under ultra/lean air/hydrogen mixtures. In particular, a 3-cylinder turbocharged hydrogen SI engine is virtually developed through a 0D/1D model, starting from a naturally aspirated single-cylinder SI unit; the latter is properly validated with experiments and 3D CFD outcomes in a previous authors’ activity. A fractal model is used for combustion modelling, coupled to a user-defined turbulence sub-model. The thermo-diffusive instability sub-model, based on Howarth theory, is integrated into the combustion model to correctly simulate the hydrogen engine operation at ultra/lean mixtures. In addition, the knock onset is evaluated with a Tabulated Kinetic of Ignition (TKI) approach, requiring a pre-computation of the auto-ignition delay times at varying the thermodynamic conditions. The main aim of the work is to forecast the hydrogen engine operation under full load and ultra-lean conditions, analysing performance, efficiency and NOx emissions at the knock limit. Subsequently, an optimization of the engine operation is carried out exploring different compression ratios, air/fuel proportions (lambda values) and water-to-fuel ratios. The objective of the initial optimisation is to optimise efficiency while respecting the safety constraint on the occurrence of shocks. Comparison with the base case, in which the maximum value is 35.6%, reveals an increase of 1.98% with CR equal to 13. However, in the case of the high-speed analysis, there is a decrease compared to the base case. The second analysis shows that the maximum lambda value that meets the imposed BMEP target is 2.1, thus minimising the NOx emissions of a multi-cylinder hydrogen engine under all conditions. A final analysis was conducted to study the impact of water injection on NOx for fixed rpm.

Background/Objectives: Oral insulin continues to constitute a challenge due to its low uptake by the gut wall and degradation by gastrointestinal proteolytic enzymes. Such concerns might be surmounted by means of nanoparticle delivery. Methods: In this study, glargine insulin has been loaded into solid lipid nanoparticles prepared via coacervation from Shea and Mango soaps, due to hydrophobic ion pairing. Subsequently, ex vivo tied-up-gut experiments were performed with fluorescently labeled peptide. Additionally, re-dispersible oral solid dosage forms (powders and tablets) were obtained from nanoparticle suspensions via freeze-drying and spray-drying. Results: Solid lipid nanoparticles are capable of enhancing peptide permeation into different gut sections. Furthermore, spray-drying permits the preparation, which can be scaled up, of a re-dispersible powder from the nanoparticle suspension. Conclusions: This engineered process is suitable for the formulation of solid oral dosage forms, such as granulates and tablets, and presents promising potential for oral insulin delivery, paving the way for the assessment of its pharmacological efficacy in further in vivo studies.

Homogeneous charge compression ignition is considered a promising solution to face the increasing regulations imposed by the legislator in the transport sector, thanks to pollutant and CO2 emissions reduction. In this work, a quasi-dimensional multi-zone HCCI model integrated with 1D commercial software is developed and validated. It is based on the control mass Lagrangian approach and computes the mixture chemistry evolution through offline tabulation of chemical kinetics (tabulated kinetic of ignition). Thus, the simulation can predict mixture auto-ignition with reduced computational effort and high accuracy. Multi-zone schematization mimics the typical thermal stratification of HCCI engines, controlling the combustion evolution. The model is coupled to sub-models for pollutant emissions estimation. Initially, the tabulated chemistry approach is validated against a chemical kinetics solver applied to a constant-volume homogeneous reactor, considering various fuel blends. The model is then used to simulate the operations of four engines using different fuels (hydrogen, methane, n-heptane, and n-heptane/toluene/ethanol blend), under various boundary conditions. The model predictivity is demonstrated against pressure traces, heat release rate, and noxious emissions. The numerical results showed to adequately agree with measured counterparts (average relative error of 1.3% on in-cylinder pressure peak, average absolute error of 0.95 CAD on pressure peak angle, average relative error of 8.4% on uHCs emissions, absolute error below 1 ppm on NOx emissions) only adapting the thermal stratification to the engines under study. The methodology proved to be a reliable tool to investigate the operation of an HCCI engine, applicable in the development of new engine architecture.

In this work, various techniques are numerically investigated to assess and quantify their relative effectiveness in reducing the Brake Specific Fuel Consumption (BSFC) of a downsized turbocharged spark-ignition Variable Valve Actuation (VVA) engine. The analyzed solutions include the Variable Compression Ratio (VCR), the port Water Injection (WI), and the external cooled Exhaust Gas Recirculation (EGR). The numerical analysis is developed in a 1D modeling framework. The engine is schematized in GT-Power™ environment, employing refined sub-models of the in-cylinder processes, such as the turbulence, combustion, knock, and heat transfer. The combustion and knock models have been extensively validated in previous papers, at different speed/load points and intake valve strategies, including operations with a relevant internal EGR rate and with liquid WI. The 1D model is coupled to an automatic optimizer, to explore the potential BSFC benefits arising from the adoption of the above-listed solutions. The base engine architecture, only including the VVA device, is preliminarily optimized to define reference BSFC levels. Then, single and combined solutions are analyzed to outline the maximum achievable BSFC gains. Operating conditions typical of a Worldwide harmonized Light vehicles Test Procedure (WLTP) driving cycle are considered. More than proposing an advanced, very complex, engine architecture, the aim of the activity is to clearly outline isolated and mutual effects of each technique at various operating points. In this way, some guidelines are offered to engine developers to select the preferred solution and to have information on the expected improvements. The optimization outcomes show that the WI proves a higher effectiveness at medium-high load, mainly thanks to its knock suppression capability. Cooled EGR is preferable at low load, to reduce the pumping work. If coupled to the WI, a high Compression Ratio (CR) is always beneficial. The combination of the above techniques provides BSFC reductions of 6.9%, 5.2%, and 9.0% at low, medium, and high loads, respectively.

Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, a common disease in older adults. Potential pharmacological treatments, based upon intranasal administration, are worthy of investigation because they might improve symptoms and avoid surgery by overcoming the blood–brain barrier and avoiding hepatic metabolism. Nasal lipid nanocarriers, such as solid lipid nanoparticles, may increase the nasal retention and permeation of drugs. To this aim, green solid lipid nanoparticles, obtained by coacervation from natural soaps, are promising vehicles due to their specific lipid matrix composition and the unsaponifiable fraction, endowed with antioxidant and anti-inflammatory properties, and thus suitable for restoring the neurovascular unit function. In this experimental work, such green solid lipid nanoparticles, fully characterized from a physico-chemical standpoint, were loaded with a drug combination suitable for reverting hydrocephalus symptoms, allowing us to obtain a non-toxic formulation, a reduction in the production of the cerebrospinal fluid in vitro, and a vasoprotective effect on an isolated vessel model. The pharmacokinetics and biodistribution of fluorescently labelled nanoparticles were also tested in animal models.

Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.

It is well known that the downsizing philosophy allows the improvement of Brake Specific Fuel Consumption (BSFC) at part load operation for spark ignition engines. On the other hand, the BSFC is penalized at high/full load operation because of the knock occurrence and of further limitations on the Turbine Inlet Temperature (TIT). Knock control forces the adoption of a late combustion phasing, causing a deterioration of the thermodynamic efficiency, while TIT control requires enrichment of the Air-to-Fuel (A/F) ratio, with additional BSFC drawbacks. In this work, a promising technique, consisting of the introduction of a low-pressure cooled exhaust gas recirculation (EGR) system, is analyzed by means of a 1D numerical approach with reference to a downsized turbocharged SI engine. Proper “in-house developed” sub-models are used to describe the combustion process, turbulence phenomenon and the knock occurrence. The effects of cooled gas recirculation are studied for various EGR and A/F levels. The presented results highlight that the proposed solution involves significant BSFC improvements. In particular, it is able to reduce the engine knock tendency, resulting in the possibility to advance the combustion phasing. Moreover, it involves a TIT reduction that allows to limit the over-fuelling. The developed numerical procedure is able to take into account the complex interactions among different driving parameters affecting the fuel consumption. It can be hence very useful to define a numerical engine pre-calibration and to realistically predict the EGRrelated BSFC advantages which can be gained at different speed and load conditions.

Despite recent progressions in cancer genomic and immunotherapies, advanced melanoma still represents a life threat, pushing to optimise new targeted nanotechnology approaches for specific drug delivery to the tumour. To this aim, owing to their biocompatibility and favourable technological features, injectable lipid nanoemulsions were functionalised with proteins owing to two alternative approaches: transferrin was chemically grafted for active targeting, while cancer cell membrane fragments wrapping was used for homotypic targeting. In both cases, protein functionalisation was successfully achieved. Targeting efficiency was preliminarily evaluated using flow cytometry internalisation studies in two-dimensional cellular models, after fluorescence labelling of formulations with 6-coumarin. The uptake of cell-membrane-fragment-wrapped nanoemulsions was higher compared to uncoated nanoemulsions. Instead, the effect of transferrin grafting was less evident in serum-enriched medium, since such ligand probably undergoes competition with the endogenous protein. Moreover, a more pronounced internalisation was achieved when a pegylated heterodimer was employed for conjugation (p < 0.05).