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Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer's disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model. Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group. Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.
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With the increasing capacity of renewable energy generators, microgrid (MG) systems have experienced rapid development, and the optimal economic operation is one of the most important and challenging issues in the MG field. To reduce the overall generation cost of microgrids, a hybrid butterfly algorithm (HBOA) is proposed to address the optimal economic operation problem in MG systems. This algorithm uses adaptive switching thresholds to balance the global exploration capability and local exploitation capability of the algorithm. It introduces a diversity learning mechanism to enhance information exchange among populations to improve the algorithm's accuracy and proposes an elite-guided guidance strategy to accelerate the convergence speed of the algorithm. Numerical simulation experiments on 10 standard test functions validate that the HBOA algorithm has higher optimization accuracy and faster convergence speed. Simulation experiments are conducted on two operation modes of microgrids: Islanded and grid-connected, and compared with other algorithms. In islanded and grid-connected modes, HBOA can reduce operating costs by up to 11.7% and 17.7%, respectively. The experimental results confirm the applicability and superiority of the proposed algorithm for solving the optimal economic operation problem in microgrids.
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The occurrence and development of human diseases are influenced by both genetic and environmental factors. Research models that describe disease occurrence only from the perspective of genetics present certain limitations. In recent years, effects of environment factors on the occurrence and development of diseases have attracted extensive attentions. Exposomics focuses on the measurement of all exposure factors in an individual's life and how these factors are related to disease development. Exposomics provides new ideas to promote studies on the relationship between human health and environmental factors. Environmental exposures are characterized with different physical and chemical properties, as well as very low concentrations in vivo, which contribute great challenges in the comprehensive measurement of chemical residues in the human body. Chromatography-mass spectrometry-based technologies combine the high-efficiency separation ability of chromatography with the high resolution and sensitive detection characteristics of mass spectrometry; the combination of these techniques can achieve the high-coverage, high-throughput, and sensitive detection of environmental exposures, thus providing a powerful tool for measuring chemical exposures. Exposomics-analysis methods based on chromatography-mass spectrometry mainly include targeted quantitative analysis, suspect screening, and non-targeted screening. To explore the relationship between environmental exposure and the occurrence and development of diseases, researchers have developed research paradigms, including exposome wide association study, mixed-exposure study, exposomics and multi-omics (genome, transcriptome, proteome, metabolome)-association study, and so on. The emergence of these methods has brought about unprecedented developments in exposomics studies. In this manuscript, analytical methods based on chromatography-mass spectrometry, exposomics research paradigms, and their relevant prospects are reviewed.
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Exposición a Riesgos Ambientales , Metaboloma , Humanos , Cromatografía Liquida , Espectrometría de Masas , Análisis EspectralRESUMEN
PURPOSE: Recently, docetaxel (DTX) micelles based on retinoic acid derivative surfactants showed lower systemic toxicity and bioequivalence to polysorbate-solubilized docetaxel (Taxotere®) in a phase II clinical study. However, the poor stability of these surfactants in vitro and in vivo led to extremely harsh storage conditions with methanol, and the formed micelles were quickly disintegrated with rapid drug burst release in vivo. To further enhance the stability and accumulation in tumors of DTX micelles, a novel surfactant based on acitretin (ACMeNa) was synthesized and used to prepare DTX micelles to improve anti-tumor efficiency. METHODS: Novel micelle-forming excipients were synthesized, and the micelles were prepared using the thin film hydration technique. The targeting effect in vitro, distribution in the tumor, and its mechanism were observed. Pharmacokinetics and anti-tumor effect were further investigated in rats and tumor-bearing female mice, respectively. RESULTS: The DTX-micelles prepared with ACMeNa (ACM-DTX) exhibited a small size (21.9 ± 0.3 nm), 39% load efficiency, and excellent stability in vitro and in vivo. Long circulation time, sustained and steady accumulation, and strong penetration in the tumor were observed in vivo, contributing to a better anti-tumor effect and lower adverse effects. CONCLUSIONS: The micelles formed by ACMeNa showed a better balance between anti-tumor and adverse effects. It is a promising system for delivering hydrophobic molecules for cancer therapy.
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Antineoplásicos , Neoplasias , Acitretina , Animales , Línea Celular Tumoral , Docetaxel/farmacocinética , Portadores de Fármacos/química , Excipientes , Femenino , Metanol , Ratones , Micelas , Neoplasias/tratamiento farmacológico , Polisorbatos , Ratas , Tensoactivos , Taxoides/farmacología , Taxoides/uso terapéutico , TretinoinaRESUMEN
Through solvothermal reaction of InCl3 and tetracarboxylate ligands with different substituent groups on diphenyl ethers, three new anionic indium-organic frameworks have been successfully prepared. They are {[(CH3)2NH2]In(G-1)(H2O)}·9DMF (1), {[(CH3)2NH2]In(G-2)}·15DMF (2), and {[(CH3)2NH2]2In2(G-3)2}·16DMF (3) {DMF = N, N'-dimethylformamide; H4(G-1) = 5',5â³â³-oxybis(2'-methoxy[1,1':3',1â³-terphenyl]-4,4â³-dicarboxylic acid); H4(G-2) = 5',5â³â³-oxybis(2'-amino[1,1':3',1â³-terphenyl]-4,4â³-dicarboxylic acid); H4(G-3) = 5',5â³â³-oxybis([1,1':3',1â³-terphenyl]-4,4â³-dicarboxylic acid)}. Compounds 1-3 can be simplified as unimodal 4-connected frameworks with different topological types: lon, cag, and dia, respectively. Compounds 1 and 3 display 2-fold interpenetrating nets, while compound 2 is non-interpenetrating. Compounds 1 and 3 can adsorb cationic methylene blue (MB) with good capacity and a high adsorption rate due to their anionic frameworks and channel-type voids. In particular, compound 1 exhibits great selectivity for cationic MB in the mixtures of MB and methyl orange. In addition, the adsorption behavior of rare earth ions (Eu3+ and Tb3+) on compounds 1 and 3 has also been studied. Due to the different structural features and channel sizes of compounds 1 and 3 caused by different substituents on the ligands, the adsorption properties of rare earth ions on the two compounds are different.
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Metal-organic frameworks (MOFs) are an exciting class of porous crystallized materials, which have attracted great interest in sustainable energy and environmental remediation. Magnetite (Fe3O4) is one of the best-known magnetic materials and has been extensively studied with respect to properties involving high saturation magnetization, biocompatibility and low toxicity. The combination of MOFs and Fe3O4 has shown its potential applications in drug delivery, catalysis and wastewater treatment. However, only classical porous MOFs are used to encapsulate magnetic nanoparticles, such as MIL-100(Fe), ZIF-8, UiO-66 and so on. Herein, we firstly synthesized a new MOF ZTB-1 and surveyed its applications in magnetic materials. As a result, a highly water-stable MOF-based magnetic material Fe3O4@ZTB-1 has been obtained, and it was for the first time used as an excellent adsorbent for the fast adsorption of Congo red (CR) from aqueous solutions, exhibiting an adsorption capacity of 458 mg CR per gram. The electrostatic interactions and hydrogen bond are responsible for binding of CR with Fe3O4@ZTB-1. The magnetic material Fe3O4@ZTB-1 shows a potential application in dyeing wastewater treatment.
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Two metal-organic frameworks (MOFs), [Zn(BIPA)(tfbdc)]n (1) and {[Cd(BIPA)(tfbdc)(H2O)]·DMF}n (2), were hydrothermally synthesized using the self-assembly of the "V-shape" BIPA ligand (bis(4-(1H-imidazol-1-yl)phenyl)amine) and the H2tfbdc ligand (2,3,5,6-tetrafluorobenzene-1,4-dicarboxylic acid) with Zn/Cd metal salts. 1 is a 2D hcb framework and 2 is a 2D sql network. Their applications in detecting metal and inorganic ions were also explored. The results indicate that 1 exhibits dual-responsive photoluminescence sensing for Fe3+ and Cr2O72- ions while 2 can detect Hg2+ and Cr2O72- ions.
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Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution. The response time of NBOH was extremely short and the photostability was proved to be good. Toxicity test and fluorescence cell imaging together with a sub-cellular localization study were carried out revealing its low biotoxicity and good cell membrane permeability. And NBOH was successfully applied to the imaging of tumor tissue in tumor-bearing mice suggesting potential application to surgery as a tumor-specific probe.