[Improving the nutritional care of oncology patients - Validation of a multidisciplinary protocol in the Spanish clinical setting]. / Mejorando la atención nutricional del paciente oncológico: validación de un protocolo multidisciplinar en el entorno clínico español.

INTRODUCTION: malnutrition is a very frequent problem in oncology patients and can have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. OBJECTIVE: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. METHODS: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. RESULTS: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. CONCLUSIONS: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

Structural Models of the First Molecular Events in the Heliorhodopsin Photocycle.

Retinylidene conformations and rearrangements of the hydrogen-bond network in the vicinity of the protonated Schiff base (PSB) play a key role in the proton transfer process in the Heliorhodopsin photocycle. Photoisomerization of the retinylidene chromophore and the formation of photoproducts corresponding to the early intermediates were modeled using a combination of molecular dynamics simulations and quantum mechanical/molecular mechanics calculations. The resulting structures were refined, and the respective excitation energies were calculated. Aided by metadynamics simulations, we constructed a photoisomerized intermediate where the 13-cis retinylidene chromophore is rotated about a parallel pair of double bonds at C13=C14 and C15=NZ double bonds. We demonstrate how the deprotonation of the Schiff base and the concomitant protonation of the Glu107 counterion are only favored because of these rearrangements.

A Humanized Mouse Model Coupled with Computational Analysis Identifies Potent Glycolipid Agonist of Invariant NKT Cells.

Invariant natural killer T (iNKT) cells play an important role in many innate and adaptive immune responses, with potential applications in cancer immunotherapy. The glycolipid KRN7000, an α-galactosylceramide, potently activates iNKT cells but has shown limited anticancer effects in human clinical trials conducted so far. In spite of almost three decades of structure-activity relationship studies, no alternative glycolipid has yet emerged as a superior clinical candidate. One reason for the slow progress in this area is that standard mouse models do not accurately reflect the specific ligand recognition by human iNKT cells and their requirements for activation. Here we evaluated a series of KRN7000 analogues using a recently developed humanized mouse model that expresses a human αTCR chain sequence and human CD1d. In this process, a more stimulatory, previously reported but largely overlooked glycolipid was identified, and its activity was probed and rationalized via molecular simulations.

Photoactivation of the orange carotenoid protein requires two light-driven reactions mediated by a metastable monomeric intermediate.

The orange carotenoid protein (OCP) functions as a sensor of the ambient light intensity and as a quencher of bilin excitons when it binds to the core of the cyanobacterial phycobilisome. We show herein that the photoactivation mechanism that converts the resting, orange-colored state, OCPO, to the active red-colored state, OCPR, requires a sequence of two reactions, each requiring absorption of a single photon by an intrinsic ketocarotenoid chromophore. Global analysis of absorption spectra recorded during continuous illumination of OCPO preparations from Synechocystis sp. PCC 6803 detects the reversible formation of a metastable intermediate, OCPI, in which the ketocarotenoid canthaxanthin exhibits an absorption spectrum with a partial red shift and a broadened vibronic structure compared to that of the OCPO state. While the dark recovery from OCPR to OCPI is a first-order, unimolecular reaction, the subsequent conversion of OCPI to the resting OCPO state is bimolecular, involving association of two OCPO monomers to form the dark-stable OCPO dimer aggregate. These results indicate that photodissociation of the OCPO dimer to form the monomeric OCPO intermediate is the first step in the photoactivation mechanism. Formation of the OCPO monomer from the dimer increases the mean value and broadens the distribution of the solvent-accessible surface area of the canthaxanthin chromophore measured in molecular dynamics trajectories at 300 K. The second step in the photoactivation mechanism is initiated by absorption of a second photon, by canthaxanthin in the OCPO monomer, which obtains the fully red-shifted and broadened absorption spectrum detected in the OCPR product state owing to displacement of the C-terminal domain and the translocation of canthaxanthin more than 12 Å into the N-terminal domain. Both steps in the photoactivation reaction of OCP are likely to involve changes in the structure of the C-terminal domain elicited by excited-state conformational motions of the ketocarotenoid.

Helichrysum stoechas (L.) Moench Inflorescence Extract for Tomato Disease Management.

Helichrysum stoechas is a singular halophyte that has been shown to have anti-inflammatory, antioxidant, and allelopathic properties. In the work presented herein, we have characterized its inflorescences hydromethanolic extract and assessed its antifungal activity for the pre- and postharvest management of tomato crop diseases. Gas chromatography-mass spectrometry characterization of the extract showed that 4-ethenyl-1,3-benzenediol, 2,3-dihydro-benzofuran, quinic acid, 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-1-benzopyran-4-one, 1,6-anhydro-ß-D-glucopyranose, catechol, scopoletin, and maltol were the main constituents. The co-occurrence of pyranones, benzenediols, and quinic acids as phytoconstituents of H. stoechas extract resulted in promising in vitro minimum inhibitory concentrations of 500, 375, 500, 187.5, 187.5, and 375 µg·mL-1 against mycelia of Alternaria alternata, Colletotrichum coccodes, Fusarium oxysporum f. sp. lycopersici, Rhizoctonia solani, Sclerotinia sclerotiorum, and Verticillium dahliae, respectively. Further, to assess the potential of H. stoechas inflorescence extract for postharvest tomato crop protection, ex situ tests were conducted against C. coccodes, obtaining high protection at a dose of 750 µg·mL-1. Taking into consideration that the demonstrated activity is among the highest reported to date for plant extracts and comparable to that of the synthetic fungicides tested as positive controls, H. stoechas inflorescence extract may be put forward as a promising biorational and may deserve further testing in field-scale studies.

Metagenomic Study of Fungal Microbial Communities in Two PDO Somontano Vineyards (Huesca, Spain): Effects of Age, Plant Genotype, and Initial Phytosanitary Status on the Priming and Selection of their Associated Microorganisms.

The study of microbial communities associated with different plants of agronomic interest has allowed, in recent years, to answer a number of questions related to the role and influence of certain microbes in key aspects of their autoecology, such as improving the adaptability of the plant host to different abiotic or biotic stresses. In this study, we present the results of the characterization, through both high-throughput sequencing and classical microbiological methods, of the fungal microbial communities associated with grapevine plants in two vineyards of different ages and plant genotypes located in the same biogeographical unit. The study is configured as an approximation to the empirical demonstration of the concept of "microbial priming" by analyzing the alpha- and beta-diversity present in plants from two plots subjected to the same bioclimatic regime to detect differences in the structure and taxonomic composition of the populations. The results were compared with the inventories of fungal diversity obtained by culture-dependent methods to establish, where appropriate, correlations between both microbial communities. Metagenomic data showed a differential enrichment of the microbial communities in the two vineyards studied, including the populations of plant pathogens. This is tentatively explained due to factors such as the different time of exposure to microbial infection, different plant genotype, and different starting phytosanitary situation. Thus, results suggest that each plant genotype recruits differential fungal communities and presents different profiles of associated potential microbial antagonists or communities of pathogenic species.

Phytochemical Profiling of Sambucus nigra L. Flower and Leaf Extracts and Their Antimicrobial Potential against Almond Tree Pathogens.

Despite extensive research on the chemical composition of elderberries and their numerous uses in pharmaceutical, beverage, and food production, there is still a lack of knowledge about Sambucus nigra leaves and flowers' antimicrobial activity against plant pathogens. In this study, the phytoconstituents of their aqueous ammonia extracts were first characterized by infrared spectroscopy and gas chromatography-mass spectrometry. The major phytocompounds identified in the flower extract were octyl 2-methylpropanoate; 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one; propyl malonic acid; adenine; and 1-methyl-2-piperidinemethanol. Concerning the leaf extract, 1,6-anhydro-ß-D-glucopyranose; oleic acid; 2,1,3-benzothiadiazole; 2,3-dihydro-benzofuran; and 4-((1E)-3-hydroxy-1-propenyl)-2-methoxyphenol and other phenol derivatives were the main constituents. The potential of the extracts to act as bioprotectants was then investigated against three almond tree pathogens: Diaporthe amygdali, Phytophthora megasperma, and Verticillium dahliae. In vitro tests showed higher activity of the flower extract, with EC90 values in the 241-984 µg·mL-1 range (depending on the pathogen) vs. 354-1322 µg·mL-1 for the leaf extract. In addition, the flower extract led to full protection against P. megasperma at a dose of 1875 µg·mL-1 in ex situ tests on artificially-infected excised almond stems. These inhibitory concentrations were lower than those of commercial fungicides. These findings suggest that S. nigra aerial organs may be susceptible to valorization as an alternative to synthetic fungicides for the protection of this important crop.

New insights in the Spanish gene pool of olive (Olea europaea L.) preserved ex situ and in situ based on high-throughput molecular markers.

In Spain, several local studies have highlighted the likely presence of unknown olive cultivars distinct from the approximately 260 ones previously described in the literature. Furthermore, recent advancements in identification techniques have significantly enhanced in terms of efficacy and precision. This scenario motivated a new nationwide prospecting effort aimed at recovering and characterizing new cultivated germplasm using high-throughput molecular markers. In the present study, the use of 96 EST-SNP markers allowed the identification of a considerable amount of new material (173 new genotypes) coming from areas with low intensification of production in different regions of Spain. As a result, the number of distinct national genotypes documented in the World Olive Germplasm Bank of IFAPA, Córdoba (WOGBC-ESP046) increased to 427. Likewise, 65 and 24 new synonymy and homonymy cases were identified, respectively. This rise in the number of different national cultivars allowed to deepen the knowledge about the underlying genetic structure. The great genetic variability of Spanish germplasm was confirmed, and a new hot spot of diversity was identified in the northern regions of La Rioja and Aragon. Analysis of the genetic structure showed a clear separation between the germplasm of southern and northern-northeastern Spain and indicated a significantly higher level of admixture in the latter. Given the expansion of modern olive cultivation with only a few cultivars, this cryptic germplasm is in great danger of disappearing. This underlines the fact that maintaining as many cultivars as possible will increase the genetic variability of the olive gene pool to meet the future challenges of olive cultivation.

Re-examining Cannabidiol: Conversion to Tetrahydrocannabinol Using Only Heat.

Introduction: In the last decade, the market for Cannabidiol (CBD) has grown to become a near $2 billion dollar industry in the United States alone. This growth can be attributed to a growing social acceptance of marijuana, a more detailed understanding of many health benefits attributed to cannabinoids, and the low cost and wide availibility of hemp-derived cannabinoids. Due to the complex legal histories of marijuana and cannabinoids, the stability and safety of CBD is still an area of interest as research has been restricted globally. Conversion of CBD to its psychoactive isomers, most notably delta-9-Tetrahydrocannabinol (Δ9-THC), presents a significant safety issue for consumers and producers of CBD products. Methods: Previous studies investigating the stability of CBD have focused mainly on replicating conditions experienced during long-term storage at room temperature or lower. Here, we report the thermal stability of CBD at 175°C. Dynamic 1H-NMR experiments and computational electronic structure calculations were used to characterize possible reaction paths from CBD to THC. Results: After 30 minutes of heating, Δ9-THC was produced in detectable amounts in aerobic and anaerobic conditions without an acid catalyst. Conclusions: Our findings support an energetically feasible reaction route that is favorable due to both an increase in phenol acidity at high temperatures and the presence of intramolecular OH-π hydrogen bonding.

Valorization of Quercus suber L. Bark as a Source of Phytochemicals with Antimicrobial Activity against Apple Tree Diseases.

Cork, an anatomic adaptation of the bark of Quercus suber L. through its suberization process, finds its main application in the production of bottle stoppers. Its processing results in a large waste stream of cork fragments, granulates, and dust, which may be susceptible to valorization. The work presented here explored the use of its extracts to inhibit the growth of phytopathogenic microorganisms associated with apple tree diseases. The in vitro antimicrobial activity of cork aqueous ammonia extract was assayed against four fungi, viz. Monilinia fructigena and M. laxa (brown rot), Neofussicoccum parvum (dieback), and Phytophthora cactorum (collar and root rot), and two bacteria, viz. Erwinia amylovora and Pseudomonas syringae pv. syringae, either alone or in combination with chitosan oligomers (COS). Effective concentration values of EC90 in the 675-3450 µg·mL-1 range, depending on the fungal pathogen, were obtained in growth inhibition tests, which were substantially improved for the conjugate complexes (340-801 µg·mL-1) as a result of strong synergism with COS. Similar enhanced behavior was also observed in antibacterial activity assays, with MIC values of 375 and 750 µg·mL-1 for the conjugate complexes against P. syringae pv. syringae and E. amylovora, respectively. This in vitro inhibitory activity was substantially higher than those exhibited by azoxystrobin and fosetyl-Al, which were tested for comparison purposes, and stood out among those reported for other natural compounds in the literature. The observed antimicrobial activity may be mainly attributed to the presence of glycerin and vanillic acid, identified by gas chromatography-mass spectroscopy. In the first step towards in-field application, the COS-Q. suber bark extract conjugate complex was further tested ex situ against P. cactorum on artificially inoculated excised stems of the 'Garnem' almond rootstock, achieving high protection at a dose of 3750 µg·mL-1. These results suggest that cork industrial leftovers may, thus, be a promising source of bioactive compounds for integrated pest management.

Multifunctional Nanocarriers Based on Chitosan Oligomers and Graphitic Carbon Nitride Assembly.

In this study, a graphitic carbon nitride and chitosan oligomers (g-C3N4−COS) nanocarrier assembly, which was obtained by cross-linking with methacrylic anhydride (MA), was synthesized and characterized. Its characterization was carried out using infrared spectroscopy, elemental and thermal analyses, and transmission electron microscopy. The new nanocarriers (NCs), with an average particle size of 85 nm in diameter and a 0.25 dispersity index, showed photocatalytic activity (associated with the g-C3N4 moiety), susceptibility to enzymatic degradation (due to the presence of the COS moiety), and high encapsulation and moderate-high release efficiencies (>95% and >74%, respectively). As a proof of concept, the visible-light-driven photocatalytic activity of the NCs was tested for rhodamine B degradation and the reduction of uranium(VI) to uranium(IV). Regarding the potential of the nanocarriers for the encapsulation and delivery of bioactive products for crop protection, NCs loaded with Rubia tinctorum extracts were investigated in vitro against three Vitis vinifera phytopathogens (viz. Neofusicoccum parvum, Diplodia seriata, and Xylophilus ampelinus), obtaining minimum inhibitory concentration values of 750, 250, and 187.5 µg·mL−1, respectively. Their antifungal activity was further tested in vivo as a pruning wound protection product in young 'Tempranillo' grapevine plants that were artificially infected with the two aforementioned species of the family Botryosphaeriaceae, finding a significant reduction of the necrosis lengths in the inner woody tissues. Therefore, g-C3N4-MA-COS NCs may be put forward as a multifunctional platform for environmental and agrochemical delivery applications.

Holm Oak (Quercus ilex subsp. ballota (Desf.) Samp.) Bark Aqueous Ammonia Extract for the Control of Invasive Forest Pathogens.

Holm oak (Quercus ilex subsp. ballota (Desf.) Samp.) bark is a commonly used remedy to treat gastrointestinal disorders, throat and skin infections, hemorrhages, and dysentery. It has also been previously reported that its methanol extracts possess antibacterial activity, which can be related to the richness of Quercus spp. extracts in phenolic compounds, such as flavonoids and tannins. However, there is no information on the antifungal (including oomycete) properties of the bark from Q. ilex or its subspecies (ilex and ballota). In this work, we report the characterization of the aqueous ammonia extract of its bark by FTIR and GC-MS and the results of in vitro and ex situ inhibition tests against three phytopathogens. The main phytochemical components identified were inositols (19.5%), trans-squalene (13%), 4-butoxy-1-butanol (11.4%), gulopyranose (9.6%), lyxose (6.5%), 2,4-dimethyl-benzo[H]quinoline (5.1%), catechol (4.5%), and methoxyphenols (4.2%). The efficacy of the extract in controlling forest phytopathogens was tested in vitro against Fusarium circinatum (responsible for pitch canker of Pinus spp.), Cryphonectria parasitica (which causes chestnut blight), and Phytophthora cinnamomi (which causes 'root and crown rot' in a variety of hosts, including Castanea, conifers, Eucalyptus, Fagus, Juglans, Quercus, etc.), obtaining EC90 values of 322, 295, and 75 µg·mL-1, respectively, much lower than those attained for a commercial strobilurin fungicide (azoxystrobin). The extract was further tested ex situ against P. cinnamomi on artificially inoculated, excised stems of 'Garnem' almond rootstock, attaining complete protection at a dose of 782 µg·mL-1. The results suggest that holm oak bark extract may be a promising source of bioactive compounds against invasive forest pathogens, including the oomycete that is causing its decline, the so-called 'seca' in Spain.

Syntheses and Aromaticity Parameters of Hexahydroxypyrrocorphin, Porphotrilactones, and Their Oxidation State Intermediates.

Triple OsO4-mediated dihydroxylation of meso-tetrakis(pentafluorophenyl)porphyrin formed a non-aromatic hexahydroxypyrrocorphin as a single stereo-isomer. A one-step oxidative conversion of all three diol functionalities to lactone moieties generated three out of the four possible porphotrilactone regioisomers that were spectroscopically and structurally characterized. This conversion recovered most of the porphyrinic macrocycle aromatic ring current, as seen in their 1H NMR spectra and modeled using DFT computations. Stepwise OsO4-mediated dihydroxylations of porpho-mono- and -di-lactones generated intermediate oxidation state compounds between the pyrrole-three pyrroline macrocycle of the pyrrocorphin and the pyrrole-three oxazolone chromophore of the trilactones. The aromaticity of these chromophores was reduced with increasing number of oxazolone to pyrroline replacements, showing the importance for the presence of three lactone moieties for the retention of the macrocycle aromaticity in the tris-ß,ß'-modified macrocycles. This work first describes hexahydoxypyrrocorphins, porphotrislactones, and the oxidation state intermediates between them; furthers the understanding of the roles of ß-lactone moieties in the expression of porphyrinic macrocycle aromaticity; and generally broadens access to chemically stable pyrrocorphins and pyrrocorphin analogues.

Microsolvation Effects in the Spectral Tuning of Heliorhodopsin.

Heliorhodopsins (HeR) are a new category of heptahelical transmembrane photoactive proteins with a covalently linked all-trans retinal. The protonated Schiff base (PSB) nitrogen in the retinal is stabilized by a negatively charged counterion. It is well-known that stronger or weaker electrostatic interactions with the counterion cause a significant spectral blue- or red-shift, respectively, in both microbial and animal rhodopsins. In HeR, however, while Glu107 acts as the counterion, mutations of this residue are not directly correlated with a spectral shift. A molecular dynamics analysis revealed that a water cluster pocket produces a microsolvation effect on the Schiff base, compensating to various extents the replacement of the native counterion. Using a combination of molecular dynamics and quantum mechanical/molecular mechanics (QM/MM), we study this microsolvation effect on the electronic absorption of the retinylidene Schiff base chromophore of HeR.

Electronic energy levels of porphyrins are influenced by the local chemical environment.

Self-assembled islands of 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin (2HTFPP) on Au(111) contain two bistable molecular species that differ by shifted electronic energy levels. Interactions with the underlying gold herringbone reconstruction and neighboring 2HTFPP molecules cause approximately 60% of molecules to have shifted electronic energy levels. We observed the packing density decrease from 0.64 ± 0.04 molecules per nm2 to 0.38 ± 0.03 molecules per nm2 after annealing to 200 °C. The molecules with shifted electronic energy levels show longer-range hexagonal packing or are adjacent to molecular vacancies, indicating that molecule-molecule and molecule-substrate interactions contribute to the shifted energies. Multilayers of porphyrins do not exhibit the same shifting of electronic energy levels which strongly suggests that molecule-substrate interactions play a critical role in stabilization of two electronic species of 2HTFPP on Au(111).

A favorable path to domain separation in the orange carotenoid protein.

The orange carotenoid protein (OCP) is responsible for nonphotochemical quenching (NPQ) in cyanobacteria, a defense mechanism against potentially damaging effects of excess light conditions. This soluble two-domain protein undergoes profound conformational changes upon photoactivation, involving translocation of the ketocarotenoid inside the cavity followed by domain separation. Domain separation is a critical step in the photocycle of OCP because it exposes the N-terminal domain (NTD) to perform quenching of the phycobilisomes. Many details regarding the mechanism and energetics of OCP domain separation remain unknown. In this work, we apply metadynamics to elucidate the protein rearrangements that lead to the active, domain-separated, form of OCP. We find that translocation of the ketocarotenoid canthaxanthin has a profound effect on the energetic landscape and that domain separation only becomes favorable following translocation. We further explore, characterize, and validate the free energy surface (FES) using equilibrium simulations initiated from different states on the FES. Through pathway optimization methods, we characterize the most probable path to domain separation and reveal the barriers along that pathway. We find that the free energy barriers are relatively small (<5 kcal/mol), but the overall estimated kinetic rate is consistent with experimental measurements (>1 ms). Overall, our results provide detailed information on the requirement for canthaxanthin translocation to precede domain separation and an energetically feasible pathway to dissociation.

Characterization and Antimicrobial Activity of a Halophyte from the Asturian Coast (Spain): Limonium binervosum (G.E.Sm.) C.E.Salmon.

The work presented herein deals with the characterization and valorization of a halophyte from the cliffs of the Asturian coast: Limonium binervosum (G.E.Sm.) C.E.Salmon (rock sea-lavender). Its biomass and hydromethanolic extracts were studied by elemental and thermal analysis, infrared spectroscopy and gas chromatography-mass spectroscopy. Tetradecanoic acid/esters and 1,2-tetradecanediol were identified in its flower extract, while the leaf extract was rich in linolenic and linoleic acids and their esters, hexadecanoic acid and its esters, and phytol. Both flower and leaf hydromethanolic extracts contained eicosane, sitosterol and tocopherols in significant amounts. With a view to its valorization, the antimicrobial activity of these extracts was investigated against three apple tree and grapevine phytopathogens. Both the hydroalcoholic extracts and their main constituents, alone or in combination with chitosan oligomers (COS), were tested in vitro. A remarkable antibacterial activity was observed for the conjugated complexes of the flower extract with COS, both against Xylophilus ampelinus (MIC = 250 µg·mL-1) and Erwinia amylovora (MIC = 500 µg·mL-1), and complete inhibition of the mycelial growth of Diplodia seriata was found at concentrations <1000 µg·mL-1. In view of these results, this extremophile plant can be put forward as a promising source of bioactive metabolites.

Activity of Anthracenediones and Flavoring Phenols in Hydromethanolic Extracts of Rubia tinctorum against Grapevine Phytopathogenic Fungi.

In this work, the chemical composition of Rubia tinctorum root hydromethanolic extract was analyzed by GC-MS, and over 50 constituents were identified. The main phytochemicals were alizarin-related anthraquinones and flavoring phenol compounds. The antifungal activity of this extract, alone and in combination with chitosan oligomers (COS) or with stevioside, was evaluated against the pathogenic taxa Diplodia seriata, Dothiorella viticola and Neofusicoccum parvum, responsible for the so-called Botryosphaeria dieback of grapevine. In vitro mycelial growth inhibition tests showed remarkable activity for the pure extract, with EC50 and EC90 values as low as 66 and 88 µg·mL-1, respectively. Nonetheless, enhanced activity was attained upon the formation of conjugate complexes with COS or with stevioside, with synergy factors of up to 5.4 and 3.3, respectively, resulting in EC50 and EC90 values as low as 22 and 56 µg·mL-1, respectively. The conjugate with the best performance (COS-R. tinctorum extract) was then assayed ex situ on autoclaved grapevine wood against D. seriata, confirming its antifungal behavior on this plant material. Finally, the same conjugate was evaluated in greenhouse assays on grafted grapevine plants artificially inoculated with the three aforementioned fungal species, resulting in a significant reduction in the infection rate in all cases. This natural antifungal compound represents a promising alternative for developing sustainable control methods against grapevine trunk diseases.

Easily accessible non-aromatic heterocycles with handles: 4-bromo-2,3-dihydrofurans from 1,2-dibromohomoallylic alcohols.

The first general preparation of 4-bromo-2,3-dihydrofurans is reported. These non-aromatic heterocycles containing a useful coupling handle are accessed via Cu-catalyzed intramolecular cyclization of 1,2-dibromohomoallylic alcohols, which are themselves available in just two steps from aromatic and aliphatic aldehydes and ketones. Molecular dynamics simulations using the simple substrates and key geometric parameters provide a rationale for the selectivities observed. The synthetic utility of the 4-bromodihydrofurans is also demonstrated.

Antifungal Activity against Botryosphaeriaceae Fungi of the Hydro-Methanolic Extract of Silybum marianum Capitula Conjugated with Stevioside.

Silybum marianum (L.) Gaertn, viz. milk thistle, has been the focus of research efforts in the past few years, albeit almost exclusively restricted to the medicinal properties of its fruits (achenes). Given that other milk thistle plant organs and tissues have been scarcely investigated for the presence of bioactive compounds, in this study, we present a phytochemical analysis of the extracts of S. marianum capitula during the flowering phenological stage (stage 67). Gas chromatography-mass spectroscopy results evidenced the presence of high contents of coniferyl alcohol (47.4%), and secondarily of ferulic acid ester, opening a new valorization strategy of this plant based on the former high-added-value component. Moreover, the application of the hydro-methanolic extracts as an antifungal agent has been also explored. Specifically, their activity against three fungal species responsible for the so-called Botryosphaeria dieback of grapevine (Neofusicoccum parvum, Dothiorella viticola and Diplodia seriata) has been assayed both in vitro and in vivo. From the mycelial growth inhibition assays, the best results (EC90 values of 303, 366, and 355 µg·mL-1 for N. parvum, D. viticola, and D. seriata, respectively) were not obtained for the hydroalcoholic extract alone, but after its conjugation with stevioside, which resulted in a strong synergistic behavior. Greenhouse experiments confirmed the efficacy of the conjugated complexes, pointing to the potential of the combination of milk thistle extracts with stevioside as a promising plant protection product in organic Viticulture.