Search Results (716)

Functional foods like flax (Linum usitatissimum L.) are rich sources of specialized metabolites that contribute to their nutritional and health-promoting properties. Understanding the biosynthesis of these compounds is essential for improving their quality and potential applications. However, dissecting complex metabolic networks in plants remains challenging due to the dynamic nature and interconnectedness of biosynthetic pathways. In this study, we present a synergistic approach combining stable isotopic labeling (SIL), Candidate Substrate–Product Pair (CSPP) networks, and a time-course study with high temporal resolution to reveal the biosynthetic fluxes shaping phenylpropanoid metabolism in young flax seedlings. By feeding the seedlings with ¹³C₃-p-coumaric acid and isolating isotopically labeled metabolization products prior to the construction of CSPP networks, the biochemical validity of the connections in the network was supported by SIL, independent of spectral similarity or abundance correlation. This method, in combination with multistage mass spectrometry (MSⁿ), allowed confident structural proposals of lignans, neolignans, and hydroxycinnamic acid conjugates, including the presence of newly identified chicoric acid and related tartaric acid esters in flax. High-resolution time-course analyses revealed successive waves of metabolite formation, providing insights into distinct biosynthetic fluxes toward lignans and early lignification intermediates. No evidence was found here for the involvement of chlorogenic or caftaric acid intermediates in chicoric acid biosynthesis in flax, as has been described in other species. Instead, our findings suggest that in flax seedlings, chicoric acid is synthesized through successive hydroxylation steps of p-coumaroyl tartaric acid esters. This work demonstrates the power of combining SIL and CSPP strategies to uncover novel metabolic routes and highlights the nutritional potential of flax sprouts rich in chicoric acid. Full article

News recommendation systems must simultaneously address multiple challenges, including dynamic user interest modeling, nonlinear popularity patterns, and diversity recommendation in cold-start scenarios. We present a Popularity-Aware Dynamic Multi-Perspective Fusion Network (PAD-MPFN) that innovatively integrates three key components: adaptive subspace projection for multi-source interest fusion, logarithmic time-decay factors for popularity bias mitigation, and dynamic gating mechanisms for personalized recommendation weighting. The framework uniquely combines sequential behavior analysis, social graph propagation, and temporal popularity modeling through a unified architecture. Experimental results on the MIND dataset, an open-source version of MSN News, demonstrate that PAD-MPFN outperforms existing methods in terms of recommendation performance and cold-start scenarios while effectively alleviating information overload. This study offers a new solution for dynamic interest modeling and diverse recommendation. Full article

To address critical technical challenges in coalbed methane fracturing, including the uncontrollable release rate of conventional breaker agents and incomplete gel breaking, this study designs and fabricates an intelligent controlled-release breaker system based on paraffin-coated mesoporous silica nanoparticle carriers. Three types of mesoporous silica (MSN) carriers with distinct pore sizes are synthesized via the sol-gel method using CTAB, P123, and F127 as structure-directing agents, respectively. Following hydrophobic modification with octyltriethoxysilane, n-butanol breaker agents are loaded into the carriers, and a temperature-responsive controlled-release system is constructed via paraffin coating technology. The pore size distribution was analyzed by the BJH model, confirming that the average pore diameters of CTAB-MSNs, P123-MSNs, and F127-MSNs were 5.18 nm, 6.36 nm, and 6.40 nm, respectively. The BET specific surface areas were 686.08, 853.17, and 946.89 m²/g, exhibiting an increasing trend with the increase in pore size. Drug-loading performance studies reveal that at the optimal loading concentration of 30 mg/mL, the loading efficiencies of n-butanol on the three carriers reach 28.6%, 35.2%, and 38.9%, respectively. The release behavior study under simulated reservoir temperature conditions (85 °C) reveals that the paraffin-coated system exhibits a distinct three-stage release pattern: a lag phase (0–1 h) caused by paraffin encapsulation, a rapid release phase (1–8 h) induced by high-temperature concentration diffusion, and a sustained release phase (8–30 h) attributed to nano-mesoporous characteristics. This intelligent controlled-release breaker demonstrates excellent temporal compatibility with coalbed methane fracturing processes, providing a novel technical solution for the efficient and clean development of coalbed methane. Full article

Background: Sirolimus (SRL, rapamycin) is a clinically important mTOR inhibitor used in immunosuppression, oncology, and cardiovascular drug-eluting devices. Despite its long-standing FDA approval, the human metabolic profile of SRL remains incompletely characterized. SRL is primarily metabolized by CYP3A enzymes in the liver and intestine, but the diversity, pharmacokinetics, and biological activity of its metabolites have been poorly explored due to the lack of structurally identified standards. Methods: To investigate SRL metabolism, we incubated SRL with pooled human liver microsomes (HLM) and isolated the resulting metabolites. Structural characterization was performed using high-resolution mass spectrometry (HRMS) and ion trap MSⁿ. We also applied Density Functional Theory (DFT) calculations to assess the energetic favorability of metabolic transformations and conducted molecular dynamics (MD) simulations to model metabolite interactions within the CYP3A4 active site. Results: We identified 21 unique SRL metabolites, classified into five major structural groups: O-demethylated, hydroxylated, didemethylated, di-hydroxylated, and mixed hydroxylated/demethylated derivatives. DFT analyses indicated that certain demethylation and hydroxylation reactions were energetically preferred, correlating with metabolite abundance. MD simulations further validated these findings by demonstrating the favorable orientation and accessibility of key sites within the CYP3A4 binding pocket. Conclusions: This study provides a comprehensive structural map of SRL metabolism, offering mechanistic insights into the formation of its metabolites. Our integrated approach of experimental and computational analyses lays the groundwork for future investigations into the pharmacodynamic and toxicodynamic effects of SRL metabolites on the mTOR pathway. Full article

Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due to its systemic toxicity, immunogenicity, poor in vivo stability, and short half-life. These challenges can be addressed through nanotechnology; in particular, biogenic mesoporous silica nanoparticles (MSNs) offer promise as drug delivery systems (DDSs) that enhance therapeutic efficacy while minimizing side effects. Methods: Biogenic MSNs were extracted from the Equisetum myriochaetum plant via acid digestion, functionalized with 3-aminopropiltrietoxysilane (APTES) and glutaraldehyde (GTA), and loaded with GOx. The free and immobilized MSNs were characterized using FTIR, DLS, XRD, SEM/EDX, and BET techniques. A colorimetric approach was employed to quantify the enzymatic activity of both the free and immobilized GOx. The MTT assay was employed to assess the viability of SKOV3 cells. The obtained IC₅₀ concentration of the nanoformulation was administered to SKOV3 cells to analyze the expression of cancer-related genes using RT-qPCR. Results: IC₅₀ values of 60.77 ng/mL and 111.6 µg/mL were ascertained for the free and immobilized GOx, respectively. Moreover, a significant downregulation of the oncogene β-catenin (CTNNB1) was detected after 24 h with the nanoformulation. Conclusions: Our findings indicate that GOx-loaded biogenic MSNs may serve as a potential therapeutic agent for ovarian cancer. This is, to the best of our knowledge, the first report exploring the effect of GOx-loaded biogenic MSNs on SKOV3 cells. Full article

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid (MSN-CAF) on powder flow properties and their tableting performance. Aminated MSNs were synthesized via co-condensation and conjugated with caffeic acid using EDC/NHS chemistry. Antioxidant capacity was evaluated using DPPH^●, ABTS^●+, ORAC, and FRAP assays. Powder blends with varying MSN-CAF concentrations (10–70%) were characterized for flow properties (angle of repose, Hausner ratio, Carr’s index), tablets were produced via direct compression, and critical quality attributes (weight uniformity, hardness, friability, disintegration, nanoparticle release) were assessed. MSN-CAF exhibited reduced antioxidant capacity compared with free caffeic acid due to pore entrapment but retained significant activity. Formulation F1 (10% MSN-CAF) showed excellent flowability (angle of repose: 12°, Hausner ratio: 1.16, Carr’s index: 14%), enabling robust tablet production with rapid disintegration, low friability, and complete nanoparticle release in 10 min. Additionally, the antioxidant nanomaterial demonstrated biocompatibility with the HepG2 cell line. MSN-CAF is a versatile nanoexcipient for direct compression tablets, offering potential as an active packaging agent and delivery system in the nutraceutical and food industries. Full article

Multistatic sonar networks (MSNs) have emerged as a powerful approach for enhancing underwater surveillance capabilities. Different from monostatic sonar systems which use collocated sources and receivers, MSNs consist of spatially distributed and independent sources and receivers. In this work, we address the problem of determining the optimal route for a mobile multistatic active sonar source to maximize area coverage, assuming all receiver locations are known in advance. For this purpose, we first develop a Mixed Integer Linear Program (MILP) formulation that determines the route for a single source within a field discretized using a hexagonal grid structure. Next, we propose an Ant Colony Optimization (ACO) heuristic to efficiently solve large problem instances. We perform a series of numerical experiments and compare the performance of the exact MILP solution with that of the proposed ACO heuristic. Full article

The phytochemical investigation and evaluation of the antioxidant activity of the leaves, bark, and roots of Cochlospermum angolense Welw ex Oliv—a valued plant that is widely used in traditional Angolan medicine—hold significant importance. Compounds were extracted from the aforementioned plant using acetone and ethanol and identified by HPLC-ESI-MSn. Both extracts demonstrated notable abilities to scavenge 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and superoxide radicals, as well as to inhibit lipid peroxidation. A HPLC analysis revealed a diverse array of bioactive compounds, including flavonoids, phenols, alkaloids, quinones, and terpenes, which help neutralize free radicals and protect cells against oxidative stress, thereby contributing to the prevention of various diseases. Moreover, the acetone and ethanol extracts proved to be excellent sources of antioxidants. For the first time, the present study identified new compounds never reported in this species, such as (+)-abscisic acid, angustine B, pinobanksin, dihydrogenistein, (−)-8-prenylnaringenin, isoquercetin, samandarine, dihydromyricetin, and eupatoriocromene, in the leaves, bark, and roots, marking a significant advance in the chemical characterization of C. angolense. These findings enhance our understanding of the bioactive phytochemicals and antioxidant properties of C. angolense and open new avenues for future therapeutic and pharmacological research, further supporting its traditional use in Angolan medicine. Full article

Mesoporous silica nanoparticles (MSNs) are gaining popularity in nanomedicine due to their large surface area, variable pore size, great biocompatibility, and chemical adaptability. In recent years, the combination of smart polymeric materials with MSNs has transformed the area of regulated drug administration, particularly under stimuli-responsive settings. Polymer-modified MSNs provide increased stability, longer circulation times, and, most crucially, the capacity to respond to diverse internal (pH, redox potential, enzymes, and temperature) and external (light, magnetic field, and ultrasonic) stimuli. These systems allow for the site-specific, on-demand release of therapeutic molecules, increasing treatment effectiveness while decreasing off-target effects. This review presents a comprehensive analysis of recent advancements in the development and application of polymer-functionalized MSNs for stimuli-triggered drug delivery. Key polymeric modifications, including thermoresponsive, pH-sensitive, redox-responsive, and enzyme-degradable systems, are discussed in terms of their design strategies and therapeutic outcomes. The synergistic use of dual or multiple stimuli-responsive polymers is also highlighted as a promising avenue to enhance precision and control in complex biological environments. Moreover, the integration of targeting ligands and stealth polymers such as PEG further enables selective tumor targeting and immune evasion, broadening the potential clinical applications of these nanocarriers. Recent progress in stimuli-triggered MSNs for combination therapies such as chemo-photothermal and chemo-photodynamic therapy is also covered, emphasizing how polymer modifications enhance responsiveness and therapeutic synergy. Finally, the review discusses current challenges, including scalability, biosafety, and regulatory considerations, and provides perspectives on future directions to bridge the gap between laboratory research and clinical translation. Full article

Carpesium cernuum L., the most widespread representative of the genus Carpesium, has been traditionally used in some regions of Asia as a remedy for various ailments or as a vegetable. Although the plant is distributed in Europe, there is no data on its medicinal use in this part of the world. The chemical composition of European Carpesium cernuum L. has remained unknown until now, except for the compositions of essential oils distilled from the roots and aerial parts of the plant. Polyphenolic profiles of hydroalcoholic extracts from C. cernuum were studied using the HPLC-MSⁿ technique. The analysis revealed the presence of 24 hydroxycinnamates, which were dominated by caffeoylquinic and caffeoylhexaric acids. Moreover, fractionation of the chloroform extracts from the plant led to the isolation of three new compounds, 8α-angeloyloxy-4β-hydroxy-5β-(3-methylbutyryloxy)-9-oxo-germacran-6α,12-olide, 9β-angeloyloxy-4β,8α-dihydroxy-5β-(3-methylbutyryloxy)-3-oxo-germacran-6α,12-olide, and a dihydrobenzofuran derivative, together with twelve known compounds. 8-Hydroxy-9,10-diisobutyryloxythymol, a monoterpenoid thymol derivative from the roots of the plant, was evaluated for potential neuroprotective and cytotoxic activities using differentiated and undifferentiated SH-SY5Y neuroblastoma cells. At a concentration range of 1–10 μM, the compound provided partial (up to 50%) protection against H₂O₂-induced cell damage in the undifferentiated cells. At concentrations higher than 25 μM, the monoterpenoid significantly reduced the viability of the cells (IC₅₀: 65.7 μM for the undifferentiated cells and 40.9 μM for the differentiated cells). Full article

Mesoporous silica nanoparticles (MSNs) functionalized with silane quaternary ammonium compounds (SiQACs) were synthesized and utilized as carriers for thymus essential oil (TO), a green bio-antifouling agent. The synthesis of MSNs functionalized with SiQACs was carried out in a single step, with clear advantages in terms of simplicity of the process, high yield (94%) and saving of reagents and solvents for the MSN purification. After loading with TO, this innovative dual-action antifouling system was able to integrate the intrinsic biocidal properties of SiQACs with the release of TO from MSN pores, resulting in an engineered material with prolonged efficacy. The antifouling compounds incorporated into the nanoparticles accounted for 42% of the total weight. The biocidal performance was evaluated by monitoring the growth inhibition of Chlorella sorokiniana, a microalga commonly associated with stone biodeterioration. Additionally, these nanoparticles were embedded in a commercial silane-based protective coating and applied to tuff stone samples to assess their ability to mitigate biofilm formation over extended periods. Results demonstrated the system’s high potential for durable protection against microbial colonization and biofilm growth on stone surfaces. Full article

The incidence of fungal infections is significantly rising, posing a challenge due to the limited class of antifungal drugs. There is a necessity to combat emerging resistant fungal infections by developing novel antifungal agents. This study aimed to evaluate the antifungal effects of lawsone (LAW), a natural component extracted from herbal medicine, and LAW-loaded mesoporous silica nanoparticles (LAW-MSNs) on growth, biofilm formation, and expression of ALS1 and EPA1 genes contributing to cell adhesion of Candida spp. Twenty C. albicans and twenty C. glabrata isolates, including ten fluconazole-resistant and ten fluconazole-susceptible isolates, were examined. The findings of the study indicated that LAW and LAW-MSNs inhibited Candida isolates growth at MIC range of 0.31–>5 µg/mL and significantly reduced biofilm formation in C. albicans and C. glabrata. Moreover, both LAW and LAW-MSNs downregulated the expression of the adhesion genes ALS1 and EPA1 in C. albicans and C. glabrata. Based on the obtained findings, LAW emerged as a promising antifungal candidate. However, the nano-formulation (LAW-MSNs) improved its antifungal properties. Full article

Background/Objectives: The absence of standardized protocols for assessing in vitro drug release from nanocarriers poses significant challenges in nanoformulation development. This study evaluated three in vitro methods: sample and separate without medium replacement (independent batch), sample and separate with medium replacement, and a dialysis bag method, to characterize the release of rhodamine B from mesoporous silica nanoparticles (MSNs). Methods: Each method was examined under varying agitation conditions (shaking versus stirring). MSNs were synthesized via the sol-gel method, exhibiting a hydrodynamic diameter of 202 nm, a zeta potential of −23.5 mV, and a surface area of 688 m²/g, with a drug loading efficiency of 32.4%. Results: Release profiles revealed that the independent batch method exhibited a rapid initial burst followed by a plateau after 4 h, attributed to surface saturation effects. Conversely, the sample and separate with medium replacement method sustained the release up to 60% over 48 h, maintaining sink conditions. The dialysis method showed agitation-dependent variability, with magnetic stirring using a longer stir bar enhancing release. Kinetic analyses indicated first-order kinetics with non-Fickian diffusion. Conclusions: Overall, the results indicate that both the selection of the in vitro method and the agitation technique play a crucial role in determining the apparent drug release kinetics from nanocarriers. These findings highlight the critical role of experimental design in interpreting nanocarrier release kinetics, advocating for tailored protocols to improve reproducibility and in vitro–in vivo correlations in nanoformulation. Full article

(1) Background: The chorioallantoic membrane (CAM) model has the potential to contribute to the development of personalized medicine based on individual cancer patients. We previously established the CAM model using patient-derived CIC-DUX4 sarcoma cells. We also used the CAM model for characterization and a comparison with the mouse model by examining the tumor accumulation of small-size, highly dispersive mesoporous silica nanoparticles (MSNs). (2) Method: In this study, we transplanted a variety of cancer cell lines, including patient-derived osteosarcoma (OS) and extraskeletal osteosarcoma (ESOS) cells. Patient-derived OS, ESOS and other cell lines were transplanted onto CAMs. The proliferation of cancer cells within CAM tumors was confirmed using H&E staining. For the comparison of the CAM and mouse models, rhodamine B-labeled MSNs were administered intravenously to CAMs and to xenograft mice. Tumor accumulation was evaluated by examining fluorescence and by confocal microscopy. The biodistribution of MSNs was examined by measuring the Si content by ICP. (3) Results: H&E staining demonstrated the proliferation of cancer cells of OS, ESOS and others on CAMs. While growth patterns and morphologies varied among different cancer types, H&E staining confirmed the establishment of tumors. As for the tumor accumulation, both the CAM and mouse models showed that MSNs were selectively accumulated in the tumors in both the CAM and mouse models. (4) Conclusions: We have expanded the range of CAM models by using a variety of cancer cells, including patient-derived cell lines. We also report that the small-size, highly dispersive MSNs exhibit excellent tumor accumulation in both the CAM and mouse models. These results point to the usefulness of the CAM model for patient-derived cancer cells as well as for evaluating drug carriers for tumor targeting. Full article

This study developed a microporous silica nanosilver antioxidant material (GT-Ag@MSN) from waste photovoltaic (PV) cells by incorporating plant polyphenols in the in situ synthesis. The biosynthesized GT-Ag@MSN had an average size of 296.5 nm, a pore size of 1.96 nm, and an Ag loading of 1.45%. The material was further evaluated through antibacterial tests, antioxidant capacity tests, and a reducing power assay. GT-Ag@MSN exhibited a minimum inhibitory concentration (MIC) of 20 mg/mL for Escherichia coli and Staphylococcus aureus, and a minimum bactericidal concentration (MBC) of 50 mg/mL for both of them, which will need further efforts to improve the performance. However, GT-Ag@MSN exhibited a notable 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging ability of 74.7 ± 1.6% at a concentration of 250 μg/mL, and its reducing power in the range of 10–100 mg was greater than that of ascorbic acid at 10–100 μg/mL. This study proposes a new waste-to-wealth strategy that utilizes purified silicon and silver from recycling used PV modules, encouraging the advancement of PV waste recycling and reuse technology. Full article