As we enter a new era of next-generation wireless systems represented by Fifth Generation (5G) New Radio (NR) technology, it is essential to grasp the recent progress in their standardization and ...development. This article offers a concise survey of the 5G NR system design that aims at introducing its features according to the relevant Third Generation Partnership (3GPP) specifications. Our focus is set on the flexibility of 5G NR, which refers to its capability to support novel services and technologies, such as enhanced Mobile Broadband (eMBB) and Internet of Things (IoT) for massive Machine Type Communications (mMTC) while satisfying the underlying quality requirements. The key enablers of the 5G NR operation are scalable numerology, ultra-lean and beam-centric design, support for low latency, spectrum extension, and forward compatibility. This work summarizes these important features by studying the overall 5G architecture and the user-/control-plane protocol stacks specified by 3GPP. Furthermore, the impact of scalable numerology on system performance is discussed. Finally, we also consider open challenges and future research directions.
Fifth-generation (5G) telecommunication systems are expected to meet the world market demands of accessing and delivering services anywhere and anytime. The Non-Terrestrial Network (NTN) systems are ...able to satisfy the requests of anywhere and anytime connections by offering wide-area coverage and ensuring service availability, continuity, and scalability. In this work, we review the 3GPP NTN features and their potential for satisfying the user expectations in 5G & beyond networks. The state of the art, current 3GPP research activities, and open issues are summarized to highlight the importance of NTN over the wireless communication landscape. Future research directions are also identified to assess the role of NTN in 5G and beyond systems.
Several phytochemical-containing herbal extracts are increasingly marketed as health-promoting products. In particular, chamomile (Matricaria recutita L.) is well known for its anti-inflammatory, ...analgesic, and antitumor properties. Here, we evaluated differences in chemical composition among six commercially available products and their potential impact on biological activity in human immortalized colonocytes. Our investigation encompassed: (i) preparation of dry extracts and yield evaluation; (ii) qualitative and quantitative analysis of phenol content; (iii) modulation of redox state; and (iv) bioavailability of main bioactive compounds. We demonstrated that apparently identical products showed huge heterogeneity, in terms of yield extraction, chemical composition, and antioxidant effects. All samples contained high amounts of flavonoids and cinnamic acid derivatives, but differentially concentrated in the six extracts. Depending on polyphenol content, chamomile samples possessed variable antioxidant potential, in terms of decreased radical generation and increased reduced glutathione levels. The observed effects might be ascribed to flavones (apigenin, luteolin, and their glycones) highly represented in the six extracts. Nonetheless, chamomile extracts exerted cytotoxic effects at high concentrations, suggesting that a herbal medicine is not always safe. In conclusion, due to the complexity and variability of plant matrices, studies evaluating effectiveness of chamomile should always be accompanied by preliminary characterization of phytochemical composition.
Mobile satellite services are extremely important when continuity of service is requested while the user is moving over a wide area. A notable example is represented by live TV services, or more in ...general by the Multimedia Broadcast/Multicast Services (MBMSs) and its evolved version enhanced MBMS. In this paper, we present the combined use of multicast resource allocation schemes based on subgrouping and application layer joint coding to enhance the performance of live video streaming in mobile satellite systems. The reference architecture foresees a satellite-based long term evolution transmission using orthogonal frequency division multiple access in the forward link. The results show that the combined use of multicast subgrouping resource allocation and application layer joint coding allows high-throughput transmissions with satisfactory user quality of experience of the received video over different satellite channel propagation environments.
Today there is a very great deal of interest among members of the global natural products community in investigating new plant constituents. Recent studies demonstrate that liquorice extracts are ...useful in the treatment of dermatitis, eczema, and psoriasis, with an efficacy comparable to that of corticosteroids. In this work, niosomes made up of surfactants (Tween 85 and Span 20) and cholesterol at various concentrations were prepared to investigate the potential application of niosomes for the delivery of ammonium glycyrrhizinate (AG), useful for the treatment of various inflammatory based diseases.
Vesicles were characterized evaluating dimensions, ζ potential, anisotropy, drug entrapment efficiency, stability, cytotoxicity evaluation and skin tolerability.
Release profiles of ammonium glycyrrhizinate/niosomes were evaluated in vitro using cellulose membranes. The best formulation was used to evaluate the in vitro/in vivo efficacy of the ammonium glycyrrhizinate/niosomes in murine and human models of inflammation.
The AG-loaded non-ionic surfactant vesicles showed no toxicity, good skin tolerability and were able to improve the drug anti-inflammatory activity in mice. Furthermore, an improvement of the anti-inflammatory activity of the niosome delivered drug was observed on chemically induced skin erythema in humans.
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Non-neuronal cell types such as astrocytes can contribute to Parkinson's disease (PD) pathology. The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is one of the most common known causes of ...familial PD. To characterize its effect on astrocytes, we developed a protocol to produce midbrain-patterned astrocytes from human induced pluripotent stem cells (iPSCs) derived from PD LRRK2 G2019S patients and healthy controls. RNA sequencing analysis revealed the downregulation of genes involved in the extracellular matrix in PD cases. In particular, transforming growth factor beta 1 (TGFB1), which has been shown to inhibit microglial inflammatory response in a rat model of PD, and matrix metallopeptidase 2 (MMP2), which has been shown to degrade α-synuclein aggregates, were found to be down-regulated in LRRK2 G2019S astrocytes. Our findings suggest that midbrain astrocytes carrying the LRRK2 G2019S mutation may have reduced neuroprotective capacity and may contribute to the development of PD pathology.
•Genome-wide RNA sequencing profiling of LRRK2 G2019S iPSC-derived astrocytes.•The extracellular matrix is perturbed in LRRK2 G2019S iPSC-astrocytes.•MMP2 and TGFB1 are down-regulated in the presence of the LRRK2 G2019S mutation.•Reduced neuroprotective potential of astrocytes may contribute to PD pathology.
To examine the pathogenic role of α-synuclein (αS) in Parkinson's Disease, we have generated induced Pluripotent Stem Cell lines from early onset Parkinson's Disease patients with SNCA A53T and SNCA ...Triplication mutations, and in this study have differentiated them to PSC-macrophages (pMac), which recapitulate many features of their brain-resident cousins, microglia. We show that SNCA Triplication pMac, but not A53T pMac, have significantly increased intracellular αS versus controls and release significantly more αS to the medium. SNCA Triplication pMac, but not A53T pMac, show significantly reduced phagocytosis capability and this can be phenocopied by adding monomeric αS to the cell culture medium of control pMac. Fibrillar αS is taken up by pMac by actin-rearrangement-dependent pathways, and monomeric αS by actin-independent pathways. Finally, pMac degrade αS and this can be arrested by blocking lysosomal and proteasomal pathways. Together, these results show that macrophages are capable of clearing αS, but that high levels of exogenous or endogenous αS compromise this ability, likely a vicious cycle scenario faced by microglia in Parkinson's disease.
Urinary tract infections (UTIs) are the most common bacterial infections and uropathogenic Escherichia coli (UPEC) is the main etiological agent of UTIs. UPEC can persist in bladder cells protected ...by immunological defenses and antibiotics and intracellular behavior leads to difficulty in eradicating the infection. The aim of this paper is to design, prepare and characterize surfactant-based nanocarriers (niosomes) able to entrap antimicrobial drug and potentially to delivery and release antibiotics into UPEC-infected cells. In order to validate the proposed drug delivery system, gentamicin, was chosen as "active model drug" due to its poor cellular penetration. The niosomes physical-chemical characterization was performed combining different techniques: Dynamic Light Scattering Fluorescence Spectroscopy, Transmission Electron Microscopy. Empty and loaded niosomes were characterized in terms of size, ζ-potential, bilayer features and stability. Moreover, Gentamicin entrapped amount was evaluated, and the release study was also carried out. In addition, the effect of empty and loaded niosomes was studied on the invasion ability of UPEC strains in T24 bladder cell monolayers by Gentamicin Protection Assay and Confocal Microscopy. The observed decrease in UPEC invasion rate leads us to hypothesize a release of antibiotic from niosomes inside the cells. The optimization of the proposed drug delivery system could represent a promising strategy to significatively enhance the internalization of antimicrobial drugs.
Drug delivery systems using vesicular carriers such as liposomes or niosomes, have distinct advantages over conventional dosage forms because the vesicles can act as drug containing reservoirs and ...the modification of the vesicular compositions or surface properties can adjust the drug release rate and/or the affinity for the target site. In recent years, niosomes have been the object of growing scientific attention as an alternative potential drug delivery system to conventional liposomes. The aim of present work was firstly to determine the critical micelle concentration (CMC) and then to analyze the capability of polysorbate 21 (Tween 21) to form niosomal formulations. Non-ionic surfactant vesicles were prepared using Tween 21 and cholesterol (CHOL) at equimolar ratio (15
mM:15
mM) by employing the “film” technique. Cholesterol was used to complete the hydrophobic moiety of single alkyl chain non-ionic surfactant for vesicle formation. Dynamic light scattering was used to determine the size, zeta (ζ)-potential, polydispersity index and colloidal stability of the niosomal formulation. The vesicles were also characterized for their microviscosity and pH-sensitivity using fluorescent probes. The present work led to a simple, but positive result in pharmaceutical technology area. In particular, we have shown that the Tween 21:CHOL vesicles (i) are a homogenous and monodisperse vesicular population; (ii) are characterized by dimension compatible with the transport of drugs across biological barriers especially those whose diameter is about 100
nm; (iii) shows a good stability at least 90 days at 4
°C and (iv) are pH-sensitive systems. In conclusion, this niosomal formulation could be used as pH-sensitive nanodevices for delivery of drugs to pathological tissues, which exhibit an acidic environment as compared to normal tissues.
All-Trans Retinoic Acid (ATRA) is the most active metabolite of vitamin A. It is critically involved in the regulation of multiple processes, such as cell differentiation and apoptosis, by activating ...specific genomic pathways or by influencing key signaling proteins. Furthermore, mounting evidence highlights the anti-tumor activity of this compound. Notably, oral administration of ATRA is the first choice treatment in Acute Promyelocytic Leukemia (APL) in adults and NeuroBlastoma (NB) in children. Regrettably, the promising results obtained for these diseases have not been translated yet into the clinics for solid tumors. This is mainly due to ATRA-resistance developed by cancer cells and to ineffective delivery and targeting. This up-to-date review deals with recent studies on different ATRA-loaded Drug Delivery Systems (DDSs) development and application on several tumor models. Moreover, patents, pre-clinical, and clinical studies are also reviewed. To sum up, the main aim of this in-depth review is to provide a detailed overview of the several attempts which have been made in the recent years to ameliorate ATRA delivery and targeting in cancer.