The ambitious role of anti angiogenesis molecules: Turning a cold tumor into a hot one

In renal cancer emerging treatment options are becoming available and there is a strong need to combine therapies to reformulate and adjourn clinical practice. We here highlight and discuss the need to take advantage of the common immune targets to design combined strategies to increase clinical responses

Mixing enhancement induced by viscoelastic micromotors in microfluidic platforms

Fine manipulation of fluid flows at the microscale has a tremendous impact on mass transport phenomena of chemical and biological processes inside microfluidic platforms. Fluid mixing in the laminar flow regime at low Reynolds number is poorly effective due to the inherently slow diffusive mechanism. As a strategy to enhance mixing and prompt mass transport, here, we focus on polyelectrolyte multilayer capsules (PMCs), embodying a catalytic polyoxometalate, as microobjects to create elastic turbulence and as micromotors to generate chaotic flows by fuel-fed propulsions. The effects of the elastic turbolence and of the artificial propulsion on some basic flow parameters, such as pressure and volumetric flow rate, are studied by a microfluidic set-up including pressure and flow sensors. Numerical-handling and physical models of the experimental data are presented and discussed to explain the measured dependence of the pressure drop on the flow rate in presence of the PMCs. As a practical outcome of the study, a strong decrease of the mixing time in a serpentine microreactor is demonstrated. Unlike our previous reports dealing with capillarity flow studies, the present paper relies on hydrodynamic pumping experiments, that allow us to both develop a theoretical model for the understanding of the involved phenomena and demonstrate a successful microfluidic mixing application. All of this is relevant in the perspective of developing microobject-based methods to overcome microscale processes purely dominated by diffusion with potential improvements of mass trasport in microfluidic platforms. \ua9 2019 Elsevier B.V

Catalytic oxygen production mediated by smart capsules to modulate elastic turbulence under a laminar flow regime

none11Liquid flow in microchannels is completely laminar and uniaxial, with a very low Reynolds number regime and long mixing lengths. To increase fluid mixing and solubility of reactants, as well as to reduce reaction time, complex three-dimensional networks inducing chaotic advection have to be designed. Alternatively, turbulence in the liquid can be generated by active mixing methods (magnetic, acoustic waves, etc.) or adding small quantities of elastic materials to the working liquid. Here, polyelectrolyte multilayer capsules embodying a catalytic polyoxometalate complex have been suspended in an aqueous solution and used to create elastic turbulence and to propel fluids inside microchannels as an alternative to viscoelastic polymers. The overall effect is enhanced and controlled by feeding the polyoxometalate-modified capsules with hydrogen peroxide, H2O2, thus triggering an on-demand propulsion due to oxygen evolution resulting from H2O2 decomposition. The quantification of the process is done by analysing some structural parameters of motion such as speed, pressure, viscosity, and Reynolds and Weissenberg numbers, directly obtained from the capillary dynamics of the aqueous mixtures with different concentrations of H2O2. The increases in fluid speed as well as the capsule-induced turbulence effects are proportional to the H2O2 added and therefore dependent on the kinetics of H2O2 dismutation.Zizzari A.; Bianco M.; Miglietta R.; del Mercato L. L.; Carraro M.; Soraru A.; Bonchio M.; Gigli G.; Rinaldi R.; Viola I.; Arima, V.Zizzari, A.; Bianco, M.; Miglietta, R.; del Mercato, L. L.; Carraro, M.; Soraru, A.; Bonchio, M.; Gigli, Giuseppe; Rinaldi, Rosaria; Viola, I.; Arima, V

Nitric Oxide-mediated cytotoxic effect induced by zoledronic acid treatment on Human Gingival Fibroblasts

Zoledronic acid (ZA) belongs to bisphosphonates (BPs), drugs administered to treat resorptive bone diseases. Although ZA is largely used in the clinical practice, significant adverse effects of ZA, such as osteonecrosis of the jaw (ONJ), were recorded. The aim of this work was to evaluate the role of Nitric Oxide (NO) in the in vitro response of Human Gingival Fibroblasts (HGFs) to 1, 5, 10 and 100μM ZA. HGFs morphology was evaluated through phase contrast microscopy and live/ dead staining; MTT and ELISA assays were applied to measure cell viability, Collagen Type I and IL6 secretion. ROS production and mitochondrial membrane potential were evaluated by flow cytometry; NO production and NOS activity by spectrophotometric analysis; eNOS and nNOS expression by fluorescence microscopy. Viable fibroblasts are evidenced in control sample while floating dead cells and cells close to detachment phase in ZA treated sample along with decreased level of Collagen Type I. Control sample shows higher number of viable cells respect to ZA treated one and ROS production increases when ZA is added. Released NO in ZA treated sample appears higher and NO overproduction is related to increased nNOS activity. IL 6 secretion level is higher in ZA treated sample than in control one. Our results suggest ROS involvement in NO overproduction, due to nNOS recruitment, both at low and high doses. In turn, NO release seems to be able to trigger the inflammatory response only when high doses are administered

Effect of surface tension and drying time on inkjet-printed PEDOT:PSS for ITO-free OLED devices

Abstract Highly conductive PEDOT:PSS is one of the most promising materials for indium tin oxide (ITO) substitution in printed electronics. Here, we report the development and optimisation of two PEDOT:PSS ink formulations for the fabrication of inkjet-printed transparent conductive layers. Starting from aqueous commercial solutions, co-solvents and a non-ionic surfactant were employed to modify the surface tension, improve the wetting capability of the ink, and obtain uniform and homogeneous thin films. In particular, the quantities of ethanol and surfactant were systematically adjusted to determine the optimal conditions for inkjet printing. The results demonstrate that a surface tension value between 28 and 40 mN/m and approximately 40 vol.% of a low-boiling-point co-solvent are fundamental to ensure the proper wetting of the glass substrate and a quick-drying process that confers uniformity to the printed thin film. The printed PEDOT:PSS thin films show good morphological, optical, and electrical properties that are similar to those observed for the corresponding spin-coated layers. The organic light-emitting diodes (OLEDs) fabricated with the inkjet-printed PEDOT:PSS electrodes showed a maximum quantum efficiency of 5.5% and maximum current efficiency of 15 cd/A, which is comparable to spin-coated reference devices. These results demonstrate the great potential of polymeric electrodes for the fabrication of high-efficiency printed OLED devices that are compatible with flexible and stretchable substrates

Hydrophobin: fluorosurfactant-like properties without fluorine

The stabilization of fluorous oil droplets in aqueous environment is a critical issue in the preparation of emulsified systems for biomedical applications and in emulsion polymerization technology, due to the extreme immiscibility of aqueous and fluorous phases. We present here a detailed study on the behavior of the hydrophobin HFBI, i.e. a small natural protein endowed with exceptional surface activity, at the interface between aqueous and fluorous phases. HFBI behaves as an efficient and sustainable surfactant at remarkably low concentrations and forms a strong and elastic film at the interface between the two phases. We also show proof-of-concept experiments on the use of HFBI as a surfactant in fluorous oil/water emulsified systems and in microfluidic circuits. This journal is © The Royal Society of Chemistry 2013

Functional heterogeneity of POMC neurons relies on mTORC1 signaling.

Hypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release γ-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic α-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior

A systematic map of studies testing the relationship between temperature and animal reproduction

Funding: This work was funded by the European Society for Evolution (which funds a Special Topic Network on Evolutionary Ecology of Thermal Fertility Limits to CF, AB, RRS and TARP), the Natural Environment Research Council (NE/P002692/1 to TARP, AB and RRS, NE/X011550/1 to LRD and TARP), the Biotechnology and \Biological Sciences Research Council (BB/W016753/1 to AB, TARP and RRS) and a Heisenberg fellowship from the German Research Foundation (FR 2973/11-1 to CF).1. Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. 2. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). 3. Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. 4. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. 5. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.Publisher PDFPeer reviewe