FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.

Unraveling the mark of surface defects on a spinterface： The nitronyl nitroxide/TiO2（110） interface

Metal-free organic radicals are fascinating materials owing to their unique properties. Having a stable magnetic moment coupled to light elements makes these materials central to develop a large variety of applications. We investigated the magnetic spinterface coupling between the surface of a single rutile TiO2（110） crystal and a pyrene-based nitronyl nitroxide radical, using a combination of thickness-dependent X-ray photoelectron spectroscopy and ab initio calculations. The radicals were physisorbed, and their magnetic character was preserved on the （almost） ideal surface. The situation changed completely when the molecules interacted with a surface defect site upon adsorption. In this case, the reactivity of the defect site led to the quenching of the molecular magnetic moment. Our work elucidates the crucial role played by the surface defects and demonstrates that photoemission spectroscopy combined with density functional theory calculations can be used to shed light on the mechanisms governing complex interfaces, such as those between magnetic molecules and metal oxides.

Liquid flow in scaffold derived from natural source:experimental observations and biological outcome

This study investigates the biological effects on a 3D scaffold based on hydroxyapatite cultured with MC3T3 osteoblasts in response to flow-induced shear stress(FSS).The scaffold adopted here(B-HA)derives from the biomorphic transformation of natural wood and its peculiar channel geometry mimics the porous structure of the bone.From the point of view of fluid dynamics,B-HA can be considered a network of micro-channels,intrinsically offering the advantages of a microfluidic system.This work,for the first time,offers a description of the fluid dynamic properties of the B-HA scaffold,which are strongly connected to its morphology.These features are necessary to determine the FSS ranges to be applied during in vitro studies to get physiologically relevant conditions.The selected ranges of FSS promoted the elongation of the attached cells along the flow direction and early osteogenic cell differentiation.These data confirmed the ability of B-HA to promote the differentiation process along osteogenic lineage.Hence,such a bioactive and naturally derived scaffold can be considered as a promising tool for bone regeneration applications.

Angle-tunable intersubband photoabsorption and enhanced photobleaching in twisted bilayer graphene

Van der Waals heterostructures obtained by artificially stacking two-dimensional crystals represent the frontier of material engineering,demonstrating properties superior to those of the starting materials.Fine control of the interlayer twist angle has opened new possibilities for tailoring the optoelectronic properties of these heterostructures.Twisted bilayer graphene with a strong interlayer coupling is a prototype of twisted heterostructure inheriting the intriguing electronic properties of graphene.Understanding the effects of the twist angle on its out-of-equilibrium optical properties is crucial for devising optoelectronic applications.With this aim,we here combine excitation-resolved hot photoluminescence with femtosecond transient absorption microscopy.The hot charge carrier distribution induced by photo-excitation results in peaked absorption bleaching and photo-induced absorption bands,both with pronounced twist angle dependence.Theoretical simulations of the electronic band structure and of the joint density of states enable to assign these bands to the blocking of interband transitions at the van Hove singularities and to photo-activated intersubband transitions.The tens of picoseconds relaxation dynamics of the observed bands is attributed to the angle-dependence of electron and phonon heat capacities of twisted bilayer graphene.