Search Results (36)

Aristolochic acid I (AAI) is widely recognized as a genotoxic and cytotoxic compound. To rationally propose detoxification strategies, it is essential to fully elucidate the in vivo disposition of AAI. Nevertheless, the toxicokinetic characteristics of AAI, particularly the possible involvement of the recirculation process, remain incompletely understood. In this research, toxicokinetics of AAI was studied following a single oral administration of AAI in Fisher rats (10, 30 and 100 mg/kg, n = 6). A method of ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QQQ-MS/MS) was developed to achieve the quantitation of AAI in rat plasma. Plasma concentration–time profiles and kinetic parameters were analyzed to characterize the toxicokinetic behavior of AAI. A secondary elevation was observed in the plasma concentration–time profiles of AAI, suggesting the existence of AAI reabsorption. The non-linear elimination kinetics of AAI might be attributed to capacity-limited excretion via bile. Additionally, the biliary excretion of AAI and several key metabolites was also explored through qualitative analysis of bile samples. For the first time, AAI-O-glucuronide was identified in bile, providing further support for enterohepatic recirculation (EHR)-mediated reabsorption of AAI. In conclusion, these findings provided solid evidence for EHR-mediated reabsorption of AAI in rats. The recirculation process might be a key mechanism responsible for the prolonged retention of AAI. In the future, detoxification strategies targeting the EHR process could be effective approaches to minimize the systemic exposure of AAI. Full article

Gnetol (trans-2,3′,5′,6-tetrahydroxystilbene), a naturally occurring stilbene structurally related to resveratrol (trans-3,5,4′-trihydroxystilbene; RES), has been reported to possess multiple health-promoting activities. In order to support its potential nutraceutical application, a reliable chromatography–tandem mass spectrometry (LC–MS/MS) assay was developed and validated for the quantitative determination of gnetol in mouse plasma and tissue samples, using isotopically labeled RES-¹³C₆ serving as the internal standard (IS). Electrospray ionization (ESI) was performed in negative mode, with multiple reaction monitoring (MRM) transitions m/z 243.2 → 175.0 for gnetol and m/z 233.1 → 191.0 for the IS. Chromatographic separation was achieved on a reversed-phase HPLC column using a 5-min gradient delivery of acetonitrile and 2 mM ammonium acetate at 0.5 mL/min and 40 °C. The linear calibration curve covered the concentration range of 5.0–1500 ng/mL, and the method validation confirmed its selectivity, accuracy, precision, stability, and dilution integrity. The developed method was subsequently applied to a biodistribution study in mice after oral administration of gnetol at 400 µmol/kg (equivalent to 97.7 mg/kg). Gnetol was rapidly absorbed and extensively distributed in key pharmacologically relevant organs. Despite its poor aqueous solubility, oral uptake was not significantly hindered. Collectively, these findings demonstrate that gnetol exhibits favorable absorption and tissue distribution profiles, supporting its promise as a candidate for nutraceutical development. Full article

Understanding three-dimensional (3D) auxetic structural responses to impact loading remains challenging due to large deformations involving failure evolution and the interaction between geometric and material instabilities. In this study, the Generalized Interpolation Material Point Method (GIMP) is used to investigate representative auxetic structures, with the focus on the negative Poisson’s ratio effect on the responses to impact loading. Using a cubic lattice model for 3D re-entrant structures, simulations with different impact speeds are performed to evaluate corresponding energy absorption characteristics and deformation behaviors. Three constitutive models for lattice materials (linear elasticity, elastoplasticity, and damage) are employed to analyze the corresponding variations in auxetic structural performance. The computational results indicate that distinct deformation mechanisms are mainly associated with microstructural geometry, while the constitutive modeling effect is not significant. The findings demonstrate the importance of the process–structure–property relationship in the impact performance of protective structures. Verification against theoretical predictions of the Poisson’s ratio–strain relationship confirms the potential of GIMP in effectively engineering auxetic structures for general applications. Full article

Background: This study examined how the concentration of calcium (Ca) influences the microstructure, mechanical characteristics, and tribological attributes of Mg–Ca–Zn–RE–Zr alloys for orthopedic medicine. Materials and methods: Experimental alloys with 0.1 and 0.5 wt% Ca were prepared in a controlled atmosphere induction furnace. The microstructure of the alloys was investigated by scanning electron microscopy, the chemical composition by X-ray fluorescence and energy-dispersive spectroscopy, the mechanical properties by indentation and scratching, and the corrosion resistance by linear and cyclic potentiometry. Results: The alloy with 0.1% Ca exhibited greater fluctuations in the coefficient of friction, while the sample with 0.5% Ca showed a higher susceptibility to cracking. Regarding corrosion resistance, both samples exhibited a generalized corrosion trend with similar corrosion currents. At lower Ca concentrations (0.1%), the refined microstructure of the alloys provided an elastic modulus closer to that of human bone, minimizing the risk of excessive local stress and promoting uniform load distribution at the bone-implant interface. Conclusion: The 0.5% Ca alloy offered superior tribological stability and better shock absorption, making it suitable for applications requiring long-term stability. The study highlighted the potential of both compositions based on the specific requirements of biodegradable orthopedic implants. Full article

Auxetic structures have garnered considerable interest for being lightweight and exhibiting superior properties such as an excellent energy absorption capability. In this paper, re-entrant and missing rib square grid auxetic structures were additively manufactured via the fused deposition modeling technique using two types of polyether imide materials: ULTEM 9085 and ULTEM 1010. In-plane quasi-static compressive tests were carried out on the proposed structures at different relative densities to investigate the Poisson’s ratio, equivalent modulus, deformation behavior, and energy absorption performance. Finite element simulations of the compression process were conducted, which confirmed the deformation behavior observed in the experiments. It was found that the Poisson’s ratio and normalized equivalent Young’s modulus of ULTEM 9085 and ULTEM 1010 with the same geometries were very close, while the energy absorption of the ductile ULTEM 9085 was significantly higher than that of the brittle ULTEM 1010 structures. Furthermore, a linear correlation exists between the relative density and specific energy absorption of missing rib square grid structures within the investigated relative density range, whereas the relationship for re-entrant structures follows a power law. This study provides a better understanding of how material properties influence the deformation behavior and energy absorption characteristics of auxetic structures. Full article

This study examines the flow dynamics of synovial fluid within a lubricated knee joint during movement, incorporating the effect of inertia and linear re-absorption at the synovial membrane. The fluid behavior is modeled using a couple-stress fluid framework, which accounts for mechanical phenomena and employs a lubricated membrane. synovial membrane plays a crucial role in reducing drag and enhancing joint lubrication for the formation of a uniform lubrication layer over the cartilage surfaces. The mathematical model of synovial fluid flow through the knee joint presents a set of non-linear partial differential equations solved by a recursive approach and inverse method through the software Mathematica 11. The results indicate that synovial fluid flow generates high pressure and shear stress away from the entry point due to the combined effects of inertial forces, linear re-absorption, and micro-rotation within the couple-stress fluid. Axial flow intensifies at the center of the knee joint during activity in the presence of linear re-absorption and molecular rotation, while transverse flow increases away from the center and near to synovium due to its permeability. These findings provide critical insights for biomedical engineers to quantify pressure and stress distributions in synovial fluid to design artificial joints. Full article

Project Managers face many difficulties when scheduling the development and production of multiple, largely independent systems required for a new capability, especially when there are multiple stakeholders, uncertainties in the expected development time, and developmental dependencies among the systems. The Systems Developmental Dependency Analysis methodology provides a systemic approach to address these challenges by offering decision support for such a ‘System-of-Systems’. The method, based on a parametric piece-wise linear model of dependencies between elements in the developmental domain, propagates the interactions between systems to estimate delays in the development of individual systems and to evaluate the impact of such delays on the expected schedule of completion for the establishment of the whole desired capability. The schedule can be automatically re-generated based on new system information, changed dependencies, and/or modified risk levels. As demonstrated in this paper using a complex space mission case, the method enhances decision-support by identifying criticalities, computing possible delay absorption strategies, and comparing different development strategies in terms of robustness to delays. Full article

Metal–organic framework materials, as innovative functional materials for nonlinear optical technologies, feature linear and nonlinear optical responses, such as a laser damage threshold, outstanding mechanical properties, thermal stability, and optical transparency. Their non-centrosymmetric crystal structure induces a higher-order nonlinear optical response, which guarantees technological applications. Zn^II– and Ag^I–squarate complexes are attractive templates for these purposes due to their good crystal growth, optical transparency, high thermal stability, etc. However, the space group type of the catena-((μ₂-squarato)-tetra-aqua-zinc(II)) complex ([Zn(C₄O₄)(H₂O)₄]) is debatable, (1) showing centro- and non-centrosymmetric monoclinic C2/c and Cc phases. The same is valid for the catena-((μ₃-squarato)-(μ₂-aqua)-silver(I)) complex (Ag₂C₄O₄), (2) exhibiting, so far, only a C2/c phase. This study is the first to report new crystallographic data on (1) and (2) re-determined at different temperatures (293(2) and 300(2)K) and the non-centrosymmetric Cc phase of (2), having different numbers of molecules per unit cell compared with the C2/c phase. There are high-resolution crystallographic measurements of single crystals, experimental electronic absorption, and vibrational spectroscopic data, together with ultra-high-resolution mass spectrometric ones. The experimental results are supported for theoretical optical and nonlinear optical properties obtained via high-accuracy static computational methods and molecular dynamics, using density functional theory as well as chemometrics. Full article

Wave energy holds significant promise as a renewable energy source due to the consistent and predictable nature of ocean waves. However, optimizing wave energy devices is essential for achieving competitive viability in the energy market. This paper presents the application of a nonlinear model predictive controller (MPC) to enhance the energy extraction of a heaving point absorber. The wave energy converter (WEC) model accounts for the nonlinear dynamics and static Froude–Krylov forces, which are essential in accurately representing the system’s behavior. The nonlinear MPC is tested under irregular wave conditions within the power production region, where constraints on displacement and the power take-off (PTO) force are enforced to ensure the WEC’s safety while maximizing energy absorption. A comparison is made with a linear MPC, which uses a linear approximation of the Froude–Krylov forces. The study comprehensively compares power performance and computational costs between the linear and nonlinear MPC approaches. Both MPC variants determine the optimal PTO force to maximize energy absorption, utilizing (1) a linear WEC model (LMPC) for state predictions and (2) a nonlinear model (NLMPC) incorporating exact Froude–Krylov forces. Additionally, the study analyzes four controller configurations, varying the MPC prediction horizon and re-optimization time. The results indicate that, in general, the NLMPC achieves higher energy absorption than the LMPC. The nonlinear model also better adheres to system constraints, with the linear model showing some displacement violations. This paper further discusses the computational load and power generation implications of adjusting the prediction horizon and re-optimization time parameters in the NLMPC. Full article

Red solar-induced chlorophyll fluorescence (SIF_B) is closely related to the photosynthetically active radiation absorbed by chlorophyll. The scattering and reabsorption of SIF_B by the vegetation canopy significantly change the spectral intensity and shape of SIF, which affects the relationship between SIF and crop stress. To address this, we propose a method of modifying SIF_B using SIF spectral shape characteristic parameters to reduce this influence. A red pseudokurtosis (PK_B) parameter that can characterize spectral shape features was calculated using full-spectrum SIF data. On this basis, we analyzed the photosynthetic physiological mechanism of PK_B and found that it significantly correlates with both the fraction of photosynthetically active radiation absorbed by chlorophyll(fPAR_chl) and the red SIF escape rate (fesc680); thus, it is closely related to the scattering and reabsorption of SIF_B by the vegetation canopy. Consequently, we constructed an expression of PK_B to modify SIF_B. To evaluate the modified SIF_B (MSIF_B) in monitoring the severity of wheat stripe rust, we analyzed the correlations between SIF_B, MSIF_B, SIF_B-VIs (a fusion of the vegetation index and SIF_B), and MSIF_B-VIs (a fusion of the vegetation index and MSIF_B) with the severity level (SL), respectively. The results show that the correlation between MSIF_B and the severity of wheat stripe rust increased by an average of 25.6% and at least 16.95% compared with that for SIF_B. In addition, we constructed remote sensing monitoring models for wheat stripe rust using linear regression methods, with SIF_B, MSIF_B, SIF_B-VIs, and MSIF_B-VIs as independent variables. PK_B significantly improves the accuracy and robustness of models based on SIF_B and its fusion index SIF_B-VIs in the constructed testing set. The R-value between the predicted SL and the measured SL of the remote sensing monitoring model for wheat stripe rust was established using MSIF_B-VIs as the independent variable, and it was improved by an average of 39.49% compared with the model using SIF_B-VIs. The RMSE was reduced by an average of 18.22%. Therefore, the SIF_B modified by PK_B can weaken the effects of chlorophyll reabsorption and canopy architecture on SIF_B and improve the ability of SIF_B to detect stress information. Full article

The quinoline alkaloid 2-(quinoline-8-carboxamido)benzoic acid (2-QBA), which is isolated from Aspergillus sp. SCSIO06786, a deep sea-derived fungus, has been suggested as a therapeutic candidate for the treatment of Parkinson’s disease. We developed an analytical method for 2-QBA using a liquid chromatography–tandem mass spectrometry (LC-MS/MS) in mouse plasma, in which a protein precipitation method for the sample preparation of 2-QBA in mouse plasma was used due to its simplicity and good extraction recovery rates (80.49–97.56%). The linearity of the calibration standard sample, inter- and intraday precision and accuracy, and stability of three quality control samples were suitable based on the assessment criteria and the lower limit of quantification (LLOQ) of the 2-QBA was 1 ng/mL. A pharmacokinetic study of 2-QBA was performed in mice divided into oral (2.0, 5.0, and 15 mg/kg) and intravenous (0.5 and 1.0 mg/kg) administration groups. The absolute oral bioavailability (BA) range of 2-QBA was calculated as 68.3–83.7%. Secondary peaks were observed at approximately 4–8 h after the oral administration of 2-QBA at all doses. The elimination half-life of the orally administered 2-QBA was significantly longer than that of the intravenous 2-QBA. In addition, glucuronide metabolites of 2-QBA were identified. They were transformed into 2-QBA using the β-glucuronidase treatment. Furthermore, the 2-QBA was readily absorbed from the jejunum to lower ileum. Taken together, the secondary peaks could be explained by the enterohepatic circulation of 2-QBA. In conclusion, the reabsorption of orally administered 2-QBA could contribute to the high oral BA of 2-QBA and could be beneficial for the efficacy of 2-QBA. Moreover, the simple and validated analytical method for 2-QBA using LC-MS/MS was applied to the pharmacokinetic study and BA assessments of 2-QBA in mice and would be helpful for subsequent pharmacokinetic studies, as well as for evaluations of the toxicokinetics and pharmacokinetic–pharmacodynamic correlation of 2-QBA to assess its potential as a drug. Full article

Jieyu Pills (JYPs), a Chinese medicine consisting of 10 herbal elements, have displayed promising clinical effectiveness and low by-effects in the treatment of depression. Prior investigations mostly focused on elucidating the mechanism and therapeutic efficacy of JYPs. In our earlier study, we provided an analysis of the chemical composition, serum pharmacochemistry, and concentrations of the main bioactive chemicals found in JYPs. However, our precise understanding of the pharmacokinetics and metabolism remained vague. This study involved a comprehensive and meticulous examination of the pharmacokinetics of 13 bioactive compounds in JYPs. Using UPLC-Orbitrap Fusion MS, we analyzed the metabolic characteristics and established the pharmacokinetic parameters in both control rats and model rats with attention deficit hyperactivity disorder (ADHD) following oral administration of the drug. Before analysis, plasma samples that were collected at different time intervals after the administration underwent methanol pre-treatment with Puerarin used as the internal standard (IS) solution. Subsequently, the sample was chromatographed on a C18 column employing gradient elution. The mobile phase consisted of methanol solution containing 0.1% formic acid in water. The electrospray ionization source (ESI) was utilized for ionization, whereas the scanning mode employed was selected ion monitoring (SIM). The UPLC-Orbitrap Fusion MS method was subjected to a comprehensive validation process to assess its performance. The method demonstrated excellent linearity (r ≥ 0.9944), precise measurements (RSD < 8.78%), accurate results (RE: −7.88% to 8.98%), and appropriate extraction recoveries (87.83–102.23%). Additionally, the method exhibited minimal matrix effects (87.58–101.08%) and satisfactory stability (RSD: 1.52–12.42%). These results demonstrated adherence to the criteria for evaluating and determining biological material. The 13 bioactive compounds exhibited unique pharmacokinetic patterns in vivo. In control rats, all bioactive compounds except Ferulic acid exhibited linear pharmacokinetics within the dose ranges. In the ADHD model, the absorption rate and amount of most of the components were both observed to have increased. Essentially, this work is an important reference for examining the metabolism of JYPs and providing guidelines for clinical therapy. Full article

The UV/Vis absorption energies (ν_max) of different solvatochromic probes measured in co-solvent/water mixtures are re-analyzed as a function of the average molar concentration (N_av) of the solvent composition compared to the use of the mole fraction. The empirical E_T(30) parameter of Reichardt’s dye B30 is the focus of the analysis. The Marcus classification of aqueous solvent mixtures is a useful guide for co-solvent selection. Methanol, ethanol, 1,2-ethanediol, 2-propanol, 2-methyl-2-propanol, 2-butoxyethanol, formamide, N-methylformamide (NMF), N,N-dimethylformamide (DMF), N-formylmorpholine (NFM), 1,4-dioxane and DMSO were considered as co-solvents. The E_T(30) values of the binary solvent mixtures are discussed in relation to the physical properties of the co-solvent/water mixtures in terms of quantitative composition, refractive index, thermodynamics of the mixture and the non-uniformity of the mixture. Significant linear dependencies of E_T(30) as a function of N_av can be demonstrated for formamide/water, 1,2-ethanediol/water, NMF/water and DMSO/water mixtures over the entire compositional range. These mixtures belong to the group of solvents that do not enhance the water structure according to the Marcus classification. The influence of the solvent microstructure on the non-linearity E_T(30) as a function of N_av is particularly clear for alcohol/water mixtures with an enhanced water structure. Full article

Nitrofurantoin (NFT) is a commonly used antibiotic for the treatment of urinary tract infections that can cause liver toxicity. Despite reports of hepatic adverse events associated with NFT exposure, there is still limited understanding of the interplay between NFT exposure, its disposition, and the risk of developing liver toxicity. In this study, we aim to develop a physiologically based pharmacokinetic (PBPK) model for NFT in three different species (rabbits, rats, and humans) that can be used as a standard tool for predicting drug-induced liver injury (DILI). We created several versions of the PBPK model using previously published kinetics data from rabbits, and integrated enterohepatic recirculation (EHR) using rat data. Our model showed that active tubular secretion and reabsorption in the kidney are critical in explaining the non-linear renal clearance and urine kinetics of NFT. We subsequently extrapolated the PBPK model to humans. Adapting the physiology to humans led to predictions consistent with human kinetics data, considering a low amount of NFT to be excreted into bile. Model simulations predicted that the liver of individuals with a moderate-to-severe glomerular filtration rate (GFR) is exposed to two-to-three-fold higher concentrations of NFT than individuals with a normal GFR, which coincided with a substantial reduction in the NFT urinary concentration. In conclusion, people with renal insufficiency may be at a higher risk of developing DILI due to NFT exposure, while at the same time having a suboptimal therapeutic effect with a high risk of drug resistance. Our PBPK model can in the future be used to predict NFT kinetics in individual patients on the basis of characteristics like age and GFR. Full article

In order to accurately obtain photometric information of high concentration SO₄²⁻ and other substances in the process industry, the spectroscopy behavior of SO₄²⁻, S²⁻, Ni²⁺ and Cu²⁺ in air and nitrogen atmosphere was compared based on the UV-visible spectrophotometer with a nitrogen replacing the oxygen. Different from Ni²⁺ and Cu²⁺, the accuracy of SO₄²⁻ and S²⁻ in the ultraviolet region was effectively improved by using a nitrogen atmosphere (P detection results were regressed within the limited standard range, RE < 5%). The nitrogen atmosphere suppressed the additional light attenuation caused by its absorption of ultraviolet rays by isolating oxygen and was also reflected in the decrease in the degree of red shift of the characteristic wavelength for SO₄²⁻ with increasing concentration. Therefore, the detection results of SO₄²⁻ showed an effective improvement in sensitivity. Nevertheless, according to the complementary experimental results and theoretical calculations, in addition to oxygen absorption, the low detection accuracy of SO₄²⁻ high concentration is also attributed to the reduction of the energy required for electronic excitation per unit group caused by the interaction between SO₄²⁻ groups, resulting in a deviation of the C-A curve from linearity at high concentrations. The influence of this intermolecular force on the detection results is far more important than oxygen absorption. The research can provide reliable theoretical guidance and technical support for the pollution-free direct measurement of high-concentration solutions in the process industry and promote the sustainable development of the process industry. Full article