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We study the dynamics of an active gel droplet with imposed orientational anchoring (normal or planar) at its surface. We find that if the activity is large enough droplets subject to strong anchoring spontaneously start to rotate, with the sense of rotation randomly selected by fluctuations. Contractile droplets rotate only for planar anchoring and extensile ones only for normal anchoring. This is because such a combination leads to a pair of stable elastic deformations which creates an active torque to power the rotation. Interestingly, under these conditions there is a conflict between the anchoring promoted thermodynamically and that favoured by activity. By tuning activity and anchoring strength, we find a wealth of qualitatively different droplet morphologies and spatiotemporal patterns, encompassing steady rotations, oscillations, and more irregular trajectories. The spontaneous rotations we observe are fundamentally different from previously reported instances of rotating defects in active fluids as they require the presence of strong enough anchoring and entail significant droplet shape deformations.

This study is funded by Portuguese national funds provided by Fundação para a Ciência e Tecnologia (FCT) UI/05704/2020, PTDC/SAU-NUT/3321/2020, and FCT202008719BD. MPG was funded by CEECINST/00051/2018.

BackgroundInhibiting programmed cell death protein 1 (PD-1) or PD-ligand 1 (PD-L1) has shown exciting clinical outcomes in diverse human cancers. So far, only monoclonal antibodies are approved as PD-1/PD-L1 inhibitors. While significant clinical outcomes are observed on patients who respond to these therapeutics, a large proportion of the patients do not benefit from the currently available immune checkpoint inhibitors, which strongly emphasize the importance of developing new immunotherapeutic agents.MethodsIn this study, we followed a transdisciplinary approach to discover novel small molecules that can modulate PD-1/PD-L1 interaction. To that end, we employed in silico analyses combined with in vitro, ex vivo, and in vivo experimental studies to assess the ability of novel compounds to modulate PD-1/PD-L1 interaction and enhance T-cell function.ResultsAccordingly, in this study we report the identification of novel small molecules, which like anti-PD-L1/PD-1 antibodies, can stimulate human adaptive immune responses. Unlike these biological compounds, our newly-identified small molecules enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy.ConclusionsWe identified a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment.

Skin is one of the organs most tested for toxicity and safety evaluation during the process of drug research and development and in the past has usually been performed in vivo using animals. Over the last few years, non-animal alternatives have been developed and validated epidermis models for human and rat skin are already available. Our goal was to develop a histotypical canine skin analog, suitable for non-animal biocompatibility and biosafety assessment. Canine keratinocytes were seeded in an air-lift culture using an adapted version of the CELLnTEC protocol. Corrosion and irritation protocols were adapted from human EpiSkinTM. For histological analysis, sample biopsies were fixed in neutral-buffered formalin, and paraffin slices were routinely processed and stained with hematoxylin and eosin. A canine multilayer and stratified epidermal-like tissue (cEpiderm), confirmed by histological analysis, was obtained. The cEpiderm tissue exhibited normal morphological and functional characteristics of epidermis, namely impermeability and an adequate response to stressors. The cEpiderm is a promising canine skin model for non-animal safety testing of veterinary pharmaceuticals and/or cosmetics, significantly contributing to reducing undesirable in vivo approaches. cEpiderm is therefore a valid canine skin model and may be made commercially available either as a service or as a product.

Fil: Di Bitetti, Mario Santiago. Centro de Investigaciones del Bosque Atlántico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; Argentina

Bovine mastitis is one of the most significant problems in intensive dairy systems because it causes substantial reductions in milk quantity and quality and increases production costs. The disease is characterised by infection and inflammation of the mammary gland caused by one of several potential pathogens. Although antibiotic therapy is currently the most common treatment for mastitis, the presence of antibiotic residues in milk from treated cattle and the emergence of resistant bacteria have led researchers to seek alternative strategies to prevent and eliminate udder infections. Various combinations of intramammary and systemic treatments or extended lengths of therapy have resulted in successful treatment rates ranging from 0 to 80%. These data highlight the need for alternative control measures. This paper provides a comprehensive overview of the major studies that have examined potential vaccines against pathogens that cause mastitis and discusses the benefits and challenges of each type of vaccine.

The confinement of liquid crystals inside curved geometries leads to exotic structures, with applications ranging from bio-sensors to optical switches and privacy windows. Here we study how curvature affects the alignment of a cholesteric liquid crystal. We model the system on the mesoscale using the Landau-de Gennes model. Our study was performed in three stages, analysing different curved geometries from cylindrical walls and pores, to toroidal domains, in order to isolate the curvature effects. Our results show that the stresses introduced by the curvature influence the orientation of the liquid crystal molecules, and cause distortions in the natural periodicity of the cholesteric that depend on the radius of curvature and on the commensurability between the pitch and the dimensions of the system. In particular, the cholesteric layers of toroidal droplets exhibit a symmetry breaking not seen in cylindrical pores and that is driven by the additional curvature.