The effect of a protective layer on the optical behavior of retro-reflective paintings for building envelopes.

Retro-reflective (RR) materials, applied to building envelopes, constitute an option to tackle Urban Heat Island phenomenon, thanks to their capability to reflect the sunlight predominantly towards the solar incidence direction. RR coatings are obtained with the deposition of glass beads on traditional diffusive materials. During their lifetime, outdoor aging and soiling affect their optical behavior. In addition, without a proper protection, some glass beads could detach from the paint and disperse in the environment. Hence, a necessity arises for the application of a safeguarding stratum on RR materials to avert the separation of glass beads in RR coatings following the aging process. In this paper, five RR samples were produced, employing a highly reflective paint as foundation, RR glass beads and a protective layer. A diffusive sample, without glass beads, was made for comparison. Samples underwent spectrophotometric and angular distribution analyses. The effect of the protective layer on the optical behavior was assessed comparing the results with those obtained for the same RR materials without the protective layer. RR samples with a protective layer exhibit a higher reflectance with respect to the same RR sample without a protective layer. In the near-infrared (NIR) region, a lower reflectance occurs for all RR samples with a protective layer. A less concentrated angular distribution of the reflected light was observed for all RR samples with the addition of a protective layer.

VHL-Modified PROteolysis TArgeting Chimeras (PROTACs) as a Strategy to Evade Metabolic Degradation in In Vitro Applications.

PROteolysis TArgeting Chimeras (PROTACs) are tripartite molecules consisting of a linker connecting a ligand for a protein of interest to an E3 ligase recruiter, whose rationale relies on proteasome-based protein degradation. PROTACs have expanded as a therapeutic strategy to open new avenues for unmet medical needs. Leveraging our expertise, we undertook a series of in vitro experiments aimed at elucidating PROTAC metabolism. In particular, we focused on PROTACs recruiting the von Hippel-Lindau (VHL) E3 ligase. After high-resolution mass spectrometry measurements, a characteristic metabolite with mass reduction of 200 units was detected and successively confirmed as a product deriving from the cleavage of the VHL ligand moiety. Subsequently, we identified hepatic and extrahepatic prolyl endopeptidases as the main putative metabolic enzymes involved. Finally, we designed and synthesized analogs of the VHL ligands that we further exploited for the synthesis of novel VHL-directed PROTACs with an improved metabolic stability in in vitro applications.

Wood waste valorization: Ethanol based organosolv as a promising recycling process.

Wood waste is a valuable material that could constitute an abundant and inexpensive source for the production of new materials the recovery of energy. In Europe, about 46% of wood waste is recycled to particleboard and fiberboard, while the other fraction is incinerated. However, a considerable quantity of wood waste shows potential for its transformation into value-added products due to its compositional quality. In this work, wood waste collected at a mechanical treatment plant underwent organosolv treatment to produce a cellulose pulp suitable for manufacturing containerboard. Three variables (temperature, acid concentration, and ethanol concentration) were investigated to find an optimal solution to produce wood pulp by means of Design of Experiment. Wood waste was microwave-heated at 160 °C for 15 min using an acidified ethanol-water solution (2% w/w H2SO4 and 0.8 w/w ethanol concentration), producing pulp with an average cellulose content of 76% where 93% of initial cellulose was retained. Thanks to a one-pot approach, ethanol was totally recovered, 62% of initial lignin was precipitated, and 20 g/l of hemicellulose-derived sugars solution was obtained. Finally, three wood waste samples collected in different periods of the year yielded comparable outcomes, suggesting a good reproducibility of the organosolv process. ANOVA test with a significance level of 0.01 showed a p-value of 0.029 and 0.235 for cellulose content and cellulose recovery, respectively. This study paves the way for an industrial symbiosis between recycling centers and paper mills located in the same territory.

Environmental assessment of four waste cooking oil valorization pathways.

Global waste is expected to grow substantially by 2050, therefore, defining an effective waste management strategy is a crucial topic for both industry and academia. Nowadays, food and green waste, in particular, represent a large share of the total waste production. All this considered, effectively processing and eventually reusing materials such as waste cooking oil is of paramount importance. This study investigates the potential environmental impact and the primary energy consumption for three waste cooking oil valorization pathways i.e. biodiesel, direct burning fuel, additive for recycling aged-asphalt, as well as a new application, i.e. phase change material, compared to their specific more common alternative based on a cradle-to-gate approach. The aim is to identify and recommend the most advantageous alternative in terms of environmental impact. Results showed that the waste cooking oil has a lower impact in all comparisons made, except as phase change material. The less effective performance in some cases was compensated by the waste oil entry as a burden-free resource under an attributional model. The best profile of the waste cooking oil is as direct burning fuel. However, the binder asphalt substitution is highly recommended due to the nature of the application. The major obstacles to the waste cooking oil usage are the limited stock, composition and quality variability, and the difficulty of proper collection.

Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications.

Hetero-bifunctional PROteolysis TArgeting Chimeras (PROTACs) represent a new emerging class of small molecules designed to induce polyubiquitylation and proteasomal-dependent degradation of a target protein. Despite the increasing number of publications about the synthesis, biological evaluation, and mechanism of action of PROTACs, the characterization of the pharmacokinetic properties of this class of compounds is still minimal. Here, we report a study on the metabolism of a series of 40 PROTACs in cryopreserved human hepatocytes at multiple time points. Our results indicated that the metabolism of PROTACs could not be predicted from that of their constituent ligands. Their linkers' chemical nature and length resulted in playing a major role in the PROTACs' liability. A subset of compounds was also tested for metabolism by human cytochrome P450 3A4 (CYP3A4) and human aldehyde oxidase (hAOX) for more in-depth data interpretation, and both enzymes resulted in active PROTAC metabolism.

Carbon and energy footprint of the hydrate-based biogas upgrading process integrated with CO2 valorization.

The present paper aims at assessing the carbon and energy footprint of an energy process, in which the energy excess from intermittent renewable sources is used to produce hydrogen which reacts with the CO2 previously separated from an innovative biogas upgrading process. The process integrates a hydrate-based biogas upgrading section and a CO2 methanation section, to produce biomethane from the biogas enrichment and synthetic methane from the CO2 methanation. Clathrate hydrates are crystalline compounds, formed by gas enclathrated in cages of water molecules and are applied to the selective separation of CO2 from biogas mixtures. Data from the experimental setup were analyzed in order to evaluate the green-house gas emissions (carbon footprint CF) and the primary energy consumption (energy footprint EF) associated to the two sections of the process. The biosynthetic methane production during a single-stage process was 0.962Nm3, obtained mixing 0.830Nm3 of methane-enriched biogas and 0.132Nm3 of synthetic methane. The final volume composition was: 73.82% CH4, 19.47% CO2, 0.67% H2, 1.98% O2, 4.06% N2 and the energy content was 28.0MJ/Nm3. The functional unit is the unitary amount of produced biosynthetic methane in Nm3. Carbon and energy footprints are 0.7081kgCO2eq/Nm3 and 28.55MJ/Nm3, respectively, when the electric energy required by the process is provided by photovoltaic panels. In this scenario, the overall energy efficiency is about 0.82, higher than the worldwide average energy efficiency for fossil methane, which is 0.75.

Synthesis and characterization of the first inhibitor of N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD).

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.

Bile Acid Recognition by NAPE-PLD.

The membrane-associated enzyme NAPE-PLD (N-acyl phosphatidylethanolamine specific-phospholipase D) generates the endogenous cannabinoid arachidonylethanolamide and other lipid signaling amides, including oleoylethanolamide and palmitoylethanolamide. These bioactive molecules play important roles in several physiological pathways including stress and pain response, appetite, and lifespan. Recently, we reported the crystal structure of human NAPE-PLD and discovered specific binding sites for the bile acid deoxycholic acid. In this study, we demonstrate that in the presence of this secondary bile acid, the stiffness of the protein measured by elastic neutron scattering increases, and NAPE-PLD is ∼7 times faster to catalyze the hydrolysis of the more unsaturated substrate N-arachidonyl-phosphatidylethanolamine, compared with N-palmitoyl-phosphatidylethanolamine. Chenodeoxycholic acid and glyco- or tauro-dihydroxy conjugates can also bind to NAPE-PLD and drive its activation. The only natural monohydroxy bile acid, lithocholic acid, shows an affinity of ∼20 µM and acts instead as a reversible inhibitor (IC50 ≈ 68 µM). Overall, these findings provide important insights into the allosteric regulation of the enzyme mediated by bile acid cofactors and reveal that NAPE-PLD responds primarily to the number and position of their hydroxyl groups.

Fluorine nuclear magnetic resonance-based assay in living mammalian cells.

Nuclear magnetic resonance (NMR)-based screening has been recognized as a powerful approach for the identification and characterization of molecules interacting with pharmaceutical targets. Indeed, several NMR methods have been developed and successfully applied to many drug discovery projects. Whereas most of these approaches have targeted isolated biomolecular receptors, very few cases are reported with the screening performed in intact cells and cell extracts. Here we report the first successful application of the fluorine NMR-based assay n-FABS (n-fluorine atoms for biochemical screening) in living mammalian cells expressing the membrane protein fatty acid amide hydrolase (FAAH). This method allows the identification of both weak and potent inhibitors and the measurement of their potency in a physiological environment.