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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, and its early detection can be critical for a prompt intervention that can potentially slow down the disease progression and improve the patient’s quality of life. However, a diagnosis based solely on clinical symptoms can be challenging, especially in the early stages, while the detection of specific biomarkers such as amyloid-β peptide (Aβ) and tau proteins can provide objective evidence for diagnosis. In this work, we explored the effects of Aβ peptide on cell membrane properties thanks to fluorescence lifetime imaging (FLIM) combined with the phasor analysis (FLIM-ϕ). The results showed that the membrane viscosity is altered by the presence of Aβ peptide and that cells experience this effect even at nanomolar concentrations of peptide. This considerable sensitivity opens up the possibility of envisioning a cell-based biosensor able to detect very low concentrations of Aβ in a biological fluid, thus enabling timely diagnosis and intervention.

Objectives: Little is known about the impact of patient age and biological sex on immune responses to melanoma vaccines, especially CD4+ T cell immune responses to peptides presented by Class II MHC molecules. Methods: We assessed the impact of age and sex on CD4+ T cell and antibody responses to a mixture of six melanoma helper peptides (6MHP) and on CD8+ T cell responses when vaccinating with 12 class I MHC-restricted melanoma peptides (12MP) plus either 6MHP or a tetanus helper T cell peptide (Tet). We hypothesized that immune responses would be greater in men and in younger patients. Results: We found differences in immune response by sex, but they favored female patients and were only evident for helper T cell responses to Tet with a weak trend to higher T cell responses to 12MP in female patients vaccinated with 12MP + Tet. The age-based differences favored younger patients but only for immune response to 12MP when inoculated with 12MP + Tet. Conclusions: These findings reinforce the importance of assessing sex- and age-based differences in immune responses to cancer vaccines and other immune therapies. There is also a need to understand the reasons for such differences.

After harvesting of cones used for beer production, the remaining hop vegetative biomass requires disposal. The hop plant contains bioactive compounds in all its parts—cones, leaves, and roots—exhibiting interesting antioxidant, antiviral, and antibacterial properties. In this work, extracts obtained from hop leaves, a plant material often neglected in the hop cultivation, have been investigated; the qualitative UHPLC-MS/MS and GC-TOF-MS characterization revealed the presence of bioactive compounds such as polyphenols, α- and β-acids and terpenes are present. The extract retained antioxidant activity, as verified by Folin-Ciocalteu, DPPH, ABTS and FRAP assays, and demonstrated some antimicrobial activity when combined with antibiotics, particularly against Gram-positive bacterial strains. Additionally, the extracts showed an ability to interact with proteins as human insulin, amyloid beta peptide, mucin and bovine serum albumin (BSA), has been detected, indicating their potential to counteract inflammatory processes and protect against Alzheimer's disease. These findings suggest that hop vegetative biomass, typically considered waste, can be potentially transformed into a valuable resource with applications in various fields, from nutraceuticals to pharmaceuticals and cosmetics, aligning with a circular economy perspective.

The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular environment. Many efforts have been and are devoted to the search for cosolvents and cosolutes able to interfere with amyloid aggregation. In this work, we intensively study the effect of saponins, bioactive compounds, on human insulin aggregation. To monitor the kinetic of amyloid aggregation following secondary structure changes, we perform fluorescence and UV-Visible absorption spectroscopies, using Thioflavin T and Congo Red as amyloid specific probes, and Circular Dichroism. To study the overall structural features and size of aggregates, we perform Synchrotron Small-Angle X-ray Scattering and Dynamic Light Scattering experiments. The morphology of the aggregates was assessed by Atomic Force Microscopy. To deepen the understanding of the saponins interaction with insulin, a Molecular Dynamics investigation is performed, too. The reported data demonstrate that saponins interfere with the amyloid aggregation by inducing a strong inhibition on the formation of insulin fibrils, likely through specific interactions with insulin monomers. A dose-dependent effect is evident, and amyloid inhibition is already clear when saponins are just 0.01% w/w in solution. We suggest that saponins, which are natural metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea stars and cucumbers, can be promising metabolites to inhibit human insulin aggregation. This basic research work can pave the way to further investigations concerning insulin amyloidosis, suggesting the use of saponins as amyloid inhibitors and/or stabilizing agents in solution.

By using linking and [Formula: see text]-theorems in this paper we prove the existence of multiple solutions for the following nonlocal problem with mixed Dirichlet–Neumann boundary data, (−Δ)su = λu + f(x,u)in Ω,u = 0 on Σ𝒟,∂u ∂ν = 0 on Σ𝒩, where [Formula: see text], [Formula: see text], is the spectral fractional Laplacian operator, [Formula: see text], [Formula: see text], is a smooth bounded domain, [Formula: see text] is a real parameter, [Formula: see text] is the outward normal to [Formula: see text], [Formula: see text], [Formula: see text] are smooth [Formula: see text]-dimensional submanifolds of [Formula: see text] such that [Formula: see text], [Formula: see text] and [Formula: see text] is a smooth [Formula: see text]-dimensional submanifold of [Formula: see text].

The simultaneous improvement of strength and toughness with grain refinement is widely known. However, the literature lacks studies on the grain refinement effect on cleavage fracture toughness in multiphase steels containing detrimental brittle inclusions. Understanding whether the grain refinement can effectively improve fracture toughness of such steels will allow for the improvement of their design. Therefore, a quenched and tempered S690QL high strength steel with Nb-rich and oxide inclusions was subjected to a rapid cyclic heating (RCH) treatment aimed at grain refinement, followed by quenching and tempering to produce a microstructure equivalent to the as-received steel. The microstructure was investigated via scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and electron backscatter diffraction (EBSD). The cleavage fracture toughness was measured via three-point bending tests at −100 °C. The RCH effectively reduced the prior austenite grain size by 55%. However, other microstructural changes occurred. The elongated, parallel-aligned block sub-structure of martensitic/bainitic grains changed to rounded, randomly distributed blocks. Also, the ferritic content increased and martensite and cementite clusters were formed. The concurrent effects of microstructural modifications and grain refinement explain the very minor improvements in hardness and tensile properties. The grain refinement, theoretically responsible for decreasing the ductile-to-brittle transition temperature, improved the fracture toughness up to a factor of 2.5 and 8.6 when Nb-rich and oxide inclusions trigger fracture, respectively. The microstructural changes have minor effects on fracture toughness. Therefore, the proposed RCH treatment is effective in reducing the grain size and improving cleavage fracture toughness in steels containing brittle inclusions.

We examine the semilinear resonant problem $$ -\Delta u = \lambda_1 u + \lambda g(u) \quad \text{in } \Omega,\ u\geq 0 \text{ in } \Omega, \ u_{|\partial\Omega}=0, $$ where $\Omega\subset\mathbb R^N$ is a smooth, bounded domain, $\lambda_1$ is the first eigenvalue of $-\Delta$ in $\Omega$, $\lambda>0$. Inspired by a previous result in literature involving power-type nonlinearities, we consider here a generic sublinear term $g$ and single out conditions to ensure: the existence of solutions for all $\lambda>0$; the validity of the strong maximum principle for sufficiently small $\lambda$. The proof rests upon variational arguments.

Objectives: Little is known about the impact of patient age and biological sex on immune responses to melanoma vaccines, especially CD4+ T cell immune responses to peptides presented by Class II MHC molecules. Methods: We assessed the impact of age and sex on CD4+ T cell and antibody responses to a mixture of six melanoma helper peptides (6MHP) and on CD8+ T cell responses when vaccinating with 12 class I MHC-restricted melanoma peptides (12MP) plus either 6MHP or a tetanus helper T cell peptide (Tet). We hypothesized that immune responses would be greater in men and in younger patients. Results: We found differences in immune response by sex, but they favored female patients and were only evident for helper T cell responses to Tet with a weak trend to higher T cell responses to 12MP in female patients vaccinated with 12MP + Tet. The age-based differences favored younger patients but only for immune response to 12MP when inoculated with 12MP + Tet. Conclusions: These findings reinforce the importance of assessing sex- and age-based differences in immune responses to cancer vaccines and other immune therapies. There is also a need to understand the reasons for such differences. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and its early detection can be critical for a prompt intervention that can potentially slow down the disease progression and improve the patient's quality of life. However, a diagnosis based solely on clinical symptoms can be challenging, especially in the early stages, while the detection of specific biomarkers such as amyloid-β peptide (Aβ) and tau proteins can provide objective evidence for diagnosis. In this work, we explored the effects of Aβ peptide on cell membrane properties thanks to fluorescence lifetime imaging (FLIM) combined with the phasor analysis (FLIM-ϕ). The results showed that the membrane viscosity is altered by the presence of Aβ peptide and that cells experience this effect even at nanomolar concentrations of peptide. This considerable sensitivity opens up the possibility of envisioning a cell-based biosensor able to detect very low concentrations of Aβ in a biological fluid, thus enabling timely diagnosis and intervention. [ABSTRACT FROM AUTHOR]

The misfolding and amyloid aggregation of proteins have been attracting scientific interest for a few decades, due to their link with several diseases, particularly neurodegenerative diseases. Proteins can assemble and result in insoluble aggregates that, together with intermediate oligomeric species, modify the extracellular environment. Many efforts have been and are devoted to the search for cosolvents and cosolutes able to interfere with amyloid aggregation. In this work, we intensively study the effect of saponins, bioactive compounds, on human insulin aggregation. To monitor the kinetic of amyloid aggregation following secondary structure changes, we perform fluorescence and UV-Visible absorption spectroscopies, using Thioflavin T and Congo Red as amyloid specific probes, and Circular Dichroism. To study the overall structural features and size of aggregates, we perform Synchrotron Small-Angle X-ray Scattering and Dynamic Light Scattering experiments. The morphology of the aggregates was assessed by Atomic Force Microscopy. To deepen the understanding of the saponins interaction with insulin, a Molecular Dynamics investigation is performed, too. The reported data demonstrate that saponins interfere with the amyloid aggregation by inducing a strong inhibition on the formation of insulin fibrils, likely through specific interactions with insulin monomers. A dose-dependent effect is evident, and amyloid inhibition is already clear when saponins are just 0.01% w/w in solution. We suggest that saponins, which are natural metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea stars and cucumbers, can be promising metabolites to inhibit human insulin aggregation. This basic research work can pave the way to further investigations concerning insulin amyloidosis, suggesting the use of saponins as amyloid inhibitors and/or stabilizing agents in solution. [ABSTRACT FROM AUTHOR]

In this work, an innovative and cheap electrochemical sensor for hydrogen peroxide quantification in exhaled breath was developed. H2O2 is the most used biomarker among the Reactive Oxygen Species (ROS) for monitoring the level of oxidative stress in the respiratory system. This is due to its stability and ability to cross biological membranes and also because it is detectable in extracellular space. The electrochemical sensor was obtained using the silver layer of wasted compact discs (CDs). All three electrodes, working (WE), counter (CE), and pseudo-reference electrode (RE), were fabricated using a laser cutter. The working electrode was used directly, while an Ag/AgCl paste and a graphite paste were applied respectively on the RE and the CE. In addition, a chitosan layer was deposited by Electro-Phoretic Deposition (EPD) on the surface of the sensor. This biopolymer improves the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. The sensor was tested in both liquid and nebulized solutions containing different concentrations of hydrogen peroxide. The detection of H2O2 was evaluated using Linear Sweep Voltammetry (LSV) as electrochemical technique. The results show that the peak current increases linearly with hydrogen peroxide concentration from 100 to 500 µM with a sensitivity of 0.068 µA µM-1 cm-2 and 0.108 µA µM-1 cm-2, a Limit Of Detection (LOD) of 60 µM and 30 µM respectively for liquid and nebulized solutions. Therefore, the use of the electrochemical sensor can allow the monitoring of hydrogen peroxide in real time with good results.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer that predominantly impacts White patients. Overall incidence and the proportion of minority patients with MCC are both rising. In the more common skin cancer, melanoma, racial disparities are well-documented in stage at presentation and patient survival. Whether racial and ethnic disparities exist in MCC remains unclear. The study of MCC disparities is hampered by limitations in data registries, including SEER and NCDB, and an evolving natural history due to the advent of immunotherapy. Published MCC immunotherapy clinical trials consistently reported the racial diversity among enrolled subjects but failed to include patients’ ethnicities. Efforts to improve data capture in cancer registries and create multi-institutional clinical databases will allow for more effective study of racial and ethnic disparities in rare cancers like MCC. Such studies are needed to advance policies promoting equity in care.