A global approach to the design of discrete-time cellular neural networks for associative memories

In this paper a global design method for associative memories using discrete-time cellular neural networks (DTCNNs) is presented. The proposed synthesis technique enables to realize associative memories with several advantageous features. First of all, grey-level as well as bipolar images can be stored. Moreover, the proposed approach generates networks with learning and forgetting capabilities. Finally, it is possible to design networks with any kind of predetermined interconnection structure. In particular, neighbourhoods without line crossings can be chosen, greatly simplifying the VLSI implementation of the designed DTCNNs. In the first part of this work a model of a multilevel threshold network is presented and a stability analysis is carried out using basic notions deriving from non-linear dynamical system theory. The synthesis procedure is then developed by means of a pseudoinversion technique, assuring learning and forgetting capabilities of the designed DTCNN. The use of a neighbourhood without line crossings is also discussed. Simulation results are reported to show the capability of the proposed approach.     

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.     

Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases

Over the last 10 years, the evaluation of the neutrophil-to-lymphocyte ratio (NLR) as an emerging marker of diseases has become a compelling field of bio-medical research. Although a precise and unique cut-off value has not been yet found, its role as a flag of immune system homeostasis is well established. NLR has a well-known prognostic value and independently correlates with mortality in the general population and in several specific subsets of disease (sepsis, pneumonia, COVID-19, cancer, etc.). Moreover, NLR was recently considered as part of the decision-making processes concerning the admission/recovery of patients with COVID-19 pneumonia. This review aims to provide an overview of the main use of this biomarker, focusing on the pathophysiology and the molecular basis underlying its central role as a reliable mirror of inflammatory status and adaptive immunity.     

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.     

The Role of Cytoskeleton Revealed by Quartz Crystal Microbalance and Digital Holographic Microscopy

The connection between cytoskeleton alterations and diseases is well known and has stimulated research on cell mechanics, aiming to develop reliable biomarkers. In this study, we present results on rheological, adhesion, and morphological properties of primary rat cardiac fibroblasts, the cytoskeleton of which was altered by treatment with cytochalasin D (Cyt-D) and nocodazole (Noc), respectively. We used two complementary techniques: quartz crystal microbalance (QCM) and digital holographic microscopy (DHM). Qualitative data on cell viscoelasticity and adhesion changes at the cell–substrate near-interface layer were obtained with QCM, while DHM allowed the measurement of morphological changes due to the cytoskeletal alterations. A rapid effect of Cyt-D was observed, leading to a reduction in cell viscosity, loss of adhesion, and cell rounding, often followed by detachment from the surface. Noc treatment, instead, induced slower but continuous variations in the rheological behavior for four hours of treatment. The higher vibrational energy dissipation reflected the cell’s ability to maintain a stable attachment to the substrate, while a cytoskeletal rearrangement occurs. In fact, along with the complete disaggregation of microtubules at prolonged drug exposure, a compensatory effect of actin polymerization emerged, with increased stress fiber formation.     

Partially fluorinated polymer networks: Surface and tribological properties

Functionalization of epoxy-based networks by the preferential surface enrichment of perfluorinated tails to achieve hydrophobic surface is described. Two series of crosslinked fluorinated epoxy-based materials containing variable fluorine contents (from 0 to 5 wt % F) were prepared using formulations based on partially fluorinated diamine, epoxy monomer and a curing agent. The epoxy monomer was based on diglycidyl ether of bisphenol A (DGEBA) while the curing agents were either propyleneoxide diamine (JEFFAMINE) or 4,4′-methylenebis(3-chloro 2,6-diethylaniline) (MCDEA). The selected fluorinated epoxies (FE) were: 2,2,3,3,4,4,5,5,6,6,7,7,8,9,9,9-hexadecafluoro-8-trifluoromethyl nonyloxirane (FED3) and 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluoro nonyloxirane (FES3). The influence on surface properties of the architecture of FE, and the molecular structure of the unit building blocks was analyzed and discussed. It was found that both series showed high hydrophobicity and oleophobicity, independently of the crosslink density, bulk composition, and curing conditions. XPS measurements showed a surface composition much richer in fluorinated segments than expected from bulk composition. Fluorine enrichment was also manifested at the polymer/aluminium interface for JEFFAMINE-based networks. This observation is discussed in terms of the molecular weight dependence of surface tension and configurational entropy of the thermosetting matrix. At least for the range of this study, while increasing the amount of fluorine incorporated in both network series, dynamic friction is reduced due to surface migration of fluorine species during polymerization     

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Comparing surface residue transfer efficiencies to hands using polar and nonpolar fluorescent tracers

Transfer of chemicals from contaminated surfaces such as foliage, floors, and furniture is a potentially significant source of both occupational exposure and children's residential exposure. Increased understanding of relevant factors influencing transfers from contaminated surfaces to skin and resulting dermal-loading will reduce uncertainty in exposure assessment. In a previously reported study, a fluorescence imaging system was developed, tested, and used to measure transfer of riboflavin residues from surfaces to hands. Parameters evaluated included surface type, surface loading, contact motion, pressure, duration, and skin condition. Results of the initial study indicated that contact duration and pressure were not significant for the range of values tested, but that there are potentially significant differences in transfer efficiencies of different compounds. In the study reported here, experimental methods were refined and additional transfer data were collected. A second fluorescent tracer, Uvitex OB, with very different physicochemical properties than riboflavin, was also evaluated to better characterize the range of transfers that may be expected for a variety of compounds. Fluorescent tracers were applied individually to surfaces and transfers to skin were measured after repeated hand contacts with the surface. Additional trials were conducted to compare transfer of tracers and co-applied pesticide residues. Results of this study indicate that dermal loadings of both tracers increase through the seventh brief contact. Dermal loading of Uvitex tends to increase at a higher rate than dermal loadings of riboflavin. Measurement of co-applied tracer and pesticide suggest results for these two tracers may provide reasonable bounding estimates of pesticide transfer.     

Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.