MicroRNAs (miRNAs) represent endogenous small RNAs that post-transcriptionally regulate gene expression and, thus they are involved in the onset and progression of various diseases and conditions (Bader et al., 2010) such as for overweight and obesity. Antiadipogenic miRNA-27a is a negative regulator in fat metabolism, which inhibits adipocyte differentiation through downregulation of adipogenic marker genes (e.g. PPARγ) (Kim et al., 2010). Reduced miRNA-27a levels are often associated with the development of obesity and, therefore, this miRNA might represent a promising candidate for miRNA mimic replacement therapy (Lin et al., 2009). However, the application of naked RNAs has shown low membrane permeability, cellular uptake, and rapid degradation in the circulation. The present study aimed to develop a cationic, lipid-based nanoparticle system for targeting adipose tissue and delivering miRNA-27a. These systems are composed of positively charged nanostructured lipid carriers (cNLCs) and negatively charged miRNAs, which results in complex formation based on electrostatic interactions between these components. Materials and methods

Omeprazole is a proton pump inhibitor commonly used in pediatric patients (Wensel, 2009). Pediatric patients are usually unable to swallow solid dosage forms and they need dose adjustment. Therefore, the dosage form of choice for this population is compounded liquid preparation. Since pharmacies don't usually dispose of pure active substances, compounded liquid preparations are most commonly prepared from commercially available solid dosage forms, in a way that tablets are simply pulverized or capsule contents emptied, adding water or one of the commercially available vehicles (Haywood and Glass, 2013). Considering the risks associated with the preparation and use of compounded preparations, the Chapter <795> of the US Pharmacopoeia states that the beyond-use date is 14 days for non-preserved aqueous oral formulations, if stored in the refrigerator. Preserved aqueous preparations can be stored for 35 days at controlled room temperature or in the refrigerator (USP, 2015).

Approximately 70-90% of the new active pharmaceutical ingredients/drugs are poorly soluble in water/biological fluids. Improvement of solubility, dissolution rate, bioavailability are the main characteristics of drug nanocrystals that are important for oral drug administration. High bioadhesive activity, depending on the type of stabilizer, is considered to be an essential feature of drug nanocrystals for oral, dermal, ocular dosage forms (Chang et al., 2015; Sheokand et al., 2018; Tuomela et al., 2016). Drug nanocrystals are solid nanosized particles of pharmacologically active substances, mainly BCS class IIa and IIb, 200 to 600 nm in diameter, homogeneously coated with 10-50% stabilizer/surfactants and/or polymers, forming ultrafine dispersion (Malamatari et al., 2018). Drug nanocrystals are usually in the crystalline state, but depending on the manufacturing method and process parameters, they may be in the amorphous state (Shete et al., 2014). Drug nanocrystals can be obtained by increasing their particle size by controlled precipitation/agglomeration from solution or by reducing drug particle size by milling to the desirable size. The two basic methods for obtaining drug nanocrystals are bottom up (e.g., precipitation) and top down (e.g., milling) methods, or drug nanocrystals can be made by a combination of these processes. By combining these two methods the desired particle size of drugs can be achieved and disadvantages of the individual methods are overcomed. These methods are intended for the preparation of liquid pharmaceutical nanosuspensions whose internal phase consists of drug nanocrystals particles, which can be converted into solid drug nanocrystals by post-production processes (spray drying, freeze drying or other process) in order to improve chemical, physical stability of drug during storage, when the selected stabilizer of drug nanocrystal could not provide long-term stability of the liquid nanosuspension (Sheokand et al., 2018).

Global Navigation Satellite Systems (GNSS) are nowadays the most common solutions used to cope with Positioning-Navigation-Timing (PNT) applications demands. GNSS are relied on in very diverse contexts and domains, yet the interest in systems such as GPS, GALILEO and Beidou is continuously increasing. However

Symptom‐focused management is one of the cornerstones of optimal atrial fibrillation (AF) therapy.

Nacre’s structure-property relationships have been a source of inspiration for designing advanced functional materials with both high strength and toughness. These outstanding mechanical properties have been mostly attributed to the interplay between aragonite platelets and organic matrices in the typical brick-and-mortar structure. Here, we show that crystallographically co-oriented stacks of aragonite platelets, in both columnar and sheet nacre, define another hierarchical level that contributes to the toughening of nacre. By correlating piezo-Raman and micro-indentation results, we quantify the residual strain energy associated with strain hardening capacity. Our findings suggest that the aragonite stacks, with characteristic dimensions of around 20 µm, effectively store energy through cooperative plastic deformation. The existence of a larger length scale beyond the brick-and-mortar structure offers an opportunity for a more efficient implementation of biomimetic design. The hierarchical structure of nacre is known to contribute to its high strength and toughness, providing inspiration for many biomimetic materials. Here, co-oriented 20 µm stacks of aragonite platelets are shown to contribute to the toughness of nacre, defining a new characteristic length scale.

Resistive random-access memories, also known as memristors, whose resistance can be modulated by the electrically driven formation and disruption of conductive filaments within an insulator, are promising candidates for neuromorphic applications due to their scalability, low-power operation and diverse functional behaviours. However, understanding the dynamics of individual filaments, and the surrounding material, is challenging, owing to the typically very large cross-sectional areas of test devices relative to the nanometre scale of individual filaments. In the present work, conductive atomic force microscopy is used to study the evolution of conductivity at the nanoscale in a fully CMOS-compatible silicon suboxide thin film. Distinct filamentary plasticity and background conductivity enhancement are reported, suggesting that device behaviour might be best described by composite core (filament) and shell (background conductivity) dynamics. Furthermore, constant current measurements demonstrate an interplay between filament formation and rupture, resulting in current-controlled voltage spiking in nanoscale regions, with an estimated optimal energy consumption of 25 attojoules per spike. This is very promising for extremely low-power neuromorphic computation and suggests that the dynamic behaviour observed in larger devices should persist and improve as dimensions are scaled down.