Search Results (7,889)

Melatonin (MEL), also known as N-acetyl-5-methoxytryptamine, has been reported in plants as a secondary messenger involved in regulating abiotic stress responses. MEL treatment, either preharvest or postharvest, regulates several physiological and biochemical processes during fruit growth and ripening in horticultural products. These include reproductive development, tissue and quality maintenance, delayed senescence, and responses to abiotic stress. Due to its natural origin, low toxicity, and multifunctional regulatory capacity, MEL has recently attracted attention as a promising ‘green preservative’ for sustainable postharvest management. Additionally, MEL coordinates through cross-talk with other plant hormones, such as abscisic acid, ethylene, polyamines, jasmonic acid, γ-aminobutyric acid, salicylic acid, and nitric oxide, to regulate postharvest ripening and senescence. Furthermore, MEL enhances antioxidant systems and improves membrane integrity, thereby alleviating chilling injury and enhancing fruit firmness and colour. Notably, recent evidence highlights the innovative regulatory mechanisms of MEL involving redox homeostasis, hormone signalling reprogramming, and transcriptional modulation of stress-responsive pathways. MEL could therefore be considered an emerging, eco-friendly tool for prolonging the shelf-life of fruit and vegetables and maintaining their quality. This review summarises the mechanisms by which MEL contributes to plant stress resistance by regulating the biosynthesis and metabolism of stress tolerance and improving fruit quality. Full article

Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted considerable interest. The primary advantage of this material is the level of structural control it affords. The fibre orientation, porosity, and overall microarchitecture can be adjusted to replicate the organisation and mechanical behaviour of the natural membrane. A range of biocompatible polymers—among them silk fibroin, poly(ε-caprolactone), poly(lactic acid), and poly(vinyl alcohol) and their composites—provide options for tuning stiffness, degradation rates, and interactions with cells, making them suitable building blocks for TM repair constructs. This review provides a comprehensive overview of contemporary fabrication methodologies, namely electrospinning, additive manufacturing, melt electrowriting, and hybrid strategies. In addition, it offers a detailed discussion of the evaluation procedures employed for these scaffolds and discusses how scaffold structure affects later performance. Mechanical testing, microstructural imaging, and in vitro biocompatibility assays help to determine how closely a construct can approach the performance of the native tissue. Bringing these elements together may support the gradual translation of fibre-based TM scaffolds into clinical practice. Full article

Background: Black spot disease severely constrains Chinese cabbage production. Methods: To elucidate the defence mechanisms underlying this response, transcriptomic and metabolomic profiles were analysed in leaves of the Chinese cabbage line 904B at 24 h post-inoculation (hpi) with Alternaria brassicicola. In parallel, gene silencing and overexpression were conducted for BraPBL, an RLCK family member in Chinese cabbage. Results: The Chinese cabbage line 904B exhibited marked suppression of cytokinin and auxin signalling, coupled with enhanced expression of genes involved in ethylene and jasmonic acid signalling. Multiple secondary metabolites exhibited differential changes, specifically the sterol compound 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol was significantly upregulated in the treatment group. These metabolites were primarily enriched in the indole alkaloid metabolism and glycerolipid metabolism pathways. Concurrently, BraPBL exhibits increasing expression with prolonged infection. BraPBL overexpression enhances resistance to black spot disease, whereas silencing reduces resistance. Subcellular localization confirmed BraPBL at the plasma membrane. Overexpression of BraPBL upregulates the reactive oxygen species-related gene RBOH and the signal transduction-related gene MEKK1, whilst simultaneously activating the JA pathway. Conclusions: Overall, 904B activates defence-related hormones while suppressing growth and development-related hormones during early infection. Secondary metabolites, particularly the sterol compound 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol, play key roles in defence, and BraPBL functions as a black spot disease–related defence gene in Chinese cabbage. Full article

Understanding how plants respond to water limitation is increasingly important under accelerating climate change. Lycoris aurea, a widely distributed ornamental and medicinal bulbous plant, frequently inhabits environments with fluctuating soil moisture, yet its molecular drought-response mechanisms remain largely unexplored. In this study, we investigated L. aurea growing under field-based, in situ soil moisture regimes, comparing low (~20% soil water content) and high (~40% soil water content) conditions. We combined soil property assessments with high-resolution transcriptomic and untargeted metabolomic profiling to characterize the adaptive responses of bulb tissues under contrasting soil water conditions. Although total nitrogen, phosphorus, and potassium levels were comparable across treatments, soil moisture, representing the primary contrasting field condition, and soil pH, a correlated environmental factor, were significantly associated with variation in gene expression and metabolite accumulation (p < 0.05, n = 3). Transcriptome analyses identified a total of 1034 differentially expressed genes enriched in pathways related to amino acid metabolism, cuticle formation, cell wall modification, and osmotic adjustment. Metabolomic analysis identified a total of 1867 differentially expressed metabolites belonging to carboxylic acids and prenol lipids, showing alterations involved in amino acids, lipids, phenolic acids, and alkaloids associated with osmoprotection, membrane stabilization, and structural reinforcement under low soil moisture. Pathway-based integration analysis highlighted four core pathways, including “alanine, aspartate and glutamate metabolism” (p = 0.00371) and “cutin, suberine and wax biosynthesis” (p = 0.00873), as central hubs linking transcriptional regulation with metabolic reconfiguration. Gene-metabolite-soil correlation networks further demonstrated that drought adaptation arises from tightly coordinated biochemical and structural adjustments rather than shifts in nutrient acquisition. Together, this species-specific study provides a comprehensive multi-omics framework for understanding drought tolerance in L. aurea, reveals key molecular targets associated with plant resilience, and offers potential targets and insights for the conservation of drought-resilient Lycoris cultivars. Full article

The endolysosomal system plays a pivotal role in cellular function. Before reaching lysosomes for degradation, the endocytosed cargoes are sorted at various stages of endosomal trafficking for recycling and/or rerouting. The proper execution of these processes depends on tightly regulated ion fluxes across endolysosomal membranes. Recent studies have demonstrated the importance of two-pore channels (TPCs), including TPC1 and TPC2, in endolysosomal trafficking. These channels are expressed in the membranes of distinct populations of endosomes and lysosomes, where they respond to nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P₂] to conduct Ca²⁺ and Na⁺ release from these acidic organelles. Here, we discuss the potential implications of Ca²⁺ and Na⁺ fluxes mediated by TPCs across endolysosomal membranes in the physiological and pathophysiological functions of these organellar channels. Full article

Dichondra (Dichondra repens) is an important thermophilic Chinese herbal medicine and a key component in traditional herbal tea and beverages. It is also commonly used as an excellent ground cover plant for landscapes and cover cropping in orchards. In temperate and transition zones, thermophilic dichondra often suffers from chilling stress resulting in growth retardation and yield loss. This study aims to compare differences in photochemical efficiency, cell membrane stability, lipid peroxidation, and global lipid remodeling between two dichondra genotypes (chilling-tolerant Dr5 and chilling-sensitive Dr17) in response to a prolonged chilling stress. The results demonstrated that chilling stress significantly accelerated membrane lipid peroxidation and chlorophyll loss, resulting in reduced cell membrane stability and photochemical efficiency in two genotypes. However, Dr5 exhibits less oxidative damage, better cell membrane stability, and higher photochemical efficiency than Dr17 under chilling stress. The analysis of lipidomics found that both Dr5 and Dr17 accumulated phospholipids (Phls), glycoglycerolipids (Glls), and sphingolipids (Spls). More importantly, Dr5 exhibited 95%, 72%, 71%, 526%, 39%, 89%, 131%, 695%, or 865% increase in phosphatidic acid (PA), ceramide (Cer), hexosyl ceramide (Hex1Cer), lyso PA (LPA), lyso phosphatidylcholine (LPC), lyso phosphatidylethanolamine (LPE), lyso phosphatidylglycerol (LPG), lyso phosphatidylinositol (LPI), or lyso phosphatidylserine (LPS) content than Dr17 on day 10 of chilling stress, respectively. Dr5 also maintained significantly higher contents of PC (52%), PE (53%), PI (24%), PS (81%), PG (30%), and digalactosyl diacylglycerol (DGDG, 53%) after 20 days of chilling stress. In addition, two genotypes could maintain a stable unsaturation level of total lipids under chilling stress. These findings indicate that lipid remodeling is attributed to genetic variation in chilling tolerance of dichondra species. The current study provides an interesting data set that could be the starting point for analyzing the underlying mechanisms of chilling tolerance in thermophilic dichondra species. Full article

Arid and semi-arid ecosystems harbor a wealth of underexplored plant biodiversity with untapped ecological and pharmacological potential. This study integrates morphological and molecular barcoding (ITS and rbcL) to confirm the identity of eight wild plant species native to the Saudi Arabian desert: Calligonum crinitum, Tribulus terrestris, Cornulaca monacantha, Cleome pallida, Leptadenia pyrotechnica, Cyperus conglomeratus, Indigofera argentea, and Artemisia monosperma. High-resolution GC–MS analysis identified over 25 bioactive compounds across these taxa, grouped into functional classes including hydrocarbons, esters, fatty acids, quinones, terpenoids, and phenolics. Notable compounds such as n-hexadecanoic acid, 2,4-di-tert-butylphenol, lupeol, and D-limonene were linked to antioxidant activity, desiccation tolerance, and membrane protection under stress. L. pyrotechnica and A. monosperma emerged as chemical outliers with unique metabolite profiles, suggesting divergent strategies for climate resilience. Our results highlight the ecological and bioeconomic value of desert flora, positioning them as candidates for future research in metabolic engineering, dryland restoration, and plant-based pharmaceuticals. This integrative approach underscores the relevance of desert plants for sustainable development in the face of climate change. Full article

Background/Objectives: Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is used in Crohn’s disease (CD) management, yet patients’ responses vary, underscoring the need for pharmacogenomic (PGx) markers. This study aimed to identify PGx pathways associated with suboptimal VDZ response using a rare-variant analytical framework. Methods: DNA from 63 CD patients treated with VDZ as first-line advanced therapy underwent whole-exome sequencing. Clinical response at week 14 classified patients as optimal responders (ORs) or suboptimal responders (SRs). Sequencing data were processed using GATK Best Practices, annotated with variant effect predictors, and filtered for rare damaging variants (damaging missense and high-confidence loss-of-function; minor allele frequency < 0.05). Variants were mapped to genes specific for SRs and ORs, and analyzed for pathway enrichment using the Reactome database. Rare-variant burden and composition differences were assessed with Fisher’s exact test and SKAT-O gene-set association analysis. Results: Suboptimal VDZ response was associated with pathways related to membrane transport (ABC-family proteins, ion channels), L1–ankyrin interactions, and bile acid recycling, while optimal response was associated with pathways involving MET signaling. SKAT-O identified lipid metabolism-related pathways as significantly different—SRs harbored variants in pro-inflammatory lipid signaling and immune cell trafficking genes (e.g., PIK3CG, CYP4F2, PLA2R1), whereas ORs carried variants in fatty acid oxidation and detoxification genes (e.g., ACADM, CYP1A1, ALDH3A2, DECR1, MMUT). Conclusions: This study underscores the potential of exome-based rare-variant analysis to stratify CD patients and guide precision medicine approaches. The identified genes and pathways are potential PGx markers for CD patients treated with VDZ. Full article

We report the first synthesis of IspH-directed prodrugs targeting the terminal enzyme of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, (E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase (IspH or LytB). A series of alkyne and pyridine monophosphate cycloSaligenyl (cycloSal) prodrugs were prepared to enhance membrane permeability by masking the phosphate group. The effects of electron-withdrawing (Cl, CF₃) and electron-donating (OCH₃, NH₂) substituents were examined, together with amino acid-functionalized and mutual prodrug analogs. Among the synthesized compounds, chlorine-substituted derivatives 5c and 6c displayed the strongest antimycobacterial activity against Mycobacterium smegmatis, surpassing isoniazid in agar diffusion assays. These results indicate that electron-withdrawing substituents accelerate prodrug hydrolysis and facilitate intracellular release of the active inhibitor. This work provides the first experimental evidence of an IspH-targeted prodrug approach, highlighting the cycloSal strategy as a valuable tool for delivering phosphorylated inhibitors and developing novel antimycobacterial agents acting through the MEP pathway. Full article

Background/Objectives: Malaria remains a major global health burden, increasingly complicated by resistance to artemisinin-based therapies. Because artemisinin activation depends on heme and porphyrin chemistry, we sought to exploit host red blood cell (RBC) heme metabolism as a therapeutic vulnerability. This study aims to develop and evaluate a host-directed “bait-and-kill” strategy that selectively sensitizes malaria-infected RBCs to artemisinin. Methods: We integrated quantitative proteomics, erythropoiesis transcriptomic analyses, flow cytometry, and in vitro malaria culture assays to characterize heme metabolism in mature RBCs and Plasmodium falciparum-infected RBCs (iRBCs). The heme precursor 5-aminolevulinic acid (ALA) was used to induce porphyrin accumulation, and dihydroartemisinin (DHA) was applied as the killing agent. Drug synergy, porphyrin accumulation, reactive oxygen species (ROS) induction, and parasite survival were assessed, including ring-stage survival assays using artemisinin-resistant clinical isolates. Results: Mature RBCs retain a truncated heme biosynthesis pathway capable of accumulating porphyrin intermediates, while uninfected RBCs are impermeable to ALA. In contrast, iRBCs exhibit increased membrane permeability, allowing selective ALA uptake and porphyrin accumulation. ALA alone did not induce cytotoxicity or ROS, whereas DHA induced ROS and parasite killing. The ALA + DHA combination resulted in synergistic parasite elimination, including complete clearance of artemisinin-resistant P. falciparum isolates from the Greater Mekong Subregion, with no recrudescence observed over three weeks of culture. Evidence supports a predominant role for host-derived heme metabolites in mediating this synergy. Conclusions: The bait-and-kill strategy selectively exploits host RBC heme metabolism to restore and enhance artemisinin efficacy while sparing uninfected cells. Using clinically safe compounds, this host-directed approach provides a promising, resistance-bypassing framework for malaria treatment and combination drug development. Full article

Background: Solenopsis invicta, commonly known as the red imported fire ant (RIFA), is an important global invasive pest, and its management is challenging because of insecticide resistance and environmental problems. Methods: In this research, we applied transcriptomics to analyze the molecular responses of S. invicta worker ants exposed to different types of pesticides, beta-cypermethrin (BC) and the entomopathogenic fungus Cordyceps cicadae (CC), as well as to different concentrations of these pesticides. Results: A total of 2727 differentially expressed genes (DEGs) were identified across all samples. The number of DEGs in the BC treatment group was significantly higher than that in the CC treatment group (2520 vs. 433), and higher concentrations resulted in more DEGs (an increase of 47 in the BC group and 229 in the CC group). KEGG pathway analysis revealed that the DEGs were significantly enriched in lipid metabolism, carbohydrate metabolism, amino acid metabolism, signal transduction, and membrane transport. Immune-related gene analysis showed more general down-regulation (average FPKM value in BC 741.37 to 756.06 vs. CK 1914.42) of pathogen recognition genes (PGRP-SC2) under BC stress conditions, while CC treatment resulted in increases in expression of important immune effectors such as various serine proteases. Conclusions: Overall, this study provides useful insights into the molecular basis of responses to different pesticides in S. invicta and offers a basis to develop new approaches to control this pest. Full article

The misuse of antibacterial agents has contributed to the growing prevalence of antibiotic resistance, highlighting an urgent need to explore alternative anti-infection therapeutic strategies. Antimicrobial peptides (AMPs) are naturally occurring molecules. They exhibit broad-spectrum antimicrobial activity and represent promising candidates for the development of novel therapeutics. A cysteine-rich antimicrobial peptide was identified and characterized from the genome of Tigriopus japonicus and designated “TjRcys1”. The precursor form of TjRcys1 comprises 96 amino acids. Structural analyses of TjRcys1 revealed random coils, two α-helices, and two β-strands. Recombinant TjRcys1 had inhibitory effects upon Staphylococcus aureus and Bacillus sp. T2, with a minimum inhibitory concentration of 64 μM for both. TjRcys1 did not show complete inhibition against Vibrio alginolyticus, Klebsiella pneumoniae, or Aeromonas hydrophila at 64 μM, but it did slow their growth rate. TjRcys1 could disrupt the permeability of the cell membrane of S. aureus. Transcriptomic analyses indicated that TjRcys1 could interfere with the ribosome biosynthesis and nucleotide metabolism of K. pneumoniae. Our results provide a valuable reference for the development of new AMPs and optimization of their design. Full article

Staphylococcus aureus (S. aureus) is a common pathogen that threatens healthcare and food safety. Vine tea extract (VTE) and its major active component, dihydromyricetin (DMY), show antibacterial activity. However, their mechanisms of action are not fully understood. In this study, we combined proteomics and lipidomics, with RT–qPCR validation of selected differentially expressed genes, to investigate how DMY and VTE affect S. aureus. Proteomics identified 210 and 535 differentially expressed proteins (DEPs) in the DMY-treated and VTE-treated groups, respectively. These DEPs were mainly enriched in cell wall- and membrane-associated pathways. DMY markedly increased proteins involved in fatty acid degradation, glyceride metabolism, and cell wall synthesis. In contrast, VTE increased proteins related to heme/iron acquisition and cell wall degradation. In addition, VTE altered proteins involved in pyrimidine metabolism and aminoacyl-tRNA biosynthesis, suggesting that non-DMY components in VTE may contribute to the antibacterial activity through additional pathways. Lipidomics further indicated membrane lipid remodeling, including increased fatty acid unsaturation and shorter acyl chain length. Collectively, DMY and VTE may inhibit S. aureus growth by remodeling membrane lipids and disturbing cell wall–cell membrane homeostasis. These findings provide mechanistic support for further development of DMY and VTE as natural antimicrobial candidates. Full article

Bacillus cereus group strains are prolific producers of diverse bacteriocins with significant application potentials; however, their industrial utilization is often hampered by short production cycles and low yields. Using the leaderless bacteriocin toyoncin as a model, we systematically evaluated the impact of culture medium, temperature, and initial pH on its production. Our findings demonstrate that these factors critically affected yield, with no production under oligotrophic, acidic, or high-temperature conditions. Optimal production was achieved in MH medium (initial pH 8.5, 25 °C), significantly enhancing fermentation duration and yield compared to original conditions (LB medium, 30 °C, pH 7.0). Transcriptional analyses revealed that these improvements were attributable to extended transcription periods and increased transcript levels of the toyoncin gene cluster. Furthermore, we demonstrated that toyoncin disappearance in the supernatant is caused by transcriptional cessation and degradation by membrane-associated proteases. By combining optimized fermentation with protease inhibition, a high and stable toyoncin yield of 53.86 mg/L was achieved, representing a 3.07-fold increase over the initial yield (17.52 mg/L). This study establishes an integrated strategy to enhance bacteriocin production through simultaneous optimization of culture conditions and inhibition of enzymatic degradation, providing important insights for advancing bacteriocin development in the Bacillus cereus group. Full article

Background/Objectives: Capric acid (CA)–therapeutic deep eutectic systems (THEDES) are emerging as a distinct class of biofunctional matrices capable of reshaping drug solubilization, permeability, and bioactivity. Methods: Relevant studies on CA–THEDES were identified through targeted database searches and screened for evidence on their design, mechanisms, and pharmaceutical performance. Results: This review synthesizes current evidence on their structural design, mechanistic behavior, and pharmaceutical performance, revealing several unifying principles. Across multiple drug classes, CA consistently drives strong, directional hydrogen bonding and drug amorphization, resulting in marked solubility enhancement and stabilization of non-crystalline or supersaturated states relative to crystalline drugs or conventional solvent systems. Its amphiphilic C10 chain further contributes to membrane fluidization, which explains the improved transdermal and transmucosal permeation repeatedly observed in CA-THEDES. Additionally, synergistic antimicrobial and anticancer effects reported in several systems confirm that CA acts not only as a solvent component but as a bioactive co-therapeutic. Collectively, the reviewed data show that CA serves as a structurally determinant element whose dual hydrogen-bonding and membrane-interacting roles underpin the high pharmaceutical performance of these systems. However, gaps remain in long-term stability, toxicological profiling, and regulatory classification. Emerging Artificial Intelligence (AI) and Machine Learning (ML)-guided predictive approaches offer promising solutions by enabling rational selection of eutectic partners, optimal ratios, and property optimization through computational screening. Conclusions: Overall, CA-THEDES represent a rationally designable platform for next-generation drug delivery, where solvent functionality and therapeutic activity converge within a single, green formulation system. Full article