Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes

Since early times, being overweight and obesity have been associated with impaired glucose metabolism and type 2 diabetes (T2D). Similarly, a less frequent adult-onset diabetes in low body mass index (BMI) people has been known for many decades. This form is mainly found in developing countries, whereby the largest increase in diabetes incidence is expected in coming years. The number of non-obese patients with T2D is also on the rise among non-white ethnic minorities living in high-income Western countries due to growing migratory flows. A great deal of energy has been spent on understanding the mechanisms that bind obesity to T2D. Conversely, the pathophysiologic features and factors driving the risk of T2D development in non-obese people are still much debated. To reduce the global burden of diabetes, we need to understand why not all obese people develop T2D and not all those with T2D are obese. Moreover, through both an effective prevention and the implementation of an individualized clinical management in all people with diabetes, it is hoped that this will help to reduce this global burden. The purpose of this review is to take stock of current knowledge about the pathophysiology of diabetes not associated to obesity and to highlight which aspects are worthy of future studies.     

Micro- and Nanoplastics’ Effects on Protein Folding and Amyloidosis

A significant portion of the world’s plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood–brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications.     

Design,Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H₂S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H₂S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H₂S donors. The H₂S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H₂S by antiglaucoma H₂S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.     

Optimization of non-uniformly sampled discrete systems

This paper deals with a general method for the optimization of multivariable systems with non-uniform sampling chosen in an optimal way. The algorithm is based on Dynamic Programming and is applied to extend the Kalman-Koepcke optimization method for a linear dynamic system, with a quadratic performance index. In the general multivariable case, the method implies the solution of a two-point boundary value problem. In the scalar case, which has only one input and one output, the sampling periods may be found separately from the control law. The computational difficulties connected with the implementation of the method are discussed and simplifications, possible for discretized continuous systems, are derived. Numerical examples are given.     

Cross-Batch Contamination in a Continuous Horizontal Decanter Centrifuge during Virgin Olive Oil Production

Cross-batch contamination in a decanter centrifuge during virgin olive oil production cannot be avoided using current technology. The extent of this contamination is investigated using industrial-scale tests, by measuring the volatile profile and color on three consecutive oil batches, collected at the decanter outlet at different extraction times. The extent of contamination varied, pointing out qualitative consequences, as defective molecules are found. The latter are often active at low concentrations, and the measured cross-batch contamination can lead both to the downgrading of large batches of virgin olive oils and to the adulteration of monovarietal and certified productions. An innovative method, based on the direct determination of the color (L and a* coordinates) of oil at the outlet of the decanter is able to identify the same compositional change point indicated by gas chromatography, and could be successfully used to mitigate the effects of cross-batch contamination. Practical applications: An in-line colorimetric system can be implemented at the decanter outlet to detect the point of change between different olive batches. Otherwise, the virgin olive oil exiting from the decanter at the beginning of one batch can be collected separately in order to avoid the contamination due to the previous batch.     

Formation and Etching of the Insulating Sr-Rich V5+ Phase at the Metallic SrVO3 Surface Revealed by Operando XAS Spectroscopy Characterizations

In the search of low cost and more efficient electronic devices, here the properties of SrVO₃ transparent conductor oxide (TCO) thin film are investigated, both visible-range optically transparent and highly conductive, it stands as a promising candidate to substitute the standard indium-tin-oxide (ITO) in applications. Its surface stability under water (both liquid and vapor) and other gaseous atmospheres is especially addressed. Through the use of spectroscopy characterizations, X-ray photoemission and operando X-ray absorption measurements, the formation of a thin Sr-rich V⁵⁺ layer located at the surface of the polycrystalline SrVO₃ film with aging is observed, and for the first time how it can be removed from the surface by solvating in water atmosphere. The surface recovery is associated to an etching process, here spectroscopically characterized in operando conditions, allowing to follow the stoichiometric modification under reaction. Once exposed in oxygen atmosphere, the Sr-rich V⁵⁺ layer forms again. The findings improve the understanding of aging effects in perovskite oxides, allowing for the development of functionalized films in which it is possible to control or to avoid an insulating surface layer. This constitutes an important step towards the large-scale use of V-based TCOs, with possible implementations in oxide-based electronics.