Search Results (796)

Phenolic acids are known allelopathic compounds that may serve as the primary cause of continuous cropping obstacles in Coix lacryma-jobi L. (Coix). However, the concentrations, types, and specific stress responses of Coix to these phenolic acids still require further investigation. In this study, the cultivar ‘Wanyi 2′ was used to examine the effects of different phenolic acids and their concentrations on the growth of Coix. Four concentrations (0 mg/L, 10 mg/L, 100 mg/L, and 1000 mg/L) and four phenolic acid types (p-hydroxybenzoic acid, salicylic acid, cinnamic acid, and ferulic acid) were used to assess their influences on plant growth, leaf physiological parameters, and metabolic pathways under greenhouse conditions. In this greenhouse pot experiment, the effects of the four phenolic acids showed a similar tendency: a low concentration (10 mg/L) tended to promote the growth and root development of Coix seedlings, whereas high concentrations (100 and 1000 mg/L) generally showed inhibitory effects. Among these phenolic acids, ferulic acid exhibited the strongest inhibitory effect at the highest concentration (1000 mg/L), while salicylic acid showed the most pronounced growth-promoting effect at low concentrations (10 mg/L). In addition, high levels of phenolic acids markedly increased antioxidant enzyme activities and oxidative stress-related substances in Coix leaves, while reducing soluble sugar (SS) and soluble protein (SP) contents. Our data suggest that under phenolic acid stress, Coix leaves exhibited changes in the metabolism of phenolic acids (e.g., 4-methoxysalicylic acid, gallic acid) and amino acids (e.g., glutathione, proline), which may be associated with the adaptive response to allelochemical-induced stress. Overall, this study provides insights that may support strategies to optimize plant growth regulators and mitigate continuous cropping barriers in Coix. Full article

While bacterial skin infections are highly prevalent worldwide, their eradication with conventional topical medications remains highly challenging. Cinnamic acid (CA) is a naturally occurring molecule with interesting antibacterial properties, but its efficacy is hindered by poor aqueous solubility and skin permeability. To overcome these challenges, CA was encapsulated within novasomes, which are multilamellar vesicles composed of fatty acids, cholesterol, and nonionic surfactants. The novasomes were optimized using a 2³ factorial design and the optimized formulation was incorporated in a carbopol gel base and evaluated for spreadability, rheological properties, drug release, ex vivo skin permeation and deposition, and antibacterial efficacy. The optimized novasomes featured desirable properties, including high drug entrapment (94.75 ± 0.05%), nanometric particle size (123.80 ± 1.44 nm), and negative zeta potential (−36.63 ± 0.61 mV). CA novasomal gel exhibited shear-thinning behavior, coupled with thixotropic properties. It also achieved approximately 1.7-fold higher flux through rat skin compared with the free CA gel. Moreover, the novasomes showed a two-fold reduction in the minimum inhibitory concentration of the drug against E. coli compared with the drug suspension. These findings support the potential of CA novasomal gel to enhance its antibacterial activity and skin permeability, making it a promising approach for topical delivery of this naturally occurring compound. Full article

Background: Dental caries is a chronic disease mediated by biofilm, which is caused by Streptococcus mutans, and enamel genetics modulates susceptibility. The variants of ENAM might alter the adhesion of enamel and bacteria. One important anti-viral target is sortase A (SrtA), which restricts colonization but does not have an impact on bacterial survival. Aim: The aim of this study was to find out the relationship between ENAM rs3796704 and dental caries vulnerability among adult Iraqi Arab females and to assess the antibiofilm capacity of eugenol and cinnamic acid against S. mutans SrtA using molecular docking, ADMET prediction, and molecular dynamics modeling. Methods: A case–control study was done on 240 women (aged 25–30 years; 120 caries, 120 controls). HRM real-time PCR was done to genotype ENAM rs3796704. An analysis of allelic and genotypic distributions was done using chi-square tests and odds ratios (p < 0.05). An in silico docking analysis aimed at SrtA (PDB: 4TQX) was performed in AutoDock Vina, and this was followed by ADMET profiling and a 50 ns molecular dynamics simulation (OPLS4/TIP3P, NPT 300 K/1 atm). Results: The level of the G allele was found to be lower in the cases than in the controls (60% vs. 70; OR = 0.6429; p = 0.02), but the level of the A allele was found to be higher in the cases (40% vs. 30; OR = 1.5556; p = 0.02). Docking showed a minor difference in binding affinities with eugenol (−4.961 kcal/mol) and cinnamic acid (−4.939 kcal/mol) as compared with chlorhexidine (−4.692 kcal/mol). Both compounds showed stable binding for more than 50 ns as well as desirable predicted pharmacokinetics. Conclusions: The caries vulnerability in this sample was associated with ENAM rs3796704. Eugenol and cinnamic acid undergo stable dissociative interactions with SrtA and were found to have favorable safety profiles in silico. Therefore, they may be considered as adjunctive anti-virulence agents in the prevention of caries. Full article

Phenylalanine ammonia-lyase (PAL) is the rate-limiting enzyme in the phenylpropane metabolic pathway, which is crucial for plant disease resistance. However, the functional roles of specific PAL members in lily defense against gray mold (Botrytis elliptica) remain unclear. Using the resistant lily cultivar ‘Sorbonne’, metabolomics analysis revealed that phenylpropane metabolites were significantly induced upon pathogen infection. Combined second- and third-generation transcriptome sequencing identified eight PAL family members. Among them, LhSorPAL1 and LhSorPAL2 were strongly induced by B. elliptica and were selected for further analysis. Both recombinant proteins exhibited PAL enzymatic activity catalyzing cinnamic acid production from L-phenylalanine. Overexpression of LhSorPAL1 or LhSorPAL2 in lily via Agrobacterium-mediated transformation had no obvious effect on plant growth but significantly increased the accumulation of lignin, flavonoids, and total phenols upon pathogen challenge, leading to enhanced resistance to gray mold. Conversely, antisense expression of LhSorPAL1 or LhSorPAL2 reduced the accumulation of these metabolites. Promoter analysis revealed that both LhSorPAL1pro and LhSorPAL2pro contain methyl jasmonate (MeJA)-, abscisic acid (ABA)-, and transcription factor-binding cis-elements. Collectively, these results demonstrate that LhSorPAL1 and LhSorPAL2 positively regulate lily resistance to B. elliptica by promoting phenylpropane metabolism, providing candidate genes for molecular breeding. Full article

This study investigated the dynamic changes and bioaccessibility of free and bound phenolics in rice bean (Vigna umbellata) during simulated gastrointestinal digestion. A total of 34 phenolic compounds were identified and quantified across oral, gastric, and intestinal phases by UPLC-MS/MS detected. Gastric digestion was identified as the critical stage for phenolic release, with multiple flavonoids increasing 2–3-fold, including rutin (205%), isoquercitrin (226%), and procyanidin B1 (134%). In contrast, in the intestinal phase, flavonoids including procyanidin B1, epicatechin, and quercetin became undetectable after extensive degradation, while phenolic acids such as p-hydroxybenzoic acid (157%) and trans-cinnamic acid (200%) accumulated gradually. Phloroglucinol showed a progressive accumulation increased continuously during digestion (10 to 36 mg/kg DW). Most bound phenolics remained remarkably stable, with over 85% retained throughout upper gastrointestinal transit, except for bound p-coumaric acid and phloroglucinol, which were gradually released. Notably, 3,4-dihydroxyphenylacetic acid was detected only in the bound form across all phases. These findings reveal the dual fates of rice bean phenolics, especially the bound fraction, and underscore the importance of their release and transformation during digestion when evaluating the bioactivity of rice bean polyphenols. Full article

Background: Root rot caused by Fusarium solani is a devastating disease in Angelica sinensis (danggui), leading to severe yield and quality losses. Sustainable control strategies are urgently needed. According to the plant “cry for help” theory, plants under pathogen attack may recruit beneficial microbes via root exudates. However, whether A. sinensis employs this strategy against F. solani remains unknown. This study aimed to identify potential “cry for help” metabolites and evaluate their biocontrol potential. Methods: LC-MS analysis revealed that F. solani infection significantly altered the metabolic profiles of both A. sinensis roots and rhizosphere soil. Results: Comparative analysis identified seven metabolites specifically upregulated in infected plants but not detected in the pathogen, including taurine, oxoadipic acid, quinolinic acid, 6-phosphogluconic acid, methyl cinnamate, 2-phenylethanol, and (R)-3-hydroxybutyric acid. Exogenous application of these seven metabolites revealed that taurine and methyl cinnamate significantly alleviated disease symptoms, improved plant growth (root length, biomass), and enhanced the activities of key defense enzymes (peroxidase, POD, phenylalanine ammonia-lyase, PAL, lipoxygenase, LOX, polyphenol oxidase, PPO). Furthermore, taurine and methyl cinnamate reshaped the rhizosphere microbiome. The incidence of root rot was reduced by 51.3% and 50.8%, respectively. Taurine enriched actinobacteria (e.g., Paeniglutamicibacter) and reduced the relative abundance of pathogenic Ascomycota fungi, while methyl cinnamate markedly enriched the nitrogen-fixing bacterium Azotobacter and the saprophytic fungus Schizothecium. Crucially, both treatments significantly suppressed the proliferation of F. solani in the rhizosphere. Conclusions: Our findings demonstrate for the first time that A. sinensis activates a “cry for help” response upon attack by F. solani, with taurine and methyl cinnamate preliminarily identified as key signaling metabolites that can directly or indirectly inhibit the development of A. sinensis root rot. These compounds enhance plant resistance and recruit beneficial microorganisms, offering a novel and promising ecological strategy for the green control of A. sinensis root rot. Full article

Background: Ensuring authenticity and verifying the floral origin of honey are persistent and critical issues in the quality control of bee products; in particular, the characteristic components and practical authenticity evaluation standards of several specialty fruit monofloral honeys are still insufficiently defined. Methods: To address this, we conducted a comparative analysis of five fruit monofloral honey (loquat, pomegranate, citrus, apple, and blueberry) phytochemicals using high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC-MS), and the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (TCM). Results: Based on the currently available literature and databases, eleven identified phytochemicals appear to be reported in honey for the first time, including quinic acid derivatives, phenolamides, and flavonoid glycosides. Characteristic components with high species dependence were identified in distinct honey samples: anisic acid in loquat honey; methyl syringate in pomegranate honey; caffeine in citrus honey; cinnamic acid and methyl syringate in apple honey; and phaseic acid, methyl syringate, isorhamnetin-3-O-neohesperidoside, and callunene in blueberry honey. Twenty-three commercial samples were collected from the retail market to assess authenticity using HPLC fingerprints and quantitative thresholds for characteristic components. Authenticity was assessed based on both chromatographic fingerprint similarity and the content thresholds of characteristic phytochemicals specific to each monofloral honey type. The results indicated that 19 commercial samples satisfied the proposed authenticity criteria, whereas four commercial samples showed inconsistencies in characteristic phytochemical profiles or fingerprint similarity. Conclusions: This research establishes reliable chemical markers and a quantitative method to assess the authentication of five monofloral honeys, supporting high-value product development. Full article

The shortage of effective chemotherapeutic agents poses a significant challenge to the global public health system. Cancer is among the leading diseases affecting the human population worldwide. Issues such as drug resistance, toxicity, lack of specificity, poor bioavailability and water solubility, and severe side effects reduce the effectiveness of many existing anticancer drugs. As a result, there is growing interest in discovering a new generation of therapeutic agents to overcome these limitations. Phenolic acids, including ferulic and caffeic acids, are cinnamic acid derivatives with numerous biological effects, including anti-inflammatory, antibacterial, antifungal, antioxidant, antiviral, cytotoxic, and antiproliferative effects. In recent years, drug repurposing and hybridization strategies have emerged as attractive approaches in medicinal chemistry because they may reduce both the cost and time associated with conventional drug discovery. As a result, several researchers have combined ferulic acid and caffeic acid scaffolds with different pharmacophores to generate hybrid compounds with enhanced anticancer potential. This review summarizes recent in vitro and in silico studies published between 2022 and 2025 on ferulic and caffeic acid hybrid compounds that exhibit cytotoxic and antiproliferative effects. Furthermore, the review discusses structure–activity relationship trends, synthetic approaches, and structural modifications associated with improved biological activity. Collectively, the findings highlight the significant potential of ferulic acid and caffeic acid scaffolds in the development of multifunctional anticancer agents. Full article

Cymodocea nodosa, growing at low water depth, is affected by various environmental changes and is expected to adapt to oxidative stress. Oxidative stress in living leaves (LC) and beach deposits (NC) of C. nodosa activated superoxide dismutase (SOD), which was higher in LC, leading to significant neutralization of the produced H₂O₂ and destruction of protein generation. Higher antioxidant capacity (using a UV/Vis spectrophotometer) to scavenge 2.2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS^•+) (IC₅₀: 5 in LC vs. 22 μg mL⁻¹ in NC) and OH^• (hydroxyl) radicals (IC₅₀: 132 in LC vs. 281.7 μg mL⁻¹ in NC), compared to 2,2-diphenyl-1-picrylhydrazyl (DPPH^•) (IC₅₀: 63 in LC vs. 45 μg mL⁻¹ in NC) and superoxide anion (O₂^•−) radicals (IC₅₀: 190 in LC vs. 94 μg mL⁻¹ in NC), and similar reducing power (RP) were recorded in LC compared with NC extracts (IC₅₀: 53 in LC vs. 52 μg ml⁻¹ in NC). Phenolic compounds were not significantly lost during plant exposure on shores (mean value: 57.00 in LC vs. 45.48 mg g⁻¹ d.w. in NC). Phenolic compounds identified, using UHPLC-DAD analysis, in both LC and NC extracts were chicoric, trans-ferulic, caftaric, p-coumaric, sinapic, and trans-cinnamic acid and rutin hydrate, whereas caffeic acid, in traces, was identified in NC extracts. NC showed higher cytotoxic activity in inhibiting LS 174 colon cancer cells than LC. In cases of plant cultivation or management plans for seagrass meadows and their beach deposits, with the least possible impacts, both LC and NC extracts could be exploited for their antioxidant and anticancer properties. In a ‘case study’, the amounts of individual phenolic compounds that can be produced from NC utilization were estimated. Full article

Phenolics in Sphagnum can inhibit its microbial decomposition. Climate warming and drainage have driven vascular plants, such as Ericaceae, to expand into Sphagnum-dominated peatland. However, the impact of fine root invasion by Rhododendron auriculatum Hemsl. on Sphagnum decomposition and changes in phenolic compounds remains unclear. This study compared Sphagnum decomposition in a Sphagnum palustre L.-dominated peatland and an R. auriculatum (Sapling)–S. palustre peatland by examining the microscopic structure of S. palustre and microbial community composition. Decomposition was higher in the R. auriculatum–S. palustre peatland. On this site, bacterial metabolic types such as aerobic chemoheterotrophy and chemoheterotrophy had higher relative abundances, as did fungal trophic modes, including those with combined ectomycorrhizal, ericoid mycorrhizal, and saprotrophic functions. Acid phosphatase, laccase, total nitrogen (TN), C/N ratio (C:N), and pH differed significantly across decomposition stages. Microbial communities are affected by physicochemical factors and enzyme activities. Untargeted metabolomics revealed more downregulated than upregulated phenolics, cinnamic acids, and tannins, indicating loss of phenolic compounds. In summary, R. auriculatum fine root invasion altered enzyme activities and physicochemical properties, driving the restructuring of bacterial and fungal trophic modes and accelerating S. palustre cell wall and hyaline cell decomposition. Full article

Spi-1 Proto-Oncogene (SPI1) encodes Purine-rich box 1 Transcription Factor (PU.1), a transcription factor of the ETS family that regulates hematopoietic lineage commitment and immune cell differentiation. Alteration of PU.1 dose or ETS domain integrity may interfere with transcriptional programs, which adds to hematopoietic dysregulation and leukemogenesis. Even though changes in SPI1 expression have been associated with acute myeloid leukemia (AML), the structural and regulatory effects of missense mutations at the PU.1 ETS domain have not been entirely studied, and targeting the PU.1 ETS domain by ligands is an area of computational analysis that should be further pursued. To computationally describe deleterious missense variants of SPI1 in terms of structural stability, evolutionary conservation, post-translational modification (PTM) context and interaction networks, and to measure ADMET-mediated molecular docking of cinnamic acid with the PU.1 ETS domain (8EQG) as a potential modulator. Missense nsSNPs were obtained through Ensembl and narrowed down by consensus prediction of pathogenicity (PredictSNP, combining SIFT, PolyPhen, SNAP and PhD-SNP and other tools). InterPro/UniProt was used for domain mapping. SWISS-MODEL was used to produce wild-type and mutant PU.1 versions, which were analyzed on the structural alignment and Cα–Cα displacement parameters in UCSF Chimera (v1.19). The estimation of stability change was carried out with I-Mutant and MUpro. Prediction of PTM sites was done using MusiteDeep and exploration of functional partners was done using STRING. Human, mouse and zebrafish orthologue conservation was measured by means of MAFFT alignment. GEPIA2 was used to compare the expression of SPI1 in AML (TCGA-LAML) and normal tissues (GTEx). AutoDock Vina (grid center 6, −2, −9 A; 20 × 20 × 20 A; 16 exhaustiveness) was used to prepare cinnamic acid and dock it into the PU.1 ETS domain (8EQG), with SwissDock being used for consistency checks. SwissADME and ADMETlab 2.0 were used to predict drug-likeness, pharmacokinetics, and toxicity. Nine missense mutations were routinely considered as deleterious with the majority of them being located in or near the ETS DNA-binding domain. Structural comparisons showed local perturbations of the structure and I189F and H211P yielded the greatest conformational changes between prioritized variants whereas other forms had minimal movements. A predominantly destabilizing trend was supported by stability prediction whereby V241G had the strongest destabilization signal with further destabilizations being predicted in I189F and R259C. PTM mapping revealed several potential regulatory residues (phosphorylation, acetylation, ubiquitination, and methylation), which indicated that there could be crosstalk between the sequence variation and the transcriptional regulation. The SPI1 was placed in a central hematopoietic transcriptional module (containing RUNX1, CEBP members, GATA1 and IRF factors) by the STRING network. The cross-species alignment showed that there was high conservation of a number of the mutation sites, which would support functional constraint at the ETS region. The expression analysis revealed that the level of SPI1 mRNA in AML was significantly elevated compared to normal tissues. Docking also indicated a slight and reproducible interaction of cinnamic acid with the ETS domain (top affinity −4.27 kcal/mol), with a solitary leading polar anchor and supportive hydrophobic interactions, which is akin to interaction between fragments. The ADMET profiling revealed the likelihood of success in the oral drug-likeness and low CYP inhibition liability, as well as signifying the presence of a possible hepatotoxicity signal that needs further confirmation through experiments. Comprehensive computational studies suggest that certain pathogenic variants of SPI1 missense defects, especially in the ETS domain, can result in loss of PU.1 structural stability and regulatory environment, which are in line with the disturbed hematopoietic regulation and AML-related dysregulation. Cinnamic acid demonstrates moderate yet reproducible binding to the PU.1 ETS domain and has an overall favorable developability profile, which indicates that it is better considered as a starting scaffold, as opposed to an active inhibitor. The results give a logical basis of focused biochemical validation and structure-directed optimization of ETS domain modulators in hematologic disease settings. Full article

The first optimal and suitable synthetic route was developed to obtain the natural product 1,3-dibehenyl-2-ferulyl glyceride (1) in four reaction steps with an overall yield of 23%. Additionally, a collection of ten derivatives of the natural product was prepared with similar reaction yields. Compound 19 showed potent antioxidant activity through the DPPH assay with an inhibition higher than 95% (IC₅₀ 17.58 ± 0.45 µM). Furthermore, its characterization using ¹H NMR, ¹³C NMR, IR and MS techniques is presented. This work is relevant because it addresses the need for a natural product with very low availability and that comes from an endangered species. The compounds feature a conjugated lipid–drug structure, with cinnamic, caffeic and ferulic acids in the pharmacologically active portion, making its evaluation in biological tests of great interest. Full article

Globba bicolor Gagnep., an ornamental ginger of cultural importance in Thailand’s “Tak Bat Dok Mai” festival, faces conservation challenges due to climate change and slow natural propagation. Limited understanding of its cultivation and chemical composition further constrains sustainable utilization. This study provides the first integrated investigation of micropropagation using rhizome-derived explants under various combinations of exogenous hormones, acclimatization strategies, and comparative phytochemical profiling between wild and in vitro-propagated plants. An optimized clonal regeneration system was established from plantlets, with Murashige and Skoog (MS) medium containing 2.0 mg/L 6-benzylaminopurine (BA) and 0.5 mg/L 1-naphthaleneacetic acid (NAA), yielding the highest multiplication (9.10 shoots/explant and 12.40 roots/explant) after eight weeks of cultivation. During acclimatization, sand substrate proved superior, facilitating a 90% survival rate and enhanced physiological vigor. Comparative analysis revealed that while wild plants possessed significantly higher total phenolic (TPC) and total flavonoid (TFC) contents and antioxidant activities (DPPH, ABTS, and FRAP) than their in vitro counterparts, both sources maintained a rich diversity of chemical constituents. HPLC analysis identified cinnamic acid, rutin, and quercetin as major metabolites, while GC–MS detected 90 volatile compounds, with β-caryophyllene and β-pinene as predominant constituents. Notably, rhizomes of wild plants exhibited particularly high-value detections. To provide a rapid and non-destructive approach for linking chemical composition with antioxidant activity, FTIR-based chemometric models were applied, demonstrating high predictive accuracy (R²–cv = 0.9712–0.9862). These results provide a scientific foundation for the conservation and sustainable commercial utilization of G. bicolor as a potential source of bioactive natural products. Full article

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, with advanced stages potentially progressing to hepatocellular carcinoma. It is a multifactorial condition associated with metabolic syndrome, diabetes, and hormonal imbalance, leading to metabolic alterations that are intensified by inflammation. An important additional factor that amplifies these effects is oxidative stress, which interacts with inflammatory pathways and contributes to disease progression. This review evaluates evidence from in vitro, in vivo, and clinical studies on widely investigated natural compounds, including cinnamic acid, stilbene and quinone derivatives, coumarinoids, tannins, and miscellaneous phenol-containing compounds and alkaloids, focusing on their antioxidant, anti-inflammatory and multi-functional properties. These compounds have demonstrated beneficial effects such as reduction of lipid accumulation, improvement of insulin resistance, modulation of inflammatory cytokines (e.g., TNF-α, IL-6), and attenuation of oxidative stress markers, with several studies reporting improvements in liver enzymes and histological features of steatosis. The aim is to assess their potential to improve NAFLD beyond their established biological activities and to explore their repositioning potential as multi-targeted agents for complementary or second-line therapeutic strategies. Their plant-derived origin and broad therapeutic profiles suggest a favorable safety margin. However, further well-designed clinical studies are required to better define their efficacy, optimal dosing, pharmacokinetics and safety, as well as to clarify their mechanisms of action and their potential role in NAFLD management. Full article

Poly(amidoamine) (PAMAM) dendrimers are widely recognized as versatile nanocarriers due to their tunable architecture and ability to associate with bioactive molecules. In this study, generation 3 PAMAM dendrimers functionalized with triphenylphosphonium (TPP) were employed to investigate the association of structurally related phenolic compounds—caffeic acid, p-coumaric acid, and cinnamic acid—through either covalent conjugation or non-covalent encapsulation. Physicochemical characterization by NMR, dynamic light scattering, and zeta potential measurements revealed the formation of supramolecular aggregates rather than isolated dendrimer units, with hydrodynamic diameters ranging from 127 to 260 nm and positive surface charge across all formulations. Encapsulation efficiencies determined by HPLC reached 93.8% for caffeic acid, 78.9% for p-coumaric acid, and 71% for cinnamic acid, indicating differential association behavior. Molecular dynamics simulations over 1 μs supported these findings, showing stronger and more stable interactions for polar antioxidants, particularly caffeic acid, driven by hydrogen bonding and electrostatic interactions, while cinnamic acid displayed preferential binding in more hydrophobic dendrimer regions. Radical scavenging assays (DPPH• and ABTS•+) demonstrated that all formulations retained antioxidant capacity, although dendrimer association modulated scavenging kinetics. In cellular assays under oxidative stress, free caffeic acid exhibited the strongest immediate reduction of intracellular reactive oxygen species, whereas dendrimer-associated systems showed reduced but significant activity, consistent with decreased solvent accessibility and slower release predicted by simulations. Overall, these results highlight a trade-off between molecular retention and immediate biological efficacy, demonstrating that the mode of association governs antioxidant accessibility and performance. This combined experimental and computational approach provides a mechanistic framework for the rational design of dendrimer-based delivery systems aimed at balancing stability and functional activity. Full article