A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.     

Patient-Derived Organoids as a Model for Cancer Drug Discovery

In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.     

Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.     

Architected Polymer Foams via Direct Bubble Writing

Polymer foams are cellular solids composed of solid and gas phases, whose mechanical, thermal, and acoustic properties are determined by the composition, volume fraction, and connectivity of both phases. A new high‐throughput additive manufacturing method, referred to as direct bubble writing, for creating polymer foams with locally programmed bubble size, volume fraction, and connectivity is reported. Direct bubble writing relies on rapid generation and patterning of liquid shell–gas core droplets produced using a core–shell nozzle. The printed polymer foams are able to retain their overall shape, since the outer shell of these bubble droplets consist of a low‐viscosity monomer that is rapidly polymerized during the printing process. The transition between open‐ and closed‐cell foams is independently controlled by the gas used, while the foam can be tailored on‐the‐fly by adjusting the gas pressure used to produce the bubble droplets. As exemplars, homogeneous and graded polymer foams in several motifs, including 3D lattices, shells, and out‐of‐plane pillars are fabricated. Conductive composite foams with controlled stiffness for use as soft pressure sensors are also produced.     

Multimedia summarization using social media content

In this work, we propose a novel multimedia summarization technique from Online Social Networks (OSNs). In particular, we model each Multimedia Social Network (MSN)—i.e. an OSN focusing on the management and sharing of multimedia information—using an hypergraph based approach and exploit influence analysis methodologies to determine the most important multimedia objects with respect to one or more topics of interest. Successively, we obtain from the list of candidate objects a multimedia summary using a summarization model together with an heuristics that aims to generate summaries with priority (with respect to some user keywords), continuity, variety and not receptiveness features. The performed experiments on Flickr shows the effectiveness of proposed approach.     

Microstructures and mechanical behavior of Inconel 718 fabricated by selective laser melting

In this study Inconel 718 cylinders were fabricated by selective laser melting in either argon or nitrogen gas from a pre-alloyed powder. As-fabricated cylinders oriented in the build direction (z-axis) and perpendicular to the build direction (x-axis) exhibited columnar grains and arrays of γ″ (body-centered tetragonal) Ni₃Nb oblate ellipsoidal precipitates oriented in a strong [2 0 0] texture determined by combined optical metallography, transmission electron microscopy, and X-ray diffraction analysis. Fabricated and hot isostatic pressed (HIP) components exhibited a more pronounced [2 0 0] columnar γ″ phase precipitate architecture parallel to the laser beam or build direction (spaced at ∼0.8 μm), and a partially recrystallized fcc grain structure. Fabricated and annealed (1160 °C for 4 h) components were ∼50% recrystallized and the recrystallized regions contained spheroidal γ′ precipitates distributed in a dense field of fine γ″ precipitates. The γ″ precipitates were always observed to be coincident with {1 0 0} planes of the γ-fcc NiCr matrix. Some δ phase precipitates in the unrecrystallized/recrystallized interfaces and recrystallized grain boundaries were also observed in the annealed samples. The microindentation (Vickers) hardness was 3.9 GPa for the as-fabricated materials, 5.7 GPa for the HIP material, and 4.6 GPa for the annealed material. Corresponding tensile properties were comparable with wrought Inconel 718 alloy.     

Temperature Dependence of Photothermal Displacement Signal in Silicon

Abstract

This letter presents the preliminary results of a study on the dependence of photothermal displacement signal on temperature in crystalline silicon wafers and coated silicon samples. The temperature enters indirectly into the signal as thermal conductivity, specific heat and thermal expansion coefficient of the material vary with temperature. The experimental results are consistent with that theoretically expected by taking into account the dependence of thermal conductivity from dopant concentration at low temperatures.     

Heat Transfer in Water-Based SiC and TiO2 Nanofluids

The article reports the results of heat transfer experimental tests on water-based TiO₂ (9 wt%) and SiC (3, 6, 9 wt%) nanofluids. Measurements were performed in a two-loop test rig for immediate comparison of the thermal performances of the nanofluid with the base fluid. The convective heat transfer is evaluated in a circular pipe heated with uniform heat flux (from 20 to 240 kW/m²) and flow regimes from laminar to turbulent. Tests have been performed to compare the heat transfer of nanofluids and water at the same velocity (from 0.7 to 1.6 m/s) or Reynolds number (from 300 to 6000), and they have also been compared with values calculated from some of the most widely used correlations. The analysis of the experimental data shows a strong dependence on the parameter used, while both the nanofluid and water data have the same agreement with the calculated values. Nanofluids were manufactured through a two-step procedure: laser synthesis of nanoparticles followed by dispersion in water.