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Background: Pyro-electrohydrodynamic jetting (p-jet) has emerged recently as a promising technique for biosensing applications, through the concentration of highly diluted biomolecules in fluorescent spots at microscale. However, a great challenge still remains in optimizing the binding strategy for the sensing interface, enabling the detection of low abundance proteins through immunofluorescence protocols. Indeed, the surface of reaction can be functionalized with different chemical groups able to bind the target molecule with a strong interaction, prior to the p-jet spots decreasing the possibility to lose sensitivity after the common rinsing steps., Results: Here, we characterize the immobilization of a model protein, specifically the bovine serum albumin (BSA), in the concentrated p-jet spots to demonstrate the reliability of the technique for highly sensitive immunodetection assays. We first performed spectroscopic measurements on BSA deposited through pipette spots at relatively high concentrations and we achieved a higher efficiency in case of the covalent bond by using the carbonate buffer and the epoxy-based slides. We then tested the covalent setting in case of the p-jet spots with highly diluted samples of pre-labelled BSA. A significant concentration-dependent behavior of the signal was obtained down to picogram levels. Finally, an immunofluorescent protocol was settled with the p-jet spots and a Limit of the Detection (LOD) of 0. 27 pg/mL was reached., Significance: The demonstration here that the p-jet spots are compatible with immunodetection procedures and provide a LOD down to 0.27 pg/mL, launches the p-jet technique towards the development in future of a point-of-care (POC) diagnostic tool. This would become a major force in analytical chemical laboratories. The identification of highly diluted biomarkers from peripheral body fluids would help clinicians performing early diagnosis, overcoming the limitations of the traditional immunochemistry tests, such as the enzyme-linked immunosorbent assay (ELISA)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this work, we report on the synthesis and properties of a new sensitizer for photodynamic therapy applications, constituted by a ruthenium(ii) complex (1) featuring a ligand inspired from natural isoquinoline alkaloids. The spectroscopic analysis revealed that 1 is characterized by an intense red emission ( λ em = 620 nm, Φ = 0.17) when excited at 550 nm, a low energy radiation warranting for a safe therapeutic approach. The phototoxicity of 1 on human breast cancer (Hs578T) and melanoma (A375) cell lines was assessed after irradiation using a LED lamp (525 nm, total fluence 10 J cm -2 ). In vitro biological assays indicated that the cytotoxicity of 1 was significantly enhanced by light reaching IC 50 values below the micromolar threshold. The cell damage induced by 1 proved to be strictly connected with the overproduction of reactive oxygen species (ROS) responsible for mitochondrial dysfunction leading to the activation of caspases and then to apoptosis, and for DNA photocleavage leading to cell cycle arrest., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Here we demonstrate for the first time that an antibody-gold nanoparticles (AuNPs)-polymer conjugate thin-film biosensor can easily be fabricated to selectively capture Tau protein. Gold nanoparticles (AuNPs) are employed as sensing elements, thus capitalizing on their propensity to undergo assembly or disassembly in response to the adsorption or conjugation of various biomolecules on their surface, thereby forming robust interactions with the target analyte. We show that the Tau protein in its different aggregation phases can be detected, by restricting the reaction area on the solid thin polymer film and thus reducing the diffusion effects usually encountered in immunosensors. A limit of detection (LOD) of 460 pg/mL was reached, demonstrating a great potential for detecting Tau in aggregation states. This sensor based on thin polymer film could open new routes for sensing and monitoring Tau protein in biological assays and biomedical diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

TiO 2 nanoparticles loaded with pistachio shell lignin (8 % and 29 % w/w) were prepared by a hydrothermal wet chemistry approach. The efficient interaction at the molecular level of the biomacromolecule and inorganic component was demonstrated by X-ray diffraction (XRD), transmission electron microscopy (TEM), UV-Visible (UV-Vis), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), and electron paramagnetic resonance (EPR) analysis. The synergistic combination of lignin and TiO 2 nanoparticles played a key role in the functional properties of the hybrid material, which exhibited boosted features compared to the separate organic and inorganic phase. In particular, the hybrid TiO 2 -lignin nanoparticles showed a broader UV-Vis protection range and remarkable antioxidant performance in aqueous media. They could also better protect human skin explants from the DNA damaging effect of UV radiations compared to TiO 2 as indicated by lower levels of p-H2A.X, a marker of DNA damage, at 6 h from exposure. In addition, the samples could protect the skin against the structural damage occurring 24 h post UV radiations by preventing the loss of keratin 10. These results open new perspectives in the exploitation of food-waste derived phenolic polymers for the design of efficient antioxidant materials for skin photoprotection in a circular economy perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: This study examines the prevalence of eating disorders, particularly anorexia and bulimia nervosa, among middle-aged Spaniards, noting their rising incidence in men as well as women. It explores how these disorders relate to sociodemographic factors and lifestyle habits., Methods: A cross-sectional survey was conducted from August 2020 to November 2021 via online platforms. Participants were Spanish nationals aged 31-50 years residing in Spain., Results: Out of 9913 respondents, 96.66% reported no diagnosed eating disorders, while 3.34% reported one or more (0.36% anorexia nervosa; 0.53% bulimia nervosa; 1.97% other eating disorders; 0.48% multiple disorders). Concerns about body image and lack of control over food intake were reported by 50% and 28%, respectively, suggesting potential undiagnosed disorders. Significant BMI differences were noted between healthy individuals and those with anorexia or bulimia., Conclusions: Anorexia and bulimia affect both adolescents and middle-aged individuals, challenging existing stereotypes. The high prevalence of undiagnosed eating disorder behaviors highlights the need for early detection. To address these issues in Spain, targeted awareness programs are essential to reduce stigma and improve service access through clinical, social, and political collaboration.

The development of biosafe theranostic nanoplatforms has attracted great attention due to their multifunctional behavior, reduced potential toxicity, and improved long-term safety. When considering photoacoustic contrast agents and photothermal conversion tools, melanin and constructs like melanin are highly appealing due to their ability to absorb optical energy and convert it into heat. Following a sustainable approach, in this study, silver-melanin like-silica nanoplatforms are synthesized exploiting different bio-available and inexpensive phenolic acids as potential melanogenic precursors and exploring their role in tuning the final systems architecture. The UV-Vis combined with X-Ray Diffraction investigation proves metallic silver formation, while Transmission Electron Microscopy analysis reveals that different morphologies can be obtained by properly selecting the phenolic precursors. By looking at the characterization results, a tentative formation mechanism is proposed to explain how phenolic precursors' redox behavior may affect the nanoplatforms' structure. The antibacterial activity experiments showed that all synthesized systems have a strong inhibitory effect on Escherichia coli, even at low concentrations. Furthermore, very sensitive Photoacoustic Imaging capabilities and significant photothermal behavior under laser irradiation are exhibited. Finally, a marked influence of phenol nature on the final system architecture is revealed resulting in a significant effect on both biological and photoacoustic features of the obtained systems. These melanin-based hybrid systems exhibit excellent potential as triggerable nanoplatforms for various biomedical applications., (© 2024 Wiley‐VCH GmbH.)

It is largely documented that neurodegenerative diseases can be effectively treated only if early diagnosed. In this context, the structural changes of some biomolecules such as Tau, seem to play a key role in neurodegeneration mechanism becoming eligible targets for an early diagnosis. Post-translational modifications are responsible to drive the Tau protein towards a transition phase from a native disorder conformation into a preaggregation state, which then straight recruits the final fibrillization process. Here, we show for the first time the detection of pre-aggregated Tau in artificial urine at femto-molar level, through the concentration effect of the pyro-electrohydrodynamic jet (p-jet) technique. An excellent linear calibration curve is demonstrated at the femto-molar level with a limit of detection (LOD) of 130 fM. Moreover, for the first time we show here the structure stability of the protein after p-jet application through a deep spectroscopic investigation. Thanks to the small volumes required and the relatively compact and cost-effective characteristics, this technique represents an innovative breakthrough in monitoring the early stage associated to neurodegeneration syndromes in different scenarios of point of care (POC) and such as for example in long-term human space exploration missions., Competing Interests: Declaration of competing interest The authors state that they are not aware of any financial or interpersonal conflicts that might have appeared to have an impact on the research presented in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Sustainable active food packaging is essential to reduce the use of plastics, preserve food quality and minimize the environmental impact. Humic substances (HS) are rich in redox-active compounds, such as quinones, phenols, carboxyl, and hydroxyl moieties, making them functional additives for biopolymeric matrices, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Herein, composites made by incorporating different amounts of HS into PHBV were developed using the electrospinning technology and converted into homogeneous and continuous films by a thermal post-treatment to obtain a bioactive and biodegradable layer which could be part of a multilayer food packaging solution. The morphology, thermal, optical, mechanical, antioxidant and barrier properties of the resulting PHBV-based films have been evaluated, as well as the antifungal activity against Aspergillus flavus and Candida albicans and the antimicrobial properties against both Gram (+) and Gram (-) bacterial strains. HS show great potential as natural additives for biopolymer matrices, since they confer antioxidant, antimicrobial, and antifungal properties to the resulting materials. In addition, barrier, optical and mechanical properties highlighted that the obtained films are suitable for sustainable active packaging. Therefore, the electrospinning methodology is a promising and sustainable approach to give biowaste a new life through the development of multifunctional materials suitable in the active bio-packaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Melanin is a multifunctional biological pigment that recently emerged as endowed with anti-inflammatory, antioxidant, and antimicrobial properties and with high potentialities in skin protection and regenerative medicine. Here, a biomimetic magnesium-doped nano-hydroxyapatite (MgHA) was synthesized and decorated with melanin molecules starting from two different monomeric precursors, i.e. 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and dopamine (DA), demonstrating to be able to polymerize on the surface of MgHA nanostructures, thus leading to a melanin coating. This functionalization was realized by a simple and green preparation method requiring mild conditions in an aqueous medium and room temperature. Complementary spectroscopy and electron imaging analyses were carried out to define the effective formation of a stable coating, the percentage of the organic compounds, and the structural properties of resulting melanin-coated nanostructures, which showed good antioxidant activity. The in vitro interaction with a cell model, i.e. mouse fibroblasts, was investigated. The excellent biocompatibility of all bioinspired nanostructures was confirmed from a suitable cell proliferation. Finally, the enhanced biological performances of the nanostructures coated with melanin from DHICA were confirmed by scratch assays. Jointly our findings indicated that low crystalline MgHA and melanin pigments can be efficiently combined, and the resulting nanostructures are promising candidates as multifunctional platforms for a more efficient approach for skin regeneration and protection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giuseppe Vitiello reports financial support was provided by University of Naples Federico II., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hydrogen is expected to largely contribute to the near-future circular economy. Today, most hydrogen is still produced from fossil fuels or renewable pathways with low efficiency and high cost. Herein, a proof of concept for a novel hydrogen production process is proposed, here named cyan hydrogen , inspired by a combination of the green and blue processes, due to the key role played by water and the low carbon content in the gas phase, respectively. The developed novel process, recently patented and demonstrated at the lab scale, is based on successive steps in which ethanol (5.0 mL) and water (10.0 mL) are alternately fed, with a fixed initial amount of sodium metaborate (2.0 g), in a batch reactor at 300 °C. Preliminary results showed the simultaneous production of a 95% v/v hydrogen stream, a polymeric byproduct with a repetitive carbon pattern -CH 2 -CH 2 -, and a liquid phase rich in oxygenated chemicals at temperatures lower than conventional hydrogen production processes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Bioinspired nanoparticles have recently been gaining attention as promising multifunctional nanoplatforms for therapeutic applications in cancer, including breast cancer. Here, the efficiency of the chemo-photothermal and photoacoustic properties of hybrid albumin-modified nanoparticles (HSA-NPs) loaded with doxorubicin was evaluated in a three-dimensional breast cancer cell model. The HSA-NPs showed a higher uptake and deeper penetration into breast cancer spheroids than healthy breast cell 3D cultures. Confocal microscopy revealed that, in tumour spheroids incubated with doxorubicin-loaded NPs for 16 h, doxorubicin was mainly localised in the cytoplasm, while a strong signal was detectable at the nuclear level after 24 h, suggesting a time-dependent uptake. To evaluate the cytotoxicity of doxorubicin-loaded NPs, tumour spheroids were treated for up to 96 h with increasing concentrations of NPs, showing marked toxicity only at the highest concentration of doxorubicin. When doxorubicin administration was combined with laser photothermal irradiation, enhanced cytotoxicity was observed at lower concentrations and incubation times. Finally, the photoacoustic properties of doxorubicin-loaded NPs were evaluated in tumour spheroids, showing a detectable signal increasing with NP concentration. Overall, our data show that the combined effect of chemo-photothermal therapy results in a shorter exposure time to doxorubicin and a lower drug dose. Furthermore, owing to the photoacoustic properties of the NPs, this nanoplatform may represent a good candidate for theranostic applications.

Humic acids (HA) consist in a multitude of heterogeneous organic molecules surviving the biological and chemical degradation of both vegetal and animal biomasses. The great abundance and chemical richness of these residues make their valorisation one of the most promising approaches to move towards a circular economy. However, the heterogeneity of the biomass from which HA are extracted, as well as the production process, significantly affects the nature and the relative content of functional groups (i.e. quinones, phenols and carboxylic and hydroxyl moieties), eventually changing HA reactivity and ultimately determining their application field. Indeed, depending on their properties, these substances can be used as flame retardants in the case of pronounced resilience degree (i.e., absent or low reactivity), or as antioxidant or antimicrobial agents in the case of pronounced reactivity, thanks to their redox behaviour. In this work we investigated the flammable, the thermal and the physico-chemical features of HA extracted from different composted biomasses to identify the reactivity or the resiliency of these moieties. Several techniques, including flammability characterization (LIT and MIE), laser diffraction granulometry, TG, XRD analyses, FTIR spectroscopy on both solid and gaseous phases, and Raman spectroscopy were integrated to investigate the correlation among the safety parameters, the distributions of particle sizes, as well as the thermal, the chemical properties of HA powders and the influence of post-extraction processes on HA final properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Photoacoustics (PA) is gaining increasing credit among biomolecular imaging methodologies by virtue of its poor invasiveness, deep penetration, high spatial resolution, and excellent endogenous contrast, without the use of any ionizing radiation. Recently, we disclosed the excellent PA response of a self-structured biocompatible nanoprobe, consisting of ternary hybrid nanoparticles with a silver core and a melanin component embedded into a silica matrix. Although preliminary evidence suggested a crucial role of the Ag sonophore and the melanin-containing nanoenvironment, whether and in what manner the PA response is controlled and affected by the self-structured hybrid nanosystems remained unclear. Because of their potential as multifunctional platforms for biomedical applications, a detailed investigation of the metal-polymer-matrix interplay underlying the PA response was undertaken to understand the physical and chemical factors determining the enhanced response and to optimize the architecture, composition, and performance of the nanoparticles for efficient imaging applications. Herein, we provide the evidence for a strong synergistic interaction between eumelanin and Ag which suggests an important role in the in situ-generated metal-organic interface. In particular, we show that a strict ratio between melanin and silver precursors and an accurate choice of metal nanoparticle dimension and the kind of metal are essential for achieving strong enhancements of the PA response. Systematic variation of the metal/melanin component is thus shown to offer the means of tuning the stability and intensity of the photoacoustic response for various biomedical and theranostic applications.

Redox-active nano-biointerfaces are gaining weight in the field of regenerative medicine since they can act as enzymes in regulating physiological processes and enabling cell homeostasis, as well as the defense against pathogen aggression. In particular, cerium oxide nanoparticles (CeO 2 NPs) stand as intriguing enzyme-mimicking nanoplatforms, owing to the reversible Ce +3 /Ce +4 surface oxidation state. Moreover, surface functionalization leads to higher catalytic activity and selectivity, as well as more tunable enzyme-mimicking performances. Conjugation with melanin is an adequate strategy to boost and enrich CeO 2 NPs biological features, because of melanin redox properties accounting for intrinsic antioxidant, antimicrobial and anti-inflammatory power. Herein, hybrid Melanin/CeO 2 nanostructures were designed by simply coating the metal-oxide nanoparticles with melanin chains, obtained in-situ through ligand-to-metal charge transfer mechanism, according to a bioinspired approach. Obtained hybrid nanostructures underwent detailed physico-chemical characterization. Morphological and textural features were investigated through TEM, XRD and N 2 physisorption. The nature of nanoparticle-melanin interaction was analyzed through FTIR, UV-vis and EPR spectroscopy. Melanin-coated hybrid nanostructures exhibited a relevant antioxidant activity, confirmed by a powerful quenching effect for DPPH radical, reaching 81 % inhibition at 33 μg/mL. A promising anti-inflammatory efficacy of the melanin-coated hybrid nanostructures was validated through a significant inhibition of BSA denaturation after 3 h. Meanwhile, the enzyme-mimicking activity was corroborated by a prolonged peroxidase activity after 8 h at 100 μg/mL and a relevant catalase-like action, by halving the H 2 O 2 level in 30 min at 50 μg/mL. Antimicrobial assays attested that conjugation with melanin dramatically boosted CeO 2 biocide activity against both Gram (-) and Gram (+) strains. Cytocompatibility tests demonstrated that the melanin coating not only enhanced the CeO 2 nanostructures biomimicry, resulting in improved cell viability for human dermal fibroblast cells (HDFs), but mostly they proved that Melanin-CeO 2 NPs were able to control the oxidative stress, modulating the production of nitrite and reactive oxygen species (ROS) levels in HDFs, under physiological conditions. Such remarkable outcomes make hybrid melanin-CeO 2 nanozymes, promising redox-active interfaces for regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This review focuses on the opportunities provided by sol-gel chemistry for the production of silica/epoxy nanocomposites, with significant representative examples of the "extra situ" approach and an updated description of the "in situ" strategy. The "extra situ" strategy enables the creation of nanocomposites containing highly engineered nanoparticles. The "in situ" approach is a very promising synthesis route that allows us to produce, in a much easier and eco-friendly manner, properly flame-retarded silica/epoxy nanocomposites endowed with very interesting properties. The review highlights the recently proposed mechanism of nanoparticles formation, which is expected to help to design the synthesis strategies of nanocomposites, changing their composition (both for the nanoparticle and matrix nature) and with in situ-generated nanoparticles possibly more complex than the ones obtained, until today, through this route.

Exploring opportunities for biowaste valorization, herein, humic substances (HS) were combined with gelatin, a hydrophilic biocompatible and bioavailable polymer, to obtain 3D hydrogels. Hybrid gels (Gel HS) were prepared at different HS contents, exploiting physical or chemical cross-linking, through 1-ethyl-(3-3-dimethylaminopropyl)carbodiimide (EDC) chemistry, between HS and gelatin. Physicochemical features were assessed through rheological measurements, X-ray diffraction, attenuated total reflectance (ATR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). ATR and NMR spectroscopies suggested the formation of an amide bond between HS and Gel via EDC chemistry. In addition, antioxidant and antimicrobial features toward both Gram(-) and Gram(+) strains were evaluated. HS confers great antioxidant and widespread antibiotic performance to the whole gel. Furthermore, the chemical cross-linking affects the viscoelastic behavior, crystalline structures, water uptake, and functional performance and produces a marked improvement of biocide action.

Stimulated Raman scattering in transparent glass-ceramics (TGCs) based on bulk nucleating phase Ba 2 NaNb 5 O 15 were investigated with the aim to explore the influence of micro- and nanoscale structural transformations on Raman gain. Nanostructured TGCs were synthesized, starting with 8BaO·15Na 2 O·27Nb 2 O 5 ·50SiO 2 (BaNaNS) glass, by proper nucleation and crystallization heat treatments. TGCs are composed of nanocrystals that are 10-15 nm in size, uniformly distributed in the residual glass matrix, with a crystallinity degree ranging from 30 up to 50% for samples subjected to different heat treatments. A significant Raman gain improvement for both BaNaNS glass and TGCs with respect to SiO 2 glass is demonstrated, which can be clearly related to the nanostructuring process. These findings show that the nonlinear optical functionalities of TGC materials can be modulated by controlling the structural transformations at the nanoscale rather than microscale.

Microbial colonization of surfaces is a sanitary and industrial issue for many applications, leading to product contamination and human infections. When microorganisms closely interact with a surface, they start to produce an exo-polysaccaridic matrix to adhere to and protect themselves from adverse environmental conditions. This type of structure is called a biofilm. The aim of our work is to investigate novel technologies able to prevent biofilm formation by surface coatings. We coated glass surfaces with melanin-ZnO 2 , melanin-TiO 2 , and TiO 2 hybrid nanoparticles. The functionalization was performed using cold plasma to activate glass-substrate-coated surfaces, that were characterized by performing water and soybean oil wetting tests. A quantitative characterization of the antibiofilm properties was done using Pseudomonas fluorescens AR 11 as a model organism. Biofilm morphologies were observed using confocal laser scanning microscopy and image analysis techniques were used to obtain quantitative morphological parameters. The results highlight the efficacy of the proposed surface coating to prevent biofilm formation. Melanin-TiO 2 proved to be the most efficient among the particles investigated. Our results can be a valuable support for future implementation of the technique proposed here in an extended range of applications that may include further testing on other strains and other support materials.

Polyethylene (PE) is high molecular weight synthetic polymer, very hydrofobic and hardly biodegradable. To increase polyethylene bio-degradability it is very important to find microorganisms that improve the PE hydrophilic level and/or reduce the length of its polymeric chain by oxidation. In this study, we isolated Cladosporium halotolerans, a fungal species, from the gastric system of Galleria mellonella larvae. Here, we show that C. halotolerans grows in the presence of PE polymer, it is able to interact with plastic material through its hyphae and secretes enzymes involved in PE degradation., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

The existing literature survey reports rare and conflicting studies on the effect of the preparation method of metal-based semiconductor photocatalysts on structural/morphological features, electronic properties, and kinetics regulating the photocatalytic H 2 generation reaction. In this investigation, we compare the different copper/titania-based photocatalysts for H 2 generation synthesized via distinct methods (i.e., photodeposition and impregnation). Our study aims to establish a stringent correlation between physicochemical/electronic properties and photocatalytic performances for H 2 generation based on material characterization and kinetic modeling of the experimental outcomes. Estimating unknown kinetic parameters, such as charge recombination rate and quantum yield, suggests a mechanism regulating charge carrier lifetime depending on copper distribution on the TiO 2 surface. We demonstrate that H 2 generation photoefficiency recorded over impregnated Cu x O y /TiO 2 is related to an even distribution of Cu(0)/Cu(I) on TiO 2 , and the formation of an Ohmic junction concertedly extended charge carrier lifetime and separation. The outcomes of the kinetic analysis and the related modeling investigation underpin photocatalyst physicochemical and electronic properties. Overall, the present study lays the groundwork for the future design of metal-based semiconductor photocatalysts with high photoefficiencies for H 2 evolution.

Heparin plays multiple biological roles depending on the availability of active sites strongly influenced by the conformation and the structure of polysaccharide chains. Combining different components at the molecular scale offers an extraordinary chance to easily tune the structural organization of heparin required for exploring new potential applications. In fact, the combination of different material types leads to challenges that cannot be achieved by each single component. In this study, hybrid heparin/silica nanoparticles were synthesized, and the role of silica as a templating agent for heparin supramolecular organization was investigated. The effect of synthesis parameters on particles compositions was deeply investigated by Fourier Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA). Transmission Electron Microscopy (TEM) reveals a different supramolecular organization of both components, leading to amazing organic-inorganic nanoparticles with different behavior in drug encapsulation and release. Furthermore, favorable biocompatibility for healthy human dermal fibroblasts (HDF) and tumor HS578T cells has been assessed, and a different biological behavior was observed, ascribed to different surface charge and morphology of synthesized nanoparticles.

CeO 2 slow redox kinetics as well as low oxygen exchange ability limit its application as a catalyst in solar thermochemical two-step cycles. In this study, Ce 0.75 Zr 0.25 O 2 catalysts doped with potassium or transition metals (Cu, Mn, Fe), as well as co-doped materials were synthesized. Samples were investigated by X-ray diffraction (XRD), N 2 sorption (BET), as well as by electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) to gain insight into surface and bulk features, which were connected to redox properties assessed both in a thermogravimetric (TG) balance and in a fixed bed reactor. Obtained results revealed that doping as well as co-doping with non-reducible K cations promoted the increase of both surface and bulk oxygen vacancies. Accordingly, K-doped and Fe-K co-doped materials show the best redox performances evidencing the highest reduction degree, the largest H 2 amounts and the fastest kinetics, thus emerging as very interesting materials for solar thermochemical splitting cycles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Exploring the chance to convert biowaste into a valuable resource, this study tests the potential role of humic acids (HA), a class of multifunctional compounds obtained by oxidative decomposition of biomass, as physical agents to improve gelatin's mechanical and thermal properties. To this purpose, gelatin-HA aqueous samples were prepared at increasing HA content. HA/gelatin concentrations changed in the range 2.67-26.67 (wt/wt)%. Multiple techniques were employed to assess the influence of HA content on the gel properties and to unveil the underlying mechanisms. HAs increased gel strength up to a concentration of 13.33 (wt/wt)% and led to a weaker gel at higher concentrations. FT-IR and DSC results proved that HAs can establish noncovalent interactions through H-bonding with gelatin. Coagulation phenomena occur because of HA-gelatin interactions, and at concentrations greater than 13.33 (wt/wt)%, HAs established preferential bonds with water molecules, preventing them from coordinating with gelatin chains. These features were accompanied by a change in the secondary structure of gelatin, which lost the triple helix structure and exhibited an increase in the random coil conformation. Besides, higher HA weight content caused swelling phenomena due to HA water absorption, contributing to a weaker gel. The current findings may be useful to enable a better control of gelatin structures modified with composted biowaste, extending their exploitation for a large set of technological applications.

Humic acids (HA) are considered a promising and inexpensive source for novel multifunctional materials for a huge range of applications. However, aggregation and degradation phenomena in aqueous environment prevent from their full exploitation. A valid strategy to address these issues relies on combining HA moieties at the molecular scale with an inorganic nanostructured component, leading to more stable hybrid nanomaterials with tunable functionalities. Indeed, chemical composition of HA can determine their interactions with the inorganic constituent in the hybrid nanoparticles and consequently affect their overall physico-chemical properties, including their stability and functional properties in aqueous environment. As a fundamental contribution to HA materials-based technology, this study aims at unveiling this aspect. To this purpose, SiO 2 nanoparticles have been chosen as a model platform and three different HAs extracted from composted biomasses, manure (HA_Man), artichoke residues (HA_Art) and coffee grounds (HA_Cof), were employed to synthetize hybrid HA-SiO 2 nanoparticles through in-situ sol-gel synthesis. Prepared samples were submitted to aging in water to assess their stability. Furthermore, antioxidant properties and physico-chemical properties of both as prepared and aged samples in aqueous environment were assessed through Scanning Electron Microscopy (SEM), N 2 physisorption, Simultaneous Thermogravimetric (TGA) and Differential Scanning Calorimetric (DSC) Analysis, Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR) spectroscopies. The experimental results highlighted that hybrid HA-SiO 2 nanostructures acted as dynamic systems which exhibit structural supramolecular reorganization during aging in aqueous environment with marked effects on physico-chemical and functional properties, including improved antioxidant activity. Obtained results enlighten a unique aspect of interactions between HA and inorganic nanoparticles that could be useful to predict their behavior in aqueous environment. Furthermore, the proposed approach traces a technological route for the exploitation of organic biowaste in the design of hybrid nanomaterials, providing a significant contribution to the development of waste to wealth strategies based on humic substances., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Green syngas production is a sustainable energy-development goal. Thermochemical H 2 O/CO 2 splitting is a very promising sustainable technology allowing the production of H 2 and CO with only oxygen as the by-product. CeO 2 -ZrO 2 systems are well known thermochemical splitting catalysts, since they combine stability at high temperature with rapid kinetics and redox cyclability. However, redox performances of these materials must be improved to allow their use in large scale plants. K-doped systems show good redox properties and repeatable performances. In this work, we studied the effect of potassium content on the performances of ceria-zirconia for CO 2 splitting. A kinetic model was developed to get insight into the nature of the catalytic sites. Fitting results confirmed the hypothesis about the existence of two types of redox sites in the investigated catalytic systems and their role at different K contents. Moreover, the model was used to predict the influence of key parameters, such as the process conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A coupled 3D hydrodynamic-ecological model was applied to the Santa Marta Coastal Area (SMCA, Colombian Caribbean) to provide insights into the role of external stressors (e.g. wastewater outfall and upwelling) on the water quality and benthic - pelagic coupling. The model was calibrated and validated based on benthic metabolic measurements, satellite-derived chlorophyll-a (Chl-a) and sea surface temperature (SST) maps, field and literature water quality data. The model was able to reproduce the complex dynamics and fast transitions of temperature, nutrients, and phytoplankton, including the stratification and mixing periods during the non-upwelling (NUPW) and upwelling (UPW) seasons. Wide and fast changes in the temperatures and the highly flushed environment prevented excess phytoplankton growth and nutrient accumulation in the benthic and pelagic compartments. The model proved to be a reliable research tool to analyze the interactive effects of upwelling and untreated wastewater on the functioning of a tropical bay., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hybrid nanomaterials have attracted research interest owing to their intriguing properties, which may offer new diagnostic options with triggering features, able to realize a new kind of tunable nanotherapeutics. Hybrid silica/melanin nanoparticles (NPs) containing silver seeds (Me-laSil_Ag-HSA NPs) disclosed relevant photoacoustic contrast for molecular imaging. In this study we explored therapeutic function in the same nanoplatform. For this purpose, MelaSil_Ag-HSA were loaded with doxorubicin (DOX) (MelaSil_Ag-HSA@DOX) and tested to assess the efficiency of drug delivery combined with concurrent photothermal treatment. The excellent photothermal properties allowed enhanced cytotoxic activity at significantly lower doses than neat chemotherapeutic treatment. The results revealed that MelaSil_Ag-HSA@DOX is a promising platform for an integrated photothermal (PT) chemotherapy approach, reducing the efficacy concentration of the DOX and, thus, potentially limiting the several adverse side effects of the drug in in vivo treatments.

Hybrid Melanin-TiO 2 nanoparticles are promising bioinspired antibacterial agents for biomedical coatings and food-packaging fields. However, due to a very low colloidal stability, they showed a high tendency to self-aggregate and rapidly precipitate, making not easy their use in aqueous medium to produce homogeneous antimicrobial coatings or nanocomposites. A valid strategy to improve their dispersion is the combination with a hydrophilic water-soluble polymer such as poly-vinyl-alcohol (PVA), which is a good choice to improve the colloidal stability of nanoparticles and to modulate their agglomeration. In this work, we propose an in-situ synthetic approach based on the hydrothermal route, by which the hybrid Melanin-TiO 2 nanoparticles were prepared starting from the inorganic and organic precursors in the presence of PVA. Combined approach of TEM, XRD, TG/DSC, EPR and DLS techniques allows for assessing the PVA role in the formation of hybrids and on their morphological features as well as colloidal stability and aqueous dispersion. Antibacterial tests demonstrated the biocide activity of PVA/Melanin-TiO 2 nanoparticles against Escherichia coli bacterial cultures, which resulted partially influenced by the PVA content. This study provides key information on the mutual influence of organic/inorganic components on the functional properties of the final hybrid nanocomposites, contributing to define a much more far-reaching implementation in the synthesis of bioinspired polymer-based nanocomposites., (Copyright © 2021 Elsevier B.V. All rights reserved.)

As humans explore and settle in space, they will need to mine elements to support industries such as manufacturing and construction. In preparation for the establishment of permanent human settlements across the Solar System, we conducted the ESA BioRock experiment on board the International Space Station to investigate whether biological mining could be accomplished under extraterrestrial gravity conditions. We tested the hypothesis that the gravity ( g ) level influenced the efficacy with which biomining could be achieved from basalt, an abundant material on the Moon and Mars, by quantifying bioleaching by three different microorganisms under microgravity, simulated Mars and Earth gravitational conditions. One element of interest in mining is vanadium (V), which is added to steel to fabricate high strength, corrosion-resistant structural materials for buildings, transportation, tools and other applications. The results showed that Sphingomonas desiccabilis and Bacillus subtilis enhanced the leaching of vanadium under the three gravity conditions compared to sterile controls by 184.92 to 283.22%, respectively. Gravity did not have a significant effect on mean leaching, thus showing the potential for biomining on Solar System objects with diverse gravitational conditions. Our results demonstrate the potential to use microorganisms to conduct elemental mining and other bioindustrial processes in space locations with non-1 × g gravity. These same principles apply to extraterrestrial bioremediation and elemental recycling beyond Earth., Competing Interests: VZ, MB, AM, SP, FC, and GL were employed by the company Kayser Italia S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cockell, Santomartino, Finster, Waajen, Nicholson, Loudon, Eades, Moeller, Rettberg, Fuchs, Van Houdt, Leys, Coninx, Hatton, Parmitano, Krause, Koehler, Caplin, Zuijderduijn, Mariani, Pellari, Carubia, Luciani, Balsamo, Zolesi, Ochoa, Sen, Watt, Doswald-Winkler, Herová, Rattenbacher, Wadsworth, Everroad and Demets.)

Developing advanced materials for wound dressings is a very challenging, yet unaddressed task. These systems are supposed to act as temporary skin substitutes, performing multiple functions, including fluid absorption and antimicrobial action, supporting cell proliferation and migration in order to promote the skin regeneration process. Following a global bioinspired approach, in this study, we developed a multifunctional textile for wound dressing applications. Biodegradable polyhydroxybutyrate/poly-3-caprolactone (PHB/PCL) mats were fabricated by electrospinning to mimic the extracellular matrix (ECM), thus providing structural and biochemical support to tissue regeneration. Furthermore, inspired by nature's strategy which exploits melanin as an effective weapon against pathogens infection, PHB/PCL mats were modified with hybrid Melanin-TiO 2 nanostructures. These were combined to PHB/PCL mats following two different strategies: in-situ incorporation during electrospinning process, alternately ex-post coating by electrospraying onto obtained mats. All samples revealed huge water uptake and poor cytotoxicity towards HaCat eukaryotic cells. Melanin-TiO 2 coating conferred PHB/PCL mats significant antimicrobial activity towards both Gram(+) and Gram(-) strains, marked hydrophilic properties as well as bioactivity which is expected to promote materials-cells interaction. This study is going to provide a novel paradigm for the design of active wound dressings for regenerative medicine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Anatomical changes and patient setup uncertainties during intensity modulated proton therapy (IMPT) of head and neck (HN) cancers demand frequent evaluation of delivered dose. This work investigated a cone-beam computed tomography (CBCT) and deformable image registration based therapy workflow to demonstrate the feasibility of proton dose calculation on synthetic computed tomography (sCT) for adaptive IMPT treatment of HN cancer., Materials and Methods: Twenty-one patients with HN cancer were enrolled in this study, a retrospective institutional review board protocol. They had previously been treated with volumetric modulated arc therapy and had daily iterative CBCT. For each patient, robust optimization (RO) IMPT plans were generated using ±3 mm patient setup and ±3% proton range uncertainties. The sCTs were created and the weekly delivered dose was recalculated using an adaptive dose accumulation workflow in which the planning computed tomography (CT) was deformably registered to CBCTs and Hounsfield units transferred from the planning CT. Accumulated doses from ±3 mm/±3% RO-IMPT plans were evaluated using clinical dose-volume constraints for targets (clinical target volume, or CTV) and organs at risk., Results: Evaluation of weekly recalculated dose on sCTs showed that most of the patient plans maintained target dose coverage. The primary CTV remained covered by the V95 > 95% (95% of the volume receiving more than 95% of the prescription dose) worst-case scenario for 84.5% of the weekly fractions. The oral cavity accumulated mean dose remained lower than the worst-case scenario for all patients. Parotid accumulated mean dose remained within the uncertainty bands for 18 of the 21 patients, and all were kept lower than RO-IMPT worst-case scenario for 88.7% and 84.5% for left and right parotids, respectively., Conclusion: This study demonstrated that RO-IMPT plans account for most setup and anatomical uncertainties, except for large weight-loss changes that need to be tracked throughout the treatment course. We showed that sCTs could be a powerful decision tool for adaptation of these cases in order to reduce workload when using repeat CTs., Competing Interests: Conflicts of Interest: The authors have no relevant conflicts of interest to disclose., (©Copyright 2021 The Author(s).)

Purpose: Radiation therapy dose escalation using stereotactic body radiation therapy may significantly improve both local control (LC) and overall survival (OS) for patients with inoperable pancreas cancer. However, ablative dose cannot be routinely offered because of the risk of causing severe injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents a novel technique that may achieve safe delivery of ablative dose and improve long-term outcomes., Methods and Materials: We performed a single institution retrospective analysis of 35 consecutive pancreatic cancer patients treated with SMART in mid-inspiration breath hold on an MR-linear accelerator. Most had locally advanced disease (80%) and received induction chemotherapy (91.4%) for a median 3.9 months before stereotactic body radiation therapy. All were prescribed 5 fractions delivered in consecutive days to a median total dose of 50 Gy (BED 10 100 Gy 10 ), typically with a 120% to 130% hotspot. Elective nodal irradiation was delivered to 20 (57.1%) patients. No patient had fiducial markers placed and all were treated with continuous intrafraction MR visualization and automatic beam triggering., Results: With median follow-up of 10.3 months from SMART, acute (2.9%) and late (2.9%) grade 3 toxicities were uncommon. One-year LC, distant metastasis-free survival, progression-free survival, cause-specific survival, and OS were 87.8%, 63.1%, 52.4%, 77.6%, and 58.9%, respectively., Conclusions: To our knowledge, this is the first report of 5-fraction pancreas SMART delivered on an MR-linear accelerator. We observed minimal severe treatment-related toxicity and encouraging early LC. Prospective confirmation of feasibility and long-term clinical outcomes of dose intensified SMART is warranted., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Humic acids (HAs) provide an important bio-source for redox-active materials. Their functional chemical groups are responsible for several properties, such as metal ion chelating activity, adsorption ability towards small molecules and antibacterial activity, through reactive oxygen species (ROS) generation. However, the poor selectivity and instability of HAs in solution hinder their application. A promising strategy for overcoming these disadvantages is conjugation with an inorganic phase, which leads to more stable hybrid nanomaterials with tuneable functionalities. In this study, we demonstrate that hybrid humic acid/titanium dioxide nanostructured materials that are prepared via a versatile in situ hydrothermal strategy display promising antibacterial activity against various pathogens and behave as selective sequestering agents of amoxicillin and tetracycline antibiotics from wastewater. A physicochemical investigation in which a combination of techniques were utilized, which included TEM, BET, 13 C-CPMAS-NMR, EPR, DLS and SANS, shed light on the structure-property-function relationships of the nanohybrids. The proposed approach traces a technological path for the exploitation of organic biowaste in the design at the molecular scale of multifunctional nanomaterials, which is useful for addressing environmental and health problems that are related to water contamination by antibiotics and pathogens., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Microorganisms are employed to mine economically important elements from rocks, including the rare earth elements (REEs), used in electronic industries and alloy production. We carried out a mining experiment on the International Space Station to test hypotheses on the bioleaching of REEs from basaltic rock in microgravity and simulated Mars and Earth gravities using three microorganisms and a purposely designed biomining reactor. Sphingomonas desiccabilis enhanced mean leached concentrations of REEs compared to non-biological controls in all gravity conditions. No significant difference in final yields was observed between gravity conditions, showing the efficacy of the process under different gravity regimens. Bacillus subtilis exhibited a reduction in bioleaching efficacy and Cupriavidus metallidurans showed no difference compared to non-biological controls, showing the microbial specificity of the process, as on Earth. These data demonstrate the potential for space biomining and the principles of a reactor to advance human industry and mining beyond Earth.

Microorganisms perform countless tasks on Earth and they are expected to be essential for human space exploration. Despite the interest in the responses of bacteria to space conditions, the findings on the effects of microgravity have been contradictory, while the effects of Martian gravity are nearly unknown. We performed the ESA BioRock experiment on the International Space Station to study microbe-mineral interactions in microgravity, simulated Mars gravity and simulated Earth gravity, as well as in ground gravity controls, with three bacterial species: Sphingomonas desiccabilis , Bacillus subtilis , and Cupriavidus metallidurans . To our knowledge, this was the first experiment to study simulated Martian gravity on bacteria using a space platform. Here, we tested the hypothesis that different gravity regimens can influence the final cell concentrations achieved after a multi-week period in space. Despite the different sedimentation rates predicted, we found no significant differences in final cell counts and optical densities between the three gravity regimens on the ISS. This suggests that possible gravity-related effects on bacterial growth were overcome by the end of the experiment. The results indicate that microbial-supported bioproduction and life support systems can be effectively performed in space (e.g., Mars), as on Earth., (Copyright © 2020 Santomartino, Waajen, de Wit, Nicholson, Parmitano, Loudon, Moeller, Rettberg, Fuchs, Van Houdt, Finster, Coninx, Krause, Koehler, Caplin, Zuijderduijn, Zolesi, Balsamo, Mariani, Pellari, Carubia, Luciani, Leys, Doswald-Winkler, Herová, Wadsworth, Everroad, Rattenbacher, Demets and Cockell.)

In this work the flammable/explosive behavior of mixtures of flammable dusts is investigated. In particular, minimum ignition temperature, minimum ignition energy, maximum pressure and deflagration index have been measured at varying the relative content of dusts in the mixtures. The thermal behavior of these mixtures has been also studied by means of DSC analysis coupled to chemical analysis performed by HPLC and ATR-FTIR. Depending on the mixtures, a synergistic behavior has been found due to physical and/or chemical reactions. For some mixtures, the more severe behavior has been attributed to the presence of a eutectic point (niacin/anthraquinone, ascorbic acid/niacin), in other cases, to chemical reactions with the formation of volatiles (ascorbic acid/irganox 1222, ascorbic acid/glucose). On this basis, we propose a new classification of dusts mixtures in three mixtures safety classes (MSC): MSC 0 (no synergistic effect, ideal behavior); MSC 1 (deviation from ideality, safety parameters included between those of the pure dusts) and MSC 2 (at least 1 parameter with more sever value than those of pure dusts)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The gut-brain axis and the intestinal microbiota are emerging as key players in health and disease. Shifts in intestinal microbiota composition affect a variety of systems; however, evidence of their direct impact on cognitive functions is still lacking. We tested whether faecal microbiota transplant (FMT) from aged donor mice into young adult recipients altered the hippocampus, an area of the central nervous system (CNS) known to be affected by the ageing process and related functions., Results: Young adult mice were transplanted with the microbiota from either aged or age-matched donor mice. Following transplantation, characterization of the microbiotas and metabolomics profiles along with a battery of cognitive and behavioural tests were performed. Label-free quantitative proteomics was employed to monitor protein expression in the hippocampus of the recipients. We report that FMT from aged donors led to impaired spatial learning and memory in young adult recipients, whereas anxiety, explorative behaviour and locomotor activity remained unaffected. This was paralleled by altered expression of proteins involved in synaptic plasticity and neurotransmission in the hippocampus. Also, a strong reduction of bacteria associated with short-chain fatty acids (SCFAs) production (Lachnospiraceae, Faecalibaculum, and Ruminococcaceae) and disorders of the CNS (Prevotellaceae and Ruminococcaceae) was observed. Finally, the detrimental effect of FMT from aged donors on the CNS was confirmed by the observation that microglia cells of the hippocampus fimbria, acquired an ageing-like phenotype; on the contrary, gut permeability and levels of systemic and local (hippocampus) cytokines were not affected., Conclusion: These results demonstrate that age-associated shifts of the microbiota have an impact on protein expression and key functions of the CNS. Furthermore, these results highlight the paramount importance of the gut-brain axis in ageing and provide a strong rationale to devise therapies aiming to restore a young-like microbiota to improve cognitive functions and the declining quality of life in the elderly. Video Abstract.

Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many biological functions ensuring homeostasis. Due to their broad-spectrum light absorption, radical scavenging, electric conductivity, and paramagnetic behavior, eumelanins are widely studied in the biomedical field. The continuing advancements in the development of biomimetic design strategies offer novel opportunities toward specifically engineered multifunctional biomaterials for regenerative medicine. Melanin and melanin-like coatings have been shown to increase cell attachment and proliferation on different substrates and to promote and ameliorate skin, bone, and nerve defect healing in several in vivo models. Herein, the state of the art and future perspectives of melanins as promising bioinspired platforms for natural regeneration processes are highlighted and discussed.

Bioconjugation of a recently developed photoacoustic nanoprobe, based on silica-templated eumelanin-silver hybrid nanoparticles (MelaSil_Ag-NPs), with human serum albumin (HSA) is disclosed herein as an efficient and practical strategy to improve photostability and to perform SPARC mediated internalization in breast cancer cells. Modification of NPs with HSA induced a slight viability decrease in breast cancer cells (HS578T) and normal breast cells (MCF10a) when incubated with HSA-NPs up to 100 μg/mL concentration for 72 h and a complete suppression of hemotoxicity for long incubation times. Uptake experiments with MelaSil_Ag-HSA NPs indicated very high and selective internalization via SPARC in HS578T (SPARC positive cells) but not in MCF10a (SPARC negative cells), as evaluated by using endocytosis inhibitors. The binding of SPARC to HSA was confirmed by Co-IP and Dot-blot assays. Additional studies were performed to analyze the interaction of MelaSil_Ag-HSA NPs with protein corona. Data showed a dramatic diminution of interacting proteins in HSA conjugated NPs compared to bare NPs. HSA-coated MelaSil_Ag-NPs are thus disclosed as a novel functional nanohybrid for potential photoacoustic imaging applications., (Copyright © 2020 Sanità, Armanetti, Silvestri, Carrese, Calì, Pota, Pezzella, d’Ischia, Luciani, Menichetti and Lamberti.)

Humic acids (HA) exhibit fascinating multifunctional features, yet degradation phenomena as well as poor stability in aqueous environments strongly limit their use. Inorganic nanoparticles are emerging as a powerful interface for the development of robust HA bio-hybrid materials with enhanced chemical stability and tunable properties. Hybrid organic-inorganic SiO 2 /HA nanostructures were synthesized via an in-situ sol-gel route, exploiting both physical entrapment and chemical coupling. The latter was achieved through amide bond formation between carboxyl groups of HA and the amino group of 3-aminopropyltriethoxysilane (APTS), as confirmed by Fourier-Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Monodisperse hybrid nanoparticles about 90 nm in diameter were obtained in both cases, yet Electron Paramagnetic Resonance (EPR) spectroscopy highlighted the different supramolecular organization of HA. The altered HA conformation was reflected in different antioxidant properties of the conjugated nanoparticles that, however, resulted in being higher than for pure HA. Our findings proved the key role of both components in defining the morphology of the final system, as well as the efficacy of the ceramic component in templating the HA supramolecular organization and consequently tuning their functional features, thus defining a green strategy for bio-waste valorization.

One of the main issues in preparing polymer-based nanocomposites with effective properties is to achieve a good dispersion of the nanoparticles into the matrix. Chemical interfacial modifications by specific coupling agents represents a good way to reach this objective. Actually, time consuming compatibilization procedures strongly compromise the sustainability of these strategies. In this study, the role of particles' architectures in their dispersion into a poly-lactic acid matrix and their subsequent influences on physical-chemical properties of the obtained nanocomposites were investigated. Two kinds of silica nanoparticles, "smooth" and "wrinkled," with different surface areas (≈30 and ≈600 m 2 /g respectively) were synthesized through a modified Stöber method and used, without any chemical surface pre-treatments, as fillers to produce poly-lactic acid based nanocomposites. The key role played by wrinkled texture in modifying the physical interaction at the polymer-filler interface and in driving composite properties, was investigated and reflected in the final bulk properties. Detailed investigations revealed the presence of wrinkled nanoparticles, leading to (i) an enormous increase of the chain relaxation time, by almost 30 times compared to the neat PLA matrix; (ii) intensification of the shear-thinning behavior at low shear-rates; and (iii) slightly slower thermal degradation of polylactic acid., Competing Interests: The authors declare no conflict of interest.

Developing safe and high efficiency contrast tools is an urgent need to allow in vivo applications of photoacoustics (PA), an emerging biomolecular imaging methodology, with poor invasiveness, deep penetration, high spatial resolution and excellent endogenous contrast. Eumelanins hold huge promise as biocompatible, endogenous photoacoustic contrast agents. However, their huge potential is still unexplored due to the difficulty to achieve at the same time poor aggregation in physiologic environment and high PA contrast. This study addresses both issues through the design of a biocompatible photoacoustic nanoprobe, named MelaSil_Ag-NPs, relying on silica-templated eumelanin formation as well as eumelanins redox and metal chelating properties to reduce Ag + ions and control the growth of generated metal nanoparticles. This strategy allowed self-structuring of the system into a core-shell architecture, where the Ag core was found to boost PA signal, despite the poor eumelanin content. Obtained hybrid nanoplatforms, showed stable photoacoustic properties even under long irradiation. Furthermore, conjugation with rhodamine isothiocyanate allowed particles detection through fluorescent imaging proving their multifunctional potentialities. In addition, they were stable towards aggregation and efficiently endocytosed by human pancreatic cancer cells (BxPC3 and Panc-1) displaying no significant cytotoxicity. Such numerous features prove huge potential of those nanoparticles as a multifunctional platform for biomedical applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nature has provided a valuable source of inspiration for developing high performance multifunctional materials. Particularly, catechol-containing amino acid l-3,4-dihydroxyphenylalanine (l-DOPA) has aroused the interest to design hybrid multifunctional materials with superior adhesive ability. DOPA oxidative polymerization mediated by either melanogenic enzymes or an alkaline environment involving catechol intermolecular cross-linking, ultimately leads to melanin oligomers. Recently, relevant studies disclosed the ability of Ti-based nanostructures to tune melanin's supramolecular structure during its formation, starting from melanogenic precursors, thus improving both antioxidant and antimicrobial properties. In this work, we propose a novel biomimetic approach to design hybrid DOPA melanin-like nanostructures through a hydrothermal synthesis opportunely modified by using citric acid to control hydrolysis and condensation reactions of titanium alkoxide precursors. UV-Vis and Electron paramagnetic resonance (EPR) spectroscopic evidences highlighted the key role of citrate-Ti(IV) and DOPA-Ti(IV) complexes in controlling DOPA polymerization, which specifically occurred during the hydrothermal step, mediating and tuning its conversion to melanin-like oligomers. Trasmission electron microscopy (TEM) images proved the efficacy of the proposed synthesis approach in tuning the formation of nanosized globular nanostructures, with high biocide performances. The obtained findings could provide strategic guidelines to set up biomimetic processes, exploiting the catechol-metal complex to obtain hybrid melanin-like nanosystems with optimized multifunctional behavior., Competing Interests: The authors declare no competing financial interest.

As a continuous source of hormonal stimulation, environmentally ubiquitous estrogenic chemicals, ie, xenoestrogens (XEs), are a potential risk factor for breast carcinogenesis. Given their wide distribution in the environment and the fact that bisphenol-A (BPA), methylparaben (MP), and perfluorooctanoic acid (PFOA) are uniformly detected in unselected body fluid samples, it must be assumed that humans are simultaneously exposed to these chemicals almost daily. We studied the effects of a ternary mixture of BPA, MP, and PFOA on benign breast epithelial cells at the range of concentrations observed for single chemicals in human samples. Measurements of exposure impact relevant to the breast were based on endpoints associated with "hallmarks" of cancer and "key characteristics" of carcinogens. These included modulation of total estrogen receptor (ER)α, phosphorylated ERα (pERα), total ERβ, S-phase induction, and apoptotic evasion. Data from live cell measurements were fit to a log-linear dose-response model. Concentration-dependent reduction of ERβ and apoptosis evasion was observed concurrently with the induction of ERα, pERα, and S-phase fraction, and an increased rate of cell proliferation. Beyond additive effects predicted by the sum of individual test XEs, mixture treatment demonstrated synergism for the ERβ and apoptosis suppression phenotypes (p > .001). Nonmalignant breast cells were more sensitive than commonly used breast cancer lines to XE treatment in 3 of 5 endpoints. All observations were validated with cells isolated from the normal breast tissue of 14 individuals. At relatively low concentrations, a chemical mixture has striking effects on normal cell function that are missed by evaluation of single components.

Intrinsic biocide efficacy of eumelanins can be markedly enhanced through a templated formation in the presence of a TiO 2 -sol, leading to hybrid TiO 2 -melanin nanostructures. However, mechanisms and processes behind biocide activity still remain poorly understood. This paper discloses the fundamental mechanism of action of these systems providing mechanistic information on their peculiar interaction with Escherichia coli strains. To this purpose biocide characterization is combined with Electron Paramagnetic Resonance (EPR) spectroscopy to investigate radical species produced by the hybrids as well as their interactions with Gram(-) external bacterial membranes. Experimental results indicate that TiO 2 mediated eumelanin polymerization leads to a peculiar mechanism of action of hybrid nanostructures, whose strong interactions with bacterial membranes enhance the action of reactive oxygen species (ROS) produced by eumelanin degradation itself, also concurring with the final biocide action. These findings provide strategic information for the development of eumelanin-based systems with enhanced activity against drug-resistant strains., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Microbial contamination still remains a major issue of the modern era, due to the widespread of drug-resistant pathogens. This has prompted researchers to come up with novel antimicrobial systems that could overcome antibiotic-resistance. In this context, nature can provide inestimable source of inspiration to design high-performance multifunctional materials with potent activity against drug-resistant pathogens. Actually, integrating the bio-inspired-approach with nanotechnology can provide cutting-edge solutions for drug-resistant infections. In this context, this review will examine recent advances in the development of bio-inspired antimicrobial nanostructures. Advantages of bioinspired approach to nanomaterials over conventional routes have been highlighted. Generally, bionspired synthesis can be carried out either by mimicking the functions of natural materials/ structures or by mimicking the biological processes employed to produce substances or materials. The review provides an overview of both strategies as applied to the synthesis of inorganic, organic as well as hybrid nanostructures. Antimicrobial efficacy and biological properties of these systems have been highlighted. Antimicrobial and antibiofouling nanostructured surfaces are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

We disclose herein the first example of stable monodispersed hybrid nanoparticles (termed MelaSil-NPs) made up of eumelanin biopolymer intimately integrated into a silica nanoscaffold matrix and endowed with high antioxidant and cytoprotective effects associated with a specific subcellular localization. MelaSil-NPs have been fabricated by an optimized sol-gel methodology involving ammonia-induced oxidative polymerization of a covalent conjugate of the eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA) with 3-aminopropyltriethoxysilanes (APTS). They displayed a round-shaped (ca. 50-80 nm) morphology, exhibited the typical electron paramagnetic resonance signal of eumelanin biopolymers, and proved effective in promoting decomposition of hydrogen peroxide under physiologically relevant conditions. When administered to human ovarian cancer cells (A2780) or cervical cancer cells (HeLa), MelaSil-NPs were rapidly internalized and colocalized with lysosomes and exerted efficient protecting effects against hydrogen peroxide-induced oxidative stress and cytotoxicity.

Eco-friendly hybrid Eumelanin-TiO 2 nanostructures, recently obtained through in situ methodology based on hydrothermal route, have shown a striking antimicrobial activity, after exposure to oxidative environment, even under visible light induction condition. Nevertheless, the role of each component in defining the efficacy of these biological properties is far from being clearly defined. Furthermore, the effect of oxidative step on hybrids structure has not yet addressed. This study aims at elucidating the role of the ratio between eumelanin precursor, 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and TiO 2 , for its polymerization in defining morphology and structural organization of TiO 2 -melanin nanostructures. Furthermore, tests on a Gram-negative Escherichia coli DH5α strain under UV irradiation and even visible light allowed to assess the contribution of each component, as well as of the TiO 2 -DHICA charge transfer complex to overall biological performance. Finally, results of biocide characterization were combined with spectroscopic evidences to prove that oxidative treatment induces a marked structural modification in melanin thus enhancing overall antimicrobial efficacy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Stable, biocompatible, multifunctional and multicompartment nanocarriers are much needed in the field of nanomedicine. Here, we report a simple, novel strategy to design an engineered nanocarrier system featuring an oil-core/hybrid polymer/silica-shell. Silica shells with a tunable thickness were grown in situ, directly around a highly mono-disperse and stable oil-in-water emulsion system, stabilized by a double bio-functional polyelectrolyte heparin/chitosan layer. Such silica showed a complete degradation in a physiological medium (SBF) in a time frame of three days. Moreover, the outer silica shell was coated with polyethyleneglycol (PEG) in order to confer antifouling properties to the final nanocapsule. The outer silica layer combined its properties (it is an optimal bio-interface for bio-conjugations and for the embedding of hydrophilic drugs in the porous structure) with the capability to stabilize the oil core for the confinement of high payloads of lipophilic tracers (e.g., CdSe quantum dots, Nile Red) and drugs. In addition, polymer layers--besides conferring stability to the emulsion while building the silica shell--can be independently exploited if suitably functionalized, as demonstrated by conjugating chitosan with fluorescein isothiocyanate. Such numerous features in a single nanocarrier system make it very intriguing as a multifunctional platform for smart diagnosis and therapy.

Understanding the mechanisms involved in the interaction of biological systems with inorganic materials is of great importance and interest in both fundamental and applied disciplines in several different fields such as astrobiology, ecology, biology, biotechnology, engineering, and medicine. In this context, this paper investigates the interaction of biomacromolecules with submicrometric silica gel particles (NP) obtained through the Stöber method. Surprisingly, particles size reduction is observed after their dispersion into two different reconstituted growth media (RPMI and M254). This effect was related to the nature of the Stöber particles and the mechanism of their formation. The experimental results can be explained arguing that a biomacromolecule corona rapidly forms on NP incubated in both RPMI and M254 growth media. The results suggest that hydrolytic attack at incompletely condensed internal surface valence sites as well as interactions between NPs surface and the components of the growth media reverse the aggregation process, giving smaller disaggregated particles surrounded by a biomacromolecule corona. Moreover it was assessed that, at longer incubation time, the particles slightly grow probably due to interlocking of biomacromolecules in the corona. Furthermore, experimental results confirm that formation of this corona is a competitive and dynamic process. The present paper shows that the described effects (as size changes) are strongly dependent on the nature of the growth medium., (Copyright © 2015 Elsevier B.V. All rights reserved.)