Mechanical squeezing of an elastomeric nanochannel device: numerical simulations and ionic current characterization

Peculiar transport phenomena appear at nanoscale, since surface effects strongly affect the behaviour of fluids. Electrostatic and steric interactions, capillary forces and entropic effects play a key role in the behaviour of fluids and biomolecules. Since these effects strongly depend on the size of the nanofluidic system, a careful characterization of the fluidic environment is necessary. Moreover, the possibility to dynamically modulate the size of nanochannels is very appealing in the field of biomolecule manipulation. Recently, we have developed a lab-on-chip made of poly(dimethylsiloxane) (PDMS). This polymeric device is based on a tuneable nanochannel able to dynamically change its dimension in order to fit the application of interest. In fact, a mechanical compression applied on the top of the elastomeric device squeezes the nanochannel, reducing the channel cross section and allowing a dynamical optimization of the nanostructures. In this paper, this squeezing process is fully characterized both numerically and experimentally. This analysis provides information on the reduction of the nanochannel dimensions induced by compression as a function of the work of adhesion and of the stiffness of the materials composing the device. Moreover, calculations demonstrate the possibility to predict the change of the nanochannel size and shape induced by the compression. The possibility to dynamically tune the channel size opens up new opportunities in biomolecular sensing or sieving and in the study of new hydrodynamics effects.     

Impact of cranberry juice and proanthocyanidins on the ability of <Emphasis Type=Italic>Escherichia coli</Emphasis> to form biofilms

The effects of cranberry juice cocktail (CJC) and proanthocyanidins (PACs) on biofilm formation were investigated. Escherichia coli strain HB101pDC1 and nonfimbriated strain HB101 were grown in 10 wt% CJC or 120 μg/mL PACs for 12 consecutive cultures. Biofilm formation was investigated by incubating bacteria in 96-well polyvinyl chloride (PVC) plates and studying the optical density of the solution using the crystal violet method. We suspect that biofilm formation occurred due to non-specific interactions between the bacteria and the polymer. Both P-fimbriated E. coli HB101pDC1 and the non-fimbriated strain HB101 formed biofilms. E. coli strain HB101pDC1 formed a thicker and more mature biofilm. Cranberry juice inhibited biofilm formation after the first culture; however, for bacteria grown in PACs, a decrease in biofilm formation was observed with increasing number of cultures. The inhibitory effect was reversible. These results demonstrate that CJC is more effective than isolated PACs at preventing biofilm formation, possibly suggesting that other cranberry compounds also play a role in anti-biofilm activity.     

Simulation of retronasal aroma of white and red wine in a model mouth system. Investigating the influence of saliva on volatile compound concentrations

The influence of saliva on aroma release from white and red wines was studied in a model mouth system. Aroma compounds were analysed in the dynamic headspace of wines by solid phase micro extraction/gas chromatography with flame ionization detection. Volatile compounds were identified by solid phase micro extraction/gas chromatography-mass spectrometry, resulting in a total of 43 compounds in white wine and 41 in red wine. The results showed a greater influence of saliva on aroma release in white wine than red wine. In white wine treated with human saliva, esters and fusel alcohols, responsible for fruity and fusel oil odours, were reduced of 32–80%; by contrast, the concentration of 2-phenylethanol and furfural, responsible for rose and toasted almond notes, increased by 27% and by 155%, respectively. In red wine, treated with human saliva, only a few esters decrease, with a reduction of 22–51% due to protein-binding ability of polyphenols that are able to inhibit the activity of the saliva. C-13 norisoprenoids, vitispirane (eucalyptol) and TDN (kerosene), decreased both in white and red wine, showing a comparable variation while, for β-damascenone, the variation was insignificant.     

Tribological Behavior of Aluminum Alloy AlSi10Mg-TiB<Subscript>2</Subscript> Composites Produced by Direct Metal Laser Sintering (DMLS)

Direct metal laser sintering (DMLS) is an additive manufacturing technique for the production of parts with complex geometry and it is especially appropriate for structural applications in aircraft and automotive industries. Aluminum-based metal matrix composites (MMCs) are promising materials for these applications because they are lightweight, ductile, and have a good strength-to-weight ratio This paper presents an investigation of microstructure, hardness, and tribological properties of AlSi10Mg alloy and AlSi10Mg alloy/TiB₂ composites prepared by DMLS. MMCs were realized with two different compositions: 10% wt. of microsize TiB₂, 1% wt. of nanosize TiB₂. Wear tests were performed using a pin-on-disk apparatus on the prepared samples. Performances of AlSi10Mg samples manufactured by DMLS were also compared with the results obtained on AlSi10Mg alloy samples made by casting. It was found that the composites displayed a lower coefficient of friction (COF), but in the case of microsize TiB₂ reinforcement the wear rate was higher than with nanosize reinforcements and aluminum alloy without reinforcement. AlSi10Mg obtained by DMLS showed a higher COF than AlSi10Mg obtained by casting, but the wear rate was higher in the latter case.     

The interpretation of the English landscape garden between 1815 and 1840 through Xavier Kurten’s work in Piedmont (north-west Italy)

Xavier Kurten (?–1840) was a Prussian landscape gardener who worked for the Savoy family in the Piedmont region of Italy in the first half of the nineteenth century. He designed or redesigned all royal parks, creating a specific style based on the English naturalistic garden approach. This research was performed with the aim of investigating the development of the English landscape garden in Italy. Historical documents relating to Kurten’s biography and his work in Piedmont, including plans, were collected and analysed. We analyse and discuss the features that characterised his work: the relationship between the landscape—garden—house, the path system, the use of water, the vegetation, and the garden as a productive landscape. Kurten’s style is compared with the projects of William Kent and Lancelot ‘Capability’ Brown.     

Monitoring Phenolic Composition of Maturing Maize Stover by High Performance Liquid Chromatography and Pyrolysis/Gas Chromatography/Mass Spectrometry*

Maize stovers collected every 14 days over an 84-day growth period were subjected to high-performance liquid chromatography with electrochemical detector (HPLC-ED) and pyrolysis/gas chromatography/mass spectrometry (PY/GC/MS) in order to monitor changes in the phenolic composition. Prior to HPLC-ED analyses, ground samples were sequentially extracted with (i) methanol, (ii) 0·1M sodium hydroxide and (iii) 2M sodium hydroxide in the presence of nitrobenzene to separate, respectively, free phenolic monomers, alkali-labile phenolic monomers and alkali-resistant lignin. In turn, solution (ii) was treated with alkaline nitrobenzene to obtain (iv) alkali-labile lignin. Pyrolysis was carried out on ground native samples by using a platinum heated filament pyrolyser. Increases in the absolute phenolic concentrations in the residues of 0·1M sodium hydroxide extraction and in the ratio of alkali-resistant lignin vs total lignin were observed by HPLC-ED during the first 28–42 days of maturation, reaching a steady level in the remaining maturation period. A linear increase of syringyl units vs guaiacyl units was for found the alkali-resistant lignin fraction over the entire period of maturation. Similar trends were showed by PY/GC/MS with regard to relative lignin content and syringyl/guaiacyl ratio. Both techniques showed their usefulness to gauge changes in the phenolic composition during the lignification process.     

Candida albicans homologue of GGP1/GAS1 gene is functional in Saccharomyces cerevisiae and contains the determinants for glycosylphosphatidylinositol attachment

The GGP1/GAS1/CWH52 gene of Saccharomyces cerevisiae encodes a major exocellular 115 kDa glycoprotein (gp115) anchored to the plasma membrane through a glycosylphosphatidylinositol (GPI). The function of gp115 is still unknown but the analysis of null mutants suggests a possible role in the control of morphogenesis. PHR1 gene isolated from Candida alibicans is homologous to the GGP1 gene. In this report we have analysed the ability of PHR1 to complement a ggp1Δ mutation in S. cerevisiae. The expression of PHR1 controlled by its natural promoter or by the GGP1 promoter has been studied. In both cases we have observed a complete complementation of the mutant phenotype. Moreover, immunological analysis has revealed that PHR1 in budding yeast gives rise to a 75–80 kDa protein anchored to the membrane through a GPI, indicating that the signal for GPI attachment present in the C. albicans gene product is functional in S. cerevisiae.     

Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.     

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.     

A Comparison of Network-Based Methods for Drug Repurposing along with an Application to Human Complex Diseases

Drug repurposing strategy, proposing a therapeutic switching of already approved drugs with known medical indications to new therapeutic purposes, has been considered as an efficient approach to unveil novel drug candidates with new pharmacological activities, significantly reducing the cost and shortening the time of de novo drug discovery. Meaningful computational approaches for drug repurposing exploit the principles of the emerging field of Network Medicine, according to which human diseases can be interpreted as local perturbations of the human interactome network, where the molecular determinants of each disease (disease genes) are not randomly scattered, but co-localized in highly interconnected subnetworks (disease modules), whose perturbation is linked to the pathophenotype manifestation. By interpreting drug effects as local perturbations of the interactome, for a drug to be on-target effective against a specific disease or to cause off-target adverse effects, its targets should be in the nearby of disease-associated genes. Here, we used the network-based proximity measure to compute the distance between the drug module and the disease module in the human interactome by exploiting five different metrics (minimum, maximum, mean, median, mode), with the aim to compare different frameworks for highlighting putative repurposable drugs to treat complex human diseases, including malignant breast and prostate neoplasms, schizophrenia, and liver cirrhosis. Whilst the standard metric (that is the minimum) for the network-based proximity remained a valid tool for efficiently screening off-label drugs, we observed that the other implemented metrics specifically predicted further interesting drug candidates worthy of investigation for yielding a potentially significant clinical benefit.