Marine macroalgae, particularly the brown alga Canistrocarpus cervicornis, are prolific sources of structurally diverse diterpenes with significant pharmacological potential. In the context of the growing need for new antibacterial scaffolds, the secondary metabolites of this species were investigated. Two new dolastane derivatives, (4R*,5R*,9S*,12R*,14S*)-4α-acetoxy-9β-methoxy-14α-hydroxydolasta-1(15),7-diene (1) and (5R*,9S*,12R*,14S*)-9β-methoxy-14α-hydroxydolasta-1(15),7-diene (2), have been isolated from C. cervicornis, together with two previously isolated secodolastanes, isolinearol (3) and isolinearol acetate (4), and three dolastanes, (4R*,5R*,8S*,9S*,12R*,14S*)-4α-acetoxy-8,9-epoxy-14α-hydroxy-7-oxodolast-1(15)-ene (5), (4R*,5R*,9S*,12R*,14S*)-4α-acetoxy-9β,14α-dihydroxydolasta-1(15),7-diene (6) and (4R*,5R*,7R*,12S*,14S*)-4α,7α-diacetoxy-14α-hydroxy-10-oxodolasta-1(15),8-diene (7). Their planar structures and relative stereochemistry were elucidated through extensive spectroscopic analyses, including HRMS and 1D and 2D NMR experiments (such as COSY, HSQC, HMBC and NOESY/t-ROESY). Compounds 1 and 6 showed antibacterial activities against clinically important bacteria, with MIC values in the range of 8–64 µg/mL.

Naegleria fowleri is the etiological agent of primary amoebic meningoencephalitis, a fulminant infection of the central nervous system that leads to death in most cases. Currently, no standardised therapy is available, and existing treatments are limited by inconsistent efficacy and significant toxicity. β-Hydroxy-γ-lactones previously described as trypanocidal and leishmanicidal agents share structural features, a reactive lactone carbonyl and a stereodefined hydroxyl group, that are commonly linked to disruption of redox and mitochondrial homeostasis in protozoan parasites. Based on this precedent, we hypothesised that the same scaffold could also be active against N. fowleri. Fourteen compounds, ten previously reported β-hydroxy-γ-lactones and four newly synthesised α, β-unsaturated-γ-lactones (butenolides, SAM-13 to SAM-16) obtained by β-elimination, were evaluated in vitro against the trophozoite and cyst stages of two N. fowleri strains (ATCC® 30808™ and ATCC® 30215™), together with cytotoxicity assays in murine macrophages (J774A.1) and human SH-SY5Y neuroblastoma cells. SAM-1 and SAM-5 emerged as the most active molecules, with low-micromolar IC₅₀ values against both trophozoites and cysts; their selectivity, however, differed markedly, with SAM-5 showing a substantially wider safety margin (selectivity index up to 12.9) than SAM-1 (selectivity index of 1.2 in neuroblastoma cells), underscoring selectivity as a key parameter for further optimisation. In contrast, three of the four newly synthesised butenolides were essentially inactive (IC₅₀ > 160 μM); the fourth, SAM-14 (derived from SAM-5), retained measurable but poorly selective activity (IC₅₀ = 56.9 μM, SI = 1.35), indicating that the requirement for the free β-hydroxyl group is substituent-dependent and providing an initial structure–activity relationship for this scaffold. Mechanistic assays showed that SAM-1 and SAM-5 induced hallmarks of programmed cell death in N. fowleri trophozoites, including phosphatidylserine externalisation, chromatin condensation, mitochondrial depolarisation, ROS overproduction, and F-actin disorganisation, together with complementary evidence of autophagic vacuole formation. In silico ADME profiling predicted favourable drug-likeness for SAM-1 and SAM-5, including compliance with Lipinski's rule of five, high gastrointestinal absorption and predicted blood–brain barrier permeability, with neither compound predicted to be a P-glycoprotein substrate. Taken together, these findings identify β-hydroxy-γ-lactones as promising, CNS-penetrant scaffolds for anti-Naegleria drug discovery and outline the structural determinants that should guide their future optimisation.

Improving crop performance under water scarcity requires fertilization strategies that not only supply nutrients but also strengthen soil–plant interactions. In this work, we evaluated a compost tea obtained from recycled organic by-products using the “Sistema de Elaboración de Fertilizante Ecológico Líquido” (SEFEL) system, as a multifunctional biofertilizer in tomato (Solanum lycopersicum) and lettuce (Lactuca sativa) grown under well-watered (WW) and deficit irrigation conditions (WD). We explored its capacity to modulate physiological responses, metabolic adjustments and soil microbiota under WW and WD. SEFEL compost tea application consistently promoted plant growth. Tomato plants showed a 63.9% increase in leaf dry weight under optimal irrigation and a 32.6% increase under WD, while root biomass rose by 30.3% and 53.3%, respectively. In lettuce, leaf dry weight increased by 34% under WW and by 23% under WD. Although drought reduced photosynthetic rates in both species, SEFEL compost tea-treated plants maintained higher carbon assimilation and stomatal conductance during prolonged stress, indicating improved physiological adjustment. These responses were accompanied by a greater accumulation of proline and soluble carbohydrates under water deficit. Interestingly, a different activation of the raffinose family oligosaccharides (RFOs) pathway was detected in tomato and lettuce, pointing to species-specific metabolic strategies. Additionally, SEFEL compost tea improved nutrient uptake under both irrigation regimes and promoted shifts in soil microbial communities, suggesting reinforced soil–plant connectivity. Our results indicate that SEFEL compost tea acts as an integrative soil–plant biostimulant, enhancing nutrient acquisition and drought tolerance while contributing to organic waste valorisation within sustainable production systems.

Oceanic islands host exceptional biodiversity and endemism but are highly vulnerable to biological invasions. We aimed to identify non-native species with high potential to invade the Canary Islands within the next decade and to prioritise them based on their environmental and socioeconomic risks.

Reactive oxygen species (ROS), reactive nitrogen species (RNS) and reactive sulphur species (RSS) constitute a coupled molecular language whose marks, the reversible post-translational modifications of cysteine and tyrosine residues, are formed, interconverted and reversed within subcellular microdomains characterised by their own geometry and kinetics. Two decades of broad-spectrum antioxidant clinical trials using vitamin E, beta-carotene, and N-acetylcysteine, amongst other compounds, have produced predominantly neutral and in some settings harmful results, although the outcomes vary appreciably with the compound, the disease, the dose and the trial design, and several of the most studied polyphenols, curcumin, resveratrol and quercetin, display a broadly comparable pattern, compounded in their case by low oral bioavailability of the parent aglycone, which limits the concentration reaching the target tissue. The redox biomarkers available in clinical practice, plasma GSH/GSSG, urinary 8-oxo-dG, and serum MDA, show disappointing individual prognostic value. The present work argues that both failures are consistent with a shared mechanistic explanation: they treat the redox language as undifferentiated noise when it is, in fact, spatially structured information. While other contributing factors, including analytical variability, clinical heterogeneity, and cohort design, are acknowledged, this mechanistic convergence offers a parsimonious interpretive framework. We analyse the failure of global antioxidants from the logic of the microdomain, suggesting that non-specific scavenging suppresses eustress and distress with comparable efficacy, and the failure of conventional redox biomarkers from the loss of spatial and temporal resolution that occurs when signals from multiple compartments are collapsed into a systemic index. Building upon this dual analysis, we propose the principles of an alternative strategy: pharmacological interventions acting on specific microdomain levers (NOS recoupling, restoration of mitochondrial -SSH tone, and Prx/Trx system support) and a precision redox diagnostic framework that replaces global indices with compartment-resolved biomarker panels. The objective is not to silence the redox language, but to learn to read it and, when necessary, to correct its grammar with precision.

Diseases caused by Leishmania spp. and Trypanosoma spp. parasites provoke thousands of annual deaths. The current treatments exhibit noticeable disadvantages such as low effectiveness, high cost, side-effects, and the occurrence of resistance. Thus, the search for new drugs is mandatory, and diversity-oriented synthesis appears as a useful tool to access libraries of small, structurally diverse, and potentially bioactive compounds in few steps. In this work, a battery of 10 new and highly substituted β-hydroxy-γ-lactones was straightforwardly synthesized from β,γ-unsaturated N-acyl oxazolidin-2-ones and evaluated against Leishmania amazonensis and Trypanosoma cruzi. Six of the compounds were found to exhibit antiparasitic activity against T. cruzi epimastigotes and/or L. amazonensis promastigotes, as well as against the amastigote forms of both parasites; among these, two compounds stood out against L. amazonensis, with selectivity indices (SI) higher than that of the reference drug. Furthermore, these two compounds appear to induce apoptosis-like cell death in L. amazonensis, as suggested by mechanistic studies. It is worth noting that the compound SAM-2 exhibited an SI four times higher than miltefosine, due to its lower toxicity compared to this drug, highlighting its potential as a promising candidate for the development of new therapies.

Food-safety risk communication depends not only on whether consumers trust expert sources, but also on whether credible information reaches everyday communication environments. This study examines three linked gaps in food-safety risk communication among 402 urban, digitally reachable consumers in Ivory Coast using an online panel survey. Respondents rated the personal relevance of food risks, their perceived information sufficiency, their trust in eleven food-safety information sources, the frequency with which they consulted each source, their self-reported information exposure for eight food-safety hazards, and their concern about those hazards. Results reveal three connected gaps. First, a relevance–sufficiency gap was observed: respondents considered food-safety risks highly relevant, but felt less sufficiently informed about them. Second, a credibility–accessibility gap was identified: doctors were the most trusted source but ranked only sixth in consultation frequency, while scientists ranked third in trust but tenth in consultation frequency. Third, a concern–information exposure gap was found across all hazards: concern exceeded self-reported information exposure, especially for microplastics, contamination during transport or poor storage, genetically modified foods, and pesticides. These findings suggest that food-safety communication in Ivory Coast is constrained less by lack of concern than by the limited conversion of credibility into reach. Preventive food-control strategies should therefore convert expert credibility into communication reach by embedding trusted actors in the interpersonal, media, market, retail, and community channels through which consumers already navigate food risk.

Archaeological studies in Kachchh, Gujarat, continue to rely on legacy data sets created before the widespread use of GPS and standardised spatial recording, yet the quality of these data sets for modern spatial analysis has been poorly evaluated. This research assesses the legacy records of Mature Harappan archaeological sites in Eastern Kachchh, which are marked by variable reporting of coordinates, repeated site names and unclear cultural attributions, and assesses the potential of Remote Sensing and Geographic Information Systems (GIS), integrated with colonial Survey of India toposheets, to inform the re-evaluation of archaeological legacy data. The study adopted a methodological approach of cleaning and cross-checking published legacy datasets, spatial analyses using historical maps, CORONA imagery, multispectral satellite data, digital elevation models, and multi-season field surveys aided by GPS recording to reidentify and validate reported sites. The findings reveal that legacy coordinates exhibit significant spatial uncertainty, with an average error of about 4 km and a range of 1 to 16 km, underscoring the need to critically assess legacy spatial datasets. Although remote sensing and GIS have limited potential for primary site detection in Kachchh due to geomorphological variability, they are useful for site boundary delineation, landscape change reconstruction and contextualisation of confirmed sites. The research suggests that archaeological interpretations are best supported by integrating critically evaluated legacy data, field verification, and geospatial analysis, with technological tools that complement field surveys.

DNA methyltransferases (DNMTs) regulate gene expression and genome stability by transferring a methyl group from S-adenosylmethionine to cytosine through a catalytic mechanism involving a conserved cysteine. Dysregulated DNA methylation contributes to cancer, chronic inflammation and persistent metabolic phenotypes, encouraging the development of non-nucleoside DNMT modulators. This narrative review examines whether electrophilic reactivity, particularly Michael acceptor chemistry, provides a plausible mechanistic framework for the reported DNMT-modulatory effects of structurally diverse natural compounds, evaluated across polyphenols, isothiocyanates, sesquiterpene lactones, alkaloids, terpenoids, polyketides and endogenous electrophilic lipids according to experimental level, distinguishing direct enzymatic inhibition from docking predictions, altered DNMT expression and broader cellular effects. The literature was retrieved from PubMed, Scopus and Web of Science and appraised with an explicit grading scheme that separates cell-free enzyme inhibition, proposed engagement of the catalytic cysteine, cellular changes in DNMT expression or methylation, and downstream biological effects. Curcumin and parthenolide provide notable precedents for catalytic-cysteine-directed hypotheses, whereas direct covalent engagement remains insufficiently demonstrated for most other candidates. The review also considers reversibility, electrophile selectivity, bioavailability and interactions with histone modifications, inflammatory signalling and the NAD+/sirtuin axis. Michael acceptor chemistry offers a useful hypothesis for prioritising natural DNMT modulators, but biochemical, structural and chemoproteomic validation is required before covalent DNMT inhibition can be regarded as a general mechanism or translated into therapeutic recommendations.

Dietary polyphenols are studied as potential adjuncts for type 2 diabetes (T2D), although many reviews still rely on an antioxidant framework that does not adequately reflect human exposure. This review organises the evidence around two metabolite waves, namely early postprandial phase-II conjugates produced by host enzymes within 0 to 4 h of a polyphenol-rich meal, and microbiome-derived catabolites including urolithins and γ-valerolactones that peak at 6 to 24 h. This biphasic interpretation is advanced as a hypothesis-generating framework rather than as an established explanation, and it offers a testable account of why polyphenol effects may be meal-contingent, metabotype-dependent and heterogeneous across clinical trials. Using randomised controlled trials and meta-analyses published between 2015 and 2025, we review the human evidence for anthocyanins, catechins, stilbenes, cocoa flavanols and olive phenolics, with briefer coverage of isoflavones, curcuminoids and ellagitannins. Anthocyanins show the most consistent glycaemic signal, with a best available pooled estimate of about 0.3% for HbA1c (−0.31%, median exposure eight weeks) derived from trials that did not verify metabolite exposure, an effect that is modest and lies at the lower bound of what is generally regarded as clinically meaningful. Green tea catechins and high-phenolic extra-virgin olive oil are associated with comparable postprandial gains, whereas cocoa flavanols and resveratrol more reliably improve vascular and inflammatory intermediates than glycaemia itself. Most interventions were well tolerated at the nutritional doses tested. Polyphenols are better regarded as meal-timed dietary adjuncts to standard T2D care than as primary glycaemic agents.