Search Results (1,424)

The chickpea (Cicer arietinum L.) is a key legume crop in Mediterranean agriculture, valued for its nutritional profile and adaptability. However, its productivity is severely impacted by drought stress. To identify microbial solutions that enhance drought resilience, we isolated seven Mesorhizobium strains from chickpea nodules collected in southern Spain and evaluated their cultivar-specific symbiotic performance. Two commercial cultivars (Pedrosillano and Blanco Lechoso) and twenty chickpea germplasms were tested under growth chamber and greenhouse conditions, both with and without drought stress. Initial screening in a sterile substrate using nodulation assays, shoot/root dry weight measurements, and acetylene reduction assays identified three elite strains (ISC11, ISC15, and ISC25) with superior symbiotic performance and nitrogenase activity. Greenhouse trials under reduced irrigation demonstrated that several strain–cultivar combinations significantly mitigated drought effects on plant biomass, with specific interactions (e.g., ISC25 with RR-98 or BT6-19) preserving over 70% of shoot biomass relative to controls. Whole-genome sequencing of the elite strains revealed diverse taxonomic affiliations—ISC11 as Mesorhizobium ciceri, ISC15 as Mesorhizobium mediterraneum, and ISC25 likely representing a novel species. Genome mining identified plant growth-promoting traits including ACC deaminase genes (in ISC11 and ISC25) and genes coding for auxin biosynthesis-related enzymes. Our findings highlight the potential of targeted rhizobial inoculants tailored to chickpea cultivars to improve crop performance under water-limiting conditions. Full article

Soil salinization is a major constraint to global crop productivity, highlighting the need to identify salt tolerance genes and their molecular mechanisms. Here, we integrated mRNA and miRNA profile analyses to investigate the molecular basis of salt tolerance of an elite Brassica napus cultivar S268. Time-course RNA-seq analysis revealed dynamic transcriptional reprogramming under 215 mM NaCl stress, with 212 core genes significantly enriched in organic acid degradation and glyoxylate/dicarboxylate metabolism pathways. Combined with weighted gene co-expression network analysis (WGCNA) and RT-qPCR validation, five candidate genes (WRKY6, WRKY70, NHX1, AVP1, and NAC072) were identified as the regulators of salt tolerance in rapeseed. Haplotype analysis based on association mapping showed that NAC072, ABI5, and NHX1 exhibited two major haplotypes that were significantly associated with salt tolerance variation under salt stress in rapeseed. Integrated miRNA-mRNA analysis and RT-qPCR identified three regulatory miRNA-mRNA pairs (bna-miR160a/BnaA03.BAG1, novel-miR-126/BnaA08.TPS9, and novel-miR-70/BnaA07.AHA1) that might be involved in S268 salt tolerance. These results provide novel insights into the post-transcriptional regulation of salt tolerance in B. napus, offering potential targets for genetic improvement. Full article

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is eroding therapeutic options for urinary tract infections. We isolated a multidrug-resistant strain from the urine of a chronically bacteriuric patient and confirmed its identity by Vitek-2 and MALDI-TOF MS. Initial disk-diffusion profiling against 48 antibiotics revealed susceptibility to only 5 agents. One month later, repeat testing showed that tetracycline alone remained active, highlighting the strain’s rapidly evolving resistome. Given the scarcity of drug options, we performed an “aromatogram” with seven pure essential oils, propolis, and two commercial phytotherapeutic blends. Biomicin Forte^® produced a 30 mm bactericidal halo, while thyme, tea tree, laurel, and palmarosa oils yielded clear inhibition zones of 11–22 mm. These in vitro data demonstrate that carefully selected plant-derived products can target CR-Kp where conventional antibiotics fail. Integrating aromatogram results into One Health’s stewardship plans may therefore help preserve last-line antibiotics and provide adjunctive options for persistent urinary infections. Full article

Consumer interest in vegetarian, ethical, and clean-label foods is reviving the use of plant-derived milk coagulants. Cardosins from Cynara cardunculus (“thistle”) are aspartic proteases with strong clotting activity, yet their technological impact in cheese remains under-explored. This study compared a commercial thistle extract (PC) with traditional bovine rennet rich in chymosin (AC) during manufacture and 60-day ripening of Caciotta cheese. Classical compositional assays (ripening index, texture profile, color, solubility) were integrated with scanning electron microscopy, three-dimensional surface reconstruction, and descriptive sensory analysis. AC cheeses displayed slower but sustained proteolysis, yielding a higher and more linear ripening index, softer body, greater solubility, and brighter, more yellow appearance. Imaging revealed a continuous protein matrix with uniformly distributed, larger pores, consistent with a dairy-like sensory profile dominated by milky and umami notes. Conversely, PC cheeses underwent rapid early proteolysis that plateaued, producing firmer, chewier curds with lower solubility and darker color. Micrographs showed a fragmented matrix with smaller, heterogeneous pores; sensory evaluation highlighted vegetal, bitter, and astringent attributes. The data demonstrate that thistle coagulant can successfully replace animal rennet but generates cheeses with distinct structural and sensory fingerprints. The optimization of process parameters is therefore required when targeting specific product styles. Full article

Mitochondria, pivotal organelles in cellular metabolism and energy production, have emerged as critical players in the pathogenesis of cancer. This review outlines the progress in mitochondrial profiling through mass spectrometry-based metabolomics and its applications in cancer research. We provide unprecedented insights into the mitochondrial metabolic rewiring that fuels tumorigenesis, metastasis, and therapeutic resistance. The purpose of this review is to provide a comprehensive guide for the implementation of mitochondrial metabolomics, integrating advanced methodologies—including isolation, detection, and data integration—with insights into cancer-specific metabolic rewiring. We first summarize current methodologies for mitochondrial sample collection and pretreatment. Furthermore, we then discuss the recent advancements in mass spectrometry-based methodologies that facilitate the detailed profiling of mitochondrial metabolites, unveiling significant metabolic reprogramming associated with tumorigenesis. We emphasize how recent technological advancements have addressed longstanding challenges in the field and explore the role of mitochondrial metabolism-driven cancer development and progression for novel drug discovery and translational research applications in cancer. Collectively, this review delineates emerging opportunities for therapeutic discovery and aims to establish a foundation for future investigations into the therapeutic modulation of mitochondrial pathways in cancer, thereby paving the way for innovative diagnostic and therapeutic approaches targeting mitochondrial pathways. Full article

Legumes are vital sources of protein, dietary fibre and nutrients, making them crucial for global food security and sustainable agriculture. However, their widespread acceptance and consumption are often limited by undesirable sensory characteristics, such as “a beany flavour”, bitterness or variable textures. Addressing these challenges requires a comprehensive understanding of the complex molecular mechanisms governing appearance, aroma, taste, flavour, texture and palatability in legumes, aiming to enhance their sensory appeal. This review highlights the transformative power of multi-omics approaches in dissecting these intricate biological pathways and facilitating the targeted enhancement of legume sensory qualities. By integrating data from genomics, transcriptomics, proteomics and metabolomics, the genetic and biochemical networks that directly dictate sensory perception can be comprehensively unveiled. The insights gained from these integrated multi-omics studies are proving instrumental in developing strategies for sensory enhancement. They enable the identification of key biomarkers for desirable traits, facilitating more efficient marker-assisted selection (MAS) and genomic selection (GS) in breeding programs. Furthermore, a molecular understanding of sensory pathways opens avenues for precise gene editing (e.g., using CRISPR-Cas9) to modify specific genes, reduce off-flavour compounds or optimise texture. Beyond genetic improvements, multi-omics data also inform the optimisation of post-harvest handling and processing methods (e.g., germination and fermentation) to enhance desirable sensory profiles and mitigate undesirable ones. This holistic approach, spanning from the genetic blueprint to the final sensory experience, will accelerate the development of new legume cultivars and products with enhanced palatability, thereby fostering increased consumption and ultimately contributing to healthier diets and more resilient food systems worldwide. Full article

Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus (CLas), is the most devastating disease threatening global citrus production. Although no commercial citrus varieties exhibit complete HLB resistance, genotype-specific tolerance variations remain underexplored. This study conducted a comparative transcriptomic profiling of six commercially citrus cultivars in South China, four susceptible cultivars (C. reticulata cv. Tankan, Gongkan, Shatangju, and C. sinensis Osbeck cv. Newhall), and two tolerant cultivars (C. limon cv. Eureka; C. maxima cv Guanxi Yu) to dissect molecular mechanisms underlying HLB responses. Comparative transcriptomic analyses revealed extensive transcriptional reprogramming, with tolerant cultivars exhibiting fewer differentially expressed genes (DEGs) and targeted defense activation compared to susceptible genotypes. The key findings highlighted the genotype-specific regulation of starch metabolism, where β-amylase 3 (BAM3) was uniquely upregulated in tolerant varieties, potentially mitigating starch accumulation. Immune signaling diverged significantly: tolerant cultivars activated pattern-triggered immunity (PTI) via receptor-like kinases (FLS2) and suppressed ROS-associated RBOH genes, while susceptible genotypes showed the hyperactivation of ethylene signaling and oxidative stress pathways. Cell wall remodeling in susceptible cultivars involved upregulated xyloglucan endotransglucosylases (XTH), contrasting with pectin methylesterase induction in tolerant Eureka lemon for structural reinforcement. Phytohormonal dynamics revealed SA-mediated defense and NPR3/4 suppression in Eureka lemon, whereas susceptible cultivars prioritized ethylene/JA pathways. These findings delineate genotype-specific strategies in citrus–CLas interactions, identifying BAM3, FLS2, and cell wall modifiers as critical targets for breeding HLB-resistant cultivars through molecular-assisted selection. This study provides a foundational framework for understanding host–pathogen dynamics and advancing citrus immunity engineering. Full article

Smokeless powders are a commonly used low explosive within the ammunition industry. Their ease of purchase has allowed criminals to use these products to build improvised explosive devices. Canines have become a vital tool in locating such improvised devices. With differing fabrication processes, one of the most difficult challenges for canine handlers is the optimal selection of training aids to choose as odor targets to allow for broad generalization. Several studies have been underway to understand the chemical odor characterization of smokeless powders, which can help provide canine teams with essential information to understand odor signatures from powder varieties. In this study, a SPME method optimization was conducted using unburned smokeless powders to provide a chemical odor profile assessment. Concurrently, statistical analysis using PCA and Spearman’s rank correlations was performed to explore whether odor volatile composition depicted associations between and within powder brands. The results showed that a longer extraction time (24 h) was optimal across all powders, as this yielded higher compound abundance and number of extracted odor volatiles. The optimal SPME fiber varied per powder, depicting the complexity of powder composition. There were 66 highly frequent compounds among the 18 powders, including 2-ethyl-1-hexanol, diphenylamine (DPA), and dibutyl phthalate. Principal component analysis (PCA) showed that while powders may be of the same type (single/double base), they can still portray clustering differences across and within brands. The Spearman’s rank correlation within powder type suggested that the double-base powders had a slightly higher similarity index when compared with the single-base powder types. Understanding the volatile odor profiles of various smokeless powders can enhance canine training by informing the selection of effective training aids and supporting odor generalization. Full article

The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, like its homologue Nrf2, further responds to oxidative stress by binding with small Maf proteins (sMaf) to the promotor antioxidant response element (ARE). Given these facts, investigating the crosstalk between Nrf1 and HCV was a logical next step. In HCV-replicating cells, we observed reduced levels of Nrf1. Furthermore, activation of Nrf1-dependent target genes is impaired due to sMaf sequestration in replicase complexes. This results in a shortage of sMaf proteins in the nucleus, trapping Nrf1 at the replicase complexes and further limiting its function. Weakened Nrf1 activity contributes to impaired cholesterol removal, which occurs alongside an elevated intracellular cholesterol level and inhibited LXRα promoter activation. Furthermore, inhibition of Nrf1 activity correlated with a kinome profile characteristic of steatosis and enhanced inflammation—factors contributing to HCV pathogenesis. Our results indicate that activation of Nrf1-dependent target genes is impaired in HCV-positive cells. This, in turn, favours viral morphogenesis, as evidenced by enhanced replication and increased production of viral progeny. Full article

Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Methods: Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, C₁₈H₁₈O₂), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Results: Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. Conclusions: The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model’s translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders. Full article

The sustainable production of plant bioactive compounds is increasingly important as natural habitats decline. This study investigates whether in vitro cell cultures of Eryngium planum, Lychnis flos-cuculi, and Kickxia elatine can serve as alternative sources of biologically active biomass with antimicrobial and anti-Acanthamoeba properties. Callus cultures were established under optimized and controlled conditions, and metabolomic profiling was completed using UPLC-HRMS/MS. In silico analysis, using a molecular docking approach, was applied to understand the interaction between target compounds and Acanthamoeba profilin and identify possible targets for antimicrobial properties. Untargeted metabolomic analysis confirmed the presence of valuable compounds in the callus cultures of the studied species. Biological activity was assessed through anti-Acanthamoeba and antimicrobial assays. Lychnis flos-cuculi and Kickxia elatine callus extracts showed significant inhibitory effects on Acanthamoeba trophozoites, with 87.5% and 80.1% inhibition at 10 mg/mL, respectively. In contrast, E. planum extract stimulated amoebic growth. The anti-Acanthamoeba activity correlated with the presence of ferulic acid and p-coumaric acid in L. flos-cuculi extract, and acteoside in K. elatine extract. Antibacterial testing revealed moderate activity of E. planum and K. elatine extracts against Staphylococcus spp., while Gram-negative bacteria and fungi were largely resistant. These findings highlight the potential of in vitro cultures—particularly those from L. flos-cuculi and K. elatine—as promising, sustainable sources of anti-Acanthamoeba and antimicrobial agents, warranting further investigation into their pharmacologically active constituents. Full article

Due to the limited scientific exploration of Argania spinosa (L.) skeel husk, this study presents the first investigation of the metabolite profile of methanol and acetone extracts analyzed by liquid chromatography coupled with electrospray ionization and high-resolution multistage mass spectrometry (LC-ESI/HRMSMS). A total of 43 compounds, including hydroxycinnamic acid and flavonoid derivatives, saponins, and triterpenic acids, were identified, some of which have not been previously reported in this species. The total phenols (TPC) and flavonoids (TFC) content were spectrophotometrically determined. A multi-target approach was applied to investigate the antioxidant potential using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), β-carotene bleaching, and Ferric Reducing Ability Power (FRAP) tests. Carbohydrate hydrolyzing enzymes and lipase inhibitory activities were also assessed. The acetone extract exhibited the highest TPC and TFC values, resulting in being the most active in β-carotene bleaching test with IC₅₀ values of 26.68 and 13.82 µg/mL, after 30 and 60 min of incubation, respectively. Moreover, it was the most active against both α-glucosidase and α-amylase enzymes with IC₅₀ values of 12.37 and 18.93 µg/mL, respectively. These results pointed out that this by-product is a rich source of bioactive phytochemicals potentially useful for prevention of type 2 diabetes and obesity. Full article

Coffee is one of the most widely consumed beverages worldwide, primarily due to the stimulating effects attributed to its caffeine content. However, excessive intake of caffeine results in negative effects, including palpitations, anxiety, and insomnia. Therefore, low-caffeine coffee has captivated growing consumer interest, highlighting its significant market potential. Traditional decaffeination methods often lead to non-selective extraction, resulting in a loss of desirable flavor compounds, thereby compromising coffee quality. In recent years, microbial fermentation has emerged as a promising, targeted, and safe approach for reducing caffeine content during processing. Additionally, mixed-culture fermentation further enhances coffee flavor and overcomes the drawbacks of monoculture fermentation, such as low efficiency and limited flavor profiles. Nonetheless, several challenges are yet to be resolved, including microbial tolerance to caffeine and related alkaloids, the safety of fermentation products, and elucidation of the underlying mechanisms behind microbial synergy in co-cultures. This review outlines the variety of microorganisms with the potential to degrade caffeine and the biochemical processes involved in this process. It explores how microbes tolerate caffeine, the safety of metabolites produced during fermentation, and the synergistic effects of mixed microbial cultures on the modulation of coffee flavor compounds, including esters and carbonyls. Future directions are discussed, including the screening of alkaloid-tolerant strains, constructing microbial consortia for simultaneous caffeine degradation for flavor enhancement, and developing high-quality low-caffeine coffee. Full article

Leymus chinensis (Trin.) Tzvel., a vital native forage grass in northern China for ecological restoration and livestock production, faces severe yield losses and grassland degradation due to rust (Puccinia spp.) infection. Current control strategies, reliant on chemical interventions, are limited by evolving resistance risks and environmental concerns, while rust-resistant breeding remains hindered by insufficient molecular insights. To address this, we systematically evaluated rust resistance in 24 L. chinensis germplasms from diverse geographic origins, identifying six highly resistant (HR) and five extremely susceptible (ES) genotypes. Integrating transcriptomics and metabolomics, we dissected molecular responses to Puccinia infection, focusing on contrasting HR (Lc71) and ES (Lc5) germplasms at 48 h post-inoculation. Transcriptomic analysis revealed 1012 differentially expressed genes (DEGs: 247 upregulated, 765 downregulated), with enrichment in cell wall biosynthesis and photosynthesis pathways but suppression of flavonoid synthesis. Metabolomic profiling identified 287 differentially accumulated metabolites (DAMs: 133 upregulated, 188 downregulated), showing significant downregulation of pterocarpans and flavonoids in HR germplasms, alongside upregulated cutin synthesis-related metabolites. Multi-omics integration uncovered 79 co-enriched pathways, pinpointing critical regulatory networks: (1) In the nucleotide metabolism pathway, genes Lc5Ns011910, Lc1Xm057211, and Lc4Xm043884 exhibited negative cor-relations with metabolites Deoxycytidine and Cytosine. (2) In flavonoid biosynthesis, Lc2Xm054924, Lc4Xm044161, novel.8850, Lc2Ns006303, and Lc7Ns021884 were linked to naringenin and naringenin-7-O-glucoside accumulation. These candidate genes likely orchestrate rust resistance mechanisms in L. chinensis. Our findings advance the molecular understanding of rust resistance and provide actionable targets for breeding resilient germplasms. Full article