Search Results (2,210)

Salicyluric acid (SUA), the main metabolite of aspirin and a natural product, is known for its ability to chelate iron and other metal ions. In particular, the chelation and increased excretion of iron by SUA may contribute to the aspirin-induced iron deficiency anemia observed in long-term aspirin users. The redox activity of iron and copper complexes of drugs and also drug metabolites, such as SUA, is an important parameter of their overall toxicity profile, including the induction of ferroptosis, which has been associated with many diseases. In this context, the effect of SUA on iron- and copper-induced lipid peroxidation and also its localization within a model lipid membrane have been investigated. A combination of physicochemical methods, including Nuclear Magnetic Resonance (¹H NMR), molecular dynamics (MD), and Nuclear Overhauser Effect Spectroscopy (¹H NOESY), has been used to demonstrate that SUA does not promote the peroxidation of linoleic acid micelles in the presence of Fe(II) or Cu(II) ions. NMR experiments revealed that SUA incorporates into the lipid bilayer, which stabilizes the ligands and inhibits its metal chelation ability in comparison to the control. NOESY experiments and MD simulations further showed that SUA localizes shallowly within the membrane, interacting primarily with the head group and upper acyl chain regions of lipids. These findings provide crucial insights into the membrane redox reactivity and other behavior of SUA, explaining its lack of pro-oxidant activity and also highlighting its complex role in the pharmacological and toxicological effects on iron metabolism in long-term aspirin users. Full article

2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the representative CHI3L1 inhibitor, has interesting biological activities, including anti-cancer and anti-inflammatory effects on neuroinflammation. Following our hit-to-lead program, we report the most active novel derivative, named CBJL-025, 2-((6,7-dimethoxy-4-oxo-3-(4-(trifluoromethyl)phenethyl)-3,4-dihydroquinazolin-2-yl)thio)-N-(4-ethylphenyl)butanamide. The title compound, CBJL-025, was successfully synthesized by S-alkylation of the p-trifluoromethyl phenethyl group possessing quinazoline and the corresponding bromide. The structure of CBJL-025 was confirmed by ¹H and ¹³C nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Full article

Molecular structural disparities between maceral components are intrinsic factors governing their reactivity and physicochemical behaviors during storage and transportation. To investigate the molecular structural differentiation between vitrain and durain in low- to medium-rank coals (R_o,max = 0.65–1.71%), this study selected samples of long-flame coal and gas coal from the Huanglong Coalfield, coking coal from the Hedong Coalfield, and fat coal from the Weibei Coalfield. The microstructural variations in macroscopic coal components during coalification were analyzed using Fourier transform infrared spectroscopy (FTIR), ¹³C nuclear magnetic resonance (¹³C-NMR), and X-ray photoelectron spectroscopy (XPS). The results indicated that the aromatic structures of vitrain are predominantly trisubstituted, with their proportion consistently exceeding that in durain. In contrast, durain exhibits a progressive transition from trisubstituted to pentasubstituted aromatics with increasing coal rank, accompanied by higher aromaticity, condensation degree, and aromatic carbon content. The d₀₀₂ size of the vitrain decreased from 3.82 to 3.47, while that of the durain decreased from 3.52 to 3.40. Both values showed a gradual decline, with the vitrain exhibiting a larger reduction than the durain. This indicates that the lateral extension of the microcrystalline structure in the durain is more developed, resulting in tighter molecular connections. ¹³C-NMR analysis further reveals that durain possesses higher f_al^H/f_al^* and bridge carbon ratios (X_BP), along with a lower f_a^S/f_a^’ ratio, reflecting a greater degree of aromatic ring condensation. XPS analysis revealed that durain generally contains a higher oxygen-functional group content but lower C-C/C-H content compared to vitrain. Collectively, these findings confirm significant structural divergence between vitrain and durain during coalification, with durain exhibiting more developed aromaticity, structural condensation, and organizational order. Full article

This study reports the synthesis and detailed characterization of pullulan-isononanoate (Pull-Iso), as well as the preparation and characterization of Pull-Iso films incorporating liposomes loaded with silibinin (SB) and smoke tree (Cotinus coggygria) extract (STExt), to explore the physicochemical and functional properties of pullulan-based biomaterials for potential biomedical applications. Pullulan was successfully esterified with isononanoic acid chloride, as confirmed by ¹H and ¹³C NMR (Nuclear Magnetic Resonance) and Fourier Transform Infrared (FTIR) spectroscopy. Modification significantly reduced the glass transition temperature (Tg), indicating enhanced chain mobility due to the introduction of bulky side chains. Prepared liposomes, embedding SB and extracted smoke tree compounds, exhibited particle sizes ~2000 nm with moderate polydispersity (~0.340) and zeta potential values around –20 mV, demonstrating lower colloidal stability over 60 days, thereby justifying their encapsulation within films. Optical microscopy revealed uniform liposome dispersion in Pull-Iso film with 0.5 g of liposomes, while higher liposome loading (0.75 g of liposomes) induced aggregation and microstructural irregularities. Mechanical analysis showed a reduction in tensile strength and strain at higher liposome content. The incorporation of liposomes encapsulating STExt and SB significantly enhanced the antioxidant activity of Pull-Iso-based films in a concentration-dependent manner, as demonstrated by DPPH and ABTS radical scavenging assays. These preliminary findings suggest that pullulan esterification and controlled liposome incorporation may enable the development of flexible, bioactive-loaded films, which could represent a promising platform for advanced wound dressing applications, warranting further investigation. Full article

The phaeozem in Northeast China is rich in soil organic carbon (SOC). However, the excessive and inefficient application of chemical fertilizers, particularly nitrogen fertilizers, has primarily led to a decrease in soil pH in this region. Currently, the relationship between soil pH and the stability of soil organic carbon (SOC) remains ambiguous. This study, conducted over 13 years of field experiments, focused on soils exhibiting varying degrees of pH resulting from different nitrogen application rates. The research employed aggregate classification, ¹³C nuclear magnetic resonance spectroscopy, and analysis of microbial community composition to investigate the alterations in the SOC stabilization mechanisms under varying nitrogen application levels. Our results demonstrated that the decline in soil pH led to reductions in macroaggregates (>2 mm) and the soil aggregate destruction rate (PAD) by 4.8–14.6%, and in soil aggregate unstable agglomerate index (E_LT) by 9.7–13.4%. The mean weight diameter (MWD) and geometric mean diameter (GMD) exhibited significant declines (p < 0.05) with decreasing pH levels. According to the ¹³C NMR analysis, the SOC was predominantly composed of O-alkyl carbon and aromatic carbon. At a pH of 5.32, the Alip/Arom values decreased, while the molecular structure of SOC became more complex under different levels of pH. In addition, the increase in [Fe(Al)-OC] (31.4–71.9%) complex indicates a shift in the stability of organic carbon from physical protection to organic mineral binding. Declining soil pH significantly reduced the diversity of soil microbial communities and promoted a shift toward copiotrophic microbial groups. Overall, declining soil pH resulted in a decline in soil aggregate stability and an increase in SOC aromaticity. This drove the shift in the stabilization mechanism of SOC in the black soil ecosystem of meadows in Northeast China from physical protection to chemical stability. Full article

Background: Consumption of fruits of different origins with specific (poly)phenolic profiles can modulate the gene expression of enzymes and the levels of metabolites in a photoperiod-dependent manner. However, there is little information on how this affects the profile of hepatic and muscular fatty acids (FAs) and how it interferes with metabolic pathways. This study aimed to determine whether consuming local or non-local cherries alters liver and muscle FA profiles under different photoperiods, and to identify the associated changes in metabolic gene expression and serum metabolites. Methods: Seventy-two Fischer 344 rats, fed a standard diet and either vehicle (VH), Local Cherry (LC), or non-Local Cherry (nLC), were exposed to different hours of light to simulate photoperiods (winter, spring/autumn, or summer) for 7 weeks. The FA profiles of the liver and muscle were determined using GC-FID, and the gene expression of key enzymes involved in FA metabolism was evaluated. Moreover, the composition of hydrophilic and lipophilic metabolites in the serum and liver was analyzed using nuclear magnetic resonance (NMR), and pathway analysis was performed. Results: Consumption of cherries in season (18 h of light) decreased saturated FAs levels in the liver, mainly palmitate, compared to their respective VH; interestingly, this effect was not observed in other photoperiods. Furthermore, muscle polyunsaturated FA (PUFAs) decreased, possibly due to increased oxidation. Conclusions: Seasonal cherry consumption improves the hepatic lipid profile and increases muscular oxidation. Future studies are needed to better define these effects and uncover the differences in lipid metabolism in response to cherry consumption. Full article

Although the impact of COVID-19, caused by SARS-CoV-2, may appear to have diminished in recent years, the emergence of new variants still continues to cause significant global health and economic challenges. While numerous metabolomic studies have explored serum-based alterations linked to the infection, investigations utilizing urine as a biological matrix remain notably limited. This gap is especially significant given the potential advantages of urine, a non-invasive and easily obtainable biofluid, in clinical settings. In the context of patients in intensive care units (ICUs), temporal monitoring through such non-invasive samples may offer a practical and effective approach for tracking disease progression and tailoring therapeutic interventions. This study retrospectively explored the longitudinal metabolomic alterations in COVID-19 patients admitted to the ICU, stratified into three prognostic outcome groups: healthy discharged (HD), polyneuropathic syndrome (PS), and Exitus. A total of 32 urine samples, collected at four distinct time points per patient during April 2020 and preserved at −80 °C, were analyzed by proton nuclear magnetic resonance (¹H-NMR) spectroscopy for comprehensive metabolic profiling. Statistical evaluation using two-way ANOVA and ANOVA–Simultaneous Component Analysis (ASCA) identified significant prognostic variations (p < 0.05) in the levels of taurine, 3-hydroxyvaleric acid and formic acid. Complementary supervised classification via random forest modeling yielded moderate predictive performance with out-of-bag error rate of 40.6% based on prognostic categories. Particularly, taurine, 3-hydroxyvaleric acid and formic acid levels were highest in the PS group. However, no significant temporal changes were observed for any metabolite in analyses. Additionally, metabolic pathway analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the “taurine and hypotaurine metabolism” pathway as the most significantly affected (p < 0.05) across prognostic classifications. Harnessing urinary metabolomics, as indicated in our preliminary study, could offer valuable insights into the dynamic metabolic responses of ICU patients, thereby facilitating more personalized and responsive critical care strategies in COVID-19 patients. Full article

Background: Trypanosoma cruzi, the causative agent of Chagas disease, remains a major public health concern, and there is a continued need for new antitrypanosomal agents. Thiosemicarbazone (TSC) derivatives have emerged as a promising class of compounds with potential antiparasitic activity. Objectives: This study aimed to report the synthesis, characterization, and biological profiling of a novel series of thiosemicarbazone derivatives as antitrypanosomal agents against Trypanosoma cruzi. Methods: Fourteen new compounds and six previously described analogues were prepared and characterized by ¹H/¹³C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). As a preliminary in vitro screen, activity was assessed by direct parasite counting in epimastigote and bloodstream trypomastigote forms, as tractable models of replicative and infective stages sharing core metabolic targets with intracellular amastigotes. Epimastigote potency was quantified as half-maximal effective concentrations (EC₅₀) derived from dose–response curves, whereas trypomastigote response was evaluated as percent viability after treatment at a fixed concentration of 20 µM. Mechanistic profiling included inhibition assays against the cysteine protease cruzipain (CZP) and selected redox defense enzymes, complemented by in silico similarity clustering and binding-pose affinity scoring. Results: A nitro-methoxy-substituted TSC showed potent CZP inhibition but limited trypomastigote efficacy, whereas brominated analogues displayed dual-stage activity independent of CZP inhibition. Tanimoto similarity analysis identified distinct structure–activity clusters, linking nitro-methoxy substitution to epimastigote selectivity and brominated scaffolds to broader antiparasitic profiles, with hydrophobicity and steric complementarity as key determinants. Enzymatic assays revealed no significant inhibition of cytosolic tryparedoxin peroxidase (cTXNPx) or glutathione peroxidase type I (TcGPx-I), suggesting redox disruption is not a primary mode of action. In vitro and in silico analyses showed low or no non-specific cytotoxicity under the tested conditions, supporting further optimization of these derivatives as antitrypanosomal preliminary hits. Key hits included derivative 3e (epimastigote EC₅₀ = 0.36 ± 0.02 µM) and brominated analogues 2c and 2e (epimastigote EC₅₀ = 3.92 ± 0.13 and 4.36 ± 0.10 µM, respectively), while docking supported favorable binding-pose affinity (e.g., ΔG_S-pose = −20.78 ± 2.47 kcal/mol for 3e). Conclusions: These results support further optimization of the identified thiosemicarbazone derivatives as preliminary antitrypanosomal hits and provide insight into structure–activity relationships and potential mechanisms of action. Full article

Grouting technology can be employed to repair cracks in an aquifer to maintain its stability; however, existing grouting materials tend to come with problems such as low flexural strength, poor cracking resistance, and the coupled effects of fiber reinforcement and sulfoaluminate cement (SAC) addition on hydrate evolution, and pore-refinement and crack-resistance mechanisms in coal-based solid-waste cementitious grouts remain insufficiently understood. In this paper, fiber-modified coal-based solid-waste grouting (F-CWG) materials were prepared by mixing different contents of sulfoaluminate cement (SAC) and different fibers. The mechanical strength, microstructure, hydration products, and pore evolution characteristics were analyzed by means of mechanical property tests, energy-dispersive X-ray spectroscopy (SEM/EDS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and nuclear magnetic resonance (NMR). The results show that the mechanical strength decreases at first due to insufficient early-stage hydration products. Specifically, the 28 d compressive and flexural strengths decrease from 15.34 MPa and 4.55 MPa at 0% SAC to 8.18 MPa and 2.99 MPa at 40% SAC but increase again to 13.36 MPa and 3.79 MPa at 60% SAC as the formation of ettringite (AFt) and C–S–H is promoted with higher SAC content. Among the tested fibers, a dosage of 0.6% generally improves mechanical strength and refines pore structure, with PVA and steel fibers showing the most pronounced effects. Our results reveal the mechanism behind the enhancement of cracking resistance in F-CWG materials, providing a scientific basis for grouting and water-preservation mining, and are of great significance in improving the utilization rate of coal-based solid waste. Full article

Purpose: To investigate associations between lipid oxidation biomarkers (oxylipins), antioxidant micronutrients, lipoprotein particles, and apolipoproteins in multiple sclerosis (MS). Methods: Blood and neurological assessments were collected from 30 healthy controls, 68 relapsing remitting MS subjects, and 37 progressive MS subjects. Hydroxy (H) and hydroperoxy lipid peroxidation products of the polyunsaturated fatty acids (PUFAs) arachidonic (20:4, ω-6), linoleic (octadecadienoic acid or ODE, 18:2, ω-6), eicosapentaenoic (20:5, ω-3), and α-linolenic (18:3, ω-3) acids were measured using liquid chromatography–mass spectrometry. Antioxidant micronutrients, including β-cryptoxanthin and lutein/zeaxanthin, were quantified by high-performance liquid chromatography. Lipoprotein and metabolite profiles were obtained using nuclear magnetic resonance spectroscopy. Regression models were adjusted for age, sex, body mass index, and disease status. Results: The 9-hydroxy octadecadienoic acid to 13-hydroxy octadecadienoic acid ratio (9-HODE/13-HODE ratio), which reflects autoxidative versus enzymatic oxidation, was associated with MS status (p = 0.002) and disability on the Expanded Disability Status Scale (p = 0.004). Lutein/zeaxanthin (p = 0.023) and β-cryptoxanthin (p = 0.028) were negatively associated with the 9-HODE/13-HODE ratio. Apolipoprotein-CII, a marker of liver-X-receptor (LXR) signaling, was associated with 9-HODE/13-HODE ratio and other oxylipins. Octadecadienoic fatty acid-derived oxylipins were negatively associated with LC3A, a mitophagy marker, and positively correlated with 7-ketocholesterol, a cholesterol autoxidation product. Conclusions: Autoxidation of PUFAs is associated with greater disability in MS. Higher β-cryptoxanthin and lutein/zeaxanthin were associated with reduced auto-oxidation. Lipid peroxidation shows associations with LXR signaling, mitophagy, inflammation, and cholesterol autoxidation. Full article

Coordination complexes play a crucial role in modern research. 4-benzopyranone-2-carboxylic acid is a fascinating class of molecules with numerous applications, including the synthesis of pharmaceuticals and valuable chiral compounds. Antibacterial and tuberculostatic medicines, HIV protease inhibitors, intermediates in organic synthesis, and organic catalysis are only a few of the biological applications of chiral complexes. In this study, the synthesis of four metal complexes, C₃₀H₂₈N₂NiO₁₂ [Ni(bzpyr)₂(py)₂(H₂O)₂] (I), C₃₀H₂₄CoN₂O₁₀ [Co(bzpyr)₂(py)₂(H₂O)₂] (II), C₂₀H₂₀O₁₃Zn [Zn(bzpyr)₂(H₂O)₃] (III), and C₃₀H₂₂CuN₂O₉ [Cu(bzpyr)₂(py)₂(H₂O)] (IV), is reported via direct reactions of 4-benzopyranone-2-carboxylic acid with metal salts and pyridine in anhydrous ethanol. Single-crystal X-ray diffraction analysis revealed that complexes I and II crystallize in the chiral space group P-1, whereas III and IV crystallize in the centrosymmetric space group P2₁/c. The structures of these complexes were further characterized by infrared spectroscopy, UV-Visible Diffuse Reflectance Spectroscopy, electrospray ionization mass spectrometry (ESI-MS), elemental analysis, nuclear magnetic resonance, electron paramagnetic resonance spectroscopy and single-crystal X-ray diffraction. In addition, the cytotoxic activities of complexes I–IV were evaluated against the human tumor cell lines K562, A549, HepG2, MDA-MB-231, and SW480, and molecular docking studies were conducted on the four complexes. Full article

Cerebrospinal fluid (CSF) is a key biological matrix that reflects the physiological and pathological states of the central nervous system (CNS). It supports brain function by regulating ionic balance, facilitating molecular transport, and clearing metabolic waste. In this article, we present a standardized protocol for CSF collection along with an integrative multiplatform metabolomic workflow that combines proton nuclear magnetic resonance spectroscopy (¹H-NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Integrating these complementary analytical modalities enhances metabolite coverage and improves analytical robustness, enabling a more comprehensive and reliable characterization of the CSF metabolome. This workflow supports the discovery of potential biomarkers and advances our understanding of neurochemical alterations within the CNS. Full article

This study investigated the effects of pH (3, 5, 7, 9, 11) on the structure–activity relationship and stability mechanism of Pickering emulsions stabilized by the gorgon euryale starch–quinoa protein complex. Analyses were performed using reverse compression test, rheology, thermal stability assessment, atomic force microscopy (AFM), and low-field nuclear magnetic resonance (LF-NMR) measurements. Reverse compression test showed that the emulsion at pH 3 exhibited the highest hardness and consistency, but the weakest cohesiveness. Rheological measurements revealed that all emulsions displayed shear-thinning behavior, the emulsion at pH 3 had the highest shear stress and apparent viscosity, while that at pH 11 showed the lowest viscosity due to the destruction of macromolecular structures. Thermal stability assessment indicated that the emulsion at pH 3 did not undergo significant stratification even at 60 °C, whereas the stability of emulsions decreased between pH 5–9. Microscopic analyses (optical microscopy, AFM, and LF-NMR) further confirmed that the emulsion at pH 3 had fine, uniform droplets, strong water-binding capacity, and an interfacial film with a “dense protrusion” structure. This study provides a basis for the environmental adaptability design of functional emulsions and contributes to the high-value utilization of gorgon euryale and quinoa resources. Full article

Revealing the evolution of micropore structure in industrial by-product solidified sludge is essential for elucidating strength development mechanisms and promoting the engineering utilization of industrial wastes. In this study, a series of tests, including unconfined compressive strength (UCS), low-field nuclear magnetic resonance, direct shear, and scanning electron microscopy coupled with energy-dispersive spectroscopy, were conducted on granulated blast furnace slag–carbide slag–titanium gypsum (GCT)-solidified sludge (GSDS) and cement-solidified sludge (CSDS). The results demonstrate that GSDS exhibits significantly superior compressive strength, deformation resistance, and pore-filling capacity compared with CSDS. With increasing curing age, both materials show logarithmic increases in UCS and mesopore volume fraction, accompanied by power-law decreases in total pore volume and the most probable pore size. On this basis, quantitative relationships between micropore characteristics and macroscopic mechanical properties are established for both solidified sludges. Microscopic analyses reveal that strength development in GSDS is primarily attributed to the formation of abundant C-(A)-S-H gels and expansive ettringite crystals, which effectively cement soil particles and refine interparticle pores. The synergistic solidification mechanism of GCT, involving ion exchange, cementitious bonding, and pore filling, promotes particle aggregation, enhances interparticle bonding, and refines pore structure, thereby markedly improving structural integrity and macroscopic strength in GSDS. Full article

Cationic arabinogalactan (AG) derivatives with a degree of substitution (0.02–0.19) containing quaternary ammonium groups were prepared by reaction of the etherification of (3-Chloro-2-hydroxypropyl)-trimethylammonium chloride (CHPTAC), catalyzed by an aqueous solution of sodium hydroxide. The effect of etherification was assessed by the degree of substitution (DS). The DS values of the AG samples were controlled by the varied pH of the reaction mixture from 10 to 12 and the duration of the process quaternization (2, 18, 24, 30 and 72 h). In comparison, the quaternized samples of the AG were characterized by physicochemical research methods, such as elemental analysis, gel permeation chromatography (GPC), Fourier Transform Infrared (FTIR), and ¹H nuclear magnetic resonance (NMR) spectroscopy, and thermogravimetric analysis (TGA). Furthermore, the improved antioxidant capacity of the quaternized AGs was evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. It was found that the most favorable conditions for the quaternization process were pH = 12, duration and temperature of the process of 31.6 h and 50 °C, respectively. The esterification reaction was accompanied by hydrolysis side reactions at a longer process. Full article