There is no degree map for 0-cycles on Artin stacks

We show that there is no way to define degrees of 0-cycles on Artin stacks with proper good moduli spaces so that (i) the degree of an ordinary point is non-zero, and (ii) degrees are compatible with closed immersions.Comment: 3 page

Mechanical Systems: Symmetry and Reduction

Reduction theory is concerned with mechanical systems with symmetries. It constructs a lower dimensional reduced space in which associated conservation laws are taken out and symmetries are \factored out" and studies the relation between the dynamics of the given system with the dynamics on the reduced space. This subject is important in many areas, such as stability of relative equilibria, geometric phases and integrable systems

Adsorption of NGF and BDNF derived peptides on gold surfaces

This study tackles the interaction between gold surfaces and two peptide fragments named NGF(1-14) and BDNF(1-12), able to mimic the proliferative activity of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), respectively. The physical adsorption processes at the solid surface from both single and binary peptide solutions, at physiological and acid pH, were investigated by QCM-D and CD experiments, as well as by molecular dynamics calculations. The relevant physicochemical properties at the hybrid bio-interface, including peptide-surface interaction, conformational changes, hydrodynamic thickness, viscoelastic parameters, competitive vs. synergic behaviour of the two peptide fragments towards the surface were scrutinized. Biological assays with neuronal cells pointed to the maintenance in the biological activity of NGF(1-14) and BDNF(1-12) peptide molecules within the adlayers on the gold surface

A simple approach for CTAB-free and biofunctionalized gold nanorods to construct photothermal active nanomedicine for potential in vivo applications in cancer cells and scar treatment

Cetyltrimethylammonium bromide (CTAB), a surfactant commonly used in the synthesis of gold nanorods (AuNR), presents challenges owing to cytotoxicity in biological applications, limiting their biomedical applicability, particularly in cancer therapy. This study introduces a straightforward methodology for the effective removal of CTAB by utilizing a combination of ligand replacement and surface bioconjugation processes that efficiently eliminates CTAB and simultaneously functionalizes nanorods with hyaluronic acid (HA) to enhance biocompatibility and introduce targeting capabilities toward cancer cells. The surface chemistry modification of CTAB-capped and CTAB-free AuNR, before and after the functionalization with HA, was scrutinized by UV–visible, surface-enhanced Raman scattering (SERS), attenuated total reflectance (ATR) Fourier-transform infrared (FTIR), and X-ray photoelectron (XPS) spectroscopies. The surface charge, size, and morphology of the different plasmonic nanoparticles were characterized by zeta potential, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The photothermal response was assessed by laser irradiation and thermal camera measurements. Proof-of-work in vitro cellular experiments of cytotoxicity and oxidative stress were carried out on prostate cancer cells, PC-3, overexpressing the CD44 cell surface receptor specifically recognized by HA, in comparison with the CD44-negative murine fibroblasts (3T3 cell line) by MTT and MitoSOX assays, respectively. Cellular uptake and organelle alteration were scrutinized by confocal laser scanning microscopy (LSM), while the perturbative effects on cell migration were studied by optical microscopy (wound scratch assay). The study’s findings offer a promising pathway to tune the gold nanorod properties in cancer treatment by reducing cytotoxicity and enhancing targeted therapeutic efficacy, as well as in the control of scar tissue formation

Agmatine prevents the Ca2+-dependent induction of permeability transition in rat brain mitochondria

The arginine metabolite agmatine is able to protect brain mitochondria against the drop in energy capacity by the Ca(2+)-dependent induction of permeability transition (MPT) in rat brain mitochondria. At normal levels, the amine maintains the respiratory control index and ADP/O ratio and prevents mitochondrial colloid-osmotic swelling and any electrical potential (DeltaPsi) drop. MPT is due to oxidative stress induced by the interaction of Ca(2+) with the mitochondrial membrane, leading to the production of hydrogen peroxide and, subsequently, other reactive oxygen species (ROS) such as hydroxyl radicals. This production of ROS induces oxidation of sulfhydryl groups, in particular those of two critical cysteines, most probably located on adenine nucleotide translocase, and also oxidation of pyridine nucleotides, resulting in transition pore opening. The protective effect of agmatine is attributable to a scavenging effect on the most toxic ROS, i.e., the hydroxyl radical, thus preventing oxidative stress and consequent bioenergetic collapse

Neuroprotective Effect of a Nutritional Supplement Containing Spearmint Extract, Forskolin, Homotaurine and Group B Vitamins in a Mouse Model of Transient Ocular Hypertension

Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management of glaucoma remains a challenge. The aim of this study was to evaluate the neuroprotective, IOP-lowering independent effects of a nutritional supplement containing forskolin, homotaurine, spearmint extract and vitamins of the B group in a model of acute glaucoma developed in mice. Glaucoma was induced in adult wild-type C57BL/6J mice by transient elevation of IOP. The dietary supplement, branded as Gangliomix® (125 mg/kg/day), was administered by oral gavage for 17 days and ocular hypertension was induced on the 10th day of treatment. A histological analysis of the retinas was performed and RGC survival was evaluated with fluorogold labeling and Brn3a immunostaining on wholemount and retinal sections. Expression of alpha-spectrin, caspase-3, PARP-1 and GFAP was studied with western blotting or immunofluorescence. A significant increase in RGC survival was reported in the retina of mice treated with the dietary supplement as compared to vehicle-treated animals. The observed neuroprotection was associated with a calpain activity decrease, reduction in caspase-3 and PARP-1 activation, and prevention of GFAP upregulation. These effects were independent from the hypotensive effects of the supplement. Altogether, our data suggest that the dietary supplementation with forskolin, homotaurine, spearmint extract and vitamins of the B group supports RGC survival and may offer beneficial effects in glaucoma patients in combination with the currently used IOP-lowering therapy

Modeling and multi-temporal characterization of total suspended matter by the combined use of sentinel 2-MSI and landsat 8-OLI Data: The Pertusillo lake case study (Italy)

The total suspended matter (TSM) variability plays a crucial role in a lake's ecological functioning and its biogeochemical cycle. Sentinel-2A MultiSpectral Instrument (MSI) and Landsat 8 Operational Land Instrument (OLI) data offer unique opportunities for investigating certain in-water constituents (e.g., TSM and chlorophyll-a) owing to their spatial resolution (10-60 m). In this framework, we assessed the potential of MSI-OLI combined data in characterizing the multi-temporal (2014-2018) TSM variability in Pertusillo Lake (Basilicata region, Southern Italy). We developed and validated a customized MSI-based TSM model (R2 = 0.81) by exploiting ground measurements acquired during specific measurement campaigns. The model was then exported as OLI data through an intercalibration procedure (R2 = 0.87), allowing for the generation of a TSM multi-temporal MSI-OLI merged dataset. The analysis of the derived multi-year TSM monthly maps showed the influence of hydrological factors on the TSM seasonal dynamics over two sub-regions of the lake, the west and east areas. The western side is more influenced by inflowing rivers and water level fluctuations, the effects of which tend to longitudinally decrease, leading to less sediment within the eastern sub-area. The achieved results can be exploited by regional authorities for better management of inland water quality and monitoring systems

Mpeg-plga nanoparticles labelled with loaded or conjugated rhodamine-b for potential nose-to-brain delivery

Nowdays, neurodegenerative diseases represent a great challenge from both the therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body, including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between the development of new drugs and their effective administration to reach the target organ or target cells at therapeutic concentrations. Currently, the nose-to-brain delivery with nanoformulations specifically designed for intranasal administration is a strategy widely investigated with the goal to reach the brain while bypassing the BBB. To produce nanosystems suitable to study both in vitro and/or in vivo cells trafficking for potential nose-to-brain delivery route, we prepared and characterized two types of fluorescent poly(ethylene glycol)-methyl-ether-block-poly(lactide-co-glycolide) (PLGA\u2013PEG) nanoparticles (PNPs), i.e., Rhodamine B (RhB) dye loaded-and grafted-PNPs, respectively. The latter were produced by blending into the PLGA\u2013PEG matrix a RhB-labeled polyaspartamide/polylactide graft copolymer to ensure a stable fluorescence during the time of analysis. Photon correlation spectroscopy (PCS), UV-visible (UV-vis) spectroscopies, differential scanning calorimetry (DSC), atomic force microscopy (AFM) were used to characterize the RhB-loaded and RhB-grafted PNPs. To assess their potential use for brain targeting, cytotoxicity tests were carried out on olfactory ensheathing cells (OECs) and neuron-like differentiated PC12 cells. Both PNP types showed mean sizes suitable for nose-to-brain delivery (<200 nm, PDI < 0.3) and were not cytotoxic toward OECs in the concentration range tested, while a reduction in the viability on PC12 cells was found when higher concentrations of nanomedicines were used. Both the RhB-labelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies

Anti-angiogenic and anti-proliferative graphene oxide nanosheets for tumor cell therapy

Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)4-NH2 peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE2) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy

Culture-based antibiotic susceptibility testing for Helicobacter pylori infection: a systematic review

Background Primary antibiotic resistance in Helicobacter pylori (H. pylori) strains is increasing worldwide, affecting therapy success. The use of therapies tailored on susceptibility pre-testing at culture has been proposed, but data are still conflicting. Method We performed a systematic review to evaluate the role of a culture-based therapeutic approach for H. pylori treatment, taking into account the sensitivity of culture and the success rates achieved with tailored therapies in different therapeutic steps. Results We analyzed data from 51 studies. Overall, H. pylori strains were isolated in 80.7% of 7889 patients, the success rates being 78.1%, 77.5%, 86.3% and 86.6%, before first-, second-, third-line or more therapies, respectively. In comparative studies, the infection was cured in 89.9% of 2052 patients treated with tailored therapies, and in 77.6% of 2516 patients receiving empiric therapy (P<0.001). However, in the subanalysis, the tailored approach achieved optimal eradication rates (>90%) only when it was applied before first-and second-line therapies, but not before third-line or more attempts (<80%). Moreover, no significant difference emerged between the 2 approaches when data from only the most recent (last 5 years) studies were considered, as well as in those performed in Western populations. Conclusions The attempt to achieve antibiotic susceptibility testing before treatment failed in 20% of infected patients managed in dedicated laboratories. Culture-tailored therapies administered after 2 or more therapies achieved suboptimal eradication rates. The role of bacterial culture in patients whose therapeutic management failed to eradicate H. pylori probably needs to be corroborated by further data