Multi-element Contamination and Health Risks in Green Leafy Vegetables from Ambagarh Chowki, Chhattisgarh, India.

Leafy plants are commonly consumed as vegetables in India due to their high nutrient and vitamin content. This study, conducted in Ambagarh Chowki (India), investigated the accumulation potential of 52 elements (including Al, As, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Ho, K, La, Li, Lu, Mg, Mn, Mo, Na, Nb, Nd, Ni, P, Pb, Pr, Rb, Sb, Sc, Se, Sm, Sn, Sr, Tb, Te, Th, Ti, Tl, Tm, U, V, W, Y, Yb, and Zn) in seven leafy vegetable species, namely Amaranthus tricolor L., Corchorus olitorius L., Cordia myxa L., Hibiscus sabdariffa L., Ipomoea batatas (L.) Lam., Moringa oleifera Lam., and Spinacia oleracea L. Technique: Inductively coupled plasma mass spectrometry (ICP-MS) was employed for analysis. The maximum concentrations of elements such as Al, Ba, Be, Bi, Cd, Co, Cr, Fe, Ga, Ge, Li, Mn, Ni, Pb, Sb, Th, Tl, U, V, W, and REEs were observed in S. oleracea leaves, indicating their highest accumulation potential. In contrast, the maximum concentrations of As were found in H. sabdariffa leaves; Ca and Si in M. oleifera leaves; Mg, Sr, and Mo in A. tricolor leaves; and P, K, Cu, and Zn in C. myxa leaves, respectively. Twenty-one elements (Cr, Cd, Pb, Ni, Co, V, Cu, Zn, Fe, Mn, Th, Sb, Ba, Be, Li, Sr, Tl, U, Se, Sn, and REEs) exceeded permissible limits set by the WHO. The elevated hazard index values indicated significant non-carcinogenic effects. The sources of these elements could be attributed to a combination of geological factors and agricultural practices. This study highlights the need for further investigation into the potential health implications of consuming these vegetables in the aforementioned region.

Transcriptome profiling reveals distinct alterations in the B-cell signature and dysregulation of peripheral B-cell subsets in sickle cell anemia patients.

Sickle cell anemia (SCA) is characterized by immune system activation and heightened susceptibility to infections. We hypothesized that SCA patients exhibit transcriptional alterations in B-cell-related genes, impacting their peripheral B-cell compartment and leading to dysregulated humoral immunity and increased infection susceptibility. Our objective was to conduct an in silico analysis of whole blood transcriptomes from SCA patients and healthy controls obtained from public repositories. We aimed to identify alterations in the adaptive immune system and validate these findings in our own SCA patient cohort. Bioinformatic analyses unveiled significant transcriptional alterations in B-cell signatures, developmental pathways, and signaling pathways. These results were validated in peripheral blood mononuclear cells from our SCA patient cohort and controls using real-time polymerase chain reaction and flow cytometry. Ninety genes exhibited differential expression, with 70 upregulated and 20 downregulated. Dysregulation in the B-cell compartment of SCA patients was evident, characterized by increased frequencies of immature and naive B-cells, and decreased percentages of memory B-cell subsets compared with healthy controls. Our findings highlight previously unexplored transcriptional and quantitative alterations in peripheral B-cells among SCA patients. Understanding these changes sheds light on the mechanisms contributing to the heightened infection risk in this population. Future studies should delve deeper into these molecular changes to develop targeted interventions and therapeutic strategies aimed at mitigating infection susceptibility in individuals with SCA.

An integrated analysis of the structural changes and gene expression of spleen in human visceral leishmaniasis with and without HIV coinfection.

The spleen plays a pivotal role in the pathogenesis of visceral leishmaniasis. In severe forms of the disease, the spleen undergoes changes that can compromise its function in surveilling blood-circulating pathogens. In this study, we present an integrated analysis of the structural and gene expression alterations in the spleens of three patients with relapsing visceral leishmaniasis, two of whom were coinfected with HIV. Our findings reveal that the IL6 signaling pathway plays a significant role in the disorganization of the white pulp, while BCL10 and ICOSLG are associated with spleen organization. Patients coinfected with HIV and visceral leishmaniasis exhibited lower splenic CD4+ cell density and reduced expression of genes such as IL15. These effects may contribute to a compromised immune response against L. infantum in coinfected individuals, further impacting the structural organization of the spleen.

Contamination, speciation, and health risk assessment of arsenic in leafy vegetables in Ambagarh Chowki (India).

Green leafy vegetables are essential for a balanced diet, providing vital nutrients for overall well-being. However, concerns arise due to contamination with toxic substances, such as arsenic, posing risks to food safety and human health. This study analyzes inorganic (iAs), monomethyl (MMA), and dimethyl arsenic (DMA) in specific leafy vegetables (Amaranthus tricolor L., Corchorus olitorius L., Cordia myxa L., Hibiscus sabdariffa L., Ipomoea batatas (L.) Lam., Moringa oleifera Lam., and Spinacia oleracea L.) grown in the heavily polluted Ambagarh Chouki region, Chhattisgarh, India. Concentrations of DMA, MMA, and iAs ranged from 0 to 155, 0 to 7, and 131 to 3579 mg·kg-1, respectively. The health quotient (HQ) for iAs ranged between 0.37 and 3.78, with an average value of 2.58 ± 1.08.

In silico approaches for drug repurposing in oncology: a scoping review.

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

Emotional regulation and self-perceived quality of life in high-performance mountain sports athletes.

Emotional regulation is an indispensable capacity for human beings, so that alterations in it can lead to the appearance of psychological, social and/or cognitive disorders. Therefore, possessing adequate emotional strategies is intimately related to the quality of life that a person presents. In this sense, high-level athletes suffer constant setbacks and frustrations due to the performance of their sporting activity, in addition to continuous modifications of their daily life activities. Thus, the objective of this research is to explore the emotional regulation and self-perceived quality of life of high-level athletes in mountain sports, analyzing the possible influences of gender, demographic location, body mass index and age. Fifty-four athletes belonging to the High Performance Technification Center of Cáceres (Extremadura, Spain) completed a sociodemographic questionnaire, as well as the Cognitive Emotion Regulation Questionnaire and the WHOQOL-BREF. The Shapiro-Wilkins test was used to analyze the normality of the variables collected and nonparametric statistics were used since the assumption was not met. Both gender and demographic location showed significant differences in the dimensions of the two questionnaires. Likewise, age was associated with the dimensions of both scales, but not body mass index, which was only associated with self-perceived quality of life. In addition, the stepwise linear regression model predicted self-perceived quality of life with a value of 60% across self-culpability, gender body mass index and planning. Therefore, it appears that gender, demographic location, age and body mass index could exert modifications on the levels of emotional regulation and self-perceived quality of life of high-level mountain athletes.

High-throughput prioritization of target proteins for development of new antileishmanial compounds.

Leishmaniasis, a vector-borne disease, is caused by the infection of Leishmania spp., obligate intracellular protozoan parasites. Presently, human vaccines are unavailable, and the primary treatment relies heavily on systemic drugs, often presenting with suboptimal formulations and substantial toxicity, making new drugs a high priority for LMIC countries burdened by the disease, but a low priority in the agenda of most pharmaceutical companies due to unattractive profit margins. New ways to accelerate the discovery of new, or the repositioning of existing drugs, are needed. To address this challenge, our study aimed to identify potential protein targets shared among clinically-relevant Leishmania species. We employed a subtractive proteomics and comparative genomics approach, integrating high-throughput multi-omics data to classify these targets based on different druggability metrics. This effort resulted in the ranking of 6502 ortholog groups of protein targets across 14 pathogenic Leishmania species. Among the top 20 highly ranked groups, metabolic processes known to be attractive drug targets, including the ubiquitination pathway, aminoacyl-tRNA synthetases, and purine synthesis, were rediscovered. Additionally, we unveiled novel promising targets such as the nicotinate phosphoribosyltransferase enzyme and dihydrolipoamide succinyltransferases. These groups exhibited appealing druggability features, including less than 40% sequence identity to the human host proteome, predicted essentiality, structural classification as highly druggable or druggable, and expression levels above the 50th percentile in the amastigote form. The resources presented in this work also represent a comprehensive collection of integrated data regarding trypanosomatid biology.

Nonadiabatic Derivative Couplings through Multiple Franck-Condon Modes Dictate the Energy Gap Law for Near and Short-Wave Infrared Dye Molecules.

Near infrared (NIR, 700-1000 nm) and short-wave infrared (SWIR, 1000-2000 nm) dye molecules exhibit significant nonradiative decay rates from the first singlet excited state to the ground state. While these trends can be empirically explained by a simple energy gap law, detailed mechanisms of nearly universal behavior have remained unsettled for many cases. Theoretical and experimental results for two representative NIR/SWIR dye molecules reported here clarify the key mechanism for the observed energy gap law behavior. It is shown that the first derivative nonadiabatic coupling terms serve as major coupling pathways for nonadiabatic decay processes from the first excited singlet state to the ground state for these NIR and SWIR dye molecules and that vibrational modes other than the highest frequency modes also make significant contributions to the rate. This assessment is corroborated by further theoretical comparison with possible alternative mechanisms of intersystem crossing to triplet states and also by comparison with experimental data for deuterated molecules.

Phytochemical study of 'tajy' (Handroanthus impetiginosus (Mart.) Mattos) and 'ka'a oveti' (Luehea divaricata Mart.) extracts.

This study explores the phytochemical composition of leaf extracts from Handroanthus impetiginosus (Mart.) Mattos and Luehea divaricata Mart., used in a contraceptive decoction by Mbya-Guarani women. The phytocompounds were identified by gas chro-matography-mass spectrometry, while Fourier-transform infrared spectroscopy, multi-elemental, and thermal analyses were used to characterise plant biomass. Notably, no phytoconstituent supporting the efficacy of these extracts as female contraceptives was found, except for a small amount (0.3%) of sitosterol. Conversely, L. divaricata leaves contained compounds like 1,3-dihydroxyacetone dimer, N-methyl-N-nitroso-2-propanamine, 2-methoxy-N-(2-methoxyethyl)-N-methyl-ethanamine, and 1,3,5-triazine-2,4,6-triamine, potentially exerting cytotoxic, genotoxic, and toxicogenomic effects. Due to the absence of scientific support for the claimed contraceptive efficacy and the presence of safety concerns, we propose an alternative valorisation pathway centred on the presence of phytochemicals exhibiting antimicrobial activity. This proposition is substantiated by their considerable in vitro efficacy against Botrytis cinerea.

Phytoconstituents and Ergosterol Biosynthesis-Targeting Antimicrobial Activity of Nutmeg (Myristica fragans Houtt.) against Phytopathogens.

In recent years, nutmeg (Myristica fragans Houtt.) has attracted considerable attention in the field of phytochemistry due to its diverse array of bioactive compounds. However, the potential application of nutmeg as a biorational for crop protection has been insufficiently explored. This study investigated the constituents of a nutmeg hydroethanolic extract via gas chromatography-mass spectrometry and vibrational spectroscopy. The research explored the extract's activity against phytopathogenic fungi and oomycetes, elucidating its mechanism of action. The phytochemical profile revealed fatty acids (including tetradecanoic acid, 9-octadecenoic acid, n-hexadecanoic acid, dodecanoic acid, and octadecanoic acid), methoxyeugenol, and elemicin as the main constituents. Previously unreported phytochemicals included veratone, gelsevirine, and montanine. Significant radial growth inhibition of mycelia was observed against Botrytis cinerea, Colletotrichum acutatum, Diplodia corticola, Phytophthora cinnamomi, and especially against Fusarium culmorum. Mode of action investigation, involving Saccharomyces cerevisiae labeled positively with propidium iodide, and a mutant strain affected in ERG6, encoding sterol C-24 methyltransferase, suggested that the extract induces a necrotic type of death and targets ergosterol biosynthesis. The evidence presented underscores the potential of nutmeg as a source of new antimicrobial agents, showing particular promise against F. culmorum.

Carvacrol Encapsulation in Chitosan-Carboxymethylcellulose-Alginate Nanocarriers for Postharvest Tomato Protection.

Advancements in polymer science and nanotechnology hold significant potential for addressing the increasing demands of food security, by enhancing the shelf life, barrier properties, and nutritional quality of harvested fruits and vegetables. In this context, biopolymer-based delivery systems present themselves as a promising strategy for encapsulating bioactive compounds, improving their absorption, stability, and functionality. This study provides an exploration of the synthesis, characterization, and postharvest protection applications of nanocarriers formed through the complexation of chitosan oligomers, carboxymethylcellulose, and alginate in a 2:2:1 molar ratio. This complexation process was facilitated by methacrylic anhydride and sodium tripolyphosphate as cross-linking agents. Characterization techniques employed include transmission electron microscopy, energy-dispersive X-ray spectroscopy, infrared spectroscopy, thermal analysis, and X-ray powder diffraction. The resulting hollow nanospheres, characterized by a monodisperse distribution and a mean diameter of 114 nm, exhibited efficient encapsulation of carvacrol, with a loading capacity of approximately 20%. Their suitability for phytopathogen control was assessed in vitro against three phytopathogens-Botrytis cinerea, Penicillium expansum, and Colletotrichum coccodes-revealing minimum inhibitory concentrations ranging from 23.3 to 31.3 µg·mL-1. This indicates a higher activity compared to non-encapsulated conventional fungicides. In ex situ tests for tomato (cv. 'Daniela') protection, higher doses (50-100 µg·mL-1, depending on the pathogen) were necessary to achieve high protection. Nevertheless, these doses remained practical for real-world applicability. The advantages of safety, coupled with the potential for a multi-target mode of action, further enhance the appeal of these nanocarriers.

Combining Digital and Molecular Approaches Using Health and Alternate Data Sources in a Next-Generation Surveillance System for Anticipating Outbreaks of Pandemic Potential.

Globally, millions of lives are impacted every year by infectious diseases outbreaks. Comprehensive and innovative surveillance strategies aiming at early alert and timely containment of emerging and reemerging pathogens are a pressing priority. Shortcomings and delays in current pathogen surveillance practices further disturbed informing responses, interventions, and mitigation of recent pandemics, including H1N1 influenza and SARS-CoV-2. We present the design principles of the architecture for an early-alert surveillance system that leverages the vast available data landscape, including syndromic data from primary health care, drug sales, and rumors from the lay media and social media to identify areas with an increased number of cases of respiratory disease. In these potentially affected areas, an intensive and fast sample collection and advanced high-throughput genome sequencing analyses would inform on circulating known or novel pathogens by metagenomics-enabled pathogen characterization. Concurrently, the integration of bioclimatic and socioeconomic data, as well as transportation and mobility network data, into a data analytics platform, coupled with advanced mathematical modeling using artificial intelligence or machine learning, will enable more accurate estimation of outbreak spread risk. Such an approach aims to readily identify and characterize regions in the early stages of an outbreak development, as well as model risk and patterns of spread, informing targeted mitigation and control measures. A fully operational system must integrate diverse and robust data streams to translate data into actionable intelligence and actions, ultimately paving the way toward constructing next-generation surveillance systems.

Early detection of respiratory disease outbreaks through primary healthcare data.

Background: The emergence of coronavirus disease 2019 (COVID-19) in 2020 highlighted the relevance of surveillance systems in detecting early signs of potential outbreaks, thus enabling public health authorities to act before the pathogen becomes widespread. Syndromic digital surveillance through web applications has played a crucial role in monitoring the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. However, this approach requires expensive infrastructure, which is not available in developing countries. Pre-existing sources of information, such as encounters in primary health care (PHC), can provide valuable data for a syndromic surveillance system. Here we evaluated the utility of PHC data to identify early warning signals of the first COVID-19 outbreak in Bahia-Brazil in 2020. Methods: We compared the weekly counts of PHC encounters due to respiratory complaints and the number of COVID-19 cases in 2020 in Bahia State - Brazil. We used the data from December 2016 to December 2019 to predict the expected number of encounters in 2020. We analysed data aggregated by geographic regions (n = 34) and included those where historical PHC data was available for at least 70% of the population. Results: Twenty-one out of 34 regions met the inclusion criteria. We observed that notification of COVID-19 cases was preceded by at least two weeks with an excess of encounters of respiratory complaints in 18/21 (86%) of the regions analysed and four weeks or more in 10/21 (48%) regions. Conclusions: Digital syndromic surveillance systems based on already established PHC databases may add time to preparedness and response to emerging epidemics.

Critical requirement of SOS1 for tumor development and microenvironment modulation in KRASG12D-driven lung adenocarcinoma.

The impact of genetic ablation of SOS1 or SOS2 is evaluated in a murine model of KRASG12D-driven lung adenocarcinoma (LUAD). SOS2 ablation shows some protection during early stages but only SOS1 ablation causes significant, specific long term increase of survival/lifespan of the KRASG12D mice associated to markedly reduced tumor burden and reduced populations of cancer-associated fibroblasts, macrophages and T-lymphocytes in the lung tumor microenvironment (TME). SOS1 ablation also causes specific shrinkage and regression of LUAD tumoral masses and components of the TME in pre-established KRASG12D LUAD tumors. The critical requirement of SOS1 for KRASG12D-driven LUAD is further confirmed by means of intravenous tail injection of KRASG12D tumor cells into SOS1KO/KRASWT mice, or of SOS1-less, KRASG12D tumor cells into wildtype mice. In silico analyses of human lung cancer databases support also the dominant role of SOS1 regarding tumor development and survival in LUAD patients. Our data indicate that SOS1 is critically required for development of KRASG12D-driven LUAD and confirm the validity of this RAS-GEF activator as an actionable therapeutic target in KRAS mutant LUAD.

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.

Which Physical Phenomena Determine the Ionization Potential of Liquid Water?

Understanding and predicting the properties of molecular liquids from the corresponding properties of the individual molecules is notoriously difficult because there is cooperative behavior among the molecules in the liquid. This is particularly relevant for water, where even the most fundamental molecular properties, such as the dipole moment, are radically different in the liquid compared to the gas phase. In this work, we focus on the ionization potential (IP) of liquid water by dissecting its individual contributions from the individual molecules making up the liquid. This is achieved by using periodic subsystem DFT, a state-of-the-art electronic structure method based on density embedding. We identify and evaluate four important electronic contributions to the IP of water: (1) mean-field, evaluated at the Hartree-Fock level; (2) electronic correlation, incorporated via DFT and wave function-based methods; (3) interaction with and (4) polarization of the environment, both evaluated ab initio with density embedding. Furthermore, we analyze their impact on the IP relative to the structural fluctuation of liquid water, revealing unexpected, hidden correlations, confirming that the broadening of the photoelectron spectra is mostly caused by intermolecular interactions confined in the first solvation shell.

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.

Chemical Constituents and Antimicrobial Activity of a Ganoderma lucidum (Curtis.) P. Karst. Aqueous Ammonia Extract.

Mushroom extracts have shown potential as a source of new antimicrobial agents. This study investigates the chemical profile of an aqueous ammonia extract obtained from the carpophores of Ganoderma lucidum, which grows on Quercus ilex trees, and explores its valorization as a biorational. The major chemical constituents of the extract, identified through gas chromatography-mass spectrometry, include acetamide, oleic acid, 1,2,3,4-butanetetrol, monomethyl azelate, undecane, and palmitic acid. The anti-oomycete and antifungal activity of G. lucidum extract was evaluated against Phytophthora cinnamomi, the primary threat to Quercus spp. in the dehesa biome, as well as three Botryosphaeriaceae fungi. In vitro tests revealed minimum inhibitory concentration (MIC) values of 187.5 µg·mL-1 against P. cinnamomi and 187.5-1000 µg·mL-1 against the fungi. Furthermore, conjugation of the G. lucidum extract with chitosan oligomers (COS) synergistically enhanced its antimicrobial activity, resulting in MIC values of 78.12 and 375-500 µg·mL-1 against P. cinnamomi and the fungi, respectively. These MIC values are among the highest reported to date for natural products against these phytopathogens. Subsequent ex situ testing of the COS-G. lucidum conjugate complex on artificially inoculated Q. ilex excised stems resulted in high protection against P. cinnamomi at a dose of 782 µg·mL-1. These findings support the potential utilization of this resource from the dehesa ecosystem to protect the holm oak, aligning with sustainable and circular economy approaches.

Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.

Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of gene therapy approaches. Generally, inducible ON systems require a chimeric transcription factor (transactivator) that becomes activated by an inductor, which is not optimal for clinical translation due to their toxicity. We generated previously the first all-in-one, transactivator-free, doxycycline (Dox)-responsive (Lent-On-Plus or LOP) lentiviral vectors (LVs) able to control transgene expression in human stem cells. Here, we have generated new versions of the LOP LVs and have analyzed their applicability for the generation of inducible advanced therapy medicinal products (ATMPs) with special focus on primary human T cells. We have shown that, contrary to all other cell types analyzed, an Is2 insulator must be inserted into the 3' long terminal repeat of the LOP LVs in order to control transgene expression in human primary T cells. Importantly, inducible primary T cells generated by the LOPIs2 LVs are responsive to ultralow doses of Dox and have no changes in phenotype or function compared with untransduced T cells. We validated the LOPIs2 system by generating inducible CAR-T cells that selectively kill CD19+ cells in the presence of Dox. In summary, we describe here the first transactivator-free, all-one-one system capable of generating Dox-inducible ATMPs.

Armeria maritima (Mill.) Willd. Flower Hydromethanolic Extract for Cucurbitaceae Fungal Diseases Control.

The cliff rose (Armeria maritima), like other halophytes, has a phenolics-based antioxidant system that allows it to grow in saline habitats. Provided that antioxidant properties are usually accompanied by antimicrobial activity, in this study we investigated the phytochemicals present in a hydromethanolic extract of A. maritima flowers and explored its antifungal potential. The main phytocompounds, identified by gas chromatography-mass spectrometry, were: hexadecanoic acid, octadecanoic acid, 9-octadecenoic acid, 3-(3,4-dihydroxy-phenyl)-acrylic acid ethyl ester, and benzeneacetaldehyde. The antifungal activity of the extract and its main constituents-alone and in combination with chitosan oligomers-was tested against six pathogenic taxa associated with soil-borne diseases of plant hosts in the family Cucurbitaceae: Fusarium equiseti, F. oxysporum f. sp. niveum, Macrophomina phaseolina, Neocosmospora falciformis, N. keratoplastica, and Sclerotinia sclerotiorum. In in vitro tests, EC90 effective concentrations in the 166-865 µg·mL-1 range were obtained for the chitosan oligomers-A. maritima extract conjugate complexes, lower than those obtained for fosetyl-Al and azoxystrobin synthetic fungicides tested for comparison purposes, and even outperforming mancozeb against F. equiseti. In ex situ tests against S. sclerotiorum conducted on artificially inoculated cucumber slices, full protection was achieved at a dose of 250 µg·mL-1. Thus, the reported results support the valorization of A. maritima as a source of biorationals for Cucurbitaceae pathogens protection, suitable for both organic and conventional agriculture.