Publications

DOI: https://doi.org/10.1007/s10048-024-00754-y
Mannosyl-oligosaccharide glucosidase - congenital disorder of glycosylation (MOGS-CDG) is determined by biallelic mutations in the mannosyl-oligosaccharide glucosidase (glucosidase I) gene. MOGS-CDG is a rare disorder affecting the processing of N-Glycans (CDG type II) and is characterized by prominent neurological involvement including hypotonia, developmental delay, seizures and movement disorders. To the best of our knowledge, 30 patients with MOGS-CDG have been published so far. We described a child who is compound heterozygous for two novel variants in the MOGS gene. He presented Early Infantile Developmental and Epileptic Encephalopathy (EI-DEE) in the absence of other specific systemic involvement and unrevealing first-line biochemical findings. In addition to the previously described features, the patient presented a Hirschprung disease, never reported before in individuals with MOGS-CDG.

DOI: https://doi.org/10.3390/polym16152096
A hydrogel formulation of 2-hydroxy ethyl methacrylate (HEMA) containing covalently linked magnetite nanoparticles was developed to actively facilitate the selective removal and photocatalytic degradation of antibiotics. To this purpose, the hybrid materials were molecularly imprinted with Lomefloxacin (Lome) or Ciprofloxacin (Cipro), achieving a selectivity of 60% and 45%, respectively, starting from a solution of XX concentration. After the adsorption, the embedded magnetite was used with the double function of (i) magnetically removing the material from water and (ii) triggering photo-Fenton (PF) reactions assisted by UVA light and H₂O₂ to oxidize the captured antibiotic. The success of the material design was confirmed by a comprehensive characterization of the system from chemical-physical and morphological perspectives. Adsorption and degradation tests demonstrated the material?s ability to efficiently degrade Lome until its complete disappearance from the electrospray ionization (ESI) mass spectra. Regeneration tests showed the possibility of reusing the material for up to three cycles. Ecotoxicological tests using algae Rapidocelis subcapitata, crustaceans Daphnia magna, and bacteria Vibrio fischeri were performed to evaluate the ecosafety of our synthesized materials.

DOI: https://doi.org/10.1016/j.scitotenv.2024.174697
The fate of black biodegradable mulch film (MF) based on starch and poly(butylene-adipate-co-terephthalate) (PBAT) in agricultural soil is investigated herein. Pristine (BIO-0) and UV-aged film samples (BIO-A192) were buried for 16 months at an experimental field in southern Italy. Visual, physical, chemical, morphological, and mechanical analyses were carried out before and after samples burial. Film residues in the form of macro- and microplastics in soil were analyzed at the end of the trial.
Progressive deterioration of both pristine and UV-aged samples, with surface loss and alterations in mechanical properties, occurred from 42 days of burial. After 478 days, the apparent surface of BIO-0 and BIO-A192 films decreased by 57 % and 66 %, respectively. Burial determined a rapid depletion of starch from the polymeric blend, especially for the BIO-A192, while the degradation of the polyester phase was slower. Upon burial, an enrichment of aromatic moieties of PBAT in the film residues was observed, as well as microplastics release to soil. The analysis of the MF degradation products extracted from soil (0.006?0.008 % by mass in the soil samples) revealed the predominant presence of adipate moieties. After 478 days of burial, about 23 % and 17 % of the initial amount of BIO-0 and BIO-A192, respectively, were extracted from the soil. This comprehensive study underscores the complexity of biodegradation phenomena that involve the new generation of mulch films in the field. The different biodegradability of the polymeric components, the climate, and the soil conditions that did not strictly meet the parameters required for the standard test method devised for MFs, have significantly influenced their degradation rate. This finding further emphasizes the importance of implementing field experiments to accurately assess the real effects of biodegradable MFs on soil health and overall agroecosystem sustainability.

DOI: https://doi.org/10.1016/j.scitotenv.2024.174325
Soil environments across the globe, particularly in agricultural settings, have now been shown to be contaminated with microplastics. Agricultural plastics ? such as mulching films ? are used in close or direct contact with soils and there is growing evidence demonstrating that they represent a potential source of microplastics. There is a demand to undertake fate and effects studies to understand the behaviour and potential long-term ecological risks of this contamination. Yet, there is a lack of test materials available for this purpose. This study describes the manufacture and characterisation of five large (1?40 kg) batches of microplastic test materials derived from agricultural mulching films. Batches were produced from either polyethylene-based conventional mulching films or starch-polybutadiene adipate terephthalate blend mulching films that are certified biodegradable in soil. Challenges encountered and overcome during the micronisation process provide valuable insights into the future of microplastic test material generation from these material types. This includes difficulties in micronising virgin polyethylene film materials. All five batches were subjected to a thorough physical and chemical characterisation - both of the original virgin films and the subsequent microplastic particles generated - including a screening for the presence of chemical additives. This is a critical step to provide essential information for interpreting particle fate or effects in scientific testing. Trade-offs between obtaining preferred particle typologies and time and cost constraints are elucidated. Several recommendations emerging from the experiences gained in this study are put forward to advance the research field towards greater harmonisation and utilisation of environmentally relevant test materials.

DOI: https://doi.org/10.3390/pharmaceutics16050642
In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial fields. This study aims to synthetise two series of methylimidazolium ILs bearing long alkyl chain in their cations (C9, C10, C12, C14, C16, C18, C20) and with tetrafluoroborate (BF₄) and the 1,3-dimethyl-5-sulfoisophthalate (DMSIP) as counter ions. The ILs were characterised using ¹H-NMR and MALDI-TOF, and their thermal behaviour was investigated through DSC and TGA. Additionally, the antimicrobial, anticancer, and cytotoxic activities of the ILs were analysed. Moreover, the most promising ILs were incorporated at different concentrations (0.5, 1, 5 wt%) into polyvinyl chloride (PVC) by solvent casting to obtain antimicrobial blend films. The thermal properties and stability of the resulting PVC/IL films, along with their hydrophobicity/hydrophilicity, IL surface distribution, and release, were studied using DSC and TGA, contact angle (CA), SEM, and UV-vis spectrometry, respectively. Furthermore, the antimicrobial and cytotoxic properties of blends were analysed. The in vitro results demonstrated that the antimicrobial and antitumor activities of pure ILs against t Listeria monocytogenes, Escherichia coli, Pseudomonas fluorescens strains, and the breast cancer cell line (MCF7), respectively, were mainly dependent on their structure. These activities were higher in the series containing the BF₄ anion and increased with the increase in the methylimidazolium cation alkyl chain length. However, the elongation of the alkyl chain beyond C16 induced a decrease in antimicrobial activity, indicating a cut-off effect. A similar trend was also observed in terms of in vitro biocompatibility. The loading of both the series of ILs into the PVC matrix did not affect the thermal stability of PVC blend films. However, their T_onset decreased with increased IL concentration and alkyl chain length. Similarly, both the series of PVC/IL films became more hydrophilic with increasing IL concentration and alkyl chain. The loading of ILs at 5% concentration led to considerable IL accumulation on the blend film surfaces (as observed in SEM images) and, subsequently, their higher release. The biocompatibility assessment with healthy human dermal fibroblast (HDF) cells and the investigation of antitumoral properties unveiled promising pharmacological characteristics. These findings provide strong support for the potential utilisation of ILs in biomedical applications, especially in the context of cancer therapy and as antibacterial agents to address the challenge of antibiotic resistance. Furthermore, the unique properties of the PVC/IL films make them versatile materials for advancing healthcare technologies, from drug delivery to tissue engineering and antimicrobial coatings to diagnostic devices.

DOI: https://doi.org/10.1021/acsapm.4c00388
Unsaturated polyester resin (UPR) is a commercially thermosetting material renowned for its favorable thermomechanical properties and exceptional chemical resistance. These characteristics are typically attributed to the use of styrene as a curing agent. However, the undiscussed toxicity and potential carcinogenicity of styrene have inspired research and industry to investigate more sustainable and environmentally friendly alternatives, such as vegetable oils, polyphenols, and carbohydrates. In this study, unsaturated polyester (UP) was synthesized and cured with a blend of acrylated epoxidized soybean oil (AESO), 2-hydroxyethyl methacrylate (HEMA), and styrene in low content. Notably, styrene was reduced from 40% to 26%. Zinc(II) acetyl acetonate was introduced into the blend to promote transesterification processes, potentially enhancing both dissolution and recycling capabilities. Following comprehensive characterization, the resulting resins were employed in composite manufacturing, with subsequent comparison to available counterparts made of commercial UP with a content of styrene at 40%. Remarkably, the mechanical properties, glass transition temperature, and thermal stability of the polyester were effectively preserved, despite the incorporation of biobased curing agents.

DOI: https://doi.org/10.1101/2024.04.26.587986
Mucopolysaccharidoses (MPS) are lysosomal storage diseases caused by defects in catabolism of glycosaminoglycans. MPS I, II, III and VII are associated with lysosomal accumulation of heparan sulphate and manifest with neurological deterioration. Most of these neurological MPS currently lack effective treatments. Here, we report that, compared to controls, neuraminidase 1 (NEU1) activity is drastically reduced in brain tissues of neurological MPS patients and in mouse models of MPS I, II, IIIA, IIIB and IIIC, but not of other neurological lysosomal disorders not presenting with heparan sulphate storage. We further show that accumulated heparan sulphate disrupts the lysosomal multienzyme complex of NEU1 with cathepsin A (CTSA), β-galactosidase (GLB1) and glucosamine-6-sulfate sulfatase (GALNS) necessary to maintain enzyme activity, and that NEU1 deficiency is linked to partial deficiencies of GLB1 and GALNS in cortical tissues and iPSC-derived cortical neurons of neurological MPS patients. Increased sialylation of N-linked glycans in brain samples of human MPS III patients and MPS IIIC mice implicated insufficient processing of brain N-linked sialylated glycans, except for polysialic acid, which was reduced in the brains of MPS IIIC mice. Correction of NEU1 activity in MPS IIIC mice by lentiviral gene transfer ameliorated previously identified hallmarks of the disease, including memory impairment, behavioural traits, and reduced levels of the excitatory synapse markers VGLUT1 and PSD95. Overexpression of NEU1 also restored levels of VGLUT1-/PSD95-positive puncta in cortical neurons derived from iPSC of an MPS IIIA patient

DOI: https://doi.org/10.1016/j.giant.2024.100258
The novelty of this work consists of synthesizing and exploiting a heterogeneous catalyst containing ammonium chloride as part of the polymeric sponge sites for CO₂ capture. To this aim, the polymerization of 2-acryloyl(oxyethyl)trimethylammonium chloride was performed in cryo-condition, in the presence of a crosslinking agent, obtaining a lightweight macroporous freestanding material. Its efficiency in converting aromatic and aliphatic epoxides to the corresponding carbonates was successfully proved by using proton Nuclear Magnetic Resonance (¹H NMR). Remarkably, the conversion of styrene oxide (SO) to styrene carbonate (SC) reached a yield of 99 % after 24 h of reaction. The calculated yield versus the aliphatic cyclohexene oxide is 71 %. Similar results were obtained by substituting the resin counter anion with Br^-, although the conversion kinetic was slower than the chloride. It is worth noticing that reactions took place in the mixture without adding the tetrabutylammonium bromide (TBAB), typically used as a co-catalyst to convert epoxides into carbonates. The recyclability of the as-prepared catalyst was evaluated for four reaction cycles, evidencing stable properties without significant depletion of CO₂ capture efficiency. Most importantly, the post-cleaning of the catalytic sponge is not required to be reused. Finally, the green chemistry metrics applied to the process demonstrated that our approach significantly mitigates risks and reduces environmental impact, thus elevating the overall cleanliness of our proof of concept.

DOI: https://doi.org/10.1039/D3MA00918A
This work reports the design of a new bacteria-killer based on maltol derivatives and β-cyclodextrin cryogels. The maltol covalently linked to the 3D polymer network chelates the iron ions efficiently, subtracting them from the bacterial environment, thus impeding microbial survival. At the same time, the hydrophobic cavities of β-cyclodextrin can work as nanocontainers to release pharmaceuticals on the infected tissue, reinforcing the bactericidal action. This non-conventional dual-acting system was successfully tested with and without the complexation of lomefloxacin by β-cyclodextrin. The material's remarkable activity was proven on Gram-positive and Gram-negative bacteria. As it turns out, such material is bactericidal owing to maltol chelating features; moreover, the material is able to improve the bactericidal activity when it releases lomefloxacin after its complexation inside β-cyclodextrin. Indeed, the presence of β-cyclodextrin nanocontainers holds the promise of compliance with various drugs, opening up exciting possibilities for diverse therapeutic applications. These innovations could potentially bring a new vista to wound dressing.

DOI: https://doi.org/10.1016/j.giant.2024.100267
Polylactide (PLA) is a promising biopolymer from renewable resources but its brittleness and poor gas barrier properties limit flexible packaging applications. Therefore, in this work PLA was blended with a biobased rubbery poly(pentamethylene furanoate) (PPeF), acting as a toughening agent, and a commercial epoxy-functionalized compatibilizer (i.e., Joncryl® ADR-4468) was added to improve the interfacial interaction. The effect of PPeF loading (1?30 wt %) on phase morphology, mechanical properties, oxygen permeability, and degradability in compost was characterized. All blends displayed a sea-island morphology with refined PPeF domains upon compatibilization. Incorporating PPeF induced major tensile ductility enhancements from 5 % strain at break for neat PLA up to 200 % for the blend with 30 wt % PPeF, accompanied by progressive stiffness and strength declines. Through the application of the essential work of fracture (EWF) approach on the prepared films, the specific essential work of fracture (w_e) was seen climbing from 6.2 to 40.0 kJ/m² with rising PPeF content, confirming its effectiveness as a toughness enhancer. PPeF contributed to increase the UV- and gas barrier properties of PLA. For example, the oxygen permeability dropped by 37 % for the blend with 30 wt % PPeF. Moreover, compost burial tests also revealed 26 % weight loss of PPeF after 60 days, proving its biodegradability. Hence, finely dispersed PPeF domains induced synergistic property improvements, making PLA/PPeF blends a promising sustainable option for flexible and biodegradable packaging.