Synthesis of Fluorescent PMMA‐Based Nanoparticles

The synthesis of PMMA‐based nanoparticles (NPs) covalently labeled with a fluorescent dye is investigated for imaging applications such as cell uptake and biodistribution. Batch emulsion polymerization (BEP) and monomer‐starved semi‐batch emulsion polymerization (MSSEP) are adopted using SDS. Fluorescent properties are added to these NPs using Rhodamine‐B (RhB) as a fluorescent dye covalently bonded to 2‐hyroxyethyl‐acrylate. The resulting HEMA‐RhB monomer is copolymerized with MMA via BEP and MSSEP to synthesize fluorescent NPs. Subsequently, SDS is substituted with a biocompatible surfactant, Tween80, through ionic‐exchange resins. ζ‐Potential measurements confirmed the complete surfactant exchange that leads to biocompatible fluorescent NPs with tunable size and narrow size distribution.

     

Composition and Physical Stability of the Colloidal Dispersion in Veiled Virgin Olive Oil

Veiled virgin olive oil (VOO) samples of nine different olive cultivars are chosen to have a wide range of physicochemical and biological properties of colloidal dispersions. The contents of proteins and phospholipids range from 40 to 190 mg kg⁻¹ and from 70 to 200 mg kg⁻¹, respectively. The effect of lab-scale centrifugation on cloudy appearance is studied measuring the decrease of turbidity grade values. The time to obtain unveiled oils (20 NTU) is modeled by a logistic equation, and a clear relationship between the initial water content and the above time is observed with a different trend between two groups of the VOO samples. Four VOO samples are selected to study the aggregation phenomena of microdroplets of water, pulp particles, and olive stone fragments via optical microscopy and dynamic light scattering during lab-scale gravity sedimentation. All VOOs are unstable with the cloudiness disappearing within the 230 days of investigation due to an overall diameter increase of cloudy components which is modeled by a power-law equation. The VOO samples, characterized by both small diameter values of dispersed components (150–250 nm) and high values of water content, show the fastest aggregation kinetics, but they have the longest time of cloudiness stability. Practical Applications: Water content and size distribution of VOO cloudy components can be key factors to control the colloidal stability. If removal of cloudy appearance is required, centrifugation can be applied to obtain a fast oil clarification which shows a power law relationship of water content with time. Instead, if physical stability of the colloidal dispersion is required, the aggregation phenomena should be slow down through VOO processing to obtain small diameters of the cloudy components. Tuning both the water content and dispersed phase diameter in the VOO can be the first step towards the control of phenomena related to the colloidal dispersion for every olive oil processing organization, above and beyond the simple removal of cloudy appearance by filtration.     

Discovery of Novel Trace Amine-Associated Receptor 5 (TAAR5) Antagonists Using a Deep Convolutional Neural Network

Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet^® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to further develop more potent TAAR5 ligands with putative anxiolytic and antidepressant activity.     

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs’ adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.     

PAPPA Expression in Indeterminate Thyroid Nodules as Screening Test to Select Patients for Molecular Testing

Pregnancy-associated plasma protein A (PAPPA) acts as an oncogene, and its expression is increased in multiple malignancies, including thyroid cancer. Molecular tests represent a useful tool in the management of indeterminate thyroid nodules; however, they are not conducted in all centers, and they contribute to increase the per-patient cost of nodule evaluation. In this study, we examined whether PAPPA expression could represent a promising new screening test in the management of indeterminate thyroid nodules. Toward this aim, PAPPA expression was evaluated in 107 fine needle aspiration cytologies (FNAC) belonging to Bethesda III–IV categories that had been sent to molecular biology to discriminate the nature of the nodules. We found that the PAPPA expression increased and showed an elevated sensitivity (97.14%) and negative predictive value (98%) in indeterminate cytological samples positive for mutations. The enhanced expression was not linked to a specific oncogene. Our findings demonstrated that assessing the PAPPA expression in indeterminate thyroid cytologies could represent a useful screening tool to select all patients that effectively need to be sent to molecular testing, thereby, leading to a potential cost reduction in the management of patients.     

Anatase-supported vanadium oxide catalysts for o-xylene oxidation: From consolidated certainties to unexpected effects

In this paper some aspects of the reaction of o-xylene oxidation, catalysed by anatase-supported vanadium oxide, are re-examined and compared with the scientific and patent literature. Specifically, the effect of vanadia loading on turnover frequency and on the distribution of products has been investigated, using catalysts having sub-monolayer and above-monolayer vanadium oxide deposited on a high-purity anatase support. It was found that even catalysts having less-than-monolayer vanadia loading, containing isolated or oligomeric VO₄ species, may give good selectivity to phthalic anhydride, provided the support does not catalyze the formation of heavy compounds. Moreover, the effect of water on the reactivity and chemical–physical characteristics of catalysts was studied by means of in situ Raman spectroscopy. Steam promoted dynamic reversible phenomena occurring at the catalyst surface, by facilitating the dispersion of bulk vanadium oxide and therefore increasing the catalyst activity.