Pubblicazioni di eccellente qualità dei ricercatori del Dipartimento SIMAU, anno 2020 – SECONDO SEMESTRE

P. Astolfi, M. Pisani, E. Giorgini, B. rossi, A. Damin, F. Vita, O. Francescangeli, L. Luciani, R. Galassi, “Synchrotron Characterization of Hexagonal and Cubic Lipidic Phases Loaded with Azolate/Phosphane Gold(I) Compounds: A New Approach to the Uploading of Gold(I)-Based Drugs”, Nanomaterials, 10 (9), 2020, 1851
Abstract:  Gold(I) phosphane compounds have recently attracted a renewed interest as potential new protagonists in cancer therapy. A class of phosphane gold(I) complexes containing azolate ligands has been successfully tested against several cancer cell lines and, in particular, against basal-like breast (BLB) cancer, a form characterized by strongly severe diagnosis and short life lapse after classic chemotherapy. Even though the anticancer activity of gold(I) phosphane compounds is thoroughly ascertained, no study has been devoted to the possibility of their delivery in nanovectors. Herein, nonlamellar lyotropic liquid crystalline lipid nanosystems, a promising class of smart materials, have been used to encapsulate gold(I) azolate/phosphane complexes. In particular, ((triphenylphosphine)-gold(I)-(4,5-dichloroimidazolyl-1H-1yl)) (C-I) and ((triphenylphosphine)-gold(I)-(4,5-dicyanoimidazolyl-1H-1yl)) (C-II) have been encapsulated in three different lipid matrices: monoolein (GMO), phytantriol (PHYT) and dioleoyl-phosphatidylethanolamine (DOPE). An integrated experimental approach involving X-ray diffraction and UV resonant Raman (UVRR) spectroscopy, based on synchrotron light and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, has been employed to establish the effects of drug encapsulation on the structure and phase behavior of the host mesophases. The results indicate that gold(I) complexes C-I and C-II are successfully encapsulated in the three lipid matrices as evidenced by the drug-induced phase transitions or by the changes in the mesophase lattice parameters observed in X-ray diffraction experiments and by the spectral changes occurring in UV resonant Raman spectra upon loading the lipid matrices with C-I and C-II.
C. Sbarbati, M. Barbieri, A. Barron, B. Bostick, N. Colombani, M. Mastrocicco, H. Prommer, S. Passaretti, Y. Zheng, M. Petitta Redox dependent arsenic occurrence and partitioning in an industrial coastal aquifer: Evidence from high spatial resolution characterization of groundwater and sediments”, Water 12(10) (October), 2020, 2932
Abstract:  Superlative levels of arsenic (As) in groundwater and sediment often result from industrial pollution, as is the case for a coastal aquifer in Southern Italy, with a fertilizer plant atop. Understanding conditions under which As is mobilized from the sediments, the source of that As, is necessary for developing effective remediation plans. Here, we examine hydrogeological and geochemical factors that affect groundwater As concentrations in a contaminated coastal aquifer. Groundwater has been subject to pump-and-treat at a massive scale for more than 15 years and is still ongoing. Nevertheless, As concentrations (0.01 to 100 mg/L) that are four orders of magnitude more than Italian drinking water standard of 10 µg/L are still present in groundwater collected from about 50 monitoring wells over three years (2011, 2016, and 2018). As was quantified in three different locations by sequential extractions of 29 sediment cores in 2018 (depth 2.5 m to −16.5 m b.g.l.), combined with groundwater As composition, the aqueous and solid partitioning of As were evaluated by partition coefficient (Kd) in order to infer the evolution of the contaminant plumes. Most sediment As is found in easily extractable and/or adsorbed on amorphous iron oxides/hydroxides fractions based on sequential extractions. The study shows that As contamination persists, even after many years of active remediation due to the partitioning to sediment solids. This implies that the choice of remediation techniques requires an improved understanding of the biogeochemical As-cycling and high spatial resolution characterization of both aqueous and solid phases for sites of interest.
M. Di Sante, “On the Compaction Characteristics of Soil-Lime Mixtures”, Geotechnical and Geological Engineering, 38(2), 2020,  2335–2344
Abstract:  Aim of the present note is to contribute to the optimization of the mix-design procedure of lime treated soils with particular reference to compaction characteristics. Seven soils with different plasticity characteristics and clay fractions are included in the experimental program, different amounts of quicklime and hydrated lime were added to the soils by wet mixing and then Standard Proctor compaction was carried out at different water contents in order to study the effect of lime treatment on compaction characteristics. Microstructural investigation was developed by means of scanning electron microscope. A general decrease in the maximum dry unit weight was observed together with a flattening of the Proctor curve. Also optimum water content changes due to lime addition. A factor that takes into account these modifications was defined and compared for several mix designs. Good correlations (confirmed by Fisher’s statistical test) between this factor and clay fractions of the soil to be treated were derived for 5% hydrated lime added. In addition, useful directions were retrieved analysing experimental results for soils treated with different types of lime in different proportions. Results contribute to have a preliminary idea of the effective mix design parameters, knowing the soil to be treated, helping, in this way, in possibly reducing the number of tests in the design phase.
L. Massaccesi, E. Laudadio, G. Mobbili, C. Minnelli, R. Galeazzi. “Cholesterol-mediated oligomerization pathways of serotonin G-coupled receptor 5-HT2C”, International Journal of Biological Macromolecules, 160 (October), 2020, 1090-1100
Abstract:  Serotonin (5-HT) receptors have been shown to homodimerize and heterodimerize with other G protein-coupled receptors (GPCRs), although the details of this process have not yet been elucidated. Here we use coarse-grained molecular dynamics on monomeric 5-HT2C receptors to predict the transmembrane (TM) helices involved in such associations. All these simulations were carried out both in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers and in mixed composition POPC-Cholesterol ones, to show whether the presence of cholesterol could directly influence and drive the dimeric association. The goal is to get insights on the self-assembly pathway leading to GPCRs 5-HT2C oligomerization, which is supposed to be the basis of its constitutional activity. From the analysis of the molecular dynamics trajectories, we observed the formation of 5-HT2C oligomers through self-assembly and we identified the main domains involved in the receptor dimerization. In particular, dimers and oligomers from the two different environments show TM4-TM5 and TM1-TM7-H8 as the preferential dimerization interfaces. Nevertheless, substantial differences arise for oligomers in POPC and in POPC-Chol membranes: in POPC-Chol the variability of dimers interfaces is strictly limited to the TM1-TM7-H8 and TM4-TM5 interfaces and the dimorphism depends on cholesterol that directly participates in its formation. These results are in agreement with both experimental evidences and other computational studies conducted on other GPCRs oligomerization.
L. Lucchetti, T. P. Fraccia, G. Nava, T. Turiv, F. Ciciulla, L. Bethge, S. Klussmann, O. D. Lavrentovich, and T. Bellini “Elasticity and Viscosity of DNA Liquid Crystals”, ACS Macroletters, 9 (June) , 2020,  1034-1039
Abstract:  Concentrated solutions of blunt-ended DNA oligomer duplexes self-assemble in living polymers and order into lyotropic nematic liquid crystal phase. Using the optical torque provided by three distinct illumination geometries, we induce independent splay, twist, and bend deformations of the DNA nematic and measure the corresponding elastic coefficients K1, K2, and K3, and viscosities ηsplay, ηtwist, and ηbend. We find the viscoelasticity of the system to be remarkably soft, as the viscoelastic coefficients are smaller than in other lyotropic liquid crystals. We find K1 > K3 > K2, in agreement with the elasticity of the nematic phase of flexible polymers, and ηbend > ηsplay > ηtwist a behavior that is nonconventional in the context of chromonic, polymeric, and thermotropic liquid crystals, indicating a possible role of the weakness and reversibility of the DNA aggregates.
Bruno Giovani, De Stefani Alberto, Caragiuli Manila, Zalunardo Francesca, Mazzoli Alida, Landi Daniele, Mandolini Marco, Gracco Antonio. "Comparison of the effects caused by three different mandibular advancement devices on the periodontal ligaments and teeth for the treatment of OSA: A finite element model study". Applied Sciences (Switzerland) 10(19), 1 October 2020, pp. 1-13
Abstract:  AIM: The purpose of this study is to compare the stress effects developed on the periodontal ligaments and teeth by three different types of mandibular advancement devices (MADs) using a finite element method (FEM) analysis. Introduction: Obstructive sleep apnea (OSA) is a disease with a high prevalence and, in recent years, the use of MADs as an alternative or support treatment to the continuous positive airway pressure (CPAP) has spread. Their use finds relative contraindications in the case of partial edentulism and severe periodontal disease. Given the widespread of periodontal problems, it is essential to know the effects that these devices cause on the periodontal ligament of the teeth. Materials and methods: Starting from the computed tomography (CT) scan of a patient’s skull, 3D reconstructions of the maxilla and mandible were implemented. Three different MADs were prepared for the patient, then 3D scanned, and lastly, coupled with the 3D models of the jaws. The devices have two different mechanics: One has a front reverse connecting rod (Orthoapnea™), and two have lateral propulsion (Somnodent™ and Herbst™). A FEM analysis was performed to calculate the stress applied on periodontal ligaments, on every single tooth and the displacement vectors that are generated by applying an advancement force on the mandible. Results: Herbst™ and Somnodent™ devices present very similar stress values, mainly concentrated on lateral teeth, but in general, the forces are very mild and distributed. The maximum stresses values are 3.27 kPa on periodontal ligaments and 287 kPa on teeth for Somnodent™ and 3.56 kPa on periodontal ligaments and 302 kPa on teeth for Herbst™. Orthoapnea™ has, instead, higher and concentrated stress values, especially in the anterior maxillary and mandibular area with 4.26 kPa and 600 kPa as maximum stress values, respectively, on periodontal ligaments and teeth. Conclusions: From the results, it is concluded that devices with a bilateral mechanism generate less and more distributed stress than an anterior connecting rod mechanism. Therefore, they may be advisable to patients with compromised periodontal conditions in the anterior area.
P.P. Natali, L. Montalto, L. Scalise, F. Davì, N. Paone, D. Rinaldi, “Fringe modelling and Photoelastic stress Measurement method in tetragonal PWO observed in the plane normal to a crystallographic a-axis”, Journal Of Instrumentation, 15, (September n 9), 2020,  09037-09056
Abstract:  Scintillator crystals like the tetragonal PbWO4 (PWO) are largely used in calorimeters, for instance the CMS at CERN and in the PANDA calorimeter project. The performances of those calorimeters are directly linked to crystals homogeneity and quality, which can be assessed using indicators such as residual stress state condition. Since it is fundamental to develop and refine new mathematical models for the structural characterization and stress analysis of the crystalline materials, in this paper we present a novel approach aimed at the evaluation of stress or defect distribution and inhomogeneity, by analysing images obtained with photoelastic conoscopic system. A new model is proposed for the correct mathematical interpretation of the fringe pattern obtained by investigating the crystal in direction orthogonal to the uniaxial optical axis and parallel to the crystallographic a-axis. The model will be validated against experimentally acquired fringe patterns. A comparison with a simplified procedure, which operatively, reduces the computational effort, will be detailed. After a complete description of the fringe pattern, a linearized model is proposed in such a way that we obtain a simple stress intensity evaluation via experimentally easy measurable parameters, thus realizing a model based measurement of stress state. The results make the proposed procedure reliable, and useful also for other crystals symmetries.
V. Notarstefano, S. Sabbatini, C. Pro, A. Belloni, G. Orilisi, C. Rubini, H. J. Byrne, L. Vaccari, E. Giorgini “Exploiting fourier transform infrared and Raman microspectroscopies on cancer stem cells from oral squamous cells carcinoma: new evidence of acquired cisplatin chemoresistance”, Analyst, 145, (October), 2020, 8038-8049
Abstract:  Oral Squamous Cells Carcinoma (OSCC) is characterised by the risk of recurrence and the onset of a refractoriness response to chemotherapy drugs. These phenomena have been recently related to a subpopulation of Cancer Stem Cells (CSCs), which have either an innate or acquired drug resistance, triggered by chemotherapy treatments. In this light, to precisely target chemotherapy regimens, it is essential to improve knowledge on CSCs, with a particular focus on their molecular features. In this work, a subpopulation of CSCs, isolated by tumour sphere formation from primary OSCC cells, were treated with cisplatin for 16, 24 and 48 hours and analysed by infrared absorption and Raman microspectroscopies. CSC spectral data were compared with those obtained in previous work, for primary OSCC cells treated under the same conditions. Routine viability/apoptosis cell-based assays evidenced in CSCs and primary OSCCs, a similar degree of sensitivity to the drug at 24 hours, while a reversion of the conventional monotonic time response exhibited by OSCCs was shown by CSCs at 48 hours. This peculiar time response was also supported by the analysis of IR and Raman data, which pinpointed alterations in the lipid composition and DNA conformation in CSCs. The results obtained suggest that CSCs, although sharing with OSCC cells a similar sensitivity to cisplatin, display the onset of a mechanism of chemoresistance and enrichment of resistant CSCs as a result of drug treatment, shedding new light on the severe issue of refractoriness of some patients to chemotherapy conventionally used for OSCC.
P. Ruggeri, V.M.E. Fruzzetti, G. Scarpelli “The Behavior of a Thread-Bar Grouted Anchor in Soils from Local Strain Monitoring”, Applied Sciences, 10 (20), 2020, pp. 1–11.  Open Access
Abstract:  International standards discourage the use of grouted anchors with a fixed length exceeding 10 m. However, grouted anchors with a fixed length between 10 and 20 m are frequently used in Italy to transfer high loads to ground with poor geotechnical properties. This paper presents the results of investigation tests on an anchor with a length of 36 m, of which 18 m is fixed, sloping 40◦ from the horizontal; the anchor is comprised of a reinforced thread-bar which was instrumented with strain gauges and founded in nonhomogeneous ground, a sand deposit followed by marly clay. The test aimed at investigating the progressive mobilization of the shear strength along the foundation. The results indicate a very low shear strength offered by the sand, probably disturbed by the drilling, and an unusually fast mobilization of the shear strength in the marly clay at the deep end of the anchor. The results are particularly useful to identify the reasons for the observed poor performance of the grouted anchor. In particular, the study once again made it clear how important the influence of the execution details on reaching the expected load capacity may be, and likewise the practice of investigation tests on suitably instrumented test anchors.
Vernon, Tebong Mbah; Pertici, Vincent; Lacroix, Céline; Verrier, Bernard; Stipa, Pierluigi; Gigmes, Didier; Trimaille, Thomas, “A Sacrificial PLA Block Mediated Route to Injectable and Degradable PNIPAAm-Based Hydrogels”, POLYMERS, 2020, 12, 925 (Published: 16 April 2020)
Abstract:  Thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)-based injectable hydrogels represent highly attractive materials in tissue engineering and drug/vaccine delivery but face the problem of long-term bioaccumulation due to non-degradability. In this context, we developed an amphiphilic poly(D,L-lactide)-b-poly(NIPAAm-co-polyethylene glycol methacrylate) (PLA-b- P(NIPAAm-co-PEGMA)) copolymer architecture, through a combination of ring-opening and nitroxide-mediated polymerizations, undergoing gelation in aqueous solution near 30 °C. Complete hydrogel mass loss was observed under physiological conditions after few days upon PLA hydrolysis. This was due to the inability of the resulting P(NIPAAm-co-PEGMA) segment, that contains sufficiently high PEG content, to gel. The copolymer was shown to be non-toxic on dendritic cells. These results thus provide a new way to engineer safe PNIPAAm-based injectable hydrogels with PNIPAAm-reduced content and a degradable feature. 
Minnelli, Cristina; Galeazzi, Roberta; Laudadio, Emiliano; Amici, Adolfo; Rusciano, Dario; Armeni, Tatiana; Cantarini, Mattia; Stipa, Pierluigi; Mobbili, Giovanna, “Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation”, ANTIOXIDANTS, 2020, 9, 208 (Published: 3 March 2020)
Abstract:  Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial eects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application in lipophilic media, in particular the cellular absorption. At this purpose the hydrophilic EGCG was modified by inserting an aliphatic C18 chain linked to the gallate ring by an ethereal bond, the structure determined by NMR (Nuclear Magnetic Resonance) and confirmed by Density Functional Theory (DFT) calculations. The in vitro antioxidant activity of the mono-alkylated EGCG (C18-EGCG) was studied by the DPPH and Thiobarbituric Acid Reactive Substances (TBARS) assays, and its ability to protect cells towards oxidative stress was evaluated in Adult Retinal Pigmented Epithelium (ARPE-19) cells. Molecular Dynamics (MD) simulation and liposomal/buer partition were used to study the interaction of the modified and unmodified antioxidants with a cell membrane model: the combined experimental-in silico approach shed light on the higher anity of C18-EGCG toward lipid bilayer. Although the DPPH assay stated that the functionalization decreases the EGCG activity against free radicals, from cellular experiments it resulted that the lipid moiety increases the antioxidant protection of the new lipophilic derivative.
Fronzi D., Di Curzio D., Rusi S., Valigi D., Tazioli A. “Comparison between periodic tracer tests and time-series analysis to assess mid-and long-term recharge model changes due to multiple strong seismic events in carbonate aquifers”, Water, 12(11): 3073, November 2020
Abstract:  Understanding the groundwater flow in carbonate aquifers represents a challenging aspect in hydrogeology, especially when they have been struck by strong seismic events. It has been proved that large earthquakes change springs hydrodynamic behaviour showing transitory or long-lasting variations and making their management much more difficult. This is the case of Sibillini Massif (central Italy), which has been hit by the well-known 2016–2017 seismic period. This work aims to improve the knowledge of carbonate aquifers groundwater circulation and their possible changes in the hydrodynamic behaviour, during and after a series of strong seismic events. The goal has been achieved by comparing long-time tracer tests and transient time-series analysis, based on a sliding-window approach. This approach allowed investigating transient variations in the carbonate aquifers recharge system, highlighting the changes of relationships between the inflow contributions to the spring discharge in the area. As a result, the seismically triggered pore pressure distribution, and the hydraulic conductivity variations, because of the ground shaking and the fault systems activation, account for all the mid-and long-term modifications in the recharge system of Sibillini aquifers, respectively. These outcomes provide valuable insights to the knowledge of aquifer response under similar hydrogeological conditions, that are vital for water management. 
A. Mobili, F. Tittarelli, H. Rahier, “One-part alkali-activated pastes and mortars prepared with metakaolin and biomass ash”, Applied Sciences, 10(16), 5610, 2020, 1-14
Abstract:  Common alkali-activated materials (AAMs) are usually manufactured with highly alkaline solutions. However, alkaline solutions are dangerous for workers who must wear gloves, masks, and glasses when handling them. This issue makes common (or two-part) AAMs not user-friendly and problematic for bulk production if no safety procedures are followed. In this paper, the possibility of manufacturing alkali-activated pastes and mortars without alkaline solution is investigated. These innovative one-partAAMshave been prepared with metakaolin as the aluminosilicate precursor, potassium-rich biomass ash as the alkaline activator, and water. AAMs have been prepared by varying the K/Al molar ratio: pastes have been studied in terms of reaction kinetics, through isothermal calorimetry, and mortars have been tested in terms of mechanical compressive strength. Results show that the K/Al molar ratio governs both the reaction kinetics and the mechanical strength of these innovative materials. The highest compressive strength is obtained when the K/Al ratio is equal to 2.5 and the water/solid ratio is equal to 0.49. If biomass ash is heated at 700 C to decompose the calcium carbonate, its reactivity and the final compressive strength increase.
G. Cosoli, A. Mobili, F. Tittarelli, G.M. Revel, P. Chiariotti, “Electrical Resistivity and Electrical Impedance Measurement in Mortar and Concrete Elements: A Systematic Review”, Applied Sciences, 10(24), 9152, 2020, 1-42
Abstract:  This paper aims at analyzing the state-of-the-art techniques to measure electrical impedance (and, consequently, electrical resistivity) of mortar/concrete elements. Despite the validity of the concept being widely proven in the literature, a clear standard for this measurement is still missing.Dierent methods are described and discussed, highlighting pros and cons with respect to their performance, reliability, and degree of maturity. Both monitoring and inspection approaches are possible by using electrical resistivity measurements; since electrical resistivity is an important indicator of the health status of mortar/concrete, as it changes whenever phenomena modifying the conductivity of mortar/concrete (e.g., degradation or attacks by external agents) occur, this review aims to serve as a guide for those interested in this type of measurements.
V. Corinaldesi, J. Donnini, C. Giosué, A. Mobili, F. Tittarelli, “Durability assessment of recycled aggregate hvfa concrete”, Applied Sciences, 10(18), 6454, 2020, 1-14
Abstract:  The possibility of producing high-volume fly ash (HVFA) recycled aggregate concrete represents an important step towards the development of sustainable building materials. In fact, there is a growing need to reduce the use of non-renewable natural resources and, at the same time, to valorize industrial by-products, such as fly ash, that would otherwise be sent to the landfill. The present experimental work investigates the physical and mechanical properties of concrete by replacing natural aggregates and cement with recycled aggregates and fly ash, respectively. First, the mechanical properties of four different mixtures have been analyzed and compared. Then, the effectiveness of recycled aggregate and fly ash on reducing carbonation and chloride penetration depth has been also evaluated. Finally, the corrosion behavior of the different concrete mixtures, reinforced with either bare or galvanized steel plates, has been evaluated. The results obtained show that high-volume fly ash (HVFA) recycled aggregate concrete can be produced without significative reduction in mechanical properties. Furthermore, the addition of high-volume fly ash and the total replacement of natural aggregates with recycled ones did not modify the corrosion behavior of embedded bare and galvanized steel reinforcement.
F. Vita, F. C. Adamo, M. Pisani, O. Francescangeli, “Nanostructure of unconventional liquid crystals investigated by synchrotron radiation”, Nanomaterials, 10 (9), 2020, 1679.
Abstract:  The macroscopic properties of novel liquid crystal (LC) systems—LCs with unconventional molecular structure as well as conventional LCs in unconventional geometries— directly descend from their mesoscopic structural organization. While X-ray diffraction (XRD) is an obvious choice to investigate their nanoscale structure, conventional diffractometry is often hampered by experimental difficulties: the low scattering power and short-range positional order of the materials, resulting in weak and diffuse diffraction features; the need to perform measurements in challenging conditions, e.g., under magnetic and/or electric fields, on thin films, or at high temperatures; and the necessity to probe micron-sized volumes to tell the local structural properties from their macroscopic average. Synchrotron XRD allows these problems to be circumvented thanks to the superior diffraction capabilities (brilliance, q-range, energy and space resolution) and advanced sample environment available at synchrotron beamlines. Here, we highlight the potentiality of synchrotron XRD in the field of LCs by reviewing a selection of experiments on three unconventional LC systems: the potentially biaxial and polar nematic phase of bent-core mesogens; the very high-temperature nematic phase of all-aromatic LCs; and polymer-dispersed liquid crystals. In all these cases, synchrotron XRD unveils subtle nanostructural features that are reflected into macroscopic properties of great interest from both fundamental and technological points of view.