LoRaWAN Behaviour Analysis through Dataset Traffic Investigation.

The large development of Internet of Things technologies is increasing the use of smart-devices to solve and support several real-life issues. In many cases, the aim is to move toward systems that, even if significant demands are not required in terms of quantity of exchanged data, they should be very reliable in terms of battery life and signal coverage. Networks that have these characteristics are the Low Power WAN (LPWAN). One of the most interesting LPWAN is LoRaWAN. LoRaWAN is a network with four principal components: end-devices, gateways, network servers, and application servers. It uses a LoRa physical layer to exchange messages between end-devices and gateways that forward these messages, through classic TCP/IP protocol, to the network server. In this work, we analyse LoRa and LoRaWAN by looking at its transmission characteristics and network behaviour, respectively, explaining the role of its components and showing the message exchange. This analysis is performed through the exploration of a dataset taken from the literature collecting real LoRaWAN packets. The goal of the work is twofold: (1) to investigate, under different perspectives, how a LoRaWAN works and (2) to provide software tools that can be used in several other LoraWAN datasets to measure the network behaviour. We carry out six different analyses to look at the most important features of LoRaWAN. For each analysis we present the adopted measurement strategy as well as the obtained results in the specific use case.

Progress in Colloid Delivery Systems for Protection and Delivery of Phenolic Bioactive Compounds: Two Study Cases-Hydroxytyrosol and Curcumin.

Insufficient intake of beneficial food components into the human body is a major issue for many people. Among the strategies proposed to overcome this complication, colloid systems have been proven to offer successful solutions in many cases. The scientific community agrees that the production of colloid delivery systems is a good way to adequately protect and deliver nutritional components. In this review, we present the recent advances on bioactive phenolic compounds delivery mediated by colloid systems. As we are aware that this field is constantly evolving, we have focused our attention on the progress made in recent years in this specific field. To achieve this goal, structural and dynamic aspects of different colloid delivery systems, and the various interactions with two bioactive constituents, are presented and discussed. The choice of the appropriate delivery system for a given molecule depends on whether the drug is incorporated in an aqueous or hydrophobic environment. With this in mind, the aim of this evaluation was focused on two case studies, one representative of hydrophobic phenolic compounds and the other of hydrophilic ones. In particular, hydroxytyrosol was selected as a bioactive phenol with a hydrophilic character, while curcumin was selected as typical representative hydrophobic molecules.

Hypoxia-Regulated miRNAs in Human Mesenchymal Stem Cells: Exploring the Regulatory Effects in Ischemic Disorders.

Human mesenchymal/stromal stem cells (hMSC) are the most promising cell source for adult cell therapies in regenerative medicine. Many clinical trials have reported the use of autologous transplantation of hMSCs in several disorders, but with limited results. To exert their potential, hMSCs could exhibit efficient homing and migration toward lesion sites among other effects, but the underlying process is not clear enough. To further increase the knowledge, we studied the co-regulation between hypoxia-regulated genes and miRNAs. To this end, we investigated the miRNA expression profile of healthy hMSCs in low oxygen/nutrient conditions to mimic ischemia and compared with cells of patients suffering from critical limb ischemia (CLI). miRNAs are small, highly conserved, non-coding RNAs, skilled in the control of the target's expression level in a fine-tuned way. After analyzing the miRNOme in CLI-derived hMSC cells and healthy controls, and intersecting the results with the mRNA expression dataset under hypoxic conditions, we identified two miRNAs potentially relevant to the disease: miR-29b as a pathological marker of the disease and miR-638 as a therapeutic target. This study yielded a deeper understanding of stem cell biology and ischemic disorders, opening new potential treatments in the future.

Adaptive Data Synchronization Algorithm for IoT-Oriented Low-Power Wide-Area Networks.

The Internet of Things (IoT) is by now very close to be realized, leading the world towards a new technological era where people's lives and habits will be definitively revolutionized. Furthermore, the incoming 5G technology promises significant enhancements concerning the Quality of Service (QoS) in mobile communications. Having billions of devices simultaneously connected has opened new challenges about network management and data exchange rules that need to be tailored to the characteristics of the considered scenario. A large part of the IoT market is pointing to Low-Power Wide-Area Networks (LPWANs) representing the infrastructure for several applications having energy saving as a mandatory goal besides other aspects of QoS. In this context, we propose a low-power IoT-oriented file synchronization protocol that, by dynamically optimizing the amount of data to be transferred, limits the device level of interaction within the network, therefore extending the battery life. This protocol can be adopted with different Layer 2 technologies and provides energy savings at the IoT device level that can be exploited by different applications.

Dialogic reading in the rehabilitation of Children with Hearing Loss and the "Born to Read" Project: A pilot study.

The "born to read" initiative entails a dialogic reading to children in poor socio-economical conditions aimed at fostering cognitive and relational skills. Reading is professionally delivered by experts to promote psycho-social development of children and their parents. In this study the project was extended to include children positive at early screening for hearing impairment. A total of 26 children were included and 14 parents were taught to read aloud and emphatically. Reading session were delivered for at least 10 minutes at least 3 times/week, usually at bedtime, for one year. The Griffiths scale were applied to explore the expressive and receptive language skills (Scale C) and eye and hand coordination (Scale D), as measures of linguistic and neurocognitive skills. Program sustainability and reactions by the parents were also investigated. All 14 families successfully received the training, becoming capable of reading aloud and emphatically and provided reading sessions for the entire duration of the study. Children receiving the intervention performed slightly better than controls and those who were exposed to increased number of sessions, performed even better although the differences with controls were not significant. Parents enjoyed reading to their children. They expressed satisfaction and gratitude for being able to play an active and productive role in children rehabilitation. The results of this pilot study suggest that the born to read initiative may be considered in adjunct to medical and psychological interventions to enhance the benefits of early screening of hearing function.

Visible light caffeic acid degradation by carbon-doped titanium dioxide.

The removal of the phenolic compound, caffeic acid, by photodegradation has been investigated using carbon-doped titanium dioxide particles as a photocatalyst under visible light. UV-vis absorption spectroscopy and gas chromatography-ion trap mass spectrometry analyses revealed a substrate concentration dependence of the removal of caffeic acid from a water solution. The k2 and t(0.5) parameters of each reaction were calculated by fitting kinetics data to a second-order kinetic adsorption model. To evaluate the photodegradation event, the effect of the adsorption process on the whole degradation was also monitored in the absence of light. Adsorption isotherm studies supported by ζ potential and scanning electron microscopy data demonstrated the pivotal role of the absorption mechanism. It was found that the whole photodegradation process is governed by a synergic mechanism in which adsorption and photodegradation are involved. This study, centered on the removal of caffeic acid from aqueous solutions, highlights the potential application of this technology for the elimination of phenolic compounds from olive mill wastewater, a fundamental goal in both the agronomical and environmental fields.

Loading and protection of hydrophilic molecules into liposome-templated polyelectrolyte nanocapsules.

Compartmentalized systems produced via the layer-by-layer (LbL) self-assembly method have been produced by alternatively depositing alginate and chitosan layers onto cores of liposomes. The combination of dynamic light scattering (DLS), ζ potential, and transmission electron microscopy (TEM) techniques provides detailed information on the stability, dimensions, charge, and wall thickness of these polyelectrolyte globules. TEM microphotographs demonstrate the presence of nanocapsules with an average diameter of below 300 nm and with a polyelectrolyte wall thickness of about 20 nm. The possibility of encapsulating and releasing molecules from this type of nanocapsule was demonstrated by loading FITC-dextrans of different molecular weights in the liposome system. The release of the loaded molecules from the nanocapsule was demonstrated after liposome core dissolution. Even at low molecular weight (20 kDa), the nanocapsules appear to be appropriate for prolonged molecule compartmentalization and protection. By means of the Ritger-Peppas model, non-Fickian transport behavior was detected for the diffusion of dextran through the polyelectrolyte wall. Values of the diffusion coefficient were calculated and yield useful information regarding chitosan/alginate hollow nanocapsules as drug-delivery systems. The influence of the pH on the release properties was also considered. The results indicate that vesicle-templated hollow polyelectrolyte nanocapsules show great potential as novel controllable drug-delivery devices for biomedical and biotechnological applications.

Alginate-Based Emulsions and Hydrogels for Extending the Shelf Life of Banana Fruit.

Edible coatings are used to extend the shelf life of various fruit, including bananas (Musa from the Musaceae family). After harvest, bananas reach the ripening and subsequent senescence phase. During senescence, the quality of the fruit deteriorates as it takes on a brown color and the tissue becomes soft. To extend the shelf life of such a fruit, effective methods to delay ripening are required. In this study, an alginate-based emulsion, i.e., an oil-in-water emulsion of lemongrass essential oil in alginate, was used to combine the mechanical properties of hydrocolloids with the water barrier properties of the oil phase. The emulsion was sprayed onto the whole fruit with an airbrush, and calcium chloride was added to promote gelling of the alginate. Compared to the uncoated fruit, coated bananas remained uniform in appearance (peel color) for longer, showed less weight loss, had a delay in the formation of total soluble solids, and in the consumption of organic acids. The shelf life of the coated fruit was extended by up to 11 days, at least 5 days more than uncoated bananas. Overall, the proposed coating could be suitable for reducing the global amount of food waste.

Alkylation of complementary ribonucleotides in nanoreactors.

The aim of the present study was to provide experimental evidence that base pairing, commonly occurring between nucleic bases in more complex supramolecular arrangements, may affect the reaction pathways associated with the alkylation of bases themselves. In pursuit of this aim, dilute aqueous solutions of Cytidine- (CMP) and Guanosine-Mono-Phosphate (GMP) as single reactants or in an equimolar mixture were treated with the electrophilic alkylating agent 1,2-Dodecyl-Epoxide (DE), which was preventively dispersed into micellar solutions prepared with the cationic surfactant hexadecyltrimethylammonium bromide (CTAB). In the early stage of the reaction, CTAB micelles acted as micro-heterogeneous nanoreactors, but as the reaction progressed the systems evolved toward the formation of polydisperse aggregates, whose size and surface-charge properties were monitored as a function of reaction time. From mass spectrometry analyses, it was found that the deamination of cytosine, a side reaction related to the alkylation of the amino group of CMP, was reduced when both the complementary ribonucleotides were present in the same reaction mixture. The involvement of specific sites able to establish C:G interactions (possibly via H-bonding or π-π stacking) could explain the reduced reactivity occurring at the level of some of the nucleophilic centers responsible for molecular recognition.

Assessment of Nutritional Value and Maillard Reaction in Different Gluten-Free Pasta.

Evaluating the nutritional quality and thermal damage effects of gluten-free foods is essential to ensure that people with gluten intolerance or celiac disease can safely meet their needs. In this work, fifteen different commercial gluten-free pasta samples made from cereals, pseudocereals, and pulses, alone or in mixed combinations, were analyzed to assess their nutritional value, essential amino acids composition, and protein chemical score. The occurrence of the Maillard reaction was investigated, and the levels of heat treatment markers (furosine, maltulose, hydroxymethylfurfural, and glucosylisomaltol) were determined. Analysis of the furosine values showed that pasta made with the same raw materials can have different degrees of thermal damage. There was no evidence of the Maillard reaction progressing in the advanced phase in any of the samples tested. Finally, the correlation between maltulose and furosine levels demonstrated the usefulness of combining the two markers to assess the extent of thermal damage.

Assessment of community efforts to advance network-based prediction of protein-protein interactions.

Comprehensive understanding of the human protein-protein interaction (PPI) network, aka the human interactome, can provide important insights into the molecular mechanisms of complex biological processes and diseases. Despite the remarkable experimental efforts undertaken to date to determine the structure of the human interactome, many PPIs remain unmapped. Computational approaches, especially network-based methods, can facilitate the identification of previously uncharacterized PPIs. Many such methods have been proposed. Yet, a systematic evaluation of existing network-based methods in predicting PPIs is still lacking. Here, we report community efforts initiated by the International Network Medicine Consortium to benchmark the ability of 26 representative network-based methods to predict PPIs across six different interactomes of four different organisms: A. thaliana, C. elegans, S. cerevisiae, and H. sapiens. Through extensive computational and experimental validations, we found that advanced similarity-based methods, which leverage the underlying network characteristics of PPIs, show superior performance over other general link prediction methods in the interactomes we considered.

The Role of the Kinase Inhibitors in Thyroid Cancers.

Thyroid cancer is the most common endocrine malignancy, accounting for about 3% of all cancer cases each year worldwide with increasing incidence, but with the mortality remaining stable at low levels. This contradiction is due to overdiagnosis of indolent neoplasms identified by neck ultrasound screening that would remain otherwise asymptomatic. Differentiated thyroid carcinomas (DTCs) are almost curable for 95% with a good prognosis. However, 5% of these tumours worsened toward aggressive forms: large tumours with extravasal invasion, either with regional lymph node or distant metastasis, that represent a serious clinical challenge. The unveiling of the genomic landscape of these tumours shows that the most frequent mutations occur in tyrosine kinase receptors (RET), in components of the MAPK/PI3K signalling pathway (RAS and BRAF) or chromosomal rearrangements (RET/PTC and NTRK hybrids); thus, tyrosine-kinase inhibitor (TKI) treatments arose in the last decade as the most effective therapeutic option for these aggressive tumours to mitigate the MAPK/PI3K activation. In this review, we summarize the variants of malignant thyroid cancers, the molecular mechanisms and factors known to contribute to thyroid cell plasticity and the approved drugs in the clinical trials and those under investigation, providing an overview of available treatments toward a genome-driven oncology, the only opportunity to beat cancer eventually through tailoring the therapy to individual genetic alterations. However, radiotherapeutic and chemotherapeutic resistances to these anticancer treatments are common and, wherever possible, we discuss these issues.

Sustainable Re-Use of Brewer's Spent Grain for the Production of High Protein and Fibre Pasta.

Brewer's spent grains are one of the principal by-products of the brewing industry. For protein and fibre content, this by-product represents an interesting raw material to be reused for manufacturing many other products. To maximize the nutritional characteristics of this by-product, in this study, ingredients derived from brewer's spent grains were included in the design of innovative dry pasta. Two brewer's spent grains derivative ingredients, one enriched in proteins and the other in fibre were blended with semolina. Based on the rheological evaluation, the optimal amount of the two ingredients for producing pasta was determined. In particular, pasta responding to the claims "High Protein" and "High Fibre" was realized using the formulation enriched with 15% of protein-rich ingredient and the claim "High Fibre" and "Source of proteins" using the formulation enriched with 10% of fibre-rich ingredient. The final products were compared to 100% semolina and 100% wholegrain semolina pasta for composition, color, texture, and cooking quality, revealing excellent quality characteristics. The newly formulated pasta represents a successful match of technological aptitude, nutritional/sensorial quality, and sustainability.

Evolution of Free Amino Acids, Histamine and Volatile Compounds in the Italian Anchovies (Engraulis encrasicolus L.) Sauce at Different Ripening Times.

In this study, the evolution of the safety, nutritional, and volatile profile of a traditional Italian anchovy sauce with protected designation of origin (PDO), called "colatura di alici di Cetara", is investigated after 12, 24, and 48 months of aging in wooden barrels. Some physicochemical parameters, free amino acids, volatile compounds, and histamine contents were evaluated during the aging of the samples. Glutamate, which together with aspartate is responsible for the umami taste, was the predominant free amino acid in the tested fish sauce, with a significant increase during the 48 months of maturation. The total amino acid content of the anchovy sauce increased from 24 to 48 months of aging. The histamine content decreased significantly from 12 to 48 months of ripening. This point is particularly interesting for the sauce safety and confirms the importance of the maturation time of at least 9 months reported in the disciplinary of production. A total of 44 volatile compounds were found in the anchovy sauce samples, of which the largest class was acids, mainly isovaleric acid. The results show that prolonged maturation improves the safety, nutritional, and volatile components of the seasoning "colatura di alici".

Oral delivery of all-trans retinoic acid mediated by liposome carriers.

All-trans retinoic acid (ATRA) is a molecule that finds wide applications in medicine. Connection between cancer cell proliferation and ATRA is a well-established item. Driven by the potential applications of liposomes in stabilizing and protecting therapeutic compounds thus enabling effective delivery of encapsulated compounds, recent research efforts have been directed to understanding mechanisms of oral delivery through the gastrointestinal tract. The surface charge of the liposome bilayers can modify the interactions between the aggregates and the gastrointestinal fluids. Here, we investigated the ability of cationic and anionic liposomes to encapsulate, protect and deliver ATRA in an in-vitro digestion process as a different oral administration route. Stability and encapsulation efficiency of ATRA in negatively and positively charged liposomes enriched with α-tocopherol were investigated by means of UV-vis spectroscopy, dynamic light scattering and ζ-potential. The applicability of the carriers was tested by means of an in-vitro digestion procedure allowing for the measurement of the bioavailability of ATRA. From this study evidence was provided that the water insoluble molecules, ATRA and α-tocopherol are intercalated in liposome membranes regardless of the surface charge of the vesicle bilayers. Comparisons between cationic and anionic liposomes incorporating retinoic acid show differences in bioavailability. The cationic vesicles are preferable for a larger amount of ATRA bioavailability, which can be understood from electrostatic interactions. Thus ATRA is ionized in a wide range of pHs but protonated in anionic vesicles.

Nutritional and Technological Quality of High Protein Pasta.

Pasta has an important role in human nutrition for its high content of complex carbohydrates and its widespread use. It can be an efficient delivery system or carrier of non-traditional raw material, including additional health-promoting ingredients. The partial replacement of semolina with high-protein raw materials leads to the improvement of the biological value of pasta proteins. In order to obtain pasta with high nutritional protein value and with excellent cooking properties, various recipes have been formulated with different percentages of semolina and unconventional high-protein raw materials (peas and soy isolate proteins, egg white, whey proteins and Spirulina platensis). High-protein pasta was produced using a pasta making pilot plant and the nutritional quality (protein content and quality) and sensorial properties were assessed. All experimental pastas showed optimal performances. Pasta prepared with pea protein isolate, whey proteins and Spirulina platensis showed improved chemical score and digestible indispensable amino acid scores, an eye-catching color, and an excellent cooking quality.

Rheological and Nutritional Assessment of Dysphagia-Oriented New Food Preparations.

Dysphagia that involves difficulty swallowing food and liquids is a symptom of different diseases. In some cases, patients who experience this symptom should be fed with modified consistency foods. Dysphagia is often accompanied by malnutrition and dehydration and an interesting approach to dealing with these conditions is to provide patients with nutrient-rich foods. In this study, two new food formulations for dysphagia patients are proposed: a cereal-based protein meal and a vegetable cream. The nutritional and rheological characteristics of the two innovative preparations were assessed and compared with those of commercial products. The proposed protein meal formulations meet the criteria for the "high protein" claim and the vegetable cream meets those of the "source of fiber" claim. The rheological investigation revealed that the flow properties of the innovative formulations were comparable to those of the commercial ones. Based on these preliminary outcomes, this investigation represents an interesting perspective potentially valuable to enlarge the offer of possibilities for people suffering from swallowing disorders.

HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring.

Maintenance of energy balance between intake and expenditure is a prerequisite of human health, disrupted in severe metabolic diseases, such as obesity and type 2 diabetes (T2D), mainly due to accumulation of white adipose tissue (WAT). WAT undergoes a morphological and energetic remodelling toward brown adipose tissue (BAT) and the BAT activation has anti-obesity potential. The mechanisms or the regulatory factors able to activate BAT thermogenesis have been only partially deciphered. Identifying novel regulators of BAT induction is a question of great importance for fighting obesity and T2D. Here, we evaluated the role of Hif3α in murine pre-adipocyte 3T3-L1 cell line, a versatile and well characterized biological model of adipogenesis, by gain- and loss-of function approaches and in thermogenesis-induced model in vivo. HIF3A is regulated by inflammation, it modulates lypolysis in adipose tissue of obese adults, but its role in energy metabolism has not previously been investigated. We characterized gene and protein expression patterns of adipogenesis and metabolic activity in vitro and mechanistically in vivo. Overexpression of Hif3α in differentiating adipocytes increases white fat cells, whereas silencing of Hif3α promotes "browning" of white cells, activating thermogenesis through upregulation of Ucp1, Elovl3, Prdm16, Dio2 and Ppargc1a genes. Investigating cell metabolism, Seahorse Real-Time Cell Metabolism Analysis showed that silencing of Hif3α resulted in a significant increase of mitochondrial uncoupling with a concomitant increase in acetyl-CoA metabolism and Sirt1 and Sirt3 expression. The causal Hif3α/Ucp1 inverse relation has been validated in Cannabinoid receptor 1 (CB1) knockout, a thermogenesis-induced model in vivo. Our data indicate that Hif3α inhibition triggers "browning" of white adipocytes activating the beneficial thermogenesis rewiring energy metabolism in vitro and in vivo. HIF3A is a novel player that controls the energy metabolism with potential applications in developing therapy to fight metabolic disorders, as obesity, T2D and ultimately cancer.

Vesicle-templated layer-by-layer assembly for the production of nanocapsules.

Hollow structures on the submicrometer scale (nm) are obtained with the assembly of polyelectrolytes according to the layer-by-layer (LbL) technique. Following the LbL procedure, polymers alginate and chitosan were alternatively adsorbed on a vesicular template made of didodecyldimethylammonium bromide (DDAB). Evidence for the removal of the vesicular template entrapped in the alginate/chitosan film is presented. The removal of the vesicular template was achieved through interactions between a nonionic surfactant (Triton X100) and the double-chained surfactant forming the vesicles. The application of this approach allowed the production of hollow nanospheres with a mild procedure, avoiding the use of strong acids or other extreme working conditions that can modify the shell integrity. The obtained nanostructures were characterized by means of dynamic light scattering (DLS), the zeta potential, and scanning electron microscopy (SEM). The SEM analysis demonstrated the presence, after the core removal process, of nanocapsules indistinguishable in size and shape from the parent core-shell system. The analysis of the surface charge of the hollow nanocapsules, after the core dissolution, by zeta potential measurements, indicates good aggregate stability. DLS measurements showed that the size of the nanocapsules is on the order of hundreds of nanometers. Moreover, the size of both the core-shell and the hollow particles did not appear to be perturbed by variations in temperature or ionic strength.

Author Correction: Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.