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Space-related stressors such as microgravity are associated with cellular and molecular alterations of the immune and inflammatory homeostasis that have been linked to the disorders that astronauts suffer from during their missions. Most of the research of the past 30 years has consistently established that innate adaptive immune cells represent a target of microgravity, which leads to their defective or dysfunctional activation, as well as to an altered ability to produce soluble mediators—e.g., cytokines/chemokines and bioactive lipids—that altogether control tissue homeostasis. Bioactive lipids include a vast array of endogenous molecules of immune origin that control the induction, intensity and outcome of the inflammatory events. However, none of the papers published so far focus on a newly characterized class of lipid mediators called specialized pro-resolving mediators (SPMs), which orchestrate the "resolution of inflammation"—i.e., the active control and confinement of the inflammatory torrent mostly driven by eicosanoids. SPMs are emerging as crucial players in those processes that avoid acute inflammation to degenerate into a chronic event. Given that SPMs, along with their metabolism and signaling, are being increasingly linked to many inflammatory disorders, their study seems of the outmost importance in the research of pathological processes involved in space-related diseases, also with the perspective of developing therapeutic countermeasures. Here, we show that microgravity, simulated in the rotary cell culture system (RCCS) developed by NASA, rearranges SPM receptors both at the gene and protein level, in human monocytes but not in lymphocytes. Moreover, RCCS treatment reduces the biosynthesis of a prominent SPM like resolvin (Rv) D1. These findings strongly suggest that not only microgravity can impair the functioning of immune cells at the level of bioactive lipids directly involved in proper inflammation, but it does so in a cell-specific manner, possibly perturbing immune homeostasis with monocytes being primary targets. [ABSTRACT FROM AUTHOR]

Calcium phosphate-based coatings are widely studied in orthopedics and dentistry for their similarity to the mineral component of bone and their capability to promote osseointegration. Different calcium phosphates have tunable properties that result in different behaviors in vitro, but the majority of studies focus only on hydroxyapatite. Here, different calcium phosphate-based nanostructured coatings are obtained by ionized jet deposition, starting with hydroxyapatite, brushite and beta-tricalcium phosphate targets. The properties of the coatings obtained from different precursors are systematically compared by assessing their composition, morphology, physical and mechanical properties, dissolution, and in vitro behavior. In addition, for the first time, depositions at high temperature are investigated for the further tuning of the coatings mechanical properties and stability. Results show that different phosphates can be deposited with good composition fidelity even if not in a crystalline phase. All coatings are nanostructured and non-cytotoxic and display variable surface roughness and wettability. Upon heating, higher adhesion and hydrophilicity are obtained as well as higher stability, resulting in better cell viability. Interestingly, different phosphates show very different in vitro behavior, with brushite being the most suitable for promoting cell viability and beta-tricalcium phosphate having a higher impact on cell morphology at the early timepoints. [ABSTRACT FROM AUTHOR]

Starting from the late 1980's, scanning probe microscopy has progressively diffused in Italy until today. In this paper, we provide a brief account of the main historical events and a current picture of the distribution of the active groups. A survey was prepared by LimeSurvey, made of six sections asking for personal and institutional data, human resources, equipment available, fields of interest, research projects, educational/dissemination activities, and two relevant publications in the last six years. It turns out that the Italian community includes more than seventy groups and two companies. It is widely diffused, although mostly concentrated near large academic and research institutions, often in locations where prominent Italian researchers have operated. This community is active in many scientific fields and can produce research of high international quality. It shows a wide competence, as proven by the list of research works published in journals ranked within the top 20% class. The diffusion of SPM microscopes in industry is still sporadic, possibly due to extensive collaborations between the research institutions and industries themselves. The authors hope that this work might be useful to the community and beyond, and that it might stimulate the formation of a more structured network. [ABSTRACT FROM AUTHOR]

Simple Summary: Platelets play a critical role in coagulation and fibrinolysis processes, but recent literature also indicates their central involvement in immune response, cancer progression and metastasis. During platelet activation, small extracellular vesicles (EVs) are released. The ascites are a fluid developing in the peritoneum of ovarian cancer patients in an advanced stage. This study analysed the expression of platelet markers GPIIb/IIIa and PF4 in small-EVs populations isolated from the ascitic fluid of patients with advanced ovarian cancer. The percentage of platelet-derived small-EVs was positively correlated with platelet distribution width to platelet count in sera (PDW/PLT), a surrogate indicator of platelet activation. Overall, we presented a method that can be helpful in future studies to determine the correlation between the extent of platelet activation in ascites and disease status. In ovarian cancer, ascites represent the microenvironment in which the platelets extravasate to play their role in the disease progression. We aimed to develop an assay to measure ascites' platelet activation. We enriched small extracellular vesicles (EVs) (40–200 nm) from ascites of high-grade epithelial ovarian cancer patients (n = 12) using precipitation with polyethylene glycol, and we conducted single-particle phenotyping analysis by nano-flow cytometry after labelling and ultra-centrifugation. Atomic force microscopy single-particle nanomechanical analysis showed heterogeneous distributions in the size of the precipitated particles and their mechanical stiffness. Samples were fluorescently labelled with antibodies specific to the platelet markers GPIIb/IIIa and PF4, showing 2.6 to 18.16% of all particles stained positive for the biomarkers and, simultaneously, the EV membrane labelling. Single-particle phenotyping analysis allowed us to quantify the total number of non-EV particles, the number of small-EVs and the number of platelet-derived small-EVs, providing a platelet activation assessment independent of the ascites volume. The percentage of platelet-derived small-EVs was positively correlated with platelet distribution width to platelet count in sera (PDW/PLT). Overall, we presented a high-throughput method that can be helpful in future studies to determine the correlation between the extent of platelet activation in ascites and disease status. [ABSTRACT FROM AUTHOR]

The squid pen (gladius) from the Loligo vulgaris was used for preparation of ß-chitin materials characterized by different chemical, micro- and nano-structural properties that preserved, almost completely the macrostructural and the mechanical ones. The ß-chitin materials obtained by alkaline treatment showed porosity, wettability and swelling that are a function of the duration of the treatment. Microscopic, spectroscopic and synchrotron X-ray diffraction techniques showed that the chemical environment of the N-acetyl groups of the ß-chitin chains changes after the thermal alkaline treatment. As a consequence, the crystalline packing of the ß-chitin is modified, due to the intercalation of water molecules between ß-chitin sheets. Potential applications of these ß-chitin materials range from the nanotechnology to the regenerative medicine. The use of gladii, which are waste products of the fishing industry, has also important environmental implications. [ABSTRACT FROM AUTHOR]

Approach and avoidance (A/A) tendencies are stable behavioral traits in responding to rewarding and fearful stimuli. They represent the superordinate division of emotion, and individual differences in such traits are associated with disease susceptibility. The neural circuitry underlying A/A traits is retained to be the cortico-limbic pathway including the amygdala, the central hub for the emotional processing. Furthermore, A/A-specific individual differences are associated with the activity of the endocannabinoid system (ECS) and especially of CB1 receptors whose density and functionality in amygdala differ according to A/A traits. ECS markedly interacts with the immune system (IS). However, how the interplay between ECS and IS is associated with A/A individual differences is still ill-defined. To fill this gap, here we analyzed the interaction between the gene expression of ECS and immune system (IS) in relation to individual differences. To unveil the deep architecture of ECS-IS interaction, we performed cell-specific transcriptomics analysis. Differential gene expression profiling, functional enrichment, and protein–protein interaction network analyses were performed in amygdala pyramidal neurons of mice showing different A/A behavioral tendencies. Several altered pro-inflammatory pathways were identified as associated with individual differences in A/A traits, indicating the chronic activation of the adaptive immune response sustained by the interplay between endocannabinoids and the IS. Furthermore, results showed that the interaction between the two systems modulates synaptic plasticity and neuronal metabolism in individual difference-specific manner. Deepening our knowledge about ECS/IS interaction may provide useful targets for treatment and prevention of psychopathology associated with A/A traits. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the most common gynecologic malignancy arising from the endometrium. Identification of serum biomarkers could be beneficial for its early diagnosis. This study compared the serum proteins of 15 patients with endometrial cancer and 15 non-cancer subjects, identifying 16 proteins with diagnostic potential. Quantification of protein expression revealed the upregulation of CLU, ITIH4, SERPINC1, and C1RL in endometrial cancer samples compared to the sera of control subjects. We built a mathematical model based on this set of proteins that detects cancer samples with excellent sensitivity and specificity levels. After a validation phase our findings support the potential to use the proposed algorithm as a diagnostic tool in the clinical stage. Endometrial cancer is the most common gynecologic malignancy arising from the endometrium. Identification of serum biomarkers could be beneficial for its early diagnosis. We have used 2D-Difference In Gel Electrophoresis (2D-DIGE) coupled with Mass Spectrometry (MS) procedures to investigate the serum proteome of 15 patients with endometrial cancer and 15 non-cancer subjects. We have identified 16 proteins with diagnostic potential, considering only spots with a fold change in %V ≥ 1.5 or ≤0.6 in intensity, which were statistically significant (p < 0.05). Western blotting data analysis confirmed the upregulation of CLU, ITIH4, SERPINC1, and C1RL in endometrial and exosome cancer sera compared to those of control subjects. The application of the logistic regression constructed based on the abundance of these four proteins separated the controls from the cancers with excellent levels of sensitivity and specificity. After a validation phase, our findings support the potential of using the proposed algorithm as a diagnostic tool in the clinical stage. [ABSTRACT FROM AUTHOR]

Since the outbreak of the COVID-19 crisis, the handling of biological samples from confirmed or suspected SARS-CoV-2-positive individuals demanded the use of inactivation protocols to ensure laboratory operators' safety. While not standardized, these practices can be roughly divided into two categories, namely heat inactivation and solvent-detergent treatments. These routine procedures should also apply to samples intended for Extracellular Vesicles (EVs) analysis. Assessing the impact of virus-inactivating pre-treatments is therefore of pivotal importance, given the well-known variability introduced by different pre-analytical steps on downstream EVs isolation and analysis. Arguably, shared guidelines on inactivation protocols tailored to best address EVs-specific requirements will be needed among the analytical community, yet deep investigations in this direction have not yet been reported. We here provide insights into SARS-CoV-2 inactivation practices to be adopted prior to serum EVs analysis by comparing solvent/detergent treatment vs. heat inactivation. Our analysis entails the evaluation of EVs recovery and purity along with biochemical, biophysical and biomolecular profiling by means of a set of complementary analytical techniques: Nanoparticle Tracking Analysis, Western Blotting, Atomic Force Microscopy, miRNA content (digital droplet PCR) and tetraspanin assessment by microarrays. Our data suggest an increase in ultracentrifugation (UC) recovery following heat treatment; however, it is accompanied by a marked enrichment in EVs-associated contaminants. On the other hand, solvent/detergent treatment is promising for small EVs (<150 nm range), yet a depletion of larger vesicular entities was detected. This work represents a first step towards the identification of optimal serum inactivation protocols targeted to EVs analysis. [ABSTRACT FROM AUTHOR]

This study proposes a climate service named Smart Climate Hydropower Tool (SCHT) and designed as a hybrid forecast system for supporting decision-making in a context of hydropower production. SCHT is technically designed to make use of information from state-of-art seasonal forecasts provided by the Copernicus Climate Data Store (CDS) combined with a range of different machine learning algorithms to perform the seasonal forecast of the accumulated inflow discharges to the reservoir of hydropower plants. The machine learning algorithms considered include support vector regression, Gaussian processes, long short-term memory, non-linear autoregressive neural networks with exogenous inputs, and a deep-learning neural networks model. Each machine learning model is trained over past decades datasets of recorded data, and forecast performances are validated and evaluated using separate test sets with reference to the historical average of discharge values and simpler multiparametric regressions. Final results are presented to the users through a user-friendly web interface developed from a tied connection with end-users in an effective co-design process. Methods are tested for forecasting the accumulated seasonal river discharges up to six months in advance for two catchments in Colombia, South America. Results indicate that the machine learning algorithms that make use of a complex and/or recurrent architecture can better simulate the temporal dynamic behaviour of the accumulated river discharge inflow to both case study reservoirs, thus rendering SCHT a useful tool in providing information for water resource managers in better planning the allocation of water resources for different users and for hydropower plant managers when negotiating power purchase contracts in competitive energy markets. [ABSTRACT FROM AUTHOR]

Supramolecular hydrogels, obtained from small organic molecules, may be advantageous over polymeric ones for several applications, because these materials have some peculiar properties that differentiate them from the traditional polymeric hydrogels, such as elasticity, thixotropy, self-healing propensity, and biocompatibility. We report here the preparation of strong supramolecular pseudopeptide-based hydrogels that owe their strength to the introduction of graphene in the gelling mixture. These materials proved to be strong, stable, thermoreversible and elastic. The concentration of the gelator, the degree of graphene doping, and the nature of the trigger are crucial to get hydrogels with the desired properties, where a high storage modulus coexists with a good thixotropic behavior. Finally, NIH-3T3 cells were used to evaluate the cell response to the presence of the most promising hydrogels. The hydrogels biocompatibility remains good, if a small degree of graphene doping is introduced. [ABSTRACT FROM AUTHOR]

The high hydrophobicity of fullerenes and the resulting formation of aggregates in aqueous solutions hamper the possibility of their exploitation in many technological applications. Noncovalent bioconjugation of fullerenes with proteins is an emerging approach for their dispersion in aqueous media. Contrary to covalent functionalization, bioconjugation preserves the physicochemical properties of the carbon nanostructure. The unique photophysical and photochemical properties of fullerenes are then fully accessible for applications in nanomedicine, sensoristic, biocatalysis and materials science fields. However, proteins are not universal carriers. Their stability depends on the biological conditions for which they have evolved. Here we present two model systems based on pepsin and trypsin. These proteins have opposite net charge at physiological pH. They recognize and disperse C60 in water. UV-Vis spectroscopy, zeta-potential and atomic force microscopy analysis demonstrates that the hybrids are well dispersed and stable in a wide range of pH’s and ionic strengths. A previously validated modelling approach identifies the protein-binding pocket involved in the interaction with C60. Computational predictions, combined with experimental investigations, provide powerful tools to design tailor-made C60@proteins bioconjugates for specific applications. [ABSTRACT FROM AUTHOR]

The squid pen (gladius) from the Loligo vulgaris was used for preparation of β-chitin materials characterized by different chemical, micro- and nano-structural properties that preserved, almost completely the macrostructural and the mechanical ones. The β-chitin materials obtained by alkaline treatment showed porosity, wettability and swelling that are a function of the duration of the treatment. Microscopic, spectroscopic and synchrotron X-ray diffraction techniques showed that the chemical environment of the N-acetyl groups of the β-chitin chains changes after the thermal alkaline treatment. As a consequence, the crystalline packing of the β-chitin is modified, due to the intercalation of water molecules between β-chitin sheets. Potential applications of these β-chitin materials range from the nanotechnology to the regenerative medicine. The use of gladii, which are waste products of the fishing industry, has also important environmental implications.