Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma

Currently,sorafenib is the only systemic therapy capable of increasing overall survival of hepatocellular carcinoma patients.Unfortunately,its side effects,particularly its overall toxicity,limit the therapeutic response that can be achieved.Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery because they can be targeted to specific sites in the body through application of a magnetic field,thus improving intratumoral accumulation and reducing adverse effects.Here,nanoformulations based on polyethylene glycol modified phospholipid micelles,loaded with both SPIONs and sorafenib,were successfully prepared and thoroughly investigated by complementary techniques.This nanovector system provided effective drug delivery,had an average hydrodynamic diameter of about 125 nm,had good stability in aqueous medium,and allowed controlled drug loading.Magnetic analysis allowed accurate determination of the amount of SPIONs embedded in each micelle.An in vitro system was designed to test whether the SPION micelles can be efficiently held using a magnetic field under typical flow conditions found in the human liver.Human hepatocellular carcinoma (HepG2) cells were selected as an in vitro system to evaluate tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib.These experiments demonstrated that this delivery platform is able to enhance sorafenib's antitumor effectiveness by magnetic targeting.The magnetic nanovectors described here represent promising candidates for targeting specific hepatic tumor sites,where selective release of sorafenib can improve its efficacy and safety profile.     

Platelet lysate and adipose mesenchymal stromal cells on silk fibroin nonwoven mats for wound healing

In this work platelet lysate (PL) and adipose‐derived mesenchymal stromal cells (ASCs) seeded on nonwoven fibroin mats were in vitro and in vivo evaluated for tissue regenerative applications. Nonwoven mats obtained by a large scale water entanglement technique were characterized for their physico‐chemical properties. Results indicated a high purity of fibroin fibers, their stability after sterilization process and appropriate technological properties suitable for tissue engineering. Moreover, the scaffolds in vitro supported adhesion and migration of ASCs and the presence of PL improved the cell proliferation. The products were then applied on epithelial/dermal wounds carried out on the dorsal surface of rabbit: the skin reparative process was solved in 9 days, with a completely restitutio ad integrum of the epithelium in animals treated with PL alone; ASCs did not further improve the wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42942.     

Pediatric Brain Tumors: Signatures from the Intact Proteome

The present investigation aimed to explore the intact proteome of tissues of pediatric brain tumors of different WHO grades and localizations, including medulloblastoma, pilocytic astrocytoma, and glioblastoma, in comparison with the available data on ependymoma, to contribute to the understanding of the molecular mechanisms underlying the onset and progression of these pathologies. Tissues have been homogenized in acidic water–acetonitrile solutions containing proteases inhibitors and analyzed by LC–high resolution MS for proteomic characterization and label-free relative quantitation. Tandem MS spectra have been analyzed by either manual inspection or software elaboration, followed by experimental/theoretical MS fragmentation data comparison by bioinformatic tools. Statistically significant differences in protein/peptide levels between the different tumor histotypes have been evaluated by ANOVA test and Tukey’s post-hoc test, considering a p-value > 0.05 as significant. Together with intact protein and peptide chains, in the range of molecular mass of 1.3–22.8 kDa, several naturally occurring fragments from major proteins, peptides, and proteoforms have been also identified, some exhibiting proper biological activities. Protein and peptide sequencing allowed for the identification of different post-translational modifications, with acetylations, oxidations, citrullinations, deamidations, and C-terminal truncations being the most frequently characterized. C-terminal truncations, lacking from two to four amino acid residues, particularly characterizing the β-thymosin peptides and ubiquitin, showed a different modulation in the diverse tumors studied. With respect to the other tumors, medulloblastoma, the most frequent malignant brain tumor of the pediatric age, was characterized by higher levels of thymosin β4 and β10 peptides, the latter and its des-IS form particularly marking this histotype. The distribution pattern of the C-terminal truncated forms was also different in glioblastoma, particularly underlying gender differences, according to the definition of male and female glioblastoma as biologically distinct diseases. Glioblastoma was also distinguished for the peculiar identification of the truncated form of the α-hemoglobin chain, lacking the C-terminal arginine, and exhibiting oxygen-binding and vasoconstrictive properties different from the intact form. The proteomic characterization of the undigested proteome, following the top-down approach, was challenging to originally investigate the post-translational events that differently characterize pediatric brain tumors. This study provides a contribution to elucidate the molecular profiles of the solid tumors most frequently affecting the pediatric age, and which are characterized by different grades of aggressiveness and localization.     

Finding Multiple Equivalence-Preserving Transformations in Combinational Circuits through Incremental-SAT

This paper introduces an approach to effectively exploit incremental SAT in order to search for multiple equivalence-preserving transformations of combinational circuits. Typical applications, such as redundancy removal with observability and external care conditions, adequate abstractions and other optimizations used in a state-of-the-art SAT-based model checker, can reap benefits from the proposed strategies. Our techniques exploit SAT incrementality, by iteratively refining the set of candidate transformations with a counter-example driven analysis, until an unsatisfiable point is reached. The key point of our technique is the ability to address satisfiable instances first, where SAT solvers are generally much faster than with unsatisfiable runs. We also discuss partitioning and problem reduction issues, that are fundamental in order to provide a scalable approach. Experimental results show the effectiveness of the proposed strategies.     

Verification of Similar FSMs by Mixing Incremental Re-encoding, Reachability Analysis, and Combinational Checks

State space exploration is often used to prove properties about sequential behavior of Finite State Machines (FSMs). For example, equivalence of two machines is proved by analyzing the reachable state set of their product machine. Nevertheless, reachability analysis is infeasible on large practical examples. Combinational verification is far less expensive, but on the other hand its application is limited to combinational circuits, or particular design schemes. Finally, approximate techniques imply sufficient, not strictly necessary conditions.The purpose of this paper is to extend the applicability of purely combinational checks. This is generally achieved through state minimization, partitioning, and re-encoding the FSMs to factor out their differences. We focus on re-encoding. In particular, we present an incremental approach to re-encoding for verification that transforms the product machine traversal into a combinational verification in the best case, and into a computationally simpler product machine traversal in the general case.Experimental results demonstrate the effectiveness of this technique on medium-large circuits where other techniques may fail.     

Effect of electric and flow parameters on PEF treatment efficiency

The effects of both the electric and flow parameters on the lethality and energy efficiency of a pulsed electric fields (PEF) treatment were studied. An experimental plan was designed in order to study the microbial inactivation of Saccharomyces cerevisiae and Escherichia coli cells inoculated in a buffer solution. The following process parameters were taken into consideration: electric field strength (13-30 kV/cm), total specific energy input (20-110 J/mL), flow rate of the processed stream (1-4 L/h) and number of passes through the chamber (up to 5).The results showed that, at a fixed flow rate (2 L/h), microbial inactivation of both microbial strains increased with increasing field strength and applied energy input. The maximum inactivation level (5.9 Log-cycles for S. cerevisiae and 7.0 Log-cycles for E. coli) corresponded to the more intensive PEF treatment (30 kV/cm and 110 J/mL). However, for any given field strength applied, the inactivation rate decreased by increasing the energy input. This behavior was attributed to the presence of heterogeneous treatment conditions due, for example, to a different morphology (size and shape) or cell membrane (composition, structure), a local variation of the electric field strength in the treatment chamber, the tendency of microbial cells to form clusters, or a non-uniform distribution of the residence time of the product in the PEF chamber.A more effective stirring of the microbial suspensions which was achieved, at a fixed field strength (18 kV/cm), either by increasing the flow rate with a single pass operation through the PEF chamber, or by operating in re-circulating mode at a constant flow rate, provided a significant increase in the effectiveness and energy efficiency of the pulse treatment.A mathematical model based on the Weibull distribution adequately described the inactivation kinetics of both microbial strains under different flow dynamic conditions.     

An experimental investigation of Fischer–Tropsch synthesis over washcoated metallic structured supports

In principle, the application of monolithic catalysts to the Fischer–Tropsch synthesis can solve many of the problems related to the classical Fischer–Tropsch reactors, in particular concerning the necessity to operate with short diffusion distances and low pressure drops, preferably according to the ideal plug-flow behavior, while still maintaining a reasonable inventory of catalytic material in the reactor volume.The preparation of prototype cobalt-based catalysts, washcoated onto metallic structured supports with different geometries, is described herein, together with the evaluation of the catalytic properties of such systems in the Fischer–Tropsch synthesis at industrially relevant process conditions (220–235 °C, 20 bar, 2.1  mol_H2/mol_CO,  5000 cm³(STP)_CO+H2/h/g_cat). Comparative tests with the same catalyst in the powdered form were also carried out at the same process conditions.It was found that the structured catalysts maintained the activity and the selectivity of the original powdered catalyst, provided that the washcoat thickness is sufficiently thin.     

Honeycomb supports with high thermal conductivity for gas/solid chemical processes

The scope of this review article is to address the use of novel monolithic catalysts with high thermal conductivity in externally cooled tubular reactors for gas/solid exothermic chemical processes in place of conventional packed beds of catalyst pellets.

After discussing the analysis and the implications of heat conduction in honeycomb monolith structures, we review herein simulation studies and experimental investigations showing that near-isothermal reactor operation can be achieved even under very high thermal loads by adopting specific materials and designs of the honeycomb supports associated with high effective radial thermal conductivities. For such monoliths, the limiting thermal resistance is located at the interface between the monolith and the inner tube wall (“gap resistance”). Recent measurements of the “gap” heat transfer coefficient point to very large values (>400 W/(m² K)), which are controlled both by the tube–monolith clearance at the actual operating conditions and by the thermal conductivity of the process gas.     

Conditioning of Rh/α-Al2O3 catalysts for H2 production via CH4 partial oxidation at high space velocity

Experimental evidence and literature indications suggest that the process of methane partial oxidation over Rh catalysts is structure sensitive. Crystal phases and Rh cluster size are thus expected to affect the final catalytic performance. In this work, it is observed that outstanding performances are obtained when the as-prepared catalysts are conditioned through repeated runs at increasing temperature and O₂/CH₄ = 0.56. Catalysts slowly activate, that is CH₄ conversion and synthesis gas selectivity progressively grow with time on stream. On the basis of TPO and CH₄ decomposition measurements, this phenomenon is herein explained as the result of a surface reconstruction driven by the repeated exposition to the reaction at high temperature; it is thought that such reconstruction tends to eliminate defect sites and disfavors C-deposition reactions (extremely fast over steps and kinks). Conditioning with O₂-enriched feed streams makes conditioning faster, since the accumulation of surface C-species is suppressed; however, the catalyst is eventually less active than a catalyst conditioned with standard feed mixtures. As an alternative, accumulation of carbon can be suppressed and surface reconstruction proceeds faster if the catalyst is directly exposed to the reaction at high temperature for several hours.