NPM1-Mutated Myeloid Neoplasms with <20% Blasts: A Really Distinct Clinico-Pathologic Entity?

Nucleophosmin (NPM1) gene mutations rarely occur in non-acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented NPM1 mutations in around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico-pathologic entities. Furthermore, fit patients with NPM1-mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS-directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing NPM1-mutated MNs with blast count <20%, since NPM1-mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to NPM1-mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether NPM1 mutations may become sufficient to diagnose AML, irrespective of blast percentage.     

Carbon Dots Boost dsRNA Delivery in Plants and Increase Local and Systemic siRNA Production

In this work, we obtained carbon dots from glucose or saccharose as the nucleation source and passivated them with branched polyethylenimines for developing dsRNA nanocomposites. The CDs were fully characterized using hydrodynamic analyses, transmission electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The ζ potential determined that the CDs had positive charges, good electrophoretic mobility and conductivity, and were suitable for obtaining dsRNA nanocomposites. DsRNA naked or coated with the CDs were delivered to leaves of cucumber plants by spraying. Quantitation of the dsRNA that entered the leaves showed that when coated with the CDs, 50-fold more dsRNA was detected than when naked dsRNA. Moreover, specific siRNAs derived from the sprayed dsRNAs were 13 times more abundant when the dsRNA was coated with the CDs. Systemic dsRNAs were determined in distal leaves and showed a dramatic increase in concentration when delivered as a nanocomposite. Similarly, systemic siRNAs were significantly more abundant in distal leaves when spraying with the CD-dsRNA nanocomposite. Furthermore, FITC-labeled dsRNA was shown to accumulate in the apoplast and increase its entry into the plant when coated with CDs. These results indicate that CDs obtained by hydrothermal synthesis are suitable for dsRNA foliar delivery in RNAi plant applications.     

Liquid chromatography-negative ion electrospray mass spectrometry detection of maleic anhydride-modified wood rosin for assessing quality of commercial citrus fruit coatings

Abstract Differently from Europe (EU), in United States (US) is allowed the use of citrus coating formulations containing pentaerythritol-ester of maleic anhydride-modified wood rosin, imputed of allergenic effects. To control the waxes used in the European citrus coating operations, a reliable LC/PDA/ESI–MS method for the simultaneous detection of abietic acid (AA) and maleopimaric acid (MPA) was developed. AA is the main resin acid, while MPA is the major product of the modification of rosin with maleic anhydride. Because of the lack of commercial standard, the MPA was synthesized in our laboratory heating AA and maleic anhydride together at 190 °C. The method was successfully applied to 190 samples of coated citrus fruits and 19 commercial waxes collected in the Italian market. The results demonstrated that about 7.5% of the investigated citrus samples contained both AA and MPA, evidencing the illicit employ of unpermitted waxes in citrus coatings. All the analyzed waxes resulted instead regular. The proposed method could be routinely applied in the control laboratories to assess quality of European citrus fruit, preserving the consumers from the commercial illicit and from potential toxicological consequences.     

S100B Protein concentration in milk-formulas for preterm and term infants. Correlation with industrial preparation procedures

Human milk S100B protein possesses important neurotrophic properties. However, in some conditions human milk is substituted by milk formulas. The aims of the present study were: to assess S100B concentrations in milk formulas, to verify any differences in S100B levels between preterm and term infant formulas and to evaluate the impact of industrial preparation at predetermined phases on S100B content. Two different set of samples were tested: (i) commercial preterm (n = 36) and term (n = 36) infant milk formulas; ii) milk preterm (n = 10) and term infant (n = 10) formulas sampled at the following predetermined industrial preparation time points: skimmed cow milk (Time 0); after protein sources supplementation (Time 1); after pasteurization (Time 2); after spray-drying (Time 3). Our results showed that S100B concentration in preterm formulas were higher than in term ones (p < 0.01). In addition, S100B concentrations during industrial preparation showed a significant increase (p < 0.001) at Time 1 followed by a slight decrease (p > 0.05) at Time 2, whereas a significant (p < 0.001) dip was observed at Time 3. In conclusion, S100B showed a sufficient thermostability to resist pasteurization but not spry-drying. New feeding strategies in preterm and term infants are therefore warranted in order to preserve S100B protein during industrial preparation.     

Influence of heat-treatment protocols on mechanical behavior of lithium silicate dental ceramics

In this work, three different commercial lithium silicate (LS) glass-ceramics for computer aided design/computer aided machining systems, CeltraDuo-Dentsply (LS-C), E-MaxCAD-Ivoclar (LS-E), and Suprinity-Vita (LS-S), were comparatively characterized. Following the protocols recommended by the manufacturers, the glass-ceramics were heat-treated under low vacuum and characterized by X-ray diffraction, scanning electron microscopy, hardness, fracture toughness, Young's modulus, and flexural strength. Rietveld refinement indicated that the materials “as-received” present mostly amorphous phase and Li₂SiO₃ as secondary crystalline phase in LS-E and LS-S specimens, while LS-C specimens also present Li₂Si₂O₅ and Li₃PO₄ as crystalline phases. All “as-received” glass-ceramics present hardness, fracture toughness, and Young's modulus of around 647-678 HV, 1.15-1.40 MPa.m^1/2, and 82-92 GPa, respectively. After heat treatment, the LS-C and LS-S specimens presented decreasing of amorphous phase associated to Li₂SiO₃ and Li₂Si₂O₅ grains with low aspect ratio, while LS-E indicates a reduction of amorphous phase and Li₂Si₂O₅ elongated grains. Fracture toughness and Young's modulus increase about 10% due to the crystallization of residual amorphous phase for all materials. Moreover, crystallographic and microstructural characteristics are responsible for the higher flexural strength of LS-E (327 MPa), regarding LS-C and LS-S. However, the glass-ceramics LS-E present lower Weibull modulus (m = 5.4) comparatively to LS-C (m = 9) and LS-S (m = 6).     

Groundwater Modeling for the Analysis of Active Slow-Moving Landslides

Active slow-moving landslides in clayey soils exhibit continuous movements generally controlled both in the accelerating and decelerating phases by the pore-water pressure regime that, in turn, is strictly correlated to the net rainfall regime. The paper stresses the importance of a reliable groundwater model to predict these types of movements. To this aim a procedure is proposed to define the transient groundwater regime in the slope on the basis of recorded rainfall and monitoring data; the model is then used to derive the time-dependent shear strength along the main slip surfaces. The displacements at selected points along the slip surface are computed using a phenomenological (i.e., empirical) relationship between the local factor of safety and the displacement rate at those points. The procedure is employed for the analysis of a well-documented case history: the Porta Cassia landslide (central Italy).     

Mechanical properties of Sn–Zn lead-free solder alloys based on the microstructure array

The aim of this study is to develop a comparative experimental study interrelating mechanical properties, solidification thermal parameters and microstructure characteristics of a hypoeutectic Sn–4 wt.% Zn, a hypereutectic Sn–12 wt.% Zn and a eutectic Sn–9 wt.% Zn solder alloys. A water-cooled vertical upward unidirectional solidification system was used to obtain the samples. It was found that a more homogeneous distribution of the eutectic mixture, which occurs for smaller dendritic spacings in hypoeutectic and hypereutectic alloys, increases the ultimate tensile strength. The resulting microstructure of the eutectic Sn-9 wt.% Zn alloy has induced higher mechanical strength than those of the Sn–4 wt.% Zn and Sn–12 wt.% Zn alloys. It was found that the eutectic alloy experiences a microstructural transition from globular-to-needle-like Zn-rich morphologies which depend on the solidification growth rate. It is also shown that a globular-like Zn-rich morphology provides higher ultimate tensile strength than a needle-like Zn-rich eutectic morphology.     

Catalytic Nanomotors: Self‐Propelled Sphere Dimers

Experimental and theoretical studies of the self‐propelled motional dynamics of a new genre of catalytic sphere dimer, which comprises a non‐catalytic silica sphere connected to a catalytic platinum sphere, are reported for the first time. Using aqueous hydrogen peroxide as the fuel to effect catalytic propulsion of the sphere dimers, both quasi‐linear and quasi‐circular trajectories are observed in the solution phase and analyzed for different dimensions of the platinum component. In addition, well‐defined rotational motion of these sphere dimers is observed at the solution–substrate interface. The nature of the interaction between the sphere dimer and the substrate in the aqueous hydrogen peroxide phase is discussed. In computer simulations of the sphere dimer in solution and the solution–substrate interface, sphere‐dimer dynamics are simulated using molecular‐dynamics methods and solvent dynamics are modeled by mesoscopic multiparticle collision methods taking hydrodynamic interactions into account. The rotational and translational dynamics of the sphere dimer are found to be in good accord with the predictions of computer simulations.     

Disturbance attenuation for a class of distributed parameter systems

This paper deals with the problem of robust stabilization and disturbance attenuation via measured feedback, for a class of dissipative collocated distributed systems with disturbances affecting both the input and the measured output. The proposed solution is based on a direct ℒ︁₂-gain characterization which avoids the usual Riccati equation argument. For this purpose only strong stabilizability of the semigroup is required. A flexible slewing link is chosen as an application example. © 1997 John Wiley & Sons, Ltd.     

Verteporfin-Loaded Mesoporous Silica Nanoparticles’ Topical Applications Inhibit Mouse Melanoma Lymphangiogenesis and Micrometastasis In Vivo

Photodynamic therapy (PDT) has been pointed out as a candidate for improving melanoma treatment. Nanotechnology application in PDT has increased its efficacy by reducing side effects. Herein, mesoporous silica nanoparticles (MSNs) conjugated with verteporfin (Ver-MSNs), in use with PDT, were administered in mice to evaluate their efficacy on lymphoangiogenesis and micrometastasis in melanoma. Melanoma was induced in mice by the subcutaneous injection of B16-F10 cells. The mice were transcutaneously treated with MSNs, Ver-MSNs, or glycerol and exposed to red light. The treatment was carried out four times until day 20. Lymphangiogenesis and micrometastasis were identified by the immunohistochemical method. Lymphoangiogenesis was halved by MSN treatment compared with the control animals, whereas the Ver-MSN treatment almost abolished it. A similar reduction was also observed in lung micrometastasis. PDT with topically administrated Ver-MSNs reduced melanoma lymphoangiogenesis and lung micrometastasis, as well as tumor mass and angiogenesis, and therefore their use could be an innovative and useful tool in melanoma clinical therapy.