Fagopyrins from Buckwheat Flowers: Structural and Stereochemical Characterization through Combined NMR/CD Spectroscopy and Theoretical Calculations.

Fagopyrins are phenantroperylenequinones present in the flowers of Fagopyrum esculentum (buckwheat) endowed with photodynamic activity. It has been reported that fagopyrin extracts actually contain a complex mixture of closely related compounds, differing only on the nature of the perylenequinone substituents. We report our systematic and detailed study on the chemical composition of fagopyrin extracts by a combination of preparative and analytical techniques. The combined use of 1H-NMR and CD spectroscopy was found to be particularly suited to fully characterize all stereochemical aspects of the extracted fagopyrins. For the first time nine isomers have been structurally characterized and their stereochemistry fully elucidated. The presence of two different heterocyclic ring substituents, two stereogenic centers and the inherent axial chirality of the aromatic system provides a complex stereochemical relationships among isomers, thus giving account of the high level of molecular multiplicity found in the extract.

Improved Process for the Continuous Acylation of 1,3-Benzodioxole.

The acylation of 1,3-benzodioxole was studied in a continuous process using a recyclable heterogeneous substoichiometric catalyst. In a short time period (30 min), at 100 °C, the conversion rate was 73%, with a selectivity of 62% of the desired acylated product; the reaction was run continuously for 6 h, showing excellent stability and selectivity. Moreover, the unreacted starting material, 1,3-benzodioxole, can be easily separated by distillation and recycled.

Antiviral, virucidal and antioxidant properties of Artemisia annua against SARS-CoV-2.

Natural products are a rich source of bioactive molecules that have potential pharmacotherapeutic applications. In this study, we focused on Artemisia annua (A. annua) and its enriched extracts which were biologically evaluated in vitro as virucidal, antiviral, and antioxidant agents, with a potential application against the COVID-19 infection. The crude extract showed virucidal, antiviral and antioxidant effects in concentrations that did not affect cell viability. Scopoletin, arteannuin B and artemisinic acid (single fractions isolated from A. annua) exerted a considerable virucidal and antiviral effect in vitro starting from a concentration of 50 µg/mL. Data from Surface Plasmon Resonance (SPR) showed that the inhibition of the viral infection was due to the interaction of these compounds with the 3CLpro and Spike proteins of SARS-CoV-2, suggesting that the main interaction of compounds may interfere with the viral pathways during the insertion and the replication process. The present study suggests that natural extract of A. annua and its components could have a key role as antioxidants and antiviral agents and support the fight against SARS-CoV-2 variants and other possible emerging Coronaviruses.

Lipase-mediated flow synthesis of nature-inspired phenolic carbonates.

A facile and convenient lipase-catalyzed flow approach for the chemoselective synthesis of tyrosol and hydroxytyrosol methyl carbonates has been developed in neat dimethylcarbonate. The products were obtained in quantitative yield with high catalyst productivity. The biocatalytic approach was then exploited for the preparation of value-added symmetrical tyrosol and hydroxytyrosol carbonates.

Caulobacter segnis Dioxygenase CsO2: A Practical Biocatalyst for Stilbenoid Ozonolysis.

Ozonolysis is a useful as well as dangerous reaction for performing alkene cleavage. On the other hand, enzymes are considered a more sustainable and safer alternative. Among them, Caulobacter segnis dioxygenase (CsO2) known so far for its ability to catalyze the coenzyme-free oxidation of vinylguaiacol into vanillin, was selected and its substrate scope evaluated towards diverse natural and synthetic stilbenoids. Under optimized conditions, CsO2 catalyzed the oxidative cleavage of the C=C double bonds of various trans-stilbenes, providing that a hydroxyl moiety was necessary in para-position of the phenyl group (e. g., resveratrol and its derivatives) for the reaction to take place, which was confirmed by modelling studies. The reactions occurred rapidly (0.5-3 h) with high conversions (95-99 %) and without formation of by-products. The resveratrol biotransformation was carried out on 50-mL scale thus confirming the feasibility of the biocatalytic system as a preparative method.

Effect of endodontic sealers on push-out bond strength of CAD-CAM or prefabricated fiber glass posts.

This study aimed to evaluate the effect of endodontic sealer (ES) on bond strength (BS) of prefabricated or milled-CAD-CAM (computer-aided design and computer-aided manufacturing) glass-fiber-posts (GFP). Canals of 90 single-rooted teeth were prepared for filling by the single-cone technique with gutta-percha and one of the following ES: AH Plus (epoxy resin), Endofill (zinc-oxide and eugenol), and Bio-C Sealer (calcium-silicate). After post-space preparation, tooth-specimens were equally divided in half according to type of GFP to be used. In the half to receive milled-CAD-CAM posts, tooth specimens were molded with acrylic resin to obtain replicas. These were scanned to enable the laboratory to produce the milled-CAD-CAM GFPs (Fiber CAD Lab, Angelus) by the subtractive technique. The other half of samples received prefabricated GFPs (Exacto, Angelus) (n=15). The GFPs were cemented with dual-cure resin cement (Panavia F2.0, Kuraray). Each root was sectioned into two slices per root region (cervical, middle, apical) that were subjected to the push-out BS test, in a universal testing machine. Failure mode (FM) was classified by scores. The BS data were submitted to generalized linear model analyses, while FM was analyzed using the chi-square test (a=0.05). BS showed no significant difference among the three ES (p > 0.05). BS was significantly higher for prefabricated (mean 10.84 MPa) versus milled-CAD-CAM GFPs (mean 6.94 MPa) (p <0.0001), irrespective of ES. The majority showed mixed failures. It could be concluded that type of ES did not affect BS of GFPs to dentin, and prefabricated-GFPs had higher bond-strength than customized-milled-CAD-CAM GFPs.

NK cell defects: implication in acute myeloid leukemia.

Acute Myeloid Leukemia (AML) is a complex disease with rapid progression and poor/unsatisfactory outcomes. In the past few years, the focus has been on developing newer therapies for AML; however, relapse remains a significant problem. Natural Killer cells have strong anti-tumor potential against AML. This NK-mediated cytotoxicity is often restricted by cellular defects caused by disease-associated mechanisms, which can lead to disease progression. A stark feature of AML is the low/no expression of the cognate HLA ligands for the activating KIR receptors, due to which these tumor cells evade NK-mediated lysis. Recently, different Natural Killer cell therapies have been implicated in treating AML, such as the adoptive NK cell transfer, Chimeric antigen receptor-modified NK (CAR-NK) cell therapy, antibodies, cytokine, and drug treatment. However, the data available is scarce, and the outcomes vary between different transplant settings and different types of leukemia. Moreover, remission achieved by some of these therapies is only for a short time. In this mini-review, we will discuss the role of NK cell defects in AML progression, particularly the expression of different cell surface markers, the available NK cell therapies, and the results from various preclinical and clinical trials.

Ligand and Gold(I) Fluorescein-AIEgens as Photosensitizers in Solution and Doped Polymers.

The synthesis of fluorescein propargyl diether (L) and two different dinuclear gold(I) derivatives containing a water-soluble phosphane [1,3,5-triaza-7-phosphatricyclo[3.3.1.13.7]decane (PTA) for complex 1 and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) for complex 2] has been successfully performed. All compounds display intrinsic emission from fluorescein, being less intense for gold(I) complexes due to the heavy-atom effect. All compounds aggregate in acetonitrile/water mixtures with the formation of larger aggregates for those samples containing more water content, as evidenced by dynamic light scattering and small-angle X-ray scattering experiments, in agreement with the absorption and emission data. The emission of the samples increases when they are used to obtain luminescent materials with four different organic matrices [poly(methyl methacrylate, polystyrene (PS), cellulose, and Zeonex]. The compounds display very high values of singlet oxygen (1O2) production in dichloromethane. Singlet oxygen production was also evaluated in the doped matrices, being the highest in PS and with an exciting increase on PS microspheres. Density functional theory (BP86-D3) and GFN2-xTB calculations were used to model the assembly of L and complexes 1 and 2 with the different organic matrices and rationalize the experimental findings based on the geometries, molecular electrostatic potential surfaces, and complementarity and HOMO-LUMO gaps.

Falsificações por troca de espécies de peixes: uma revisão sistemática das espécies mais comumente substituídas / Fish mislabeling: a systematic review of the most commonly mislabeled species

O objetivo deste artigo é determinar quais são as espécies de peixes mais comumente substituídas, relatadas em revisões sobre falsificações por troca de espécies, em artigos científicos publicados entre 2002 e 2022, assim como expor quais são os fatores que levam à ocorrência de casos de falsificação, quais os danos sociais que tal prática ilegal pode gerar e em que tipo de estabelecimentos as falsificações normalmente são detectadas. Assim, por meio de uma revisão sistemática de literatura, foi verificado que as espécies de peixes mais comumente falsificadas foram Anoplopoma fimbria, Gadus morhua, Solea solea, Thunnus albacares, Scomberomorus commerson, Lates calcarifer e Rastrelliger brachysoma. As motivações por trás das falsificações intencionais foram predominantemente econômicas, tendo sido observados impactos negativos das falsificações na economia, na saúde pública e no meio ambiente. A maioria das falsificações foi encontrada no final da cadeia produtiva, em locais como varejos, restaurantes e peixarias. Dessa forma, ao saber como as falsificações acontecem e suas razões, torna-se possível saber como minimizar a sua ocorrência.

The aim of this article is to identify the most frequently mislabeled fish species, based on reports and reviews of species mislabeling-related falsifications, in scientific articles published between 2002 and 2022. It also aims to explore the factors contributing these counterfeiting incidents, the social harms associated with this illegal practice and the types of establishments where counterfeits are typically detected. Through a systematic literature review, it was verified that the most commonly mislabeled fish species were Anoplopoma fimbria, Gadus morhua, Solea solea, Thunnus albacares, Scomberomorus commerson, Lates calcarifer and Rastrelliger brachysoma. The primary motivations behind intentional counterfeiting were economic in nature, and negative impacts of counterfeiting on the economy, public health and the environment were widely recognized. Most counterfeits were found at the end of the production chain, in places such as retail stores, restaurants and fishmongers' businesses. By understanding the mechanisms and motivations behind counterfeiting, we can effectively minimize its prevalence.

Survey on Intrusion Detection Systems Based on Machine Learning Techniques for the Protection of Critical Infrastructure.

Industrial control systems (ICSs), supervisory control and data acquisition (SCADA) systems, and distributed control systems (DCSs) are fundamental components of critical infrastructure (CI). CI supports the operation of transportation and health systems, electric and thermal plants, and water treatment facilities, among others. These infrastructures are not insulated anymore, and their connection to fourth industrial revolution technologies has expanded the attack surface. Thus, their protection has become a priority for national security. Cyber-attacks have become more sophisticated and criminals are able to surpass conventional security systems; therefore, attack detection has become a challenging area. Defensive technologies such as intrusion detection systems (IDSs) are a fundamental part of security systems to protect CI. IDSs have incorporated machine learning (ML) techniques that can deal with broader kinds of threats. Nevertheless, the detection of zero-day attacks and having technological resources to implement purposed solutions in the real world are concerns for CI operators. This survey aims to provide a compilation of the state of the art of IDSs that have used ML algorithms to protect CI. It also analyzes the security dataset used to train ML models. Finally, it presents some of the most relevant pieces of research on these topics that have been developed in the last five years.

Identification of the novel HLA-A*01:01:01:111 allele in two individuals from Uttar Pradesh, India.

The novel HLA-A*01:01:01:111 allele was detected during routine HLA typing.

Identification of the HLA-B*40:01:02:59 and -C*05:01:73 alleles in individuals from the northern regions of India.

The novel HLA-B*40:01:02:59 and HLA-C*05:01:73 alleles were detected during the routine HLA typing process.

Exploration of Novel Scaffolds Targeting Cytochrome b of Pyricularia oryzae.

The fulfilment of the European "Farm to Fork" strategy requires a drastic reduction in the use of "at risk" synthetic pesticides; this exposes vulnerable agricultural sectors-among which is the European risiculture-to the lack of efficient means for the management of devastating diseases, thus endangering food security. Therefore, novel scaffolds need to be identified for the synthesis of new and more environmentally friendly fungicides. In the present work, we employed our previously developed 3D model of P. oryzae cytochrome bc1 (cyt bc1) complex to perform a high-throughput virtual screening of two commercially available compound libraries. Three chemotypes were selected, from which a small collection of differently substituted analogues was designed and synthesized. The compounds were tested as inhibitors of the cyt bc1 enzyme function and the mycelium growth of both strobilurin-sensitive (WT) and -resistant (RES) P. oryzae strains. This pipeline has permitted the identification of thirteen compounds active against the RES cyt bc1 and five compounds that inhibited the WT cyt bc1 function while inhibiting the fungal mycelia only minimally. Serendipitously, among the studied compounds we identified a new chemotype that is able to efficiently inhibit the mycelium growth of WT and RES strains by ca. 60%, without inhibiting the cyt bc1 enzymatic function, suggesting a different mechanism of action.

Investigation of the Effects of Monomeric and Dimeric Stilbenoids on Bacteria-Induced Cytokines and LPS-Induced ROS Formation in Bone Marrow-Derived Dendritic Cells.

Stilbenoids are anti-inflammatory and antioxidant compounds, with resveratrol being the most investigated molecule in this class. However, the actions of most other stilbenoids are much less studied. This study compares five monomeric (resveratrol, piceatannol, pterostilbene, pinostilbene, and trimethoxy-resveratrol) and two dimeric (dehydro-δ-viniferin and trans-δ-viniferin) stilbenoids for their capability to modulate the production of bacteria-induced cytokines (IL-12, IL-10, and TNF-α), as well as lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), in murine bone marrow-derived dendritic cells. All monomeric species showed dose-dependent inhibition of E. coli-induced IL-12 and TNF-α, whereas only resveratrol and piceatannol inhibited IL-10 production. All monomers, except trimethoxy-resveratrol, inhibited L. acidophilus-induced IL-12, IL-10, and TNF-α production. The dimer dehydro-δ-viniferin remarkably enhanced L. acidophilus-induced IL-12 production. The contrasting effect of resveratrol and dehydro-δ-viniferin on IL-12 production was due, at least in part, to a divergent inactivation of the mitogen-activated protein kinases by the two stilbenoids. Despite having moderate to high total antioxidant activity, dehydro-δ-viniferin was a weak inhibitor of LPS-induced ROS formation. Conversely, resveratrol and piceatannol potently inhibited LPS-induced ROS formation. Methylated monomers showed a decreased antioxidant capacity compared to resveratrol, also depending on the methylation site. In summary, the immune-modulating effect of the stilbenoids depends on both specific structural features of tested compounds and the stimulating bacteria.

Nutritional epigenomic and DNA-damage modulation effect of natural stilbenoids.

The aim of the present work is the evaluation of biological effects of natural stilbenoids found in Vitis vinifera, with a focus on their activity as epigenetic modulators. In the present study, resveratrol, pterostilbene and for the first time their dimers (±)-trans-δ-viniferin, (±)-trans-pterostilbene dehydrodimer were evaluated in Caco-2 and HepG-2 cell lines as potential epigenetic modulators. Stilbenoids were added in a Caco-2 cell culture as a model of the intestinal epithelial barrier and in the HepG-2 as a model of hepatic environment, to verify their dose-dependent toxicity, ability to interact with DNA, and epigenomic action. Resveratrol, pterostilbene, and (±)-trans-pterostilbene dehydrodimer were found to have no toxic effects at tested concentration and were effective in reversing arsenic damage in Caco-2 cell lines. (±)-trans-δ-viniferin showed epigenomic activity, but further studies are needed to clarify its mode of action.

Detection of novel HLA-A*33:03:62, HLA-B*52:01:01:25 alleles and confirmation of HLA-A*02:01:209.

Novel HLA-A*33:03:62, -B*52:01:01:25 alleles and confirmatory HLA-A*02:01:209 allele were detected during the HLA typing process.

Characterization of the novel HLA-B*58:01:01:19 allele by next-generation sequencing.

The novel HLA-B*58:01:01:19 allele was characterized using next generation sequencing technology.

Identification of the novel HLA-DPA1*01:03:01:64 allele in an individual from Uttar Pradesh, India.

The novel HLA-DPA1*01:03:01:64 allele was detected during routine HLA typing.

Identification of the novel HLA allele, HLA-B*37:01:01:19, in an individual from northern India.

The novel allele HLA-B*37:01:01:19 differs from B*37:01:01:01 by one nucleotide A->G in Intron 3 at gDNA1430.

Identification of the novel HLA-DQA1*01:01:01:11 and -DQA1*01:03:01:13 alleles in individuals from India.

The novel alleles HLA-DQA1*01:01:01:11 and -DQA1*01:03:01:13 were detected during the routine HLA typing process.