Publications of excellent quality of the SIMAU Department researchers, year 2019 – SECOND SEMESTER


Mastrocicco, M. Busico, G.,Colombani, N., Vigliotti, M., Ruberti, D. “Modelling Actual and Future Seawater Intrusion in the Variconi Coastal Wetland (Italy) Due to Climate and Landscape Changes”, Water, 11(7) (July), 2019, 1502

Coastal freshwater resources are commonly under high risk of being contaminated from seawater. The main processes that affect seawater intrusion are groundwater overexploitation, land use change, and climate change effects. In this context coastal lagoons represent the more sensitive environments prone to seawater intrusion. Numerical modelling is a useful tool to understand and predict seawater intrusion. In this study, a three-dimensional SEAWAT model is employed to simulate the seawater intrusion to coastal aquifers of Variconi Oasis (Italy). The present simulation was divided into a calibration and a validation model, then the model was used to predict the salinization trend up to 2050. Results show the role of the sea in salinizing the beach front, while the retrodunal environment is characterized by transitional environments. Future seawater intrusion scenarios considering only climate data showed no significative differences in respect to the actual situation. The same happens considering also a low sea level rise prediction. On the contrary, the worst scenario (high sea level rise prediction), depicts a quite different situation, with a saline intrusion in the Variconi oasis that will severely affect the fragile transitional ecosystem. This modelling framework can be used to quantify the effects of climate changes in similar coastal environments.


Colombani, N.,Mastrocicco, M.,Castaldelli, G.,Aravena, R.“Contrasting biogeochemical processes revealed by stable isotopes of H2O, N, C and S in shallow aquifers underlying agricultural lowlands”, Science of the Total Environment, 691 (November), 2019, 1282-1296

Lowland coastal areas as the Po Delta (Italy) are often intensively cultivated and affected by nitrogen imbalance due to fertilizers leaching to groundwater and export via run-off. To address this issue several agricultural best practices have been proposed, like limiting the amount of fertilizers and increasing soil organic matter content. In this study, groundwater samples were analysed for major ions and stable isotopes of H2O, C, N and S using multi-level sampler (MLS) from two contrasting depositional environments, one representative of alluvial plain (AP) and the other representative of a reclaimed coastal plain (RCP). In each site, controlled plots with different agriculture practice including fertilizers and tillage and compost amendment and no tillage were considered in the study. Tracer test results highlight that recharge water infiltrated at the start of the controlled study has not yet reached the saturated zone, thus current groundwater concentrations are representative of former agricultural practices. Stable isotopes show a clear distinction between different sources of nitrogen in both sites, from synthetic fertilizers to sedimentary nitrogen pool and atmospheric input. The main source of sulphate in groundwater is pyrite and fertilizers. Denitrification, sulphate reduction and methanogenesis were involved in the C, N and S cycle in the RCP site characterized by low hydraulic conductivity sediments and high SOM. These processes were not relevant in the AP site characterized by oxic condition and low SOM, but some evidence of denitrification was found in one of the AP sites. High resolution monitoring was a key tool to identify the different redox zones responsible for N, C and S cycling in these aquifers. This study shows that a clear understanding of transit times in the vadose zone is a key prerequisite to evaluate the effect of controlled agriculture practice on the quality of shallow groundwater.


Mastrocicco, M., Soana, E., Colombani, N., Vincenzi, F., Castaldi S., Castaldelli, G. “Effect of ebullition and groundwater temperature on estimated dinitrogen excess in contrasting agricultural environments”, Science of the Total Environment, 693 (November), 2019, 133638

Denitrification is a key microbial-mediated reaction buffering the impact of agriculturally-derived nitrate loads. Groundwater denitrification capacity is often assessed by measuring the magnitude and patterns of dinitrogen excess, although this method can be biased by dissolved gasses exsolution and ebullition. To address this issue, shallow groundwater was sampled in two field sites via nested mini-wells on a monthly basis over an entire hydrological year and analysed for dissolved gasses, nitrate and physical parameters. Both sites are located in lowland areas of the Po River basin (Italy) and are characterized by intensive agriculture. The GUA site, a freshwater paleo-river environment, with a low content of organic matter (SOM) and oxic sub-oxic groundwater. The BAN site, a reclaimed brackish swamp environment, with abundant SOM and sulphidic-methanogenic groundwater. Groundwater samples evidenced a general deficit of dinitrogen and Argon concentrations, because of ebullition induced by a total dissolved gasses pressure exceeding the hydrostatic pressure. Ebullition was recorded only during winter at the reclaimed brackish soil and was triggered by methane exsolution. While in summer both sites were affected by ebullition because of the water table drawdown. Denitrification evaluated using dinitrogen excess via dinitrogen-Argon ratio technique, was not only affected by gas exsolution, but also by groundwater temperature fluctuations. In fact, the latter induced large biases in the calculated N2 excess even in the freshwater paleo-river environment. For these reasons, dinitrogen excess estimate with standard methods resulted to be unreliable in both lowland environments and a modified method is here presented to overcome this issue.


Mercer, E., Davey, C.J., Azzini, D., Eusebi, A.L., Tierney, R., Williams, L., Jiang, Y., Parker, A., Kolios, A., Tyrrel, S., Cartmell, E., Pidou, M., McAdam, E.J., 2019, Hybrid membrane distillation reverse electrodialysis configuration for water and energy recovery from human urine: An opportunity for off-grid decentralised sanitation. Journal of Membrane ScienceVolume 584, 15 August 2019, Pages 343-352

The integration of membrane distillation with reverse electrodialysis has been investigated as a sustainable sanitation solution to provide clean water and electrical power from urine and waste heat. Reverse electrodialysis was integrated to provide the partial remixing of the concentrate (urine) and diluate (permeate) produced from the membrane distillation of urine. Broadly comparable power densities to those of a model salt solution (sodium chloride) were determined during evaluation of the individual and combined contribution of the various monovalent and multivalent inorganic and organic salt constituents in urine. Power densities were improved through raising feed-side temperature and increasing concentration in the concentrate, without observation of limiting behaviour imposed by non-ideal salt and water transport. A further unique contribution of this application is the limited volume of salt concentrate available, which demanded brine recycling to maximise energy recovery analogous to a battery, operating in a ‘state of charge’. During recycle, around 47% of the Gibbs free energy was recoverable with up to 80% of the energy extractable before the concentration difference between the two solutions was halfway towards equilibrium which implies that energy recovery can be optimised with limited effect on permeate quality. This study has provided the first successful demonstration of an integrated MD-RED system for energy recovery from a limited resource, and evidences that the recovered power is sufficient to operate a range of low current fluid pumping technologies that could help deliver off-grid sanitation and clean water recovery at single household scale.


Palmieri, S., Cipolletta, G, Pastore, C., Giosuè, C., Akyol, Ç., Eusebi, A.L., Frison, N., Tittarelli, F., Fatone, F., 2019, Hybrid membrane distillation reverse electrodialysis configuration for water and energy recovery from human urine: An opportunity for off-grid decentralised sanitation. Waste ManagementVolume 100, December 2019, Pages 208-218

The recovery of cellulose in toilet paper from municipal wastewater is one of the most innovative actions in the circular economy context. In fact, fibres could address possible new uses in the building sector as reinforcing components in binder-based materials. In this paper, rotating belt filters were tested to enhance the recovery of sludge rich in cellulose fibres for possible valorisation in construction applications. Recovered cellulosic material reached value up to 26.6 gm−3 with maximum solids removal of 74%. Content of cellulose, hemicellulose and lignin was found averagely equal to 87% of the total composition. Predictive equation of cellulosic material was further obtained. The addition of recovered cellulose fibres in mortars bring benefits in terms of lightness, microstructure and moisture buffering value (0.17 g/m2%UR). Concerning mechanical properties, flexural strength was improved with the addition of 20% of recovered cellulose fibres. In addition, a simplified economic assessment was reported for two possible pre-mixed blends with 5% and 20% of recovered fibres content.


Vasilaki, V., Massara, T.M., Stanchev, P., Fatone, F.Katsou, E., 2019, A decade of nitrous oxide (N2O) monitoring in full-scale wastewater treatment processes: A critical review. Water ResearchVolume 161, 15 September 2019, Pages 392-412.

Direct nitrous oxide (N2O) emissions during the biological nitrogen removal (BNR) processes can significantly increase the carbon footprint of wastewater treatment plant (WWTP) operations. Recent onsite measurement of N2O emissions at WWTPs have been used as an alternative to the controversial theoretical methods for the N2O calculation. The full-scale N2O monitoring campaigns help to expand our knowledge on the N2O production pathways and the triggering operational conditions of processes. The accurate N2O monitoring could help to find better process control solutions to mitigate N2O emissions of wastewater treatment systems. However, quantifying the emissions and understanding the long-term behaviour of N2O fluxes in WWTPs remains challenging and costly. A review of the recent full-scale N2O monitoring campaigns is conducted. The analysis covers the quantification and mitigation of emissions for different process groups, focusing on techniques that have been applied for the identification of dominant N2O pathways and triggering operational conditions, techniques using operational data and N2O data to identify mitigation measures and mechanistic modelling. The analysis of various studies showed that there are still difficulties in the comparison of N2O emissions and the development of emission factor (EF) databases; the N2O fluxes reported in literature vary significantly even among groups of similar processes. The results indicated that the duration of the monitoring campaigns can impact the EF range. Most N2O monitoring campaigns lasting less than one month, have reported N2O EFs less than 0.3% of the N-load, whereas studies lasting over a year have a median EF equal to 1.7% of the N-load. The findings of the current study indicate that complex feature extraction and multivariate data mining methods can efficiently convert wastewater operational and N2O data into information, determine complex relationships within the available datasets and boost the long-term understanding of the N2O fluxes behaviour. The acquisition of reliable full-scale N2O monitoring data is significant for the calibration and validation of the mechanistic models -describing the N2O emission generation in WWTPs. They can be combined with the multivariate tools to further enhance the interpretation of the complicated full-scale N2O emission patterns. Finally, a gap between the identification of effective N2O mitigation strategies and their actual implementation within the monitoring and control of WWTPs has been identified. This study concludes that there is a further need for i) long-term N2O monitoring studies, ii) development of data-driven methodological approaches for the analysis of WWTP operational and N2O data, and iii) better understanding of the trade-offs among N2O emissions, energy consumption and system performance to support the optimization of the WWTPs operation.


Dominijanni, A.; Fratalocchi, E.; Guarena, N.; Manassero, M.; Mazzieri, F., “Critical issues in the determination of the bentonite cation exchange capacity”  Géotechnique letters,  vol .9 (2019), 1-6; 10.1680/jgele.18.00229

The swelling pressure and transport properties of bentonites are controlled by the electric charge density of solid particles, which is commonly estimated from the laboratory measurement of the cation exchange capacity (CEC). However, the standard ammonium displacement method for CEC determination does not take into account the fabric changes that occur in bentonites under exposure to high salt concentration solutions. A series of laboratory tests was conducted to assess the relevance of such a critical issue, by varying the concentration of the extracted potassium chloride (KCl) solution with respect to that of the standard test. The obtained results show that the release of the adsorbed ammonium cations depends on the bentonite fabric, which is controlled by the potassium chloride concentration. As a consequence, the ammonium displacement method may provide an unrepresentative estimate of the CEC of bentonites. The methylene blue titration method, despite its apparently more limited accuracy, instead, seems to provide a more reliable estimation of the CEC, as the bentonite fabric is maintained dispersed during the test.


P. Astolfi, E. Giorgini, F. C. Adamo, F. Vita, S. Logrippo, O. Francescangeli, M. Pisani “Effects of a cationc surfactant incorporation in phytantriol bulk cubic phases and dispersions loaded with the anticancer drug 5-fluorouracil”, Langmuir, 286 (July), 2019, 110954

Ordered lyotropic liquid crystalline phases, which are particularly interesting for several biological and biomedical applications, can show the advantage of having a tunable three-dimensional nanostructure. Addition of ionic surfactants to lipid/water binary systems may influence their phase behavior and their structural properties, such as bilayer thickness, water channel diameter and interfacial curvature, resulting in specific amphiphile self-assembly materials. Understanding the effects of such additives is thus of considerable interest and, in this context, we studied the incorporation of a cationic surfactant (didodecyldimethylammonium bromide) in the phytantriol cubic phase, unloaded and loaded with the anticancer drug 5-fluorouracil. In particular, an anionic form of the drug was also used which could further influence the mesophase structure of the lipid matrix and its entrapment efficiency. The formulations, prepared as bulk and dispersed phases, were characterized by synchrotron small angle X-ray scattering, attenuated total reflection Fourier transform infrared and UV–Vis spectroscopies and dynamic light scattering. Addition of increasing amounts of the cationic surfactant resulted in phase changes following the sequence Pn3mIm3mLα, which was almost unaltered when the drug in its neutral form was encapsulated in the systems. On the contrary, the presence of the anionic 5-fluorouracil stabilized the Pn3m cubic phase at all the cationic surfactant concentrations used.


L. A. Maiorova, S. I. Erokhina, M. Pisani, G. Barucca, M. Marcaccio, O. I. Koifman, D. S. Salnikov, O. A. Gromova, P. Astolfi, V. Ricci, V. Erokhin, “Encapsulation of vitamin B12 into nanoengineered capsules and soft matter nanosystems for targeted delivery”, Colloids and Surfaces B: Biointerfaces, 182 (October), 2019, 110366-

Targeted delivery of vitamins to a desirable area is an active branch in a modern pharmacology. The most important and difficult delivery of vitamin B12 is that to bone marrow and nerve cells. Herein we present a first step towards the development of two types of smart carriers, polymer capsules and lyotropic liquid-crystalline nanosystems, for vitamin B12 targeted delivery and induced release. A vitamin B12 encapsulation technique into nanoengineered polymeric capsules produced by layer-by-layer assembling of polymeric shells on CaCO3 templates has been developed. The effectiveness of the process was demonstrated by optical absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM) and small-angle X-ray diffraction. TEM and AFM analyses performed on capsules after their drying, confirmed the presence of the vitamin B12 inside the capsules in the form of crystalline nanoaggregates, 50–300nm in diameter. Soft lipid nanovectors consisting of amphiphilic phytantriol molecules, which in water excess spontaneously self-assembly in 3D well-ordered inverse bicontinuous cubic bulk phase, were used as alternative carriers for vitamin B12. It was shown that about 30% of the vitamin added in the preparation of the soft lipid system was actually encapsulated in cubosomes andthatnostructural changesoccurreduponloading.TheVitaminstabilizes thelipidsystemplaying the role of its structure-forming element. The biocompatible nature, the stability and the feasibility of these systems make them good candidates as carriers for hydrophilic vitamins.


Chiara Lo Porto, Fabio Palumbo, Gerardo Palazzo, Gianni Barucca, Francesco Fracassi, Pietro Favia.
On the Formation of Nanocapsules in Aerosol-Assisted Atmospheric-Pressure Plasma.
Plasma Processes and Polymers, 16(11), 1900116 (November) (2019)
Aerosol-assisted atmospheric-pressure plasma can lead to the deposition of very appealing core-shell structured nanocapsules. In this work, the aerosol solution composition has been changed in terms of solute nature and concentration in order to better understand the nanocapsule formation and structure. In particular, electron microscopy techniques and microanalysis characterization have been carried out to provide a rationale for such one-step deposition of nanocapsules in plasma. A possible mechanism for the formation of the nanocapsules is suggested, based on the current theories on droplet evaporation in atomization processing, and on the implications of the coupling of aerosol with plasma environment.


F. Sayed, G. Muscas, S. Jovanovic, G. Barucca, F. Locardi,  G.Varvaro, D. Peddis, R. Mathieu and T. Sarkar.
Controlling magnetic coupling in bi-magnetic nanocomposites.
Nanoscale 11 (30), 14256-14265 (August) (2019)
Magnetic nanocomposites constitute a vital class of technologically relevant materials, in particular for next-generation applications ranging from biomedicine, catalysis, and energy devices. Key to designing such materials is determining and controlling the extent of magnetic coupling in them. In this work, we show how the magnetic coupling in bi-magnetic nanocomposites can be controlled by the growth technique. Using four different synthesis strategies to prepare prototypical LaFeO3-CoFe2O4 and LaFeO3-Co0.5Zn0.5Fe2O4 nanocomposite systems, and by performing comprehensive magnetic measurements, we demonstrate that the final material exhibits striking differences in their magnetic coupling that is distinct to the growth method. Through structural and morphological studies, we confirm the link between the magnetic coupling and growth methods due to distinct levels of particle agglomeration at the very microscopic scale. Our studies reveal an inverse relationship between the strength of magnetic coupling and the degree of particle agglomeration in the nanocomposites. Our work presents a basic concept of controlling the particle agglomeration to tune magnetic coupling, relevant for designing advanced bi-magnetic nanocomposites for novel applications.


E. Santecchia, A. Gatto, E. Bassoli, L. Denti, B. Rutkowski, P. Mengucci, G. Barucca.
Precipitates formation and evolution in a Co-based alloy produced by powder bed fusion
Journal of Alloys and Compounds 797, 652-658 (August) (2019)
Metal additive manufacturing is strongly employed in aerospace and biomedical applications, whose high degree of customization and low production volumes are the main characteristics. Cobalt-based alloys have been widely used for dental prosthesis and can be produced via metal additive manufacturing, or rather powder bed fusion, in a more convenient way compared to traditional manufacturing techniques. In the present paper, a comprehensive study of the tight correlation between the microstructure and the static mechanical properties of Co-Cr-Mo-W samples produced by powder bed fusion, is reported. In particular, the formation of precipitates during the sintering process is observed, and the evolution of their size, shape and frequency due to post-processing and to a heat-treatment typical of dental applications, is exhaustively studied. By coupling different characterization techniques such as scanning transmission electron microscopy and small-angle neutron scattering, it was possible to correlate the ductility degradation of the samples with the formation and growth of coarse and elongated precipitates.


Sergio Loffredo; Carlo Paternoster; Nicolas Giguère; Gianni Barucca; Maurizio Vedani; Diego Mantovani.
The addition of silver affects the deformation mechanism of a twinning-induced plasticity steel: Potential for thinner degradable stents
Acta Biomaterialia 98, 103-113 (October) (2019)
While Fe-based alloys have already been reported to possess all mechanical properties required for vascular stenting, their relatively low degradation rate in vivo still constitutes their main bottleneck. The inflammatory reaction generated by a stent is inversely proportional to its mass. Therefore, the tendency in stenting is to lower the section so to reduce the inflammatory reaction. Twinning-induced plasticity steels (TWIP) possess excellent mechanical properties for envisaging the next generation of thinner degradable cardiovascular stents. To accelerate the degradation, the addition of noble elements was proposed, aimed at promoting corrosion by galvanic coupling. In this context, silver was reported to generally increase the degradation rate. However, its impact on the deformation mechanism of TWIP steels has not been reported yet. Results show that the use of Ag significantly reduces the ductility without altering the strength of the material. Furthermore, the presence of Ag was found to promote a different deformation texture, thus stimulating the formation of mechanical martensite. Since a stent works in the deformed state, understanding the microstructure and texture resulting from plastic deformation can effectively help to forecast the degradation mechanisms taking place during implantation and the expected degradation time. Moreover, knowing the deformed microstructure allows to understand the formability of very small tubes, as precursors of the next generation of thin section degradable stents. Statement of significance: Commercial degradable magnesium stents are limited from their relatively big structure size. Twinning-induced plasticity steels possess outstanding mechanical properties, but their degradation time goes beyond the timeframe expected from clinics. The inclusion of noble Ag particles, which favor galvanic coupling, is known to promote corrosion and solve this limitation. However, it is necessary to understand the impact that Ag has on the deformation microstructure and on the mechanical properties. The addition of Ag reduces the ductility of a twinning-induced plasticity steel because of a different deformation microstructure. Since a stent works in a deformed state inside an artery, understanding the microstructural evolution after plastic deformation allows to better predict the device performances during service life.


Barbara Ballarin, Elisa Boanini, Luigi Montalto, Paolo Mengucci, Daniele Nanni, Chiara Parise, Ilaria Ragazzini, Daniele Rinaldi, Nicola Sangiorgi, Alessandra Sanson, Maria Cristina Cassani.
PANI/Au/Fe3O4 nanocomposite materials for high performance energy storage
Electrochimica Acta 322, 134707 (November) (2019)
In this work new energy storage components were prepared depositing films made of polyaniline (PANI) modified with gold/magnetite nanoparticles on flexible graphite foils. Three types of composite materials termed PANI/Fe3O4, PANI/Au/Fe3O4 and PANI/Au/Fe3O4@Yne (where @Yne is a propynylcarbamate group) were obtained by electrosynthesis. Galvanostatic charge-discharge (CD) and impedance tests (EIS) were performed to verify their efficiency in charge storage properties: for the gold-containing electrodes PANI/ Au/Fe3O4 and PANI/Au/Fe3O4@Yne areal capacities values of 45.6 and 46.5 mAh cm2 were found in 0.5MH2SO4 þ 0.1 M LiClO4 electrolyte solution at a current density of 0.5 mAcm2. These values are twofold higher than those found for PANI/Fe3O4 electrodes and fourfold greater than those for PANI alone (11.0 mAh cm2). In turn PANI/Au/Fe3O4 and PANI/Au/Fe3O4@Yne were employed to assemble gel-state symmetric devices. CD, EIS and long-time resistance tests were made on the new devices that displayed an areal capacity of 100.0 mAh cm2 for PANI/Au/Fe3O4 and 73.6 mAh cm2 PANI/Au/Fe3O4@Yne respectively. To our knowledge this is the first time that AuNPemodified magnetite nanoparticles are used in energy storage devices preparation.


Rinaldi, D., Daví, F., Montalto, L.
On the photoelastic constants for anisotropic stressed crystals
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment 947, 162782 (December) (2019)
The need for high-quality and high-performance crystals for high-energy physics (e.g. scintillators) and biomedical applications require a good knowledge of their mechanical and optical properties, amongst the others. This is a mandatory step in many qualities control process aimed at the improvement of the technological processes for crystals growth. Following the first analysis already done for Tetragonal crystals, in this paper we study the elasto-optic behavior of optically biaxial (Monoclinic and Orthorhombic groups) and uniaxial crystals (Trigonal and Hexagonal groups). We evaluate the photoelastic constants, the optic angle and the optic plane associated to various states of stress, in terms of the components of the Piezo-Optic tensor.


A. Managò, V.Audrito, F. Mazzola, L. Sorci, F. Gaudino, K. Gizzi, N. Vitale, D. Incarnato, G. Minazzato, A. Ianniello, A. Varriale, S. D’Auria, G. Mengozzi, G. Politano, S. Oliviero, N. Raffaelli, S. Deaglio, “Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation”, Nature Communications, 10 (September), 2019, 4116

Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.


Audrito V, Managò A, Gaudino F, Sorci L, Messana VG, Raffaelli N, Deaglio S.“NAD-Biosynthetic and Consuming Enzymes as Central Players of Metabolic Regulation of Innate and Adaptive Immune Responses in Cancer”, Frontiers in Immunology,10 (July), 2019, 1720

Cancer cells, particularly in solid tumors, are surrounded by non-neoplastic elements, including endothelial and stromal cells, as well as cells of immune origin, which can support tumor growth by providing the right conditions. On the other hand, local hypoxia, and lack of nutrients induce tumor cells to reprogram their metabolism in order to survive, proliferate, and disseminate: the same conditions are also responsible for building a tumor-suppressive microenvironment. In addition to tumor cells, it is now well-recognized that metabolic rewiring occurs in all cellular components of the tumor microenvironment, affecting epigenetic regulation of gene expression and influencing differentiation/proliferation decisions of these cells. Nicotinamide adenine dinucleotide (NAD) is an essential co-factor for energy transduction in metabolic processes. It is also a key component of signaling pathways, through the regulation of NAD-consuming enzymes, including sirtuins and PARPs, which can affect DNA plasticity and accessibility. In addition, both NAD-biosynthetic and NAD-consuming enzymes can be present in the extracellular environment, adding a new layer of complexity to the system. In this review we will discuss the role of the “NADome” in the metabolic cross-talk between cancer and infiltrating immune cells, contributing to cancer growth and immune evasion, with an eye to therapeutic implications.


P. Stipa, E. Laudadio, R. Galeazzi, G. Mobbili, C. Minnelli, D. Rusciano, T. Armeni, M. Cantarini, “Synthesis, characterization and antioxidant properties of a new lipophilic derivative of edaravone”, ANTIOXIDANTS, 2019, 8, 258.

As part of a program aimed to obtain antioxidants able to interact with cell membrane,edaravone (EdV, 3-methyl-1-phenyl-2-pyrazolin-5-one), a well-known free radical scavenger, hasbeen modified by alkylation at its allylic position (4) with a C-18 hydrocarbon chain, and theincreased lipophilicity has been determined towards the interaction with liposomes. The obtainedderivative has been studied by means of density functional theory (DFT) methods in order tocharacterize its lowest energy conformers and predict its antioxidant properties with respect tothe parent compound EdV. The in vitro antioxidant activity of C18-edaravone was studied bymeans of the a,a-diphenyl-b-picrylhydrazyl (DPPH) assay and in lipid peroxidation experimentsperformed on artificial lipid membranes using water-soluble as well as lipid-soluble radical initiators.Moreover, since oxidative stress is involved in numerous retinal degenerative diseases, the ability ofC18-edaravone to contrast 2,2-azobis (2-amidinopropane hydrochloride) (AAPH)-induced cell deathwas assessed in adult retinal pigmented epithelium (ARPE-19) cells. Overall, the results demonstratedthat the newly synthesized molecule has a high a nity for lipid membrane, increasing the e cacy ofthe unmodified edaravone under stress conditions.


Tazioli A., Cervi F., Doveri M., Mussi M., Deiana M., Ronchetti F. “Estimating the isotopic altitude gradient for hydrogeological studies in mountainous areas: Are the low-yield springs suitable? Insights from the northernApennines of Italy”, Water, 11(9), 2019, 1764

Several prior studies investigated the use of stable isotopes of water in hydrogeological applications, most on a local scale and often involving the isotopic gradient (evaluated by exploiting the so-called altitude effect), calculated on the basis of rainwater isotopes. A few times, this gradient has been obtained using the stable isotopic contents of low-yield springs in a limited time series. Despite the fact that this method has been recognized by the hydrogeological community, marked differences have been observed with respect to the mean stable isotopes content of groundwater and rainwater. The present investigation compares the stable isotopic signatures of 23 low-yield springs discharging along two transects from the Tyrrhenian sea to the Po Plain of Italy, evaluates the different isotopic gradients and assesses their distribution in relation to some climatic and topographic conditions. Stable isotopes of water show that groundwater in the study area is recharged by precipitation and that the precipitation regime in the eastern portion of the study area is strongly controlled by a shadow effect caused by the Alps chain on the air masses from central Europe. Stable isotopes (in particular theδ18O and deuterium excess (d-excess) contents together with the obtained isotopic gradients) allow us to identify in the study area an opposite oriented orographic effect and a different provenance of the air masses. When the windward slope is located on the Tyrrhenian side, the precipitation shows a predominant oceanic origin; when the windward slope moves to the Adriatic side, the precipitation is characterized by a continental origin. The main results of this study confirm the usefulness of low-yield springs and the need for a highly detailed survey-scale hydrological investigation in the mountainous context. © 2019 by the authors.


C. Giosué, A. Mobili, Q.L. Yu, H.J.H. Brouwers, F. Tittarelli, “Properties of multifunctional lightweight mortars containing zeolite and natural fibers”, Journal of Sustainable Cement-Based Materials, 8(4) (July), 2019, 214-227

The article focuses on the development of innovative and multifunctional mortars with low environmental impact for indoor applications acting as passive systems to moderate extremes of humidity and to lower the concentration of pollutants. Mortars are manufactured by keeping constant the water/binder ratio, using sand as reference aggregate, and by replacing the total volume of sand with zeolite. In some mixes the aggregate, is also at 25vol% by wool natural fibers. Regardless lightness, zeolite thanks to its pozzolanic activity, helps to improve the compressive strength of mortars manufactured with wool fibers. In addition, the combination of zeolite and wool increases the hygro-thermal performance of mortars: water vapor resistance factor (22% lower than the reference), moisture buffering value (100% higher than the reference), and thermal conductivity (66% lower than the reference), respectively. Depolluting properties of zeolite-based mortars, in terms of adsorption capacity, are 65% lower than that of reference mortar.

C. Giosué, A. Mobili, C. Di Perna, F. Tittarelli, “Performance of lightweight cement-based and alkali-activated mortars exposed to high-temperature”, Construction and Building Materials, 220 (September), 2019, 565-576

The behavior of lightweight cement-based and alkali-activated mortars after exposure to temperatures of 500, 750, and 1000 °C was compared. In cement-based mortars, cement was partially replaced (40 vol%) by several refractory fillers (coal fly-ash, biomass fly-ash, cocciopesto, metakaolin). In alkali-activated mortars, metakaolin was partially substituted (0, 25, 50 wt%) by coal fly-ash. The substitution of cement by 40% metakaolin and the substitution of metakaolin by 50% fly ash enhances the resistance to high temperatures of cement-based and alkali-activated mortars, respectively. After exposure to 1000 °C, the high residual compressive strength of cement-based mortars with metakaolin is due to the formation of new crystalline species, whereas in alkali-activated mortars is due to their high densification.


J. Rissanen, C. Giosué, K. Ohenoja, P. Kinnunen, M. Marcellini, M.L. Ruello, F. Tittarelli, M. Illikainen, “The effect of peat and wood fly ash on the porosity of mortar”, Construction and Building Materials, 223 (October), 2019, 421-430

Fluidized bed combustion fly ash (FBCFA), notably different from regular (coal) fly ash, is a promising industrial side stream to be used as a supplementary cementitious material (SCM). Peat and wood are important sources of biomass for energy production in Nordic countries and generate formidable amounts of un-used ash yearly. Two FBCFAs from the co-combustion of peat and wood, fly ash from coal combustion, and limestone filler were used to replace 10 wt%, 20 wt%, and 40 wt% of cement in mortar specimens. The compressive strength, porosity, water absorption, water vapor permeability, and drying shrinkage of the mortars were measured and compared. It was found that in almost all properties FBCFAs outperformed un-reactive limestone filler. Compared to coal fly ash, FBCFAs produced mortars with comparable compressive strength although with higher porosity, water absorption, and water vapor permeability.


Manea E., Dell’Anno A., Rastelli E., Tangherlini M., Nunoura T., Nomaki H., Danovaro R., Corinaldesi C.Viral infections boost prokaryotic biomass production and organic C cycling in hadal trench. Vol. 10 (August). Frontiers in Microbiology. 2019. 1952.

Hadal trenches are among the most remote and least explored ecosystems on Earth and can support high benthic microbial standing stocks and activities. However, information on the role of viruses in such ecosystems and their interactions with prokaryotic hosts is very limited. Here, we investigated activities of benthic viruses and prokaryotes and their interactions in three hadal trenches (Japan, Izu-Ogasawara and Mariana trenches) and in their surrounding abyssal sites. Our findings reveal that these hadal trenches, compared with the surrounding abyssal sites, support higher abundances and biomasses of prokaryotes. In addition, the high prokaryotic biomasses of hadal trenches could favour high rates of viral infection and cell lysis, especially in the Japan Trench. Hadal viruses can release large amounts of highly labile and promptly available organic material by inducing cell lysis, which could contribute to sustain benthic prokaryotes and decrease their dependency on the enzymatic digestion of the more refractory fraction of sediment organic matter. Our results suggest that this process can contribute to explain the discrepancy between high prokaryote biomass and apparent low efficiency in the utilization of the sedimentary organic matter in the hadal ecosystems. Hadal trenches may be characterized by highly dynamic viral component, which can enhance prokaryotic biomass production, thereby profoundly influencing the functioning of these remote and extreme ecosystems.


Da Ros Z., Dell’Anno, A., Morato T., Sweetman A. K., Carreiro-Silva M., Smith C. J., Papadopoulou N., Corinaldesi C……… &Danovaro R.The deep sea: The new frontier for ecological restoration. Vol. 108 (October). Marine Policy. 2019. 103642.

Deep-sea ecosystems are the most extensive on Earth and provide key goods and services for human well-being, such as genetic resources and climate regulation. Maintaining the sustainable functioning of the global biosphere therefore requires protection of deep-sea ecosystems, particularly because these ecosystems face major changes related to human and climate-induced impacts. Although we lack data to evaluate the spatial scale of degraded deep-sea habitats, numerous studies document human impacts on the whole ocean. However, protection alone can be insufficient to reverse habitat degradation in the deep sea. Scientifically, deep-sea restoration actions may be feasible, but whether such actions will achieve sustainability goals when applied at broad spatial scales of impact remain questionable. Successful application of most restoration efforts will first require a deeper understanding of biodiversity and functioning of deep-sea ecosystems, and better knowledge of ecosystem resilience and recovery rates of deep-sea fauna. In addition to limited data availability, expensive technologies (with estimated costs up to millions of dollars ha−1) represent a major obstacle to large-scale deep-sea restoration, but international cooperation (like a stronger collaboration between industry and scientists belonging to the academia) could significantly reduce this operational cost. Future deep-sea ecosystem restoration could offer an important business opportunity for technological development and application and an investment in natural capital for a new and competitive blue-growth sector.


Rastelli E., Corinaldesi C., Dell’Anno A., Tangherlini M., Lo Martire M., Nishizawa M., … &Danovaro R. Drivers of Bacterial α-and β-Diversity Patterns and Functioning in Subsurface Hadal Sediments. Vol. 10 (November). Frontiers in Microbiology, 2019. 2609.

Oceanic trenches at hadal (>6,000 m) depths are hot spots of organic matter deposition and mineralization and can host abundant and active bacterial assemblages. However, the factors able to shape their biodiversity and functioning remain largely unexplored, especially in subsurface sediments. Here, we investigated the patterns and drivers of benthic bacterial α- and β-diversity (i.e., OTU richness and turnover diversity) along the vertical profile down to 1.5 m sediment depth in the Izu-Bonin Trench (at ~10,000 m water depth). The protease and glucosidase enzymatic activity rates were also determined, as a proxy of organic matter degradation potential in the different sediment layers. Molecular fingerprinting based on automated ribosomal intergenic spacer analysis (ARISA) indicated that the α-diversity of bacterial assemblages remained high throughout the vertical profile and that the turnover (β-) diversity among sediment horizons reached values up to 90% of dissimilarity. Multivariate distance-based linear modeling (DISTLM) pointed out that the diversity and functioning of the hadal bacterial assemblages were influenced by the variability of environmental conditions (including the availability of organic resources and electron donors/acceptors) and of viral production rates along the sediment vertical profile. Based on our results, we can argue that the heterogeneity of physical-chemical features of the hadal sediments of the Izu-Bonin Trench contribute to increase the niches availability for different bacterial taxa, while viruses contribute to maintain high levels of bacterial turnover diversity and to enhance organic matter cycling in these extremely remote and isolated ecosystems.


L. Cianfruglia, C. Minnelli, E. Laudadio, A. Scirè, T. Armeni, “Side effects of curcumin: Epigenetic and antiproliferative implications for normal dermal fibroblast and breast cancer cells”, Antioxidants, 8(9), (September) 2019, 382

Background: Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa,which is known to exert beneficial effects in several diseases, including cancer. However, at high doses,it may produce toxic and carcinogenic effects in normal cells. In this context, we studied the effects ofcurcumin on normal human dermal fibroblast (HDF) cells and breast cancer cells (MCF7). Methods:We used cellular viability and growth assays to evaluate the antiproliferative action of curcumin,analyzed the endogenous glutathione levels, conducted cell cycle, apoptosis, and necrosis analyses,and performed immunodetection of glutathionylated and acetylated H3 histones. Results: We foundthat HDFs are more sensitive to curcumin treatment than MCF7 cells, resulting in pronounced arrestof cell cycle progression and higher levels of cellular death. In both cell types, the homeostasis of theredox cellular environment did not change after curcumin treatment; however, significant differenceswere observed in glutathione (GSH) levels and in S-glutathionylation of H3 histones. Conclusion:Curcumin administration can potentially confer benefits, but high doses may be toxic. Thus, its useas a dietary supplement or in cancer therapies has a double edge.


E. Laudadio, N. Cedraro, G. Mangiaterra, B. Citterio, G. Mobbili, C. Minnelli, D. Bizzaro, F. Biavasco, R. Galeazzi,”Natural AlkaloidBerberine Activity against Pseudomonas aeruginosa MexXY-MediatedAminoglycosideResistance: In Silico and in Vitro Studies” Journal of Natural Products82, 7, (July) 2019, 1935-1944

The multidrug efflux system MexXY-OprM,inside the resistance-nodulation-division family, is a majordeterminant of aminoglycoside resistance in Pseudomonasaeruginosa. In the fight aimed to identify potential efflux pumpinhibitors among natural compounds, the alkaloid berberineemerged as a putative inhibitor of MexXY-OprM. In this work,we elucidated its interaction with the extrusor protein MexYand assessed its synergistic activity with aminoglycosides. Inparticular, we built an in silico model for the MexY protein inits trimeric association using both AcrB (E. coli) and MexB (P.aeruginosa) as 3D templates. This model has been stabilized inthe bacterial cytoplasmic membrane using a moleculardynamics approach and used for ensemble docking to obtainthe binding site mapping. Then, through dynamic docking, we assessed its binding affinity and its synergism withaminoglycosides focusing on tobramycin, which is widely used in the treatment of pulmonary infections. In vitro assays validatedthe data obtained: the results showed a 2-fold increase of the inhibitory activity and 2−4 log increase of the killing activity of theassociation berberine−tobramycin compared to those of tobramycin alone against 13/28 tested P. aeruginosa clinical isolates.From hemolytic assays, we preliminarily assessed berberine’s low toxicity.


T.H. Ogunwa, E. Laudadio, R. Galeazzi, T. Miyanishi,”Insights into the molecular mechanisms of Eg5 inhibition by (+)-morelloflavone” Pharmaceuticals, 12, 2, (June) 2019, 58

(+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garciniaspecies. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-glidingactivities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insightsinto the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitorto the loop5/2/3 allosteric pocket. Molecular dynamics simulations were carried out for100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP-S-trityl-l-cysteine(Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP),Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyseswere done using Umbrella sampling, Molecular Mechanics Poisson–Boltzmann Surface Area(MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities.The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our datastrongly support a stable Eg5-MF complex, with significantly low binding energy and reducedflexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 wastrapped in a downward position to keep the allosteric pocket of Eg5 in the so-called “closedconformation”, comparable to observations for STLC. Altered structural conformations werealso visible within various regions of Eg5, including switch I, switch II, 2/3 helices, and thetubulin-binding region, indicating that MF might induce modifications in the Eg5 structure tocompromise its ATP/ADP binding and conversion process as well as its interaction with microtubules.The described mechanisms are crucial for understanding Eg5 inhibition by MF.


V. Notarstefano, S. Sabbatini, C. Conti, M. Pisani, P. Astolfi, C. Pro, C. Rubini, L. Vaccari, E. Giorgini, “Investigation of human pancreatic cancer tissues by Fourier Transform Infrared Hyperspectral Imaging”, Journal of Biophotonics, Accepted: 16 October 2019, 2019,  1-10

Fourier‐transform infrared hyperspectral imaging (FTIRHSI) provides hyperspectral images containing both morphological and chemical information. It is widely applied in the biomedical field to detect tumor lesions, even at the early stage, by identifying specific spectral biomarkers. Pancreatic neoplasms present different prognoses and are not always easily classified by conventional analyses. In this study, tissue samples with diagnosis of pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumor were analyzed by FTIRHSI and the spectral data compared with those from healthy and dysplastic samples. Multivariate/univariate approaches were complemented to hyperspectral images, and definite spectral markers of the different lesions identified. The malignant lesions were recognizable both from healthy/dysplastic pancreatic tissues (high values of phospholipids and triglycerides with shorter, more branched and less unsaturated alkyl chains) and between each other (different amounts of total lipids, phosphates and carbohydrates). These findings highlight different metabolic pathways characterizing the different samples, well detectable by FTIR‐HSI.


S. Castiglioni, P. Astolfi, C. Conti, E. Monaci, M. Stefano and P. Carloni,“Morphological, Physicochemical and FTIR Spectroscopic Properties of Bee Pollen Loads from Different Botanical Origin”, Molecules24 (2019), 3974; DOI:10.3390/molecules24213974

Bee pollen loads generally have a homogeneous and monospecific pollen content and assume a typical form and color, due to the typical bee foraging habits, thus having a typical composition related to the botanical origin. The present study aims to characterize bee pollen loads belonging to different botanical species using morphological, spectroscopic and color properties and to find relationships between these variables. IR spectra analysis allowed to have a reliable picture of the components present in the different samples; color and granulometry permits a visual identification of pollen load belonging to different species. Multivariate analysis enabled differentiation among the botanical origin of most of the bee pollen samples, grouping them according to the family and the genus and confirming the possibility to use IR and color measurements for the evaluative analysis and classification of bee pollen samples, to promote the consumption of this bee product as functional food.