Search Results (872)

Acetyl L-carnitine is an ester of the trimethylated amino acid L-carnitine with well-documented neuroprotective properties. Despite its ability to cross the blood–brain barrier, acetyl L-carnitine requires high and repeated doses to achieve and maintain therapeutic concentrations in the central nervous system. To overcome these limitations, nanotechnology-based delivery systems have emerged as a promising strategy to improve drug bioavailability, targeting, and therapeutic efficacy. In this study, we evaluated the efficacy of nanoparticle-based formulations of acetyl L-carnitine in comparison with its conventional bulk form using in vitro cultures of SH-SY5Y neuroblastoma cell line. The ALC nanoparticles were produced through an organic solvent-free mechanical ball milling process employing a planetary ball mill. The dimension and stability of the nanoparticles were analyzed by Dynamic Light Scattering and Thermogravimetric Analysis. The biological effects were evaluated using quantitative Real Time-Polymerase Chain Reaction, Enzyme-linked Immunosorbent Assay and immunofluorescence experiments. ALC nanoparticles, at low concentration of nanoparticles compared to the non-nanoparticle form, were able to decrease the alarmin S100B release, pro-inflammatory interleukin mRNA and protein expression as well as p65 activation, confirming their involvement in NF-κB pathway. Moreover, it was able to stimulate the nerve growth factor release and to increase intracellular Ca⁺⁺ levels, showing neuroprotective effects in addition to anti-inflammatory ones. Our findings allow us to highlight the therapeutic potential of ALC nanoparticles for neurological disorders, with the prospect of enhancing efficacy while reducing dosage and administration frequency. Full article

Sustainable aviation fuel is among the most practical near-term routes for aviation decarbonization because it can be used in existing aircraft, engines, and airport fuel systems with limited infrastructure changes while minimizing disruption to the aviation fuel supply chain. This review examines SAF applications in aerospace propulsion systems, focusing on production pathways, aero-engine compatibility, property prediction, and fuel heat sink potential. It compares hydroprocessed esters and fatty acids (HEFA), Fischer–Tropsch (FT), alcohol-to-jet (ATJ), synthesized iso-paraffins (SIP), and power-to-liquid (PtL) fuels in terms of feedstock type, process complexity, product composition, and blending constraints. It also assesses how molecular composition governs density, cold-flow behavior, thermal stability, coking propensity, seal compatibility, and emissions. Recent advances in molecular dynamics, machine learning, spectroscopic analysis, and uncertainty quantification show a shift from empirical estimation toward composition-based prediction, prescreening, and fuel design. For high-thermal-load propulsion systems, SAF is further evaluated as a fuel heat sink in active regenerative cooling. Current evidence points to advantages in thermal stability and low coking tendency, but important gaps remain in transcritical and supercritical heat transfer, pyrolytic heat absorption, wall-material effects, coke deposition, and heat sink capacity modeling across wide operating ranges. Full article

Glioblastoma (GBM) is a devastating brain tumor heavily reliant on metabolic reprogramming for survival. The DNA aptamer AS1411 specifically targets cell-surface nucleolin (NCL), a protein overexpressed in GBM; however, its precise metabolic consequences remain largely unexplored. This study investigated the direct impact of AS1411-mediated NCL inhibition on the lipidomic profile of U-87 glioblastoma cells. It was demonstrated that AS1411 treatment induced acute cytotoxicity within 24 h. Subsequently, high-resolution mass spectrometry (MS) lipidomics was utilized to identify the lipidomic rewiring triggered by AS1411. Significant changes, such as the upregulation and/or exclusive emergence of specific long-chain and highly polyunsaturated diacylglycerol (DAG), triacylglycerol (TAG), and glycerophospholipid (GP) species, were determined in the species-level analyses. Additionally, our findings revealed that AS1411 treatment induced substantial alterations that profoundly affected membrane biophysics by modifying lipid saturation and acyl chain lengths. An increase in fully saturated sphingomyelin (SM) and cholesteryl ester (CE) levels was observed, leading to the formation of saturated lipid microdomains (lipid rafts) in endosomal and ER membranes, which causes membrane rigidification and decreased fluidity. Our results also demonstrate that PEs containing long-chain polyunsaturated fatty acids (PUFAs)—the primary substrates for ferroptosis—were upregulated. While AS1411 subjects cancer cells to methuotic vacuolization stress, it simultaneously reduces internal structural membrane fluidity and renders the cells metabolically vulnerable to ferroptosis. In conclusion, these detailed lipidomic results indicate that AS1411 treatment proceeds strictly through targeted remodeling and an adaptive scaffolding response. Full article

The instability of marine low-sulfur fuel oil caused by asphaltene precipitation poses significant operational challenges in the shipping industry. This study systematically investigates the dispersing effects of biodiesel derived from three different feedstocks—palm oil, waste cooking oil (WCO), and microalgae oil—and their individual fatty acid methyl ester components on asphaltenes extracted from VLSFO. Biodiesel was selected as a dispersant due to its renewable nature, polar ester functional groups, and variable unsaturation levels, which enable favorable interactions with asphaltene molecules through hydrogen bonding and π-π stacking. Using UV–Visible spectrophotometry, the dispersion performance was quantitatively evaluated under various conditions including dispersant concentration, temperature, storage time, and molecular structural characteristics. The results demonstrate that microalgae oil biodiesel exhibits the most superior asphaltene dispersion capability among the three biodiesels, with a dispersion improvement index of 35% at 12 g/L, compared to 28% and 22% for waste cooking and palm oil biodiesels. Optimal performance is achieved at 80 °C, where the asphaltene concentration increases by 68% relative to the control, and remains stable within the first 10 days of storage but deteriorates significantly after 30 days due to oxidative degradation. Among individual FAME components, the dispersion effectiveness increases with alkyl chain length from C10 to C20, with the latter reaching a 30% improvement index. Functional group polarity plays a critical role, with carboxylic acid exhibiting a 45% improvement at 14 g/L, substantially outperforming alcohol at 32% and ester at 28%. The degree of unsaturation further enhances dispersion, as the improvement index rises progressively from 20% for saturated methyl stearate to 42% for tri-unsaturated methyl linolenate, representing a 2.1-fold increase. Dynamic light scattering (DLS) measurements confirm that biodiesel addition reduces asphaltene particle size from the micrometer range of 2 to 5 μm down to submicron levels of 200 to 500 nm, while microscopic observations reveal inhibited aggregation. These findings provide theoretical foundations for biodiesel application in marine fuel systems. Full article

Endocannabinoids are lipid mediators consisting of esters, amides and ethers of long-chain polyunsaturated fatty acids. In this work, attention was focused on N-arachidonoyl tyrosine (NA-Tyr) and N-arachidonoyl dopamine (NADA), the amides of arachidonic acid with tyrosine and dopamine, respectively. NADA is an endogenous ligand of both type 1 cannabinoid receptors and type 1 vanilloid channel receptors. NADA is considered an endogenous compound with capsaicin-like activity and is distributed in several brain areas. The metabolic fate of endocannabinoids involves numerous enzymatic activities, which are only partially characterized. In particular, the biological activity of these biomolecules is terminated by enzymes with hydrolytic or oxygenase/oxidase activity. As part of this problem, we studied the oxidation of NADA and NA-Tyr mediated by mushroom tyrosinase. Our experimental data show that tyrosinase can oxidize both NADA and NA-Tyr. The oxidation of these biomolecules was also carried out in the presence of cysteine, allowing us to observe the formation of endocannabinoid/endovanilloid adducts with cysteine. These results were derived from chromatographic analyses and mass spectral experiments. During the tyrosinase-mediated oxidation in the presence of cysteine, it was possible to observe the production of a melanin-like pigment. The spectral characteristics of this pigment are consistent with those of pheomelanin, the pigment that contributes to the structure of neuromelanin. While mushroom tyrosinase serves here as a convenient biomimetic model to investigate the oxidative susceptibility of NADA and NA-Tyr, extrapolating these in vitro findings to mammalian physiology requires caution. Nevertheless, considering the neuronal distribution of these precursors and the documented, albeit debated, presence of tyrosinase-like activity in the central nervous system (CNS), these results offer a chemical rationale to further investigate whether similar oxidative pathways occur in vivo and potentially contribute to neurodegenerative mechanisms. Full article

Camellia japonica L. (Theaceae) seed oil is an essential component for skin protection, attributed to its antioxidant properties and anti-aging effects. In this study, Camellia japonica seed oil underwent fermentation with Sporidiobolus pararoseus (Fell & Tallman, CGMCC No. 39106, commercial name: Longevity yeast of 1021-year-Camellia japonica). The post-fermented oil, designated Longevity Yeast Oil (LYO), was used in the present research. Gas chromatography–mass spectrometry analysis demonstrated that methyl esterification of LYO afforded twelve fatty acid methyl esters. We used an aging model in human epidermal keratinocytes and human skin fibroblasts exposed to ultraviolet B (UVB) to explore the anti-skin aging effects and mechanisms of LYO. The results of the CCK-8 assay demonstrated that LYO exhibited no cytotoxicity but instead displayed potential proliferative activity, indicating its excellent safety profile. Quantitative real-time polymerase chain reaction analyses confirmed that LYO downregulated the expression of autophagy marker p62 and upregulated LC3B, thereby activating the autophagic pathway. Further investigation revealed that LYO protected against UVB-induced apoptosis, promoted the synthesis of collagen and elastin, and upregulated the expression of loricrin, filaggrin, and ceramides, effectively reversing UVB-induced skin cellular aging. Notably, we further revealed that LYO alleviated UVB-induced cutaneous photoaging via activating cellular autophagy pathway. In conclusion, LYO demonstrated biocompatibility and conferred protection to skin cells against photoaging, thereby establishing a theoretical basis for the development of innovative autophagy-targeted anti-aging therapies. Full article

Conventional gelatin-based hydrogels lack responsiveness to the tumor microenvironment and exhibit low drug-loading efficiency for hydrophobic drugs, which limits their application in targeted cancer therapy. In this study, a reduction-responsive gelatin hydrogel was developed by grafting hydrophobic tert-butoxycarbonyl (Boc) groups onto gelatin chains, followed by EDC/NHS-mediated chemical cross-linking with L-cysteine dimethyl ester dihydrochloride, which contains disulfide bonds. The success of Boc grafting was confirmed by ¹H NMR, and free amine quantitative analysis. Rheological characterization confirmed the formation of a stable elastic network with controllable gelation times (5–12 min), demonstrating excellent injectability. Reduction-triggered degradation was observed in the presence of DTT or GSH, with the cleavage of disulfide bonds further evidenced by the detection of free sulfhydryl (-SH) groups via X-ray Photoelectron Spectroscopy. Microscale thermophoresis (MST) demonstrated measurable binding between Boc-modified gelatin and hydrophobic drugs, with dissociation constants (K_d) of 0.46 ± 0.37 μM for curcumin and 0.14 ± 0.14 μM for camptothecin. Drug loading assays show dramatically enhanced encapsulation efficiency for hydrophobic drugs (62.7% for curcumin, 66.6% for camptothecin) compared to unmodified hydrogels (7.2% and 16.8%, respectively). In vitro release kinetics follow the Korsmeyer–Peppas model, indicating a non-Fickian diffusion–erosion mechanism, and can be precisely tuned by gelatin concentration and reducing agent levels. Complete drug release occurs within approximately 325 min in 15 mM GSH. MTT and hemolysis assays confirm high biocompatibility. Collectively, this reduction-responsive system offers a promising platform for controlled, site-specific delivery of hydrophobic anticancer agents. Full article

Background/Objectives: This study aimed to improve the biological profile of oleanolic acid (OA) through structural modification at the C-17 carboxyl group and the C-3 hydroxyl group, with a focus on the design of short-chain alkyl esters and 3-O-furoyl hybrids. Methods: Two series of OA derivatives were synthesized and characterized using spectroscopic methods, including ¹H NMR, ¹³C NMR and MS. In silico structure–activity relationship (SAR) analysis, ADMETox profiling, and molecular docking to the epidermal growth factor receptor (EGFR) tyrosine kinase domain were performed as predictive and hypothesis-generating tools. Anticancer activity was evaluated in vitro using the MTT assay against human cancer cell lines, including HeLa, MCF-7, A-549, SKBR-3, PC-3 and SKOV-3, as well as non-malignant human dermal fibroblasts (HDFs). Antioxidant properties were assessed using cell-free CUPRAC and DPPH assays. Results: The C-17 esterification markedly enhanced cytotoxic potency compared to the parent OA, while the introduction of the 3-O-furoyl moiety further improved antiproliferative activity in several derivatives. Selected compounds showed low-micromolar IC₅₀ values and moderate selectivity toward cancer cells. Molecular docking suggested favorable accommodation of selected derivatives within the EGFR ATP-binding pocket, mainly through hydrophobic and π-related interactions; however, these results do not confirm direct EGFR binding and require experimental validation. The CUPRAC and DPPH assays provided preliminary insight into chemical redox behavior but should not be directly extrapolated to intracellular antioxidant or pro-oxidant activity. Predicted ADMETox profiles indicated moderate permeability and relatively low predicted risk for selected toxicity endpoints, while also highlighting high lipophilicity, poor aqueous solubility and potential metabolic liabilities. Conclusions: Overall, the results identify several OA derivatives as promising anticancer lead compounds for further optimization and mechanistic investigation. Full article

Pixian Doubanjiang (PXDB) is a traditional Chinese fermented condiment whose characteristic aroma and taste are strongly influenced by fermentation conditions. This study aimed to systematically compare the flavor profiles of PXDB produced via traditional open fermentation (TOF) and industrial closed fermentation (ICF), aiming to elucidate the chemical basis of sensory divergence and provide scientific support for industrial process optimization. In this study, PXDB samples were evaluated using sensory evaluation, GC-IMS, ¹H-NMR metabolomics, and multivariate statistical analysis. Sensory evaluation revealed that ICF exhibited a stronger soy sauce-like aroma, alcohol note, and umami intensity, whereas TOF and ICF showed comparable sweetness, sourness, chili-like aroma, and roasted aroma. GC-IMS putatively identified 126 volatile compounds, and multivariate analyses demonstrated a clear separation between the two fermentation modes. Based on combined criteria of VIP > 1, FDR-adjusted p < 0.05, and |fold change| > 2, 35 differential volatile compounds were identified. ICF was characterized by higher levels of esters, particularly ethyl esters, and selected ketones, while TOF showed enrichment of higher alcohols, terpenes, and sulfur compounds. ¹H-NMR analysis identified 54 non-volatile metabolites, of which 16 differed significantly between TOF and ICF, mainly involving amino acids, organic acids, and carbohydrates. Pathway analysis highlighted branched-chain amino acid and glutamate-related metabolism as key contributors to flavor divergence. Correlation analysis further revealed that soy sauce-like aroma and umami perception were strongly associated with amino acid-derived metabolites, esters, sulfur-containing compounds, and branched-chain aldehydes, highlighting the coordinated contribution of volatile and non-volatile compounds to flavor differentiation. Overall, fermentation mode was found to reshape PXDB flavor through coordinated modulation of volatile and non-volatile metabolism, providing experimental insight for improving industrial fermentation quality. Full article

To mitigate the environmental footprint of the aviation sector, this study proposes an integrated cascading biorefinery scheme to produce Sustainable Aviation Fuel (SAF) precursor bloodstock via enzymatic transesterification of coconut oil. Utilizing a synergistic binary alcohol system (ethanol-butanol) and the liquid lipase Eversa Transform 2.0, a strategic molecular reconfiguration of fatty acid esters was achieved. Optimization through Response Surface Methodology (RSM) identified critical parameters—5% catalyst loading, total binary alcohol-to-oil molar ratio of 7:1 (specifically comprised of a 2.5:4.5:1 ethanol/butanol/coconut oil matrix), and an operation temperature of 57.5 °C—yielding a 97% conversion efficiency. A sequential vacuum fractional distillation process was implemented to partition the ethyl-butyl esters into high-value streams. Notably, the light distillate fraction, characterized by a specific carbon chain distribution (C6: 27.2%, C8: 52.5%, C10: 6%, and C12: 13.6%), perfectly aligns with the molecular window of aviation kerosene. This fraction exhibits excellent cold-flow properties, viscosity, and volatility profiles, positioning it as an ideal high-performance SAF precursor blendstock to increase the renewable content of current aviation fuels. Simultaneously, the remaining C16–C18 residue serves as a high-density energy source for internal refinery processes, while C8–C14 species are recovered as high-purity chemical feedstocks. This circular model maximizes carbon atom economy and economic viability by cogenerating high added-value biochemicals alongside jet-grade blendstocks. These findings provide a scalable, enzymatic framework for the next generation of decarbonized aviation fuels. Full article

Sophorolipids (SLs) produced from Starmerella bombicola using four different secondary substrates such as refined, bleached, and deodorized palm olein (RBD PO), RBD palm kernel olein (RBD PKO), RBD coconut olein (RBD CO) and fatty acid methyl ester (FAME) waste are reported. Their interfacial characteristics at medium-chain triglyceride (MCT) oil-water interface and ability to form nano/submicron emulsions were studied. The effects of SLs from different sources, SL concentrations and blend ratios of SLs and soybean lecithin on characteristics of emulsions produced by ultrasonication were examined. Initially, emulsion formed using SLs coded (from F2 to F5) showed large droplets (d₃₂ > 1000 nm) and poor stability. They were then blended with soybean lecithin at a ratio of 3:1 to produce emulsions coded F6 to F9 with smaller droplets (d₃₂ < 400 nm) and great stability over a range of temperatures (from 40 °C to 90 °C) and pH values (from 3 to 9). However, highly acidic (pH 2) and low ionic strength (1 mM NaCl) processing caused the separation of the emulsions. These emulsions also displayed potential antimicrobial activities towards Bacillus cereus and Pseudomonas aeruginosa, as well as cytotoxic effects against the human epithelial colorectal adenocarcinoma cell line (Caco-2). These results illustrated that stable emulsions required a mixture of SLs and soybean lecithin. Full article

The rise in antimicrobial resistance and the resilience of microbial biofilms demand innovative strategies that combine, for instance, membrane-active agents with marketed drugs. Arginine-based surfactants are promising alternatives to conventional quaternary ammonium compounds, but comparative data on their antimicrobial, antibiofilm and modulatory activities remain limited. Five arginine-derived surfactants, the single-chain Nα-lauroyl-L-arginine methyl ester (LAM) and ethyl ester (LAE), together with their double-chain homologues LANHC₃, LANHC₅ and LANHC₈ were evaluated against Gram-positive and Gram-negative bacteria and four Candida spp. Minimum inhibitory (MIC) and lethal (MLC) concentrations were determined by broth microdilution method. Antibiofilm activity was assessed through minimum biofilm inhibitory (MBIC) and eradication (MBEC) concentrations. Checkerboard assays were used to evaluate the synergism between the surfactants and conventional therapeutic antibacterial and antifungal agents. LANHC₃ and LANHC₈ exhibited uniform antibacterial MICs of 19.53 µg/mL, while LAM and LANHC₅ showed MICs of 19.53 µg/mL for most strains, with Enterococcus faecalis requiring 39.06 µg/mL. LANHC₃ was the most potent surfactant over Candida spp. With MICs of 9.76 µg/mL for all species, and similarly to LAM, both were fungicidal at 39.06 µg/mL. LAM and LANHC₃ also showed the lowest MBIC and MBEC values, inhibiting the Candida biofilm formation at 39.06 µg/mL and eradicating mature biofilms at 78.12 µg/mL, while the other surfactants required higher concentrations to disrupt the microbial biofilms. Synergic or additive interactions were found between the surfactants and selected β-lactam and macrolide antibiotics, as well as azole antifungals, with no antagonism observed. LAM and particularly LANHC₃ combined broad-spectrum antimicrobial activity, relevant antibiofilm effects and the ability to potentiate the activity of conventional agents, supporting their choice as alternative or complementary antimicrobial adjuvants over resistant microorganisms and their biofilms. Full article

Background/Objectives: Despite the availability of multiple pharmacological treatment options, up to one-third of patients with depressive disorders fail to achieve adequate symptom relief following first-line antidepressant therapy, representing a major unmet clinical need. Fatty acids—including short-chain (SCFAs), medium-chain (MCFAs), and long-chain polyunsaturated fatty acids (PUFAs)—are increasingly implicated in depression pathogenesis through neuroinflammation, gut–brain axis signaling, and neurotransmitter metabolism, but their potential as predictors of antidepressant response remains largely unexplored. The primary aim is to evaluate whether baseline fatty acid profiles can predict pharmacological antidepressant treatment efficacy. The secondary objective is to assess the association between blood fatty acid profile and clinical presentation of depressive disorders. Methods: Sixty adults diagnosed with depressive disorders (ICD-11) at the initiation of a new antidepressant treatment will be recruited from psychiatric settings. Fasting blood samples collected at baseline will undergo gas chromatographic analysis of fatty acid methyl esters (FAMEs) and GC-MS quantification of SCFAs (acetic, propionic, and butyric acids). Clinical outcomes will be assessed at baseline and at 3, 6, and 12 weeks using the Beck Depression Inventory-II (BDI-II) and the Depression Anxiety Stress Scales (DASS-42). The primary endpoint is the change in BDI-II total score from baseline to week 6. Treatment response, defined as a ≥50% reduction in BDI-II total score at week 6, and remission, defined as a BDI-II score ≤12 at week 6, will be examined as secondary outcomes. Dietary habits, physical activity, quality of life, and anthropometric parameters will be collected as potential confounders. Discussion: This study is among the first prospective investigations to comprehensively characterize the circulating fatty acid spectrum as potential predictors of antidepressant outcomes. Findings may support identification of metabolic phenotypes of depression and contribute to personalized treatment strategies. Full article

Lipolytic and esterase-like enzymes are crucial in the food industry for flavor production and ester hydrolysis. This study presents an exploratory, baseline feasibility approach to evaluate esterase-like enzyme production by Serratia marcescens 11E via a sustainable co-valorization matrix, where vegetable wax residues serve as structural solid support and cheese whey acts as the primary lipid nutritional source. Under fixed 48-h screening conditions, the recovered cell-free extract exhibited a distinct catalytic preference for short-chain esters, showing higher specific activity toward 4-nitrophenyl acetate (0.743 U/mg) than 4-nitrophenyl palmitate (0.125 U/mg), confirming a predominant carboxylesterase-like profile. Biochemical characterization revealed an initial optimal activity at pH 9.0 and 30 °C, along with a noteworthy bimodal catalytic behavior featuring a secondary activity peak at 70 °C. Size-exclusion chromatography resolved the extract into two distinct active elution pools (17.8 and 26.2 U/mg), which corresponded to candidate protein bands of 35–40 kDa on SDS-PAGE. Although definitive molecular identification remains subject to ongoing zymographic and proteomic characterization, these foundational findings demonstrate the potential of co-valorizing lipid- and carbohydrate-rich industrial wastes to produce resilient proteins with esterase-like activity at elevated temperatures. Full article

In this work, we investigated the incorporation of a fluorescent side group, fluorescein octyl ester (FOE), in benzodithiophene-based donor–acceptor terpolymers as a strategy to modulate excited-state behavior. Three FOE-containing terpolymers (P2-iIa-c), obtained at different polymerization times, were systematically evaluated against an analogous material without the fluorescent pendant unit (P1-iI). Thermal analysis revealed good thermal stability and an increase in glass transition temperature upon FOE incorporation, suggesting restricted segmental mobility and increased conformational constraints within the conjugated backbone. Optical characterization showed distinct absorption spectra with reaction time and shorter fluorescence lifetimes for the FOE-containing materials, consistent with the presence of additional excited-state deactivation pathways and intramolecular energy transfer processes within the terpolymer backbone. An approximate estimation of energy transfer efficiencies (≈60–65%) suggested that such processes may be operative within the system. Cyclic voltammetry measurements showed only minor variations in HOMO and LUMO energy levels between P1-iI and P2-iIa-c series, indicating that the conjugated backbone predominantly determined the frontier orbital energies despite side chain modification. Furthermore, photocurrent measurements from the bilayer device configuration exhibited a systematic increase in photocurrent for the FOE-containing material, supporting the role of excitonic modulation, rather than significant changes in interfacial energetic alignment. These results suggest that fluorescent side chain incorporation provides an effective strategy for regulating exciton dynamics while maintaining the electronic structure of the donor–acceptor terpolymer. Full article