Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.     

Influence of Plant Extract Addition to Marinades on Polycyclic Aromatic Hydrocarbon Formation in Grilled Pork Meat

Marinating is one of the most common methods of pre-processing meat. Appropriate selection of marinade ingredients can influence the physicochemical properties of the meat and can reduce the level of polycyclic aromatic hydrocarbons (PAHs) in the final product. The effects of the inclusion of natural plant extracts such as bay leaf (BL), black pepper (BP), turmeric (TU), jalapeno pepper (JP) and tamarind paste (TA) in marinades on the physicochemical properties of grilled pork neck were studied. The addition of spice extracts to marinades increased the proportion of colour components L* and b*. The use of TU, TA, JP, MX and C marinades lowered the hardness and pH of the meat. The highest phenolic compound levels were observed in the case of the mixture of all extracts (MX) and JP marinades, and the highest total antioxidant capacity was exhibited by the BL and MX marinades. The highest PAH content was recorded in the CON marinade (Σ12PAH 98.48 ± 0.81 µg/kg) and the lowest in the JP marinade (4.76 ± 0.08 µg/kg), which had the strongest, statistically significant reducing effect (95% reduction) on PAH levels. Analysis of correlation coefficients showed a relationship between the total antioxidant capacity of the marinades and the PAH content in grilled pork.     

Nucleotide Analogues Bearing a C2′ or C3′-Stereogenic All-Carbon Quaternary Center as SARS-CoV-2 RdRp Inhibitors

The design of novel nucleoside triphosphate (NTP) analogues bearing an all-carbon quaternary center at C2′ or C3′ is described. The construction of this all-carbon stereogenic center involves the use of an intramoleculer photoredox-catalyzed reaction. The nucleoside analogues (NA) hydroxyl functional group at C2′ was generated by diastereoselective epoxidation. In addition, highly enantioselective and diastereoselective Mukaiyama aldol reactions, diastereoselective N-glycosylations and regioselective triphosphorylation reactions were employed to synthesize the novel NTPs. Two of these compounds are inhibitors of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, the causal virus of COVID-19.     

Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies

Trying to meet the multitarget-directed ligands strategy, a series of previously described aryl-substituted phenylalanine derivatives, reported as competitive antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, were screened in vitro for their free-radical scavenging and antioxidant capacity in two different assays: ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity fluorescent (ORAC-FL) assays. The most active antioxidants 1 and 8 were further examined to evaluate their neuroprotective properties in vitro. In this study, compound 1 showed a significant neuroprotective effect against the neurotoxin 6-hydroxydopamine in neuroblastoma SH-SY5Y and IMR-32 cell lines. Both compounds also showed prevention from high levels of reactive oxygen species (ROS) in SH-SY5Y cells. Furthermore, the desired monoamine oxidase B (MAO-B) inhibition effect (IC₅₀ = 278 ± 29 nM) for 1 was determined. No toxic effects up to 100 µM of 1 and 8 against neuroblastoma cells were observed. Furthermore, in vivo studies showed that compound 1 demonstrated significant anticonvulsant potential in 6-Hz test, but in neuropathic pain models its antiallodynic and antihyperalgesic properties were not observed. Concluding, the compound 1 seems to be of higher importance as a new phenylalanine-based lead candidate due to its confirmed promise in in vitro and in vivo anticonvulsant activity.     

Electrochemical Oxidation of Nitrogen towards Direct Nitrate Production on Spinel Oxides

Nitrates are widely used as fertilizer and oxidizing agents. Commercial nitrate production from nitrogen involves high‐temperature‐high‐pressure multi‐step processes. Therefore, an alternative nitrate production method under ambient environment is of importance. Herein, an electrochemical nitrogen oxidation reaction (NOR) approach is developed to produce nitrate catalyzed by ZnFe_xCo_2?xO₄ spinel oxides. Theoretical and experimental results show Fe aids the formation of the first N?O bond on the *N site, while high oxidation state Co assists in stabilizing the absorbed OH^? for the generation of the second and third N?O bonds. Owing to the concerted catalysis, the ZnFe_0.4Co_1.6O₄ oxide demonstrates the highest nitrate production rate of 130±12 μmol h^?1 g_MO^?1 at an applied potential of 1.6 V versus the reversible hydrogen electrode (RHE).     

Synthesis of New Phenolic Derivatives of Quinazolin-4(3H)-One as Potential Antioxidant Agents—In Vitro Evaluation and Quantum Studies

Considering the important damage caused by the reactive oxygen (ROS) and nitrogen (RNS) species in the human organism, the need for new therapeutic agents, with superior efficacy to the known natural and synthetic antioxidants, is crucial. Quinazolin-4-ones are known for their wide range of biological activities, and phenolic compounds display an important antioxidant effect. Linking the two active pharmacophores may lead to an increase of the antioxidant activity. Therefore, we synthesized four series of new hybrid molecules bearing the quinazolin-4-one and phenol scaffolds. Their antioxidant potential was evaluated in vitro, considering different possible mechanisms of action: hydrogen atom transfer, ability to donate electrons and metal ions chelation. Theoretical quantum and thermodynamical calculations were also performed. Some compounds, especially the ortho diphenolic ones, exerted a stronger antioxidant effect than ascorbic acid and Trolox.     

SDEs with constraints driven by semimartingales and processes with bounded p-variation

We study the existence, uniqueness and stability of solutions of general stochastic differential equations with constraints driven by semimartingales and processes with bounded $p$-variation. Applications to SDEs with constraints driven by fractional Brownian motion and standard Brownian motion are given.     

Simultaneous optical coherence tomography--Indocyanine Green dye fluorescence imaging system for investigations of the eye's fundus

We have developed a dual-channel optical coherence tomography-Indocyanine Green dye (OCT-ICG) fluorescence system based on a previously reported ophthalmic OCT confocal imaging system. The confocal channel is tuned to the fluorescence wavelength range of the ICG, and light from the same optical source is used to generate the OCT image and to excite the ICG fluorescence. The system enables the clinician to visualize simultaneously en face OCT slices and corresponding ICG angiograms of the ocular fundus, displayed side by side. C-scan (constant depth) and B-scan (cross section) images are collected by a fast en face scan (T scan). The pixel-to-pixel correspondence between the OCT and angiography images allows the user to capture OCT B scans precisely at selected points on the ICG confocal images.     

Approximating the maximum 2- and 3-edge-colorable subgraph problems

For a fixed value of a parameter k≥2, the Maximum k-Edge-Colorable Subgraph Problem consists in finding k edge-disjoint matchings in a simple graph, with the goal of maximising the total number of edges used. The problem is known to be -hard for all k, but there exist polynomial time approximation algorithms with approximation ratios tending to 1 as k tends to infinity. Herein we propose improved approximation algorithms for the cases of k=2 and k=3, having approximation ratios of 5/6 and 4/5, respectively.     

Inverse minimum flow problem

In this paper we consider the inverse minimum flow (ImF) problem, where lower and upper bounds for the flow must be changed as little as possible so that a given feasible flow becomes a minimum flow. A linear time and space method to decide if the problem has solution is presented. Strongly and weakly polynomial algorithms for solving the ImF problem are proposed. Some particular cases are studied and a numerical example is given.