Melanin and Light.

Melanin is responsible, in Nature, for photoprotection, for this reason it is expected to be poorly photoreactive. However, the photo-reactivity of melanin and related materials is well documented. Here we discuss some relevant recent examples to demonstrate that, indeed, the actual mechanism of interaction of melanin with light is complex and still not completely understood. Photochemical and photothermal processes are involved, giving a contribution that strongly depends on light wavelength and intensity. Moreover, some interesting experiments demonstrated that photochemical reactivity of melanin related compounds is likely to be indirect, in the sense that the effect of light is to increase the number of radical species rather than creating photoreactive excited state. These suggestions open-up new perspectives in the interpretation of the role of melanin in photoprotection and in the design of new melanin based photoactive materials for energy conversion, environmental remediation, and nanomedicine. Further complication is given by the role of atmospheric oxygen and humidity in the photoinduced processes. Beside this complexity of behavior makes it difficult a systematic understanding of the interaction of melanin with light, it surely strongly contributes to make the properties of melanin and related materials unique.

Herpes zoster (HZ) vaccine coverage and confidence in Italy: a Nationwide cross-sectional study, the OBVIOUS project.

BACKGROUND: Herpes Zoster is an age dependent disease and as such it represents a problem in the Italian social context, where the demographic curve is characterized by an overrepresentation of the elderly population. Vaccines against Herpes Zoster are available, safe and effective, however coverage remains sub-optimal. This study was therefore conducted to examine the variations in Herpes Zoster vaccine uptake and confidence across different regions in Italy. METHODS: This study utilized a cross-sectional computer-assisted web interview (CAWI) methodology. The survey was conducted by Dynata, an online panel provider, and involved 10,000 respondents recruited in Italy between April 11 and May 29, 2022. The sample was stratified based on geographic region, gender, and age group. Data management adhered to European Union data protection regulations, and the survey covered demographics, living conditions, and vaccination against herpes zoster (HZ), following the BeSD framework. RESULTS: The findings indicate regional disparities in herpes zoster vaccine uptake across Italy. Notably, the Islands region exhibits a particularly low vaccination rate (2.9%), highlighting the need for targeted interventions. The multivariate regression analysis showed that sociodemographic factors, limited access to healthcare services, and inadequate awareness of vaccine eligibility contribute to the lower uptake observed in this region. CONCLUSION: In conclusion, this research emphasizes regional disparities in herpes zoster (HZ) vaccination uptake in Italy. Demographic, socioeconomic, and geographic factors impact individuals' willingness to receive the vaccine. The study highlights the importance of awareness of vaccine eligibility and accessible vaccination facilities in increasing uptake rates.

Pneumococcal vaccine uptake among high-risk adults and children in Italy: results from the OBVIOUS project survey.

BACKGROUND: Streptococcus pneumoniae infections, including Invasive Pneumococcal Diseases (IPDs), pose a substantial public health challenge, causing significant morbidity and mortality, especially among children and older adults. Vaccination campaigns have played a vital role in reducing pneumococcal-related deaths. However, obstacles related to accessibility and awareness might impede optimal vaccine adoption. This study aims to provide comprehensive data on pneumococcal vaccine coverage and attitudes within at-risk groups in Italy, with the goal of informing public health strategies and addressing vaccination barriers. METHODS: Between April 11 and May 29, 2022, a questionnaire investigating vaccine uptake and attitudes toward several vaccinations was administered to 10,000 Italian adults, chosen through population-based sampling. Respondents who were targets of the campaign according to the 2017-2019 National Vaccination Plan, accessed questions regarding pneumococcal vaccination. Data on uptake, awareness of having the right to free vaccination, opinion on vaccine safety, concern with pneumococcal disease, and ease of access to vaccination services were summarized and presented based on statistical regions. Multinomial logistic regression analysis was used to explore factors influencing vaccine uptake. RESULTS: Out of 2357 eligible adult respondents (42.6% women; mean age: 58.1 ± 15.7), 39.5% received pneumococcal vaccination. Uptake differed among at-risk groups: respondents aged ≥65 (33.7%), with lung disease (48.4%), cardiovascular disease (46.6%), and diabetes (53.7%). Predictors of not being vaccinated and unwilling to included female gender, residing in rural areas, lower education, low concern about pneumococcal disease, vaccine safety concerns, and associations with vaccine-opposed acquaintances. Health access issues predicted willingness to be vaccinated despite non-vaccination. Pneumopathy, heart disease, diabetes, and living in Northeastern or Central Italy were linked to higher uptake. Among the 1064 parents of eligible children, uptake was 79.1%. Parental unawareness of children's free vaccination eligibility was a predictor of non-vaccination. Vaccine safety concerns correlated with reluctance to vaccinate children, while perceived healthcare access challenges were associated with wanting but not having received vaccination. CONCLUSIONS: Pneumococcal vaccination uptake within prioritized groups and children in Italy remains inadequate. Scarce awareness of vaccine availability and obstacles in accessing vaccinations emerge as principal barriers influencing this scenario.

Rates and determinants of Rotavirus vaccine uptake among children in Italy: a cross-sectional study within the 2022 OBVIOUS* project.

INTRODUCTION: The World Health Organization defines rotavirus as among the most severe causes of viral gastroenteritis affecting children under 5 year old. Italy and other European countries do not release disaggregated data on rotavirus vaccination coverage. This study aimed to assess the uptake and drivers of rotavirus vaccination in Italy. METHODS: We administered a survey to 10,000 Italian citizens recruited via an online panel and proportionate to key demographic strata. We examined rotavirus vaccine uptake among parents whose youngest child was aged 6 weeks to 4 years, their sociodemographic characteristics, their beliefs about vaccine administration, and who recommended the rotavirus vaccination. RESULTS: A total of 711 respondents met the inclusion criteria for the rotavirus vaccine questionnaire. The uptake was estimated at 60.3% nationwide (66.4% among mothers and 50.2% among fathers). Being a mother and living in cities/suburbs was significantly associated with a higher likelihood of vaccine uptake, while fathers were more likely to be uncertain of their children's vaccine status. Living in Central Italy and having friends/relatives opposed to vaccination were found to be significantly associated with a lower likelihood of vaccine uptake, while parents' education level and children's demographics were not found to correlate with any outcomes. In 90.3% of cases, the rotavirus vaccination was recalled as being recommended by a paediatrician. CONCLUSIONS: Consistent collection of behavioural preferences and socioeconomic characteristics of recipients of rotavirus vaccine campaigns, their epidemiological information, cost-benefit, and national policy data are crucial for designing effective vaccination strategies in Italy and other European countries with similar social profiles to reach the target uptake.

Melanin as a Photothermal Agent in Antimicrobial Systems.

Bacterial infection is one of the most problematic issues for human health and the resistance of bacteria to traditional antibiotics is a matter of huge concern. Therefore, research is focusing on the development of new strategies to efficiently kill these microorganisms. Recently, melanin is starting to be investigated for this purpose. Indeed, this very versatile material presents outstanding photothermal properties, already studied for photothermal therapy, which can be very useful for the light-induced eradication of bacteria. In this review, we present antibacterial melanin applications based on the photothermal effect, focusing both on the single action of melanin and on its combination with other antibacterial systems. Melanin, also thanks to its biocompatibility and ease of functionalization, has been demonstrated to be easily applicable as an antimicrobial agent, especially for the treatment of local infections.

Melanin for Photoprotection and Hair Coloration in the Emerging Era of Nanocosmetics.

Nanotechnology is revolutionizing fields of high social and economic impact. such as human health preservation, energy conversion and storage, environmental decontamination, and art restoration. However, the possible global-scale application of nanomaterials is raising increasing concerns, mostly related to the possible toxicity of materials at the nanoscale. The possibility of using nanomaterials in cosmetics, and hence in products aimed to be applied directly to the human body, even just externally, is strongly debated. Preoccupation arises especially from the consideration that nanomaterials are mostly of synthetic origin, and hence are often seen as "artificial" and their effects as unpredictable. Melanin, in this framework, is a unique material since in nature it plays important roles that specific cosmetics are aimed to cover, such as photoprotection and hair and skin coloration. Moreover, melanin is mostly present in nature in the form of nanoparticles, as is clearly observable in the ink of some animals, like cuttlefish. Moreover, artificial melanin nanoparticles share the same high biocompatibility of the natural ones and the same unique chemical and photochemical properties. Melanin is hence a natural nanocosmetic agent, but its actual application in cosmetics is still under development, also because of regulatory issues. Here, we critically discuss the most recent examples of the application of natural and biomimetic melanin to cosmetics and highlight the requirements and future steps that would improve melanin-based cosmetics in the view of future applications in the everyday market.

Localized Crystallization of Calcium Phosphates by Light-Induced Processes.

Medical treatment options for bones and teeth can be significantly enhanced by taking control over the crystallization of biomaterials like hydroxyapatite in the healing process. Light-induced techniques are particularly interesting for this approach as they offer tremendous accuracy in spatial resolution. However, in the field of calcium phosphates, light-induced crystallization has not been investigated so far. Here, proof of principle is established to successfully induce carbonate-hydroxyapatite precipitation by light irradiation. Phosphoric acid is released by a photolabile molecule exclusively after irradiation, combining with calcium ions to form a calcium phosphate in the crystallization medium. 4-Nitrophenylphosphate (4NPP) is established as the photolabile molecule and the system is optimized and fully characterized. A calcium phosphate is crystallized exclusively by irradiation in aqueous solution and identified as carbonate apatite. Control over the localization and stabilization of the carbonate apatite is achieved by a pulsed laser, triggering precipitation in calcium and 4NPP-containing gel matrices. The results of this communication open up a wide range of new opportunities, both in the field of chemistry for more sophisticated reaction control in localized crystallization processes and in the field of medicine for enhanced treatment of calcium phosphate containing biomaterials.

Optical absorption and dichroism of single melanin nanoparticles.

Melanin nanoparticles (NPs) have important biological functions including photoprotection and colouration, and artificial melanin-like NPs are relevant for catalysis, drug delivery, diagnosis and therapy. Despite their importance, the optical properties of single melanin NPs have not been measured. We combine quantitative differential interference contrast (qDIC) and extinction microscopy to characterise the optical properties of single NPs, both naturally sourced from cuttlefish ink, as well as synthetic NPs using polydopamine (PDA) and L-3,4-dihydroxyphenylalanine (L-DOPA). Combining qDIC with extinction, we determine the absorption index of individual NPs. We find that on average the natural melanin NPs have a higher absorption index than the artificial melanin NPs. From the analysis of the polarisation-dependent NP extinction, the NP aspect ratio is determined, with mean values at 405 nm wavelength in agreement with transmission electron microscopy. At longer wavelengths, we observe an additional optical anisotropy which is attributed to dichroism by structural ordering of the melanin. Our quantitative analysis yields a dichroism of 2-10% of the absorption index, increasing with wavelength from 455 nm to 660 nm for L-DOPA and PDA. Such an in-depth quantification of the optical properties of single melanin NPs is important for the design and future application of these ubiquitous bionanomaterials.

Functionalization of and through Melanin: Strategies and Bio-Applications.

A unique feature of nanoparticles for bio-application is the ease of achieving multi-functionality through covalent and non-covalent functionalization. In this way, multiple therapeutic actions, including chemical, photothermal and photodynamic activity, can be combined with different bio-imaging modalities, such as magnetic resonance, photoacoustic, and fluorescence imaging, in a theragnostic approach. In this context, melanin-related nanomaterials possess unique features since they are intrinsically biocompatible and, due to their optical and electronic properties, are themselves very efficient photothermal agents, efficient antioxidants, and photoacoustic contrast agents. Moreover, these materials present a unique versatility of functionalization, which makes them ideal for the design of multifunctional platforms for nanomedicine integrating new functions such as drug delivery and controlled release, gene therapy, or contrast ability in magnetic resonance and fluorescence imaging. In this review, the most relevant and recent examples of melanin-based multi-functionalized nanosystems are discussed, highlighting the different methods of functionalization and, in particular, distinguishing pre-functionalization and post-functionalization. In the meantime, the properties of melanin coatings employable for the functionalization of a variety of material substrates are also briefly introduced, especially in order to explain the origin of the versatility of melanin functionalization. In the final part, the most relevant critical issues related to melanin functionalization that may arise during the design of multifunctional melanin-like nanoplatforms for nanomedicine and bio-application are listed and discussed.

pH Switchable Water Dispersed Photocatalytic Nanoparticles.

Photogeneration of Reactive Oxygen Species (ROS) finds applications in fields as different as nanomedicine, art preservation, air and water depollution and surface decontamination. Here we present photocatalytic nanoparticles (NP) that are active only at acidic pH while they do not show relevant ROS photo-generation at neutral pH. This dual responsivity (to light and pH) is achieved by stabilizing the surface of TiO2 NP with a specific organic shell during the synthesis and it is peculiar of the achieved core shell-structure, as demonstrated by comparison with commercial photocatalytic TiO2 NP. For the investigation of the photocatalytic activity, we developed two methods that allow real time detection of the process preventing any kind of artifact arising from post-treatments and delayed analysis. The reversibility of the pH response was also demonstrated as well as the selective photo-killing of cancer cells at acidic pH.

Epidemiology and clinical evolution of non-multisystem inflammatory syndrome (MIS-C) dermatological lesions in pediatric patients affected by SARS-CoV-2 infection: A systematic review of the literature.

COVID-19 can present with a range of skin manifestations, some of which specific of the pediatric age. The aim of this systematic literature review was to determine the type, prevalence, time of onset, and evolution of cutaneous manifestations associated with COVID-19 in newborns, children, and adolescents, after excluding multisystem inflammatory syndrome in children (MIS-C). PubMed, Tripdatabase, ClinicalTrials, and Cochrane Library databases were searched using an ad hoc string for case reports/series and observational studies, published between December 2019 and February 2022. Study quality was assessed using the STROBE and CARE tools. Seventy-three (49 case reports/series and 24 studies) out of 26,545 identified articles were included in the analysis. Dermatological lesions were highly heterogeneous for clinical presentation, time of onset, and association with other COVID-19 manifestations. Overall, they mainly affected the acral portions, and typically presented a favorable outcome. Pseudo-chilblains were the most common. CONCLUSIONS: Mucocutaneous manifestations could be the only/predominant and early manifestation of COVID-19 that could precede other more severe manifestations by days or weeks. Therefore, physicians of all disciplines should be familiar with them. WHAT IS KNOWN: • A variety of cutaneous manifestations have been reported in association with COVID-19. • Urticaria, maculopapular, or vesicular rashes can occur at any age, while chilblains and erythema multiforme are more common in children and young patients. WHAT IS NEW: • Skin lesions related to SARS-CoV-2 infection often show a peculiar acral distribution. • Mucocutaneous lesions of various type may be the only/predominant manifestation of COVID-19; they could present in paucisymptomatic and severely ill patients and occur at different stages of the disease.

Glutathionylation primes soluble glyceraldehyde-3-phosphate dehydrogenase for late collapse into insoluble aggregates.

Protein aggregation is a complex physiological process, primarily determined by stress-related factors revealing the hidden aggregation propensity of proteins that otherwise are fully soluble. Here we report a mechanism by which glycolytic glyceraldehyde-3-phosphate dehydrogenase of Arabidopsis thaliana (AtGAPC1) is primed to form insoluble aggregates by the glutathionylation of its catalytic cysteine (Cys149). Following a lag phase, glutathionylated AtGAPC1 initiates a self-aggregation process resulting in the formation of branched chains of globular particles made of partially misfolded and totally inactive proteins. GSH molecules within AtGAPC1 active sites are suggested to provide the initial destabilizing signal. The following removal of glutathione by the formation of an intramolecular disulfide bond between Cys149 and Cys153 reinforces the aggregation process. Physiological reductases, thioredoxins and glutaredoxins, could not dissolve AtGAPC1 aggregates but could efficiently contrast their growth. Besides acting as a protective mechanism against overoxidation, S-glutathionylation of AtGAPC1 triggers an unexpected aggregation pathway with completely different and still unexplored physiological implications.

Photoluminescence-Based Techniques for the Detection of Micro- and Nanoplastics.

The growing numbers related to plastic pollution are impressive, with ca. 70 % of produced plastic (>350 tonnes/year) being indiscriminately wasted in the environment. The most dangerous forms of plastic pollution for biota and human health are micro- and nano-plastics (MNPs), which are ubiquitous and more bioavailable. Their elimination is extremely difficult, but the first challenge is their detection since existing protocols are unsatisfactory for microplastics and mostly absent for nanoplastics. After a discussion of the state of the art for MNPs detection, we specifically revise the techniques based on photoluminescence that represent very promising solutions for this problem. In this context, Nile Red staining is the most used strategy and we show here its pros and limitations, but we also discuss other more recent approaches, such as the use of fluorogenic probes based on perylene-bisimide and on fluorogenic hyaluronan nanogels, with the added values of biocompatibility and water solubility.

The Photophysics and Photochemistry of Melanin- Like Nanomaterials Depend on Morphology and Structure.

Melanin-like nanomaterials have found application in a large variety of high economic and social impact fields as medicine, energy conversion and storage, photothermal catalysis and environmental remediation. These materials have been used mostly for their optical and electronic properties, but also for their high biocompatibility and simplicity and versatility of preparation. Beside this, their chemistry is complex and it yields structures with different molecular weight and composition ranging from oligomers, to polymers as well as nanoparticles (NP). The comprehension of the correlation of the different compositions and morphologies to the optical properties of melanin is still incomplete and challenging, even if it is fundamental also from a technological point of view. In this minireview we focus on scientific papers, mostly recent ones, that indeed examine the link between composition and structural feature and photophysical and photochemical properties proposing this approach as a general one for future research.

Local Light-Controlled Generation of Calcium Carbonate and Barium Carbonate Biomorphs via Photochemical Stimulation.

Photochemical activation is proposed as a general method for controlling the crystallization of sparingly soluble carbonates in space and time. The photogeneration of carbonate in an alkaline environment is achieved upon photo-decarboxylation of an organic precursor by using a conventional 365 nm UV LED. Local irradiation was conducted focusing the LED light on a 300 µm radius spot on a closed glass crystallization cell. The precursor solution was optimized to avoid the precipitation of the photoreaction organic byproducts and prevent photo-induced pH changes to achieve the formation of calcium carbonate only in the corresponding irradiated area. The crystallization was monitored in real-time by time-lapse imaging. The method is also shown to work in gels. Similarly, it was also shown to photo-activate locally the formation of barium carbonate biomorphs. In the last case, the morphology of these biomimetic structures was tuned by changing the irradiation intensity.

Stable and Biocompatible Monodispersion of C60 in Water by Peptides.

The lack of solubility in water and the formation of aggregates hamper many opportunities for technological exploitation of C60. Here, different peptides were designed and synthesized with the aim of monomolecular dispersion of C60 in water. Phenylalanines were used as recognizing moieties, able to interact with C60 through π-π stacking, while a varying number of glycines were used as spacers, to connect the two terminal phenylalanines. The best performance in the dispersion of C60 was obtained with the FGGGF peptidic nanotweezer at a pH of 12. A full characterization of this adduct was carried out. The peptides disperse C60 in water with high efficiency, and the solutions are stable for months both in pure water and in physiological environments. NMR measurements demonstrated the ability of the peptides to interact with C60. AFM measurements showed that C60 is monodispersed. Electrospray ionization mass spectrometry determined a stoichiometry of C60@(FGGGF)4. Molecular dynamics simulations showed that the peptides assemble around the C60 cage, like a candy in its paper wrapper, creating a supramolecular host able to accept C60 in the cavity. The peptide-wrapped C60 is fully biocompatible and the C60 "dark toxicity" is eliminated. C60@(FGGGF)4 shows visible light-induced reactive oxygen species (ROS) generation at physiological saline concentrations and reduction of the HeLa cell viability in response to visible light irradiation.

Tuning Mechanical Properties of Pseudopeptide Supramolecular Hydrogels by Graphene Doping.

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

Dual-Mode, Anisotropy-Encoded, Ratiometric Fluorescent Nanosensors: Towards Multiplexed Detection.

A nanosensor with dual-mode fluorescence response to pH and an encoded identification signal, was developed by exploiting excitation energy transfer and tailored control of molecular organization in core-shell nanoparticles. Multiple signals were acquired in a simple single-excitation dual-emission channels set-up.

Source and Biological Response of Biochar Organic Compounds Released into Water; Relationships with Bio-Oil Composition and Carbonization Degree.

Water-soluble organic compounds (WSOCs) were extracted from corn stalk biochar produced at increasing pyrolysis temperatures (350-650 °C) and from the corresponding vapors, collected as bio-oil. WSOCs were characterized by gas chromatography (semivolatile fraction), negative electron spray ionization high resolution mass spectrometry (hydrophilic fraction) and fluorescence spectroscopy. The pattern of semivolatile WSOCs in bio-oil was dominated by aromatic products from lignocellulose, while in biochar was featured by saturated carboxylic acids from hemi/cellulose and lipids with concentrations decreasing with decreasing H/C ratios. Hydrophilic species in poorly carbonized biochar resembled those in bio-oil, but the increasing charring intensity caused a marked reduction in the molecular complexity and degree of aromaticity. Differences in the fluorescence spectra were attributed to the predominance of fulvic acid-like structures in biochar and lignin-like moieties in bio-oil. The divergence between pyrolysis vapors and biochar in the distribution of WSOCs with increasing carbonization was explained by the hydrophobic carbonaceous matrix acting like a filter favoring the release into water of carboxylic and fulvic acid-like components. The formation of these structures was confirmed in biochar produced by pilot plant pyrolysis units. Biochar affected differently shoot and root length of cress seedlings in germination tests highlighting its complex role on plant growth.

Variable Doping Induces Mechanism Swapping in Electrogenerated Chemiluminescence of Ru(bpy)32+ Core-Shell Silica Nanoparticles.

The impact of nanotechnology on analytical science is hardly overlooked. In the search for ever-increasing sensitivity in biomedical sensors, nanoparticles have been playing a unique role as, for instance, ultrabright labels, and unravelling the intimate mechanisms which govern their functioning is mandatory for the design of ultrasentitive devices. Herein, we investigated the mechanism of electrogenerated chemiluminescence (ECL) in a family of core-shell silica-PEG nanoparticles (DDSNs), variously doped with a Ru(bpy)32+ triethoxysilane derivative, and displaying homogeneous morphological, hydrodynamic, and photophysical properties. ECL experiments, performed in the presence of 2-(dibutylamino)ethanol (DBAE) as coreactant, showed two parallel mechanisms of ECL generation: one mechanism (I) which involves exclusively the radicals deriving from the coreactant oxidation and a second one (II) involving also the direct anodic oxidation of the Ru(II) moieties. The latter mechanism includes electron (hole) hopping between neighboring redox centers as evidenced in our previous studies and supported by a theoretical model we have recently proposed. Quite unexpectedly, however, we found that the efficiency of the two mechanisms varies in opposite directions within the DDSNs series, with mechanism I or mechanism II prevailing at low and high doping levels, respectively. Since mechanism II has an intrinsically lower efficiency, the ECL emission intensity was also found to grow linearly with doping only at relatively low doping levels while it deviates negatively at higher ones. As the ζ-potential of DDSNs increases with the doping level from negative to slightly positive values, as a likely consequence of the accumulating cationic charge within the silica core, we attributed the observed change in the ECL generation mechanism along the DDSN series to a modulation of the electrostatic and hydrophobic/hydrophilic interactions between the DDSNs and the radical cationic species involved in the ECL generation. The results we report therefore show that the ECL intensity of a nanosized system cannot be merely incremented acting on doping, since other parameters come into play. We think that these results could serve as valuable indications to design more efficient ECL nano- and microsized labels for ultrasensitive bioanalysis.