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The presence in seawater of low-molecular-weight polyethylene (PE) and polydimethylsiloxane (PDMS), synthetic polymers with high chemical resistance, has been demonstrated in this study for the first time by developing a novel methodology for their recovery and quantification from surface seawater. These synthetic polymer debris (SPD) with very low molecular weights and sizes in the nano- and micro-metre range have escaped conventional analytical methods. SPD have been easily recovered from water samples (2 L) through filtration with a nitrocellulose membrane filter with a pore size of 0.45 μm. Dissolving the filter in acetone allowed the isolation of the particulates by centrifugation followed by drying. The isolated SPD were analysed by 1H nuclear magnetic resonance spectroscopy (1H NMR), identifying PE and PDMS. These polymers are thus persisting on seawater because of their low density and the ponderal concentrations were quantified in mg/m3. This method was used in an actual case study in which 120 surface seawater samples were collected during two sampling campaigns in the Mediterranean Sea (from the Gulf of Salerno to the Gulf of Policastro in South Italy). The developed analytical protocol allowed achieving unprecedented simplicity, rapidity and sensitivity. The 1H and 13C NMR structural analysis of the PE debris indicates the presence of oxidised polymer chains with very low molecular weights. Additionally, the origin of those low molecular weight polymers was investigated by analysing influents and effluents from a wastewater treatment plant (WWTP) in Salerno as a hot spot for the release of SPD: the analysis indicates the presence of low molecular weight polymers compatible with wax-PE, widely used for coating applications, food industry, cosmetics and detergents. Moreover, the origin of PDMS debris found in surface seawater can be ascribed to silicone-based antifoamers and emulsifiers.

Recycling of all-trans-retinal to 11-cis-retinal through the visual cycle is a fundamental metabolic pathway in the eye. A potent retinoid isomerase (RPE65) inhibitor, (R)-emixustat, has been developed and tested in several clinical trials; however, it has not received regulatory approval for use in any specific retinopathy. Rapid clearance of this drug presents challenges to maintaining concentrations in eyes within a therapeutic window. To address this pharmacokinetic inadequacy, we rationally designed and synthesized a series of emixustat derivatives with strategically placed fluorine and deuterium atoms to slow down the key metabolic transformations known for emixustat. Crystal structures and quantum chemical analysis of RPE65 in complex with the most potent emixustat derivatives revealed the structural and electronic bases for how fluoro substituents can be favorably accommodated within the active site pocket of RPE65. We found a close (∼3.0 Å) F-π interaction that is predicted to contribute ∼2.4 kcal/mol to the overall binding energy.

The discovery of how a photon is converted into a chemical signal is one of the most important achievements in the field of vision. A key molecule in this process is the visual chromophore retinal. Several eye diseases are attributed to the abnormal metabolism of retinal in the retina and the retinal pigment epithelium. Also, the accumulation of two toxic retinal derivatives, N-retinylidene-N-retinylethanolamine and the retinal dimer, can damage the retina leading to blindness. RPE65 (Retinal pigment epithelium-specific 65 kDa protein) is one of the central enzymes that regulates the metabolism of retinal and the formation of its toxic metabolites. Its inhibition might decrease the rate of the retinas degeneration by limiting the amount of retinal and its toxic byproducts. Two RPE65 inhibitors, (R)-emixustat and (R)-MB001, were recently developed for this purpose.

Abstract An advanced concept of aerobic membrane bioreactors (MBRs) for highly efficient wastewater treatment has been disclosed by introduction of an electro and encapsulated self-forming dynamic biomembrane (e-ESFDM). The biological filtering membrane is intercalated between two woven polyester fabrics as supports that assist the formation and protect the biomembrane. The innovative architecture of the e-ESFDM in combination with electrocoagulation processes resulted in efficient and cost-effective wastewater treatment and control of the membrane fouling. The performance of the e-ESFDMBR was compared to a yet highly efficient ESFDMBR, where the electric field was not present. The ESFDM-based reactors both showed comparable results in the removal of organic matter, in terms of COD and DOC. On the other hand, e-ESFDMBR exceeded the performance of the ESFDMBR in the reduction of nitrogen- and phosphorous-containing pollutants, responsible for eutrophication processes in the environment, and recalcitrant molecules, such as humic-like substances. In addition, an extremely low fouling rate was observed for the e-ESFDM bioreactor. Insights on the biological processes involved in the developed MBR were provided by investigations on the microbiological diversity found in reactor mixed liquor, ESFDM layer and treated wastewater.

Pancreatic β-cell membranes and presynaptic areas of neurons contain analogous protein complexes that control the secretion of bioactive molecules. These complexes include the neuroligins (NLs) and their binding partners, the neurexins (NXs). It has been recently reported that both insulin secretion and the proliferation rates of β-cells increase when cells are co-cultured with full-length NL-2 clusters. The pharmacological use of full-length protein is always problematic due to its unfavorable pharmacokinetic properties. Thus, NL-2-derived short peptide was conjugated to the surface of polyamidoamine-based (PAMAM) dendrimers. This nanoscale composite improved β-cell functions in terms of the rate of proliferation, glucose-stimulated insulin secretion (GSIS), and functional maturation. This functionalized dendrimer also protected β-cells under cellular stress conditions. In addition, various novel peptidomimetic scaffolds of NL-2-derived peptide were designed, synthesized, and conjugated to the surface of PAMAM in order to increase the biostability of the conjugates. However, after being covered by peptidomimetics, PAMAM dendrimers were inactive. Thus, the original peptide-based PAMAM dendrimer is a leading compound for continued research that might provide a unique starting point for designing an innovative class of antidiabetic therapeutics that possess a unique mode of action.

BACKGROUND: Apelin receptor (APJ) is a G protein-coupled receptor (GPCR) activated by the endogenous peptide apelin. The apelin-APJ system has emerged as an important regulator of cardiovascular homeostasis. Recently, a potent benzimidazole-derived apelin peptidomimetic, CMF-019, was patented but without a comprehensive description of its synthesis and a complete spectroscopic characterization of the intermediates. OBJECTIVE: Here, a detailed preparation of CMF-019 through a modified and improved synthetic pathway is described. METHOD: In particular, the benzimidazole ring in 7 was tailored by the condensation of methyl 3- amino-4-(pentan-3-ylamino)benzoate (4) with (thiophene-2-yl)acetimidate salt 6. Saponification of 7 and the subsequent condensation of the free acid 8 with the corresponding enantiopure β-amino acid methyl ester generated methyl (S)-5-methyl-3-{1-(pentan-3-yl)-2-(thiophen-2-ylmethyl)-1Hbenzo[ d]imidazole-5-carboxamido}hexanoate (9). Hydrolysis of the latter with KOH in THF/water, followed by HPLC-purification, afforded the desired product, CMF-019 (potassium salt) 10. RESULTS & CONCLUSION: The approach reported herein enables preparation of 10 at a total yield of 12% over seven linear steps. Additionally, it does not require applying expensive designated microwave reactors and high-pressure hydrogenators. Thus, the elaborate synthesis provides a latent availability of potent agonist 10 for further exploring the physiologically essential apelin-APJ system.

Wastewater-based epidemiology (WBE) is a powerful tool that has the potential to reveal the extent of an ongoing disease outbreak or to predict an emerging one. Recent studies have shown that SARS-CoV-2 concentration in wastewater may be correlated with the number of COVID-19 cases in the corresponding population. Most of the recent studies and applications of wastewater-based surveillance of SARS-CoV-2 applied the “gold standard” real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) detection method. However, this method also has its limitations. The paper aimed to present recent improvements and applications of the PCR-based methods for SARS-CoV-2 monitoring in wastewater. Furthermore, it aimed to review alternative methods utilized and/or proposed for the detection of the virus in wastewater matrices. From the review, it was found that several studies have investigated the use of reverse-transcription digital polymerase reaction (RT-dPCR), which was generally shown to have a lower limit of detection (LOD) over the RT-qPCR. Aside from this, non-PCR-based and non-RNA based methods have also been explored for the detection of SARS-CoV-2 in wastewater, with detailed attention given to the detection of SARS-CoV-2 proteins. The potential methods for protein detection include mass spectrometry, the use of immunosensors, and nanotechnological applications. In addition, the review of recent studies also revealed two types of emerging methods related to the detection of SARS-CoV-2 in wastewater: i) capsid-integrity assays to infer about the infectivity of SARS-CoV-2 present in wastewater, and ii) alternative methods for detection of SARS-CoV-2 variants of concern (VOCs) in wastewater. The recent studies on proposed methods of SARS-CoV-2 detection in wastewater have considered improving this approach in one or more of the following aspects: rapidity, simplicity, cost, sensitivity, and specificity. However, further studies are needed in order to realize the full application of these methods for WBE in the field.

This work provides a brief overview of the application of Sewage Sludge-Derived Biochar (SSBC) for the removal of micropollutants from aqueous solutions and wastewater. A particular emphasis is placed on the adsorption efficiency of SSBC regarding the Priority Substances defined under the scope of the EU Water Framework Directive.