Toxic Effects on Thyroid Gland of Male Adult Lizards (Podarcis Siculus) in Contact with PolyChlorinated Biphenyls (PCBs)-Contaminated Soil

Skin exposure is considered a potentially significant but little-studied pathway for PolyChlorinated Biphenyls uptake in terrestrial reptiles. In this study, a native Italian lizard, Podarcis siculus, was exposed to PCBs-contaminated soil for 120 days. Tissues distribution of PCBs, thyroid hormone levels, and thyroid histo-physiopathology were examined. The accumulation of PCBs in skin, plasma, liver, kidney, and brain were highest at 120 days. The alteration of triiodothyronine (T₃) and thyroxine (T₄) levels after different concentrations and times to exposure of PCBs was accompanied by the changes in the hormones involved in the hypothalamus-pituitary-thyroid (HPT) axis, namely Thyrotropin Releasing Hormone (TRH) and Thyroid Stimulating Hormone (TSH). Moreover, hepatic levels of deiodinase II (5′ORDII) and content of T₃ were positively correlated to exposure to PCBs. These results indicated that in lizards, PCBs exposure through the skin has the potential to disrupt the thyroid endocrine system. Overall, the observed results indicate that PCBs could be associated with changes in thyroid homeostasis in these reptiles, through direct interactions with the metabolism of T₄ and T₃ through the HPT axis or indirect interactions with peripheral deiodination.     

MicroRNA Signatures in the Upper Urinary Tract Urothelial Carcinoma Scenario: Ready for the Game Changer?

Upper urinary tract urothelial carcinoma (UTUC) represents a minor subgroup of malignancies arising in the urothelium of the renal pelvis or ureter. The estimated annual incidence is around 2 cases per 100,000 people, with a mean age at diagnosis of 73 years. UTUC is more frequently diagnosed in an invasive or metastatic stage. However, even though the incidence of UTUC is not high, UTUC tends to be aggressive and rapidly progressing with a poor prognosis in some patients. A significant challenge in UTUC is ensuring accurate and timely diagnosis, which is complicated by the non-specific nature of symptoms seen at the onset of disease. Moreover, there is a lack of biomarkers capable of identifying the early presence of the malignancy and guide-tailored medical treatment. However, the growing understanding of the molecular biology underlying UTUC has led to the discovery of promising new biomarkers. Among these biomarkers, there is a class of small non-coding RNA biomarkers known as microRNAs (miRNAs) that are particularly promising. In this review, we will analyze the main characteristics of UTUC and focus on microRNAs as possible novel tools that could enter clinical practice in order to optimize the current diagnostic and prognostic algorithm.     

Rheological,mechanical, thermal,and morphological properties of blends poly(butylene adipate-co-terephthalate), thermoplastic starch,and cellulose nanoparticles

The objective of the present study was the preparation and characterization of poly(butylene adipate-co-terephthalate) (PBAT) and thermoplastic starch (TPS) blends reinforced with cellulose nanoparticles (CNCs) by extrusion. The work was conducted in four steps. Initially, the CNCs were prepared from eucalyptus cellulose pulp by acid hydrolysis. The second step was the preparation of the nanocomposite (TPS-CNC), composed of cassava starch, CNC, glycerol, and citric and stearic acids, by double screw extrusion. The third step was the preparation of PBAT/TPS-CNC blends in twin-screw extruders. In the fourth step, the films were produced by flat extrusion. Blends exhibited similar rheological behavior, increasing the CNC concentration in blends increased the viscosity as a function of the shear rate, and altered the behavior of the shear storage (G′) and shear loss (G″) curves as a function of the oscillation frequency (ω). The presence of CNC in blend provided improvements significant in mechanical properties, with 120% increase in Young's modulus, and 46% increase in maximum tensile. Thermal behavior (thermogravimetric analysis and differential scanning calorimetry) was altered with the incorporation of the CNC, showing a single melt peak (T_m) and a slight increase in T_g, indicating good dispersion between the phases of the blends, corroborating with the fracture surface microscopy of films.     

Influence of post-casting treatments on sulphonated polyetheretherketone composite membranes

Since the post-casting treatments influence the water entrapped in polymeric matrix and consequently its proton conductivity, an evaluation of annealing at 200 °C and acid treatments was conducted on previously developed composite s-PEEK (1.55 mequiv. g⁻¹) membranes, containing a commercial aminopropyl-functionalised silica. DSC, WAXS, SEM-EDX and laser microscope measurements carried out on membranes swollen at different temperatures highlighted different membrane properties depending on post-casting treatments. It was found that composite membranes have different structural and morphological characteristics than pristine polymer membranes. The silica distribution was modified when different treatments are used. The state of water changed when silica was inserted into the membranes. Actually, contrary to the pristine membranes the presence of freezable water was revealed at temperature lower than 80 °C. The proton conductivity was also affected by the presence and the amount of water trapped into the membranes and was particularly influenced by the post-casting treatments. The silica introduction reduced the swelling effect and improved the robustness of the membranes even if a higher water content in the freezable state was observed. Acid treatment leads to significant improvement in membrane properties, but the present work shows that annealing before acid treatment can affect the membrane morphology more strongly than other treatments resulting in a much better fuel cell performance.     

Hexagonal Voronoi pattern detected in the microstructural design of the echinoid skeleton

Repeated polygonal patterns are pervasive in natural forms and structures. These patterns provide inherent structural stability while optimizing strength-per-weight and minimizing construction costs. In echinoids (sea urchins), a visible regularity can be found in the endoskeleton, consisting of a lightweight and resistant micro-trabecular meshwork (stereom). This foam-like structure follows an intrinsic geometrical pattern that has never been investigated. This study aims to analyse and describe it by focusing on the boss of tubercles—spine attachment sites subject to strong mechanical stresses—in the common sea urchin Paracentrotus lividus. The boss microstructure was identified as a Voronoi construction characterized by 82% concordance to the computed Voronoi models, a prevalence of hexagonal polygons, and a regularly organized seed distribution. This pattern is interpreted as an evolutionary solution for the construction of the echinoid skeleton using a lightweight microstructural design that optimizes the trabecular arrangement, maximizes the structural strength and minimizes the metabolic costs of secreting calcitic stereom. Hence, this identification is particularly valuable to improve the understanding of the mechanical function of the stereom as well as to effectively model and reconstruct similar structures in view of future applications in biomimetic technologies and designs.     

Monitoring Somatic Genetic Alterations in Circulating Cell-Free DNA/RNA of Patients with “Oncogene-Addicted” Advanced Lung Adenocarcinoma: A Real-World Clinical Study

Liquid biopsy has advantages over tissue biopsy, but also some technical limitations that hinder its wide use in clinical applications. In this study, we aimed to evaluate the usefulness of liquid biopsy for the clinical management of patients with advanced-stage oncogene-addicted non-small-cell lung adenocarcinomas. The investigation was conducted on a series of cases—641 plasma samples from 57 patients—collected in a prospective consecutive manner, which allowed us to assess the benefits and limitations of the approach in a real-world clinical context. Thirteen samples were collected at diagnosis, and the additional samples during the periodic follow-up visits. At diagnosis, we detected mutations in ctDNA in 10 of the 13 cases (77%). During follow-up, 36 patients progressed. In this subset of patients, molecular analyses of plasma DNA/RNA at progression revealed the appearance of mutations in 29 patients (80.6%). Mutations in ctDNA/RNA were typically detected an average of 80 days earlier than disease progression assessed by RECIST or clinical evaluations. Among the cases positive for mutations, we observed 13 de novo mutations, responsible for the development of resistance to therapy. This study allowed us to highlight the advantages and disadvantages of liquid biopsy, which led to suggesting algorithms for the use of liquid biopsy analyses at diagnosis and during monitoring of therapy response.     

Macrocyclic statine-based inhibitors of BACE-1

Minimal sequence requirements for binding of substrate-derived statine peptides to the aspartyl enzyme were established on the basis of the X-ray cocrystal structure of the hydroxyethylene-octapeptide OM00-3 in complexation with BACE-1. With this information to hand, macrocyclic compounds that conformationally restrict and preorganize the peptide backbone for an entropically favoured binding to the enzyme active site cleft were designed. By means of a side chain-to-side chain ring closure between two aspartyl residues in the P2 and P3' positions through phenylene-1,3-dimethanamine, a 23-membered ring structure was obtained; this structure retained an extended conformation of the peptide backbone, including the transition state analogue statine for tight interactions with the two aspartyl residues of the active centre. The conformational preorganization of the inhibitor molecule was verified by NMR structural analysis and was then confirmed by the crystal structure of the BACE-1/inhibitor complex. Detailed insights into the binding mode of this macrocyclic inhibitor explained its moderate binding affinity in cell-free assays (K(i)=2.5 microM) and yielded precious information for possible structural optimization in view of the lack of steric clashes of the macrocycle with the flap domain of the enzyme.     

Cyclopenta[d]pyrimidines and dihydropyrrolo[2,3-d]pyrimidines as potent and selective corticotropin-releasing factor 1 receptor antagonists

Two new classes of potent and selective CRF(1) receptor antagonists are presented. Exploration of general templates 3 and 4 through modifications of the top amine and bottom phenyl substituents led to optimization of the in vitro affinity and pharmacokinetic profiles. The typical alkyl chains present in the top region of CRF(1) antagonists were replaced by substituted heteroaryl moieties, leading to a dramatic improvement of the metabolic stability. This improvement was apparent when the compounds were dosed in vivo: several compounds exhibited low plasma clearance, good oral bioavailability, and high brain penetration. As a consequence of their outstanding pharmacokinetic profiles, these CRF(1) antagonists, as exemplified by compound 4 fi (4-(4-bromo-3-methyl-1H-pyrazol-1-yl)-7-(2,4-dichlorophenyl)-2-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine), produced a dose-dependent "anxiolytic-like" effect when administered orally, decreasing the vocalization of rat pups.     

Preliminary chemical characterization of Tunisian monovarietal virgin olive oils and comparison with Sicilian ones

Work was carried out on the characterization of monovarietal virgin olive oils (VOO) from Tunisia and Sicily (Italy). The two main Tunisian VOO (cvv. Chétoui of the North and cv. Chemlali grown in the Center and some regions of the South) and three principal Sicilian VOO (cvv. Nocellara del Belice, Biancolilla and Cerasuola) were studied. Moreover, the Chétoui oils were tested in a rain‐fed control and an irrigation regime. All olive samples were picked at three different stages of ripeness. Analyses of major components (fatty acids and triacylglycerols) and minor ones (squalene, tocopherols and phenolic compounds) were carried out. Chétoui oils had a higher level of phenolic compounds followed by Chemlali. Generally, in the Sicilian oils these natural antioxidant contents were lower. These preliminary results indicate that it was possible to classify the Tunisian and Sicilian oils tested in their original growing area based on their chemical composition.     

The filler content of the dental composite resins and their influence on different properties

The purpose of this study was to compare the inorganic content and morphology of one nanofilled and one nanohybrid composite with one universal microhybrid composite. The Vickers hardness, degree of conversion and scanning electron microscope of the materials light‐cured using LED unit were also investigated. One nanofilled (Filtek? Supreme XT), one nanohybrid (TPH®₃) and one universal microhybrid (Filtek? Z‐250) composite resins at color A₂ were used in this study. The samples were made in a metallic mould (4 mm in diameter and 2 mm in thickness). Their filler weight content was measured by thermogravimetric analysis (TG). The morphology of the filler particles was determined using scanning electron microscope equipped with a field emission gun (SEM‐FEG). Vickers hardness and degree of conversion using FT‐IR spectroscopy were measured. Filtek? Z‐250 (microhybrid) composite resin shows higher degree of conversion and hardness than those of Filtek? Supreme XT (nanofilled) and TPH®₃ (nanohybrid) composites, respectively. The TPH₃® (nanohybrid) composite exhibits by far the lowest mechanical property. Nanofilled composite resins show mechanical properties at least as good as those of universal hybrids and could thus be used for the same clinical indications as well as for anterior restorations due to their high aesthetic properties. Microsc. Res. Tech. 75:758–765, 2012. © 2011 Wiley Periodicals, Inc