Search Results (100)

Background/Objectives: The poor aqueous solubility of curcumin (CUR) limits its pharmaceutical application. Although amorphization can enhance its solubility, the amorphous form often exhibits insufficient physical stability. Co-amorphization, particularly drug–drug co-amorphous (CAM) formation, offers a promising approach to improve solubility, stability, and therapeutic efficacy. This study aimed to prepare and evaluate two CUR-based CAM systems using isoquinoline alkaloids berberine hydrochloride (BER) and palmatine hydrochloride (PAL) as co-formers to achieve simultaneous stabilization and synergistic bioactivity. Methods: CUR-BER and CUR-PAL CAM systems were prepared via rotary evaporation under vacuum at a 1:1 molar ratio. The solid-state properties were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and ¹³C solid-state nuclear magnetic resonance spectroscopy (ssNMR). Dissolution, solubility, and stability studies were conducted, while antioxidant and anticancer activities were assessed by DPPH/ABTS⁺ radical-scavenging and MTT assays using HT-29 colorectal cancer cells. Results: PXRD and DSC confirmed the formation of single-phase amorphous systems with higher glass transition temperatures, indicating strong intermolecular interactions between CUR and BER/PAL. ¹³C ssNMR spectroscopy evidenced hydrogen-bond formation between the enolic hydroxyl moiety of CUR and the methoxy oxygen atoms in BER or PAL molecules. Both CAM systems significantly enhanced the solubility and dissolution rate of CUR, with CUR-PAL CAM showing up to a 15.1-fold solubility improvement. The CAM systems also displayed superior thermal stability, photolytic stability, and improved short-term humidity resistance, together with enhanced antioxidant and anticancer activities compared with pure amorphous CUR. Conclusions: Co-amorphization of CUR with isoquinoline alkaloids effectively improved solubility, stability, antioxidant and anticancer activities, representing a promising strategy for the rational design of multifunctional amorphous CUR-based drug formulations. Full article

Background/Objectives: Recurrent oral ulceration (ROU) is the most prevalent disorder of the oral mucosa, affecting approximately 20% of the global population. Current therapies are limited by adverse effects and high recurrence rates. Ai-Fen, enriched in the anti-inflammatory monoterpenoid L-borneol (54.3% w/w), exhibits therapeutic potential but suffers from poor aqueous solubility and low bioavailability. This study aimed to improve the physicochemical properties and in vivo efficacy of Ai-Fen through the preparation of solid dispersions. Methods: Ai-Fen solid dispersions (AF-SD) were prepared by a melt-fusion method using polyethylene glycol 6000 (PEG 6000) as the carrier. An L₉(3³) orthogonal design was employed to optimize three critical parameters: drug-to-carrier ratio, melting temperature, and melting duration. The resulting dispersions were systematically characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR). A chemically induced ROU model in rats (n = 8 per group) was established to evaluate the effects of AF-SD on ulcer area, serum inflammatory cytokines (TNF-α, IL-6), vascular endothelial growth factor (VEGF) levels, and histopathological outcomes. Results: The optimal formulation was obtained at a drug-to-carrier ratio of 1:2, a melting temperature of 70 °C, and a melting time of 5 min. Under these conditions, L-borneol release increased 2.5-fold. DSC and PXRD confirmed complete conversion of Ai-Fen to an amorphous state, while FTIR revealed a 13 cm⁻¹ red shift in the O-H stretching band, indicating hydrogen-bond formation. In vivo, AF-SD reduced ulcer area by 60.7% (p < 0.001) and achieved a healing rate of 74.16%. Serum TNF-α and IL-6 decreased by 55.5% and 49.6%, respectively (both p < 0.001), whereas VEGF increased by 89.6% (p < 0.001). Histological analysis confirmed marked reduction in inflammatory infiltration, accelerated re-epithelialization (score 2.50), and a 5.9-fold increase in neovascularization. Conclusions: AF-SD markedly enhanced the bioavailability of Ai-Fen through amorphization and accelerated ROU healing, likely via dual mechanisms involving suppression of nuclear factor kappa-B (NF-κB)-mediated inflammation and promotion of angiogenesis. This formulation strategy provides a promising approach for modernizing traditional herbal medicines. Full article

The issue of antibiotic resistance is becoming increasingly severe, urgently requiring the development of new antibacterial strategies. Photodynamic therapy (PDT) has gradually emerged as a promising alternative due to its spatiotemporal controllability, low risk of drug resistance, and broad-spectrum antibacterial properties. However, most existing photosensitizers (PSs) are hydrophobic, which limits their application efficiency in PDT. To address this problem, we designed and synthesized a water-soluble perylene diimide derivative (PDICN-CBn) as a photosensitizer. By introducing quaternary ammonium salt groups, its water solubility was improved, and antibacterial activity was enhanced. Subsequently, PDICN-CBn was assembled into silk fibroin/polylactic acid (SF/PLA) nanofibrous membranes via electrospinning technology, successfully constructing a visible-light-responsive ternary composite nanofibrous membrane (SF/PLA@PDICN-CBn). Using various characterization methods such as nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM), the microstructure, chemical composition, and structural characteristics of the nanofibrous membranes were systematically analyzed, verifying the successful synthesis of the photosensitizer and its assembly into the nanofibrous membranes. In the reactive oxygen species (ROS) experiment, electron spin resonance (ESR) spectra showed that PDICN-CBn efficiently generated singlet oxygen (¹O₂), superoxide anion (·O₂⁻), and hydroxyl radical (·OH) under visible light irradiation, confirming its ability to produce different types of ROS through both type I and type II photodynamic reactions. In the antibacterial experiments, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA) were selected for a series of tests, including plate-counting antibacterial assays, bacterial live/dead staining, and SEM observation of morphology. The results showed that 8 μg/mL of PDICN-CBn effectively destroyed the bacterial cell membrane structure and killed bacteria (bactericidal rate > 95%) after 2 h of visible light irradiation. This work successfully developed a novel visible-light-responsive SF/PLA@PDICN-CBn nanofibrous membrane with a dual antibacterial system combining photodynamic and electrostatic adsorption antibacterial properties, providing new ideas and methods for the design and development of photodynamic antibacterial materials. The prepared nanofibrous membrane has potential application values in fields such as wound dressings and medical protective materials and is expected to provide strong support for solving clinical infection problems. Full article

The low flexural strength and high brittleness of cement-based materials greatly compromise their safety, durability, and service life. In situ polymerization is a promising strategy for enhancing the toughness of cement-based materials. However, the underlying mechanisms responsible for this mechanical improvement remain insufficiently understood. This study introduces acrylamide (AM) monomer into a cement matrix, where in situ polymerization forms a strong polymer–cement network, demonstrably enhancing mechanical performance. The factors influencing this mechanical enhancement were investigated across multiple scales using techniques including nanoindentation, crack width measurement, solid-state silicon nuclear magnetic resonance (²⁹Si NMR), thermogravimetric analysis (TGA), and so on. This research confirms that in situ polymerization influences silicate chain length (from 3.405 to 3.714) and pore structure at the nanoscale, modifies the morphology of hydration products, enhances the hardness of the interfacial transition zone (0.025 ± 0.002 to 0.055 ± 0.004 GPa) at the microscale, and reveals that at monomer concentrations below 1 wt%, both the compressive and flexural strengths of the cement-based material are improved, with 28d compressive and flexural strength increasing by 23.86% and 26.58%, respectively. Conversely, higher monomer dosages lead to a simultaneous reduction in both compressive and flexural strengths. Consequently, through tracking the hydration process on the mechanical properties of cement-based materials across multiple scales, this study provides deeper insights into the in situ polymerization system and offers an effective strategy for the design and preparation of high-performance concrete. Full article

Stelechocarpus burahol (kepel) is valued for its aromatic fruits and medicinal leaves, yet its genomic and phytochemical features remain poorly characterized. This study estimated the nuclear DNA content of kepel leaves at 3.96 pg per haploid genome (genome size: 3873 Mbp) and comprehensively profiled their bioactive metabolites. Leaf extracts prepared with water and 70% ethanol, with or without pulsed electric field (PEF) treatment, were analyzed using HPLC-MS, UHPLC-QTOF-MS, HPLC-DAD, and GC-MS. Leaf extracts showed the highest phenolic and flavonoid contents, with PEF markedly improving ethanolic extraction efficiency. A total of 72 phenolics, 2 tocopherols, 3 tocotrienols, and several novel vitamin E derivatives were detected, alongside abundant catechins, tannic acid, and gallic acid. PEF significantly enhanced catechin recovery: catechin (C) increased from 153.7 to 846.8 mg/g and epicatechin (EC) from 338.2 to 921.4 mg/g in water extracts, while ethanolic extracts rose from 335.3 to 905.1 mg/g (C) and 245.0 to 616.9 mg/g (EC). Epigallocatechin 3-gallate (EGCG), absent in untreated leaves, reached 799.9 mg/g in water and 231.9 mg/g in ethanol extracts after PEF. In fruits, PEF reduced phenolic recovery in water extracts (C: 236.7 → 136.8 mg/g; EC: 135.4 → 118.2 mg/g; EGCG: 2892.2 mg/g → undetectable), but slightly improved ethanolic extracts (C: 237.8 → 289.4 mg/g). GC-MS identified 19 volatile compounds contributing to the fruit’s aroma. This work provides the first integrated report of kepel genome size and phytochemical composition, highlighting PEF as a promising strategy to enhance leaf catechin extraction and supporting kepel’s potential as a functional food and medicinal resource. Full article

An integrated microalgae biorefinery producing high-purity xanthophylls using a sustainable and efficient strategy still faces critical challenges. In this study, the microalga Amphidinium carterae can accumulate peridinin and diadinoxanthin cycle carotenoids. Notably, valorization of wet A. carterae using integrated preparation of peridinin and diadinoxanthin cycle carotenoids was developed, containing four main steps including microalgae cultivation, solvent extraction, octadecylsilyl open-column chromatography, and ethanol precipitation for the first time. Under the optimum integrated preparation conditions, the purities of obtained peridinin, diadinoxanthin, and diatoxanthin were all more than 95%, with total recovery rates of approximately 70%, 51%, and 74%, respectively. Based on nuclear magnetic resonance techniques, the purified peridinin, diadinoxanthin, and diatoxanthin were identified as all-trans-peridinin, all-trans-diadinoxanthin, and all-trans-diatoxanthin, respectively. In all, the developed method may hold significant implications for future purification of peridinin and diadinoxanthin cycle carotenoids, as well as for the integrated biorefinery of wet A. carterae. Full article

The development of advanced energy materials is critical for the safety and efficiency of next-generation nuclear energy systems. Aluminum alloys present a compelling option due to their excellent neutronic properties, notably a low thermal neutron absorption cross-section. However, their historically poor high-temperature performance has limited their use in commercial power reactors. This makes them prime candidates for specialized, lower-temperature but high-radiation environments, such as research reactors, spent fuel storage systems, and spallation neutron sources. In these applications, mitigating radiation damage—particularly swelling and embrittlement from helium produced during irradiation—remains a paramount challenge. Grain Boundary Engineering (GBE) is a potent strategy to mitigate radiation damage by increasing the fraction of low-energy Coincident Site Lattice (CSL) boundaries. These interfaces act as effective sinks for radiation-induced point defects (vacancies and self-interstitials), suppressing their accumulation and subsequent clustering into damaging dislocation loops and voids. By controlling the defect population, GBE can substantially reduce macroscopic effects like volumetric swelling and embrittlement, enhancing material performance in harsh radiation environments. In this article we evaluate the efficacy of GBE in an AlSi10Mg alloy, a candidate material for nuclear applications. Samples were prepared via KOBO extrusion, with a subset undergoing subsequent annealing to produce varied initial grain sizes and grain boundary character distributions. This allows for a direct comparison of how these microstructural features influence the material’s response to helium ion irradiation, which simulates damage from fission and fusion reactions. The resulting post-irradiation defect structures and their interaction with the engineered grain boundary network were characterized using a combination of Transmission Electron Microscopy (TEM) and High-Resolution Transmission Electron Microscopy (HRTEM), providing crucial insights for designing next-generation, radiation-tolerant energy materials. Full article

Gastroesophageal reflux disease (GERD) is associated with symptoms such as heartburn, resulting from gastric content reflux. Alginate-based raft-forming gel formulations represent a non-pharmacological strategy for GERD management by forming a floating gel barrier in the stomach. This study evaluated three commercial anti-reflux oral gel systems under simulated fed-state gastric conditions, using in vitro magnetic resonance relaxometry techniques. Magnetic resonance imaging (MRI) was performed in 0.01 M hydrochloric acid (HCl) to visualize gel raft formation, spatial structure, and spatial distribution of effective T₂ relaxation time. Nuclear magnetic resonance (NMR) relaxometry in 0.01 M deuterium chloride (DCl) measured T₁ and T₂ relaxation times of the protons that were initially included in the preparation to assess its molecular mobility within the gel matrix. Two formulations formed floating, coherent gels, whereas the remaining one exhibited only polymer swelling without flotation. In one case, relaxometry data revealed a solid-like component that can be detected, indicating enhanced mechanical stability. The performance of each formulation was influenced by interactions among alginate, bicarbonates, and calcium ions, which determined gel consistency and flotation behavior. MRI and NMR relaxometry in vitro provide valuable non-invasive insights into the structural and functional behavior of alginate-based gel formulations. This approach supports the rational design of advanced gel-based therapies for GERD by linking molecular composition with in situ performance. Full article

This study focuses on the synthesis and characterization of thermoresponsive hydrogels of poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), PLA–PEG copolymers, aiming at the targeted and controlled release of deferoxamine (DFO), a clinically applied iron-chelating drug. Triblock (PLA-PEG-PLA) and diblock (mPEG-PLA) copolymers were synthesized using ring-opening polymerization (ROP) with five different PEGs with molecular weights of 1000, 1500, 2000, 4000, and 6000 g/mol and two types of lactide (L-lactide and D-lactide). Emulsions of the polymers in phosphate-buffered saline (PBS) were prepared at concentrations ranging from 10% to 50% w/w to study the sol–gel transition properties of the copolymers. Amongst the synthesized copolymers, only those that demonstrated thermoresponsive sol-to-gel transitions near physiological temperature (37 °C) were selected for further analysis. Structural and molecular confirmation was performed by Nuclear Magnetic Resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR), while the molecular weights were determined via Gel Permeation Chromatography (GPC). The thermal transitions were studied by calorimetry (DSC) and crystallinity via X-ray diffraction (XRD) analysis. DFO-loaded hydrogels were prepared, and their drug release profiles were investigated under simulated physiological conditions (37 °C) for seven days using HPLC analysis. The thermoresponsive characteristics of these systems can offer a promising strategy for injectable drug delivery applications, where micelles serve as drug carriers and undergo in situ gelation, enabling controlled release. This alternative procedure may significantly improve the bioavailability of DFO and enhance patient compliance by addressing key limitations of conventional administration routes. Full article

Transfer RNA-derived small RNAs (tDRs) are increasingly being recognized as versatile regulators, yet their physiological landscape remains poorly charted. We analyzed tDR expression in seven adult mouse tissues to explore tissue-specific tDR enrichment using a tDR-optimized library preparation methodology. We catalogued 26,901 unique nuclear tDRs (ntDRs) and 5114 mitochondrial tDRs (mtDRs). Clustering analysis segregated the tissues, with the spleen and lungs forming a distinct immune cluster. Tissue-versus-all and pairwise differential analysis showed the spleen harboring unique ntDRs and mtDRs. Tissue-enriched tDRs arose from specific isoacceptor and isodecoder tRNAs, independent of mature tRNA abundance, suggesting selective biogenesis rather than bulk turnover. G-quadruplex prediction revealed a pronounced enrichment of potentially quadruplex-forming ntDRs in the kidneys, heart, and spleen, predominantly derived from i-tRFs and tRF3 fragments, suggesting structure-dependent functions in immune regulation. We also benchmarked our library strategy against the PANDORA-seq method. Despite comparable or lower sequencing depth, our method detected ~3–10-fold more unique ntDRs and we observed a clearer representation of tRF-3 fragments and greater isotype diversity. Our tissue atlas and improved tDR sequencing method reveal extensive tissue-specific heterogeneity in tDR biogenesis, sequencing, and structure, providing a framework for understanding the context-dependent regulatory roles of tDRs. Full article

Geopolymers represent an innovative and environmentally sustainable alternative to traditional construction materials, offering significant potential for reducing anthropogenic CO₂ emissions. Among these, phosphoric acid-activated metakaolin-based systems have attracted increasing attention for their chemical and thermal resilience. In this study, we present a comprehensive structural and mechanical evaluation of metakaolin-based geopolymers synthesized across a wide range of Al/P molar ratios (0.8–4.0). Six formulations were systematically prepared and analyzed using X-ray powder diffraction (XRPD), small-angle X-ray scattering (SAXS), Fourier-transform infrared spectroscopy (FTIR), solid-state nuclear magnetic resonance (ssNMR), and complementary mechanical testing. The novelty of this work lies in the integrated mapping of composition–structure–property relationships across the broad Al/P spectrum under controlled synthesis, combined with the rare application of SAXS to reveal composition-dependent nanoscale domains (~18–50 nm). We identify a stoichiometric window at Al/P ≈ 1.5, where complete acid consumption leads to a structurally homogeneous AlVI–O–P network, yielding the highest compressive strength. In contrast, acid-rich systems exhibit divergent flexural and compressive behaviors, with enhanced flexural strength linked to hydrated silica domains arising from metakaolin dealumination, quantitatively tracked by ²⁹Si MAS NMR. XRPD further reveals the formation of uncommon Si–P crystalline phases (SiP₂O₇, Si₅P₆O₂₅) under low-temperature curing in acid-rich compositions. Together, these findings provide new insights into the nanoscale structuring, phase evolution, and stoichiometric control of silica–alumino–phosphate geopolymers, highlighting strategies for optimizing their performance in demanding thermal and chemical environments. Full article

Chamaecyparis obtusa (Siebold & Zucc.) Endl. (C. obtusa) is an evergreen conifer native to temperate regions such as South Korea and Japan, traditionally used for its anti-inflammatory properties. However, the molecular mechanisms underlying the anti-inflammatory effects of C. obtusa bark extracts remain poorly understood. In this study, I compared the biological activities of C. obtusa bark extracts prepared using boiling water (COWB) and 70% ethanol (COEB), and investigated their anti-inflammatory mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. COEB significantly suppressed both mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), along with decreased production of their respective inflammatory mediators, nitric oxide (NO) and prostaglandin E₂ (PGE₂). Additionally, COEB selectively downregulated interleukin (IL)-1β expression, without affecting tumor necrosis factor-α (TNF-α), and unexpectedly upregulated IL-6. Notably, COEB did not inhibit the LPS-induced activation of major inflammatory signaling pathways, including mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). These findings suggest that COEB exerts anti-inflammatory effects by modulating key inflammatory mediators independently of canonical signaling pathways and may offer a novel therapeutic strategy for controlling inflammation. Full article

A previously undescribed cis-clerodane diterpenoid, diangelate solidagoic acid J (1), along with two known cis-clerodane diterpenoids, solidagoic acid C (2) and solidagoic acid D (3), as well as two known unsaturated monoacylglycerols, 1-linoleoyl glycerol (4) and 1-α-linolenoyl glycerol (5), were isolated and characterized from the n-hexane leaf extract of Solidago gigantea (giant goldenrod). Compounds 2–5 were identified first in this species, and compounds 4 and 5 are reported here for the first time in the Solidago genus. The bioassay-guided isolation procedure included thin-layer chromatography (TLC) coupled with a Bacillus subtilis antibacterial assay, preparative flash column chromatography, and TLC–mass spectrometry (MS). Their structures were elucidated via extensive spectroscopic and spectrometric techniques such as one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and high-resolution tandem mass spectrometry (HRMS/MS). The antimicrobial activities of the isolated compounds were evaluated by a microdilution assay. All compounds exhibited weak to moderate antibacterial activity against the Gram-positive plant pathogen Clavibacter michiganensis, with MIC values ranging from 17 to 133 µg/mL, with compound 5 being the most potent. Only compound 1 was active against Curtobacterium flaccumfaciens pv. flaccumfaciens, while compound 3 demonstrated a weak antibacterial effect against B. subtilis and Rhodococcus fascians. Additionally, the growth of B. subtilis and R. fascians was moderately inhibited by compounds 1 and 5, respectively. None of the tested compounds showed antibacterial activity against Gram-negative Pseudomonas syringae pv. tomato and Xanthomonas arboricola pv. pruni. No bactericidal activity was observed against the tested microorganisms. Compounds 2 and 3 displayed weak antifungal activity against the crop pathogens Bipolaris sorokiniana and Fusarium graminearum. Our results demonstrate the efficacy of bioassay-guided strategies in facilitating the discovery of novel bioactive compounds. Full article

It is well established that different fasting strategies offer a range of benefits and may even serve as potential therapeutic approaches for metabolic diseases. The biological effects of intermittent fasting (IF) are multidimensional, involving the induction of metabolic switching from glucose to fatty acid and ketone utilization, thereby enhancing fat metabolism and improving glucose tolerance and insulin sensitivity. In addition, IF modulates the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis by lowering IGF-1 levels, a change associated with enhanced cellular protection, reduced tumorigenesis, and delayed aging. Moreover, IF modulates key signaling pathways, including mitogen-activated protein kinases, Notch, and nuclear factor kappa B, which collectively contribute to reduced oxidative stress, attenuated inflammation, and hepatoprotection. Although fasting may present certain challenges, it is essential to be adequately informed about its potential benefits and appropriate preparatory strategies before undertaking various fasting protocols. This review summarizes the current knowledge on various IF protocols and periodic short-term fasting (PSTF) lasting more than 24 h and up to 72 h, highlighting the signaling pathways through which these interventions affect metabolic processes. Additionally, it aims to provide a practical guide for the safe preparation for PSTF lasting more than 24 h and up to 72 h. Full article

The rising demand for alternative solutions to diabetes mellitus has prompted significant interest in the exploration of plant-derived anti-diabetic compounds, especially within a circular economy framework that seeks sustainable and profitable reuse options. In this context, red (RSGO) and white (WGSO) grape seed oils, by-products of Sicilian vineyards, were prepared, analyzed for their fatty acid, polyphenol, carotenoid, and chlorophyll content, and evaluated for their glucose-lowering ability on HepG2 cells. Utilizing cytochemical techniques, flow cytometry, and protein blotting, we explored the effects of non-toxic oil dilutions on (i) glycogen storage, (ii) glucose consumption/uptake, (iii) GLUT-2, GLUT-4, and hepatocyte nuclear factor-1α (HNF1α) expression levels, and (iv) AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), AKT, and PKCζ phosphorylation states, which are involved in insulin-mediated and -independent regulation of GLUT-4 membrane exposure. RGSO and WGSO, despite adopting slightly varying molecular strategies, were both proven to be effective stimulators of glucose absorption and glycogenesis. Specifically, RSGO promoted GLUT-2 and GLUT-4 up-regulation, whereas the WGSO-induced effect was associated with an increase in GLUT-4 levels alone. Moreover, the oils activated both pathways responsible for GLUT-4 translocation. Therefore, these wine-making residues have substantial potential as anti-diabetic solutions, holding promise for integration into the biomedical and food sectors. Full article