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The extremely low stability of lanthanide clusters with precise structures and nanometer dimensions in aqueous solutions limits their application in the field of photodynamic sterilization. In this study, an hourglass-shaped nine-nucleated Dy9 cluster (1) with excellent light-driven reactive oxygen species (ROS) generation ability and photodynamic sterilization property was constructed using acylhydrazone multidentate chelating ligands obtained via an in situ reaction. The eight chelating ligands were distributed outside cluster 1, tightly wrapping the cluster core, thus preventing solvent molecules from attacking the cluster nucleus and ensuring the stability of cluster 1 in solution, which was demonstrated via X-ray diffraction and high-resolution electrospray ionization mass spectrometry (HRESI-MS). Time-dependent HRESI-MS monitoring of the self-assembly process of cluster 1 allowed two possible self-assembly mechanisms. The heavy atom effect of multiple Dy(III) ions in the Dy9 cluster enhanced the ISC pathway through spin-orbit coupling, promoting energy transfer from the excited singlet state (S1) to the triplet state (T1), which was stabilized, inducing the generation of more ROS. Cluster 1 showed a remarkable sterilization effect due to the generation of abundant ROS under light irradiation conditions. To our knowledge, this is a rare instance of lanthanide clusters with photodynamic sterilization, providing new horizons for the construction of fast and efficient sterilizers.
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It is difficult to subject simple reaction starting materials to a "one-pot" in situ tandem reaction without post-treatment under mild reaction conditions to obtain multimers with complex structural linkages. In organic synthesis, acetal reactions are often used to protect derivatives containing carbonyl functional groups. Therefore, acetal products tend to have very low stability, and performing multi-step condensation to obtain complex multimeric products is difficult. Herein, we achieved the first efficient multiple condensation of o-vanillin derivatives using Dy(OAc)3·6H2O undergoing a "one-pot" in situ tandem reaction under mild solvothermal conditions to obtain a series of dimers (I and II, clusters 1 and 2) and trimers (I and II, clusters 3 and 4). When methanol or ethanol is used as the solvent, the alcoholic solvent participates in acetal and dehydration reactions to obtain dimers (I and II). Surprisingly, when using acetonitrile as the reaction solvent, the o-vanillin derivatives undergo acetal and dehydration reactions to obtain trimers (I and II). In addition, clusters 1-4 all showed distinct single-molecule magnetic behaviors under zero-field conditions. To the best of our knowledge, this is the first time that multiple acetal reactions catalyzed by coordination-directed catalysis under "one-pot" conditions have been realized, opening a new horizon for the development of fast, facile, green, and efficient synthetic methods for complex compounds.
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Pinacol lanthanide complexes PyraLn (Ln = Dy and Tb) with the restriction of intramolecular vibration were obtained for the first time via an in situ solvothermal coordination-catalyzed tandem reaction using cheap and simple starting materials, thereby avoiding complex, time-consuming, and expensive conventional organic synthesis strategies. A high-resolution electrospray ionization mass spectrometry (HRESI-MS) analysis confirmed the stability of PyraLn in an organic solution. The formation process of PyraLn was monitored in detail using time-dependent HRESI-MS, which allowed for proposing a mechanism for the formation of pinacol complexes via in situ tandem reactions under one-pot coordination-catalyzed conditions. The PyraLn complexes constructed using a pinacol ligand with a butterfly configuration exhibited distinct aggregation-induced emission (AIE) behavior, with the αAIE value as high as 60.42 according to the AIE titration curve. In addition, the PyraLn complexes in the aggregated state exhibit a rapid photoresponse to various 3d metal ions with low detection limits. These findings provide fast, facile, and high-yield access to dynamic, smart lanthanide complex emissions with bright emission and facilitate the rational construction of molecular machines for artificial intelligence.
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AIM: To provide a summary of the available evidence concerning prevalence and risk factors of frailty in elderly patients with CHF. METHODS: PubMed, Embase, Web of Science, CINAHL, The Cochrane Library, China National Knowledge Infrastructure Database (CNKI), Chinese Biomedical Database (Sinomed), Weipu Database (VIP), and Wanfang database were searched from inception to July 2023. This study strictly followed the PRISMA guidelines. The quality of the included studies was rated by the Agency for Healthcare and Research and Quality and the Newcastle-Ottawa Scale. RESULTS: A total of 21 original studies were included, involving 4,797 patients. Meta-analysis results showed that the prevalence of frailty in older patients with heart failure was 38% (95%CI: 0.32-0.44). Age, cardiac function grading, left atrial diameter, left ventricular ejection fraction, hemoglobin, polypharmacy, BNP, nutritional risk, and hospitalization day are the influential factors of frailty in older patients with CHF. CONCLUSION: The prevalence of frailty in older patients with CHF is high, and clinical medical personnel should identify and intervene early to reduce or delay the frailty in older patients with CHF as much as possible.
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Fragilidade , Insuficiência Cardíaca , Idoso , Humanos , Doença Crônica , Fragilidade/epidemiologia , Insuficiência Cardíaca/epidemiologia , Prevalência , Fatores de Risco , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Tillering is a complicated process in plant and is a significant trait that affects biomass and seed yield of bunch grass Psathyrostachys juncea, a typical perennial forage species. To clarify the regulatory mechanisms of tillering in P. juncea and to explore related candidate genes could be helpful to improve the seed and forage yield of perennial gramineous forages. We selected the tiller node tissues of P. juncea for transcriptome sequencing to determine the differentially expressed genes (DEG) between dense and sparse tillering genotypes. The metabolic pathway was studied, candidate genes were screened, and reference genes stability were evaluated. RESULTS: The results showed that approximately 5466 DEGs were identified between the two genotypes with dense and sparse tillers of P. juncea, which significantly differed in tiller number. Tillering regulation pathways analysis suggested that DEGs closely related to the biosynthesis of three plant hormones, namely auxin (IAA), cytokinin (CTK), and strigolactones (SLs), while "biosynthesis of lignin" and "nitrogen metabolism" have remarkable differences between the dense and sparse tillering genotypes. Meanwhile, the reference gene Actin1, having the best stability, was screened from twelve genes with highest expression level and was used in verification of ten tillering related candidate genes. CONCLUSIONS: The tillering mechanism of perennial grass P. juncea was expounded by transcriptome analysis of tiller node tissues. We demonstrated that dense-tillering genotypes may be distinguished by their low expression patterns of genes involved in SL, IAA, and high expression patterns of genes involved in CTK biosynthesis at the tillering stage, and nitrogen metabolism and lignin biosynthesis can also affect the number of tillers. Furthermore, the expression level of ten tillering related candidate genes were verified using Actin1 as reference gene. These candidate genes provide valuable breeding resources for marker assisted selection and yield traits improvement of P. juncea.
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Reguladores de Crescimento de Plantas , Transcriptoma , Citocininas , Ácidos Indolacéticos , Lignina , Nitrogênio , Melhoramento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismo , TecnologiaRESUMO
Lanthanoid metal ions have large ionic radii, complex coordination modes, and easy distortion of coordination spheres, but the design and synthesis of high-nucleation lanthanoid clusters with high stability in solution (especially aqueous solution) are challenging. Herein, a diacylhydrazone ligand (H2L1) with multidentate chelating coordination sites was used to react with Dy(OAc)3·4H2O under solvothermal conditions to obtain an example of a 34-nucleus crown-shaped dysprosium cluster [Dy34(L)8(µ2-OH)(µ3-OH)21(µ3-O)14(OAc)31(OCH3)2(H2O)15](OAc)3 (1). Structural analysis showed that the bisacylhydrazone ligand H2L1 with polydentate chelate coordination sites could rapidly capture DyIII ions, thereby forming 34-nucleus crown-shaped dysprosium cluster 1 following the out-to-in growth mechanism. Cluster 1 remained stable after immersion in solutions with different pH values (3-14) for 24 h. To the best of the authors' knowledge, high-nucleation lanthanoid clusters with excellent strong acid and base stability and water stability are very rare. Meanwhile, high-resolution electrospray mass spectrometry molecular ion peaks produced by cluster 1 were captured, which proved to be stable also in organic solvents. Magnetic research showed that cluster 1 exhibited frequency-dependent behavior. This work provides a new idea for designing and synthesizing high-nucleation lanthanoid clusters with high stability.
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Widespread concern has been raised over the synthesis of highly nucleated lanthanide clusters with special shapes and/or specific linkages. Construction of lanthanide clusters with specific shapes and/or linkages can be achieved by carefully regulating the hydrolysis of lanthanide metal ions and the resulting hydrolysis products. However, studies on the manipulation of lanthanide-ion hydrolysis to obtain giant lanthanide-oxo clusters have been few. In this study, we obtained a tetraicosa lanthanide cluster (3) by manipulating the hydrolysis of Dy(III) ions using an anion (OAc-). As far as we know, cluster 3 has the highest nucleation among all lanthanide-oxo clusters reported. In 3, two triangular Dy3O4 are oriented in opposite directions to form the central connecting axis Dy6(OH)8, which is in turn connected to six Dy3O4 that are oriented in different directions. Meanwhile, a sample of a chiral trinuclear dysprosium cluster (1) was obtained in a mixed CH3OH and CH3CN solvent and by replacing the anion in the reaction to Cl- ions. In this cluster, 1,3,4-thiadiazole-2,5-diamine (L2) is free on one side through π···π interactions and is parallel to the o-vanillin (L1)- ligand, thus resulting in a triangular arrangement. The arrangement of L2 affects the end group coordination in the cluster 1 structure through hydrogen bonding and induces the cluster to exhibit chirality. When the reaction solvent was changed to CH3OH, a sample of cluster 2, composed of two independent triangular Dy3 that have different end group arrangements, was obtained. Magnetic analysis showed that clusters 1 and 3 both exhibit distinctive single-molecule magnetic properties under zero-magnetic-field conditions. This study thus provides a method for the creation of chiral high-nucleation clusters from achiral ligands and potentially paves the way for the synthesis of high-nucleation lanthanide clusters with unique forms.
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Elementos da Série dos Lantanídeos , Elementos da Série dos Lantanídeos/química , Ânions , Ligantes , Hidrólise , ÍonsRESUMO
By changing the coordination anions (OAc- and Cl-), reaction temperature, solvent, and ligand substituents, four Dy(III)-based complexes were obtained by directed synthesis, which are [Dy4(L1)2(L2)2(OAc)4]·4C2H5OH·3H2O (1, L1 = 1,3,4-thiadiazole-2,5-diamine, H4L2 = 6,6'-(((1,3,4-thiadiazole-2,5-diyl)bis(azanediyl))bis(((3-ethoxy-2-hydroxybenzyl)oxy)methylene))bis(2-ethoxyphen), [Dy4(L3)4(OAc)4]·C2H5OH·H2O (2, H3L3 = 2-(((5-amino-1,3,4-thiadiazol-2-yl)amino)((3-ethoxy-2-hydroxybenzyl)oxy)methyl)-6-ethoxyphenol)), [Dy6(L4)4(L5)2(µ3-OH)4(CH3O)4Cl4]Cl2 (3, H2L4 = 2-hydroxy-3-methoxybenzaldehyde, H2L5 = 2-(((5-amino-1,3,4-thiadiazol-2-yl)amino)(hydroxy)methyl)-6-methoxyphenol), and [Dy6(L6)4(L7)2(µ3-OH)4(CH3O)4Cl4]Cl2·2H3O (4, H2L6 = 2-hydroxy-3-ethoxybenzaldehyde, H2L7 = 2-(((5-amino-1,3,4-thiadiazol-2-yl)amino)(hydroxy)methyl)-6-ethoxyphenol). A series of acetal products (H4L2, H3L3, H2L5, and H2L7) were obtained through dehydration in situ tandem reactions. Magnetic studies show that complexes 1-4 exhibited different single-molecule magnet behavior under zero-field conditions. The best fitting results showed that under zero DC field, the effective energy barriers (Ueff) and magnetic relaxation times (τ0) of complexes 1-4 are Ueff = 117.0 (2.1) K and τ0 = 6.07 × 10-7 s; Ueff = 83.91 (1.5) K and τ0 = 4.28 × 10-7 s; Ueff = 1.28 (0.2) K and τ0 = 0.73 s, and Ueff = 104.43 (13.3) K and τ0 = 8.25 × 10-8 s, respectively.
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INTRODUCTION: Data is currently lacking regarding association between the cholecystectomy/hepatectomy/pancreatectomy and the development of osteoporotic fracture. A retrospective cohort study was conducted to investigate the relationship between cholecystectomy/hepatectomy/pancreatectomy and the subsequent risk of developing osteoporotic fracture. MATERIALS AND METHODS: Patients having undergone cholecystectomy, hepatectomy, or pancreatectomy between 2000 and 2012 were selected from the All Population Based Hospitalization File as the surgery cohort (n = 304,081), which was frequency matched with the control cohort (n = 304,081). The Cox proportional hazard model and Kaplan-Meier analysis were applied to measure the hazard ratios and the cumulative incidence of osteoporotic fracture. RESULTS: A total of 1136 patients in the surgery cohort and 1179 patients in the control cohort were newly diagnosed with osteoporotic fracture. The overall osteoporotic fracture risk in the surgery cohort was 1.12-fold higher [95% confidence interval (CI), 1.03-1.21]. Specifically, surgery cohort had higher vertebral fracture risk than non-surgery cohort [adjusted hazard ratio (aHR) 1.12, Cl, 1.03-1.22]. In addition, patients underwent cholecystectomy (includes open and laparoscopic approaches), hepatectomy (only open approach), and pancreatectomy group (only open approach) were 1.10 (95% CI, 1.01-1.19), 1.49 (95% CI, 1.10-2.01), and 1.88 (95% CI, 1.23-2.87) times more likely to develop osteoporotic fracture, respectively. No significant difference of osteoporotic fracture risk was observed between open and laparoscopic cholecystectomy. The risk of osteoporotic fracture was significantly increased in females, patients aged ≥ 40 years old, and patients with some comorbidity. CONCLUSIONS: Patients post cholecystectomy, hepatectomy, or pancreatectomy significantly increased risk of developing osteoporotic fracture, suggesting closer attention in post-operative care is needed.
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Colecistectomia/efeitos adversos , Hepatectomia/efeitos adversos , Fraturas por Osteoporose/epidemiologia , Pancreatectomia/efeitos adversos , Fraturas da Coluna Vertebral/epidemiologia , Estudos de Coortes , Comorbidade , Feminino , Hospitalização , Humanos , Incidência , Estimativa de Kaplan-Meier , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de RiscoRESUMO
The serialized expansion of high-nuclear clusters usually includes the controlled variable method and changes only a single variable. However, changing both variables will greatly increase the complexity of the reaction simultaneously. Therefore, the use of a two-component regulation reaction is rare. Herein, we used a diacylhydrazone ligand (H4L1) with multidentate chelating coordination sites for the reaction with Gd(NO3)3·6H2O under solvothermal conditions to obtain an example of 16-nucleus disc-shaped cluster 1 with a brucite structure. The overall structure of cluster 1 can be regarded as an equilateral triangle, which is formed by three (L1)4- ions that can be regarded as "sides" and wrap the four-layer metal center Gd(III) ions. Notably, upon simultaneous regulation of the substituent of the ligand and the coordination anion, heptanuclear gadolinium cluster 2 was obtained. Cluster 2 can be regarded as a butterfly structure, which was formed by connecting two Gd3L2 molecules that were not in the same plane and through the central Gd(III) ion as an intersection. Moreover, hexanuclear gadolinium cluster 3 was obtained by changing the ligand substituent and adding an auxiliary ligand. Cluster 3 can be regarded as a chair structure, which was composed of two molecules of diacylhydrazone ligand (L2)4- wrapping vacant cubane shared by four vertices. This study was the first to construct a series of high-nuclear gadolinium clusters through two-component regulation manipulation. The study of the magnetocaloric effect showed that the maximum values of -ΔSm for clusters 1-3 were 34.05, 29.04, and 24.32 J kg-1 K-1, respectively, when T = 2 K and ΔH = 7 T.
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To improve the efficiency of the Fe(II)/Fe(III) cycle and continuous reactivity of pyrite, a pyrite/H2O2/hydroxylamine (HA) system was proposed to treat rhodamine B (RhB). The results showed that near-complete decolorization and 52.8% mineralization 50 mg L-1 RhB were achieved under its optimum conditions: HA 0.8 mM, H2O2 1.6 mM, pyrite 0.4 g L-1, and initial pH 4.0. The degradation reaction was dominated by an â¢OH radical produced by the reaction of Fe2+ with H2O2 in solution. HA primarily had two roles: in solution, HA could accelerate the Fe(II)/Fe(III) cycle through its strong reducibility to enhance RhB decolorization; on the pyrite surface, HA could improve the continuous reactivity of pyrite by inhibiting the oxidation of pyrite. In addition, the dosing manner of HA had a significant effect on RhB decolorization. In addition, the high decolorization and mineralization efficiency of other dye pollutants suggested that the pyrite/H2O2/HA system might be widely used in textile wastewater treatment.
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Peróxido de Hidrogênio , Poluentes Químicos da Água , Compostos Férricos , Hidroxilamina , Hidroxilaminas , Ferro , Oxirredução , Rodaminas , Sulfetos , Poluentes Químicos da Água/análiseRESUMO
Polygala tenuifolia Willd. is a traditional Chinese herbal medicine that is widely used in treating nervous system disorders. Triterpene saponins in P. tenuifolia (polygala saponins) have excellent biological activity. As a precursor for the synthesis of presenegin, oleanolic acid (OA) plays an important role in the biosynthesis of polygala saponins. However, the mechanism behind the biosynthesis of polygala saponins remains to be elucidated. In this study, we found that CYP716A249 (GenBank: ASB17946) oxidized the C-28 position of ß-amyrin to produce OA. Using quantitative real-time PCR, we observed that CYP716A249 had the highest expression in the roots of 2-year-old P. tenuifolia, which provided a basis for the selection of samples for gene cloning. To identify the function of CYP716A249, the strain R-BE-20 was constructed by expressing ß-amyrin synthase in yeast. Then, CYP716A249 was co-expressed with ß-amyrin synthase to construct the strain R-BPE-20 by using the lithium acetate method. Finally, we detected ß-amyrin and OA by ultra-HPLC-Q Exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry and GC-MS. The results of this study provide insights into the biosynthesis pathway of polygala saponins.
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Clonagem Molecular/métodos , Polygala/genética , Polygala/metabolismo , Proteínas de Saccharomyces cerevisiae/biossíntese , Proteínas de Saccharomyces cerevisiae/genética , Triterpenos/metabolismo , Proteínas de Arabidopsis/biossíntese , Proteínas de Arabidopsis/genética , Sistema Enzimático do Citocromo P-450/biossíntese , Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica de Plantas , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/genética , Ácido Oleanólico/metabolismo , Filogenia , Saccharomyces cerevisiae , Saponinas/biossíntese , Saponinas/genéticaRESUMO
In this study, total flavonoids and total triterpenoid acid were extracted with ethyl acetate from Hedyotis diffusa Willd, and hepatoprotective activities of them and five compounds from total flavonoids against H2 O2 induced hepatocyte damage on HL-02 cells were determined. In particular, amentoflavone and total flavonoids had influence on the leakage of ALT, AST, LDH, the activities of SOD and the content of MDA. They effectively reduced the loss of MMP, the release of Cyt C, and then inhibited activation of caspase-3/caspase-9 cascade in hepatotoxic cells. The contents of ROS were significantly reduced to inhibit p38 in amentoflavone and flavonoids groups which decreased ASK1 and p-p38 levels through increasing thioredoxin Trx1 and reductase TrxR1. These results suggesting that the antioxidant protection of amentoflavone and flavonoids might be reducing ROS to inhibit the H2 O2 -induced upstream of pathway via increasing levels of Trx1 and TrxR1, which were pivotal in blocking the down streaming effectors of ASK1/p38 MAPK pathway and alleviating hepatotoxicity.
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Antioxidantes/farmacologia , Flavonoides/farmacologia , Hedyotis/química , MAP Quinase Quinase Quinase 5/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , MAP Quinase Quinase Quinase 5/metabolismo , Estrutura Molecular , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Relação Estrutura-Atividade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
With the removal of bisphenol A (BPA) from many consumer products, the potential use of alternatives such as bisphenol S (BPS) and its derivatives is causing some concerns. These studies investigated the comparative in vitro hepatic clearance and metabolism of BPS and derivatives and the disposition and metabolism of BPS in rats and mice following gavage and intravenous administration. The clearance of BPS and its derivatives was slower in human hepatocytes than in rodents. In male rats following gavage administration of 50, 150, and 500â¯mg/kg [14C]BPS the main route of excretion was via urine; the urinary excretion decreased (72 to 48%) and the fecal excretion increased (16 to 30%) with increasing dose. The disposition was similar in female rats and male and female mice following gavage administration. Radioactivity remaining in tissues at 72â¯h in both species and sexes was ≤2.4%. In bile duct cannulated rats 53% of a gavage dose was secreted in bile suggesting extensive enterohepatic recirculation of [14C]BPS. Following an intravenous dose in rats and mice, the pattern of excretion was similar to gavage. These data suggest that the dose excreted in feces folowing gavage administration is likely the absorbed dose. Urinary metabolites included the glucuronide and sulfate conjugates with a moderate amount of parent. The pattern of in vitro hepatic metabolsim was similar to in vivo with some difference among derivatives. These data suggest that similar to other bisphenol analogues, BPS was well absorbed following oral expsosure and extensively excreted with minimal tissue retention.
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Poluentes Ocupacionais do Ar/metabolismo , Poluentes Ocupacionais do Ar/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fenóis/metabolismo , Fenóis/toxicidade , Sulfonas/metabolismo , Sulfonas/toxicidade , Adulto , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Taxa de Depuração Metabólica/fisiologia , Camundongos , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologiaRESUMO
A new method-multifractal temporally weighted detrended cross-correlation analysis (MF-TWXDFA)-is proposed to investigate multifractal cross-correlations in this paper. This new method is based on multifractal temporally weighted detrended fluctuation analysis and multifractal cross-correlation analysis (MFCCA). An innovation of the method is applying geographically weighted regression to estimate local trends in the nonstationary time series. We also take into consideration the sign of the fluctuations in computing the corresponding detrended cross-covariance function. To test the performance of the MF-TWXDFA algorithm, we apply it and the MFCCA method on simulated and actual series. Numerical tests on artificially simulated series demonstrate that our method can accurately detect long-range cross-correlations for two simultaneously recorded series. To further show the utility of MF-TWXDFA, we apply it on time series from stock markets and find that power-law cross-correlation between stock returns is significantly multifractal. A new coefficient, MF-TWXDFA cross-correlation coefficient, is also defined to quantify the levels of cross-correlation between two time series.
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1. Plasma clearance of dolutegravir, an unboosted HIV-1 integrase inhibitor, was low in rat and monkey (0.23 and 2.12 mL/min/kg, respectively) as was the volume of distribution (0.1 and 0.28 L/kg, respectively) with terminal elimination half-life approximately 6 h. Dolutegravir was rapidly absorbed from oral solution with a high bioavailability in rat and monkey (75.6 and 87.0% respectively), but solubility or dissolution rate limited when administered as suspension. 2. Dolutegravir was highly bound (>99%) to serum proteins in rat and monkey, similar to binding to plasma and serum proteins in human. Radioactivity was associated with the plasma versus cellular components of blood across all species. 3. Following oral administration to rats, [(14)C]dolutegravir-related radioactivity was distributed to most tissues, due in part to high permeability; however, because of high plasma protein binding, tissue to blood ratios were low. In mouse, rat and monkey, the absorbed dose was extensively metabolized and secreted into bile, with the majority of the administered radioactivity eliminated in feces within 24 h. 4. The primary route of metabolism of dolutegravir was through the formation of an ether glucuronide. Additional biotransformation pathways: benzylic oxidation followed by hydrolysis to an N-dealkylated product, glucose conjugation, oxidative defluorination, and glutathione conjugation.
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Inibidores de Integrase de HIV/metabolismo , Compostos Heterocíclicos com 3 Anéis/metabolismo , Animais , Bile/química , Disponibilidade Biológica , Radioisótopos de Carbono , Feminino , Inibidores de Integrase de HIV/análise , Inibidores de Integrase de HIV/farmacocinética , Compostos Heterocíclicos com 3 Anéis/análise , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Macaca fascicularis , Masculino , Camundongos , Oxazinas , Piperazinas , Piridonas , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
In this paper, the RP-HPLC specific chromatography was adopted, with DIKMA-C18 (4.6 mm x 250 mm, 5 µm) as the chromatographic column, with a gradient elution compose of acetonitrile and 0.1% phosphoric acid at flow rate of 0.8 mL · min(-1), the detection wavelength was 220 nm. The difference of the HPLC specific chromatograms between the Lu Dangshen and other different base sources and different producing area of Codonopsis Radix was compared, involved in the similarities and differences of the number and the relative peak area of characteristic peaks in the HPLC specific chromatograms. The HPLC specific chromatograms of Lu Dangshen was established and the relative retention times of seven peaks was determined, and the peaks of codonopyrrolidium B, syringin, lobetyolin, tangshenoside I and atractylenoide III were identified; The HPLC specific chromatograms of Lu Dangshen provided a method for scientific evaluation and effective control the quality of Lu Dangshen from Shanxi famous-region.
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Cromatografia Líquida de Alta Pressão/métodos , Codonopsis/química , Medicamentos de Ervas Chinesas/análise , Raízes de Plantas/química , Glucosídeos/análise , Fenilpropionatos/análise , Controle de QualidadeRESUMO
Rhizomes are prostrate subterranean stems that provide primitive mechanisms of vegetative dispersal, survival, and regrowth of perennial grasses and other monocots. The extent of rhizome proliferation varies greatly among grasses, being absent in cereals and other annuals, strictly confined in caespitose perennials, or highly invasive in some perennial weeds. However, genetic studies of rhizome proliferation are limited and genes controlling rhizomatous growth habit have not been elucidated. Quantitative trait loci (QTLs) controlling rhizome spreading were compared in reciprocal backcross populations derived from hybrids of rhizomatous creeping wildrye (Leymus triticoides) and caespitose basin wildrye (L. cinereus), which are perennial relatives of wheat. Two recessive QTLs were unique to the creeping wildrye backcross, one dominant QTL was unique to the basin wildrye backcross, and one additive QTL was detectable in reciprocal backcrosses with high log odds (LOD = 31.6) in the basin wildrye background. The dominant QTL located on linkage group (LG)-2a was aligned to a dominant rhizome orthogene (Rhz3) of perennial rice (Oryza longistamina) and perennial sorghum (Sorghum propinquum). Nonparametric 99 % confidence bounds of the 31.6-LOD QTL were localized to a distal 3.8-centiMorgan region of LG-6a, which corresponds to a 0.7-Mb region of Brachypodium Chromosome 3 containing 106 genes. An Aux/IAA auxin signal factor gene was located at the 31.6-LOD peak, which could explain the gravitropic and aphototropic behavior of rhizomes. Findings elucidate genetic mechanisms controlling rhizome development and architectural growth habit differences among plant species. Results have possible applications to improve perennial forage and turf grasses, extend the vegetative life cycle of annual cereals, such as wheat, or control the invasiveness of highly rhizomatous weeds such as quackgrass (Elymus repens).
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Poaceae/crescimento & desenvolvimento , Poaceae/genética , Locos de Características Quantitativas , Rizoma/crescimento & desenvolvimento , Rizoma/genética , Clonagem Molecular , Cruzamentos Genéticos , Genes de Plantas , Ligação Genética , Genômica , Hibridização Genética , Oryza/genética , Fenótipo , Análise de Sequência de DNA , Sorghum/genéticaRESUMO
Sepsis is one of the most common causes of mortality in intensive care units. Although sepsis-associated encephalopathy (SAE) is reported to be a leading manifestation of sepsis, its pathogenesis remains to be elucidated. In this study, we investigated whether exogenous recombinant human erythropoietin (rhEPO) could protect brain from neuronal apoptosis in the model of SAE. We showed that application of rhEPO enhanced Bcl-2, decreased Bad in lipopolysaccharide treated neuronal cultures, and improved neuronal apoptosis in hippocampus of cecal ligation and peroration rats. We also found that rhEPO increased the expression of phosphorylated AKT, and the antiapoptotic role of rhEPO could be abolished by phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002 or SH-5. In addition, systemic sepsis inhibited the hippocampal-phosphorylated mammalian target of rapamycin (mTOR) and p70S6K (downstream substrates of PKB/AKT signaling), which were restored by administration of exogenous rhEPO. Moreover, treatment with mTOR-signaling inhibitor rapamycin or transfection of mTOR siRNA reversed the neuronal protective effects of rhEPO. Finally, exogenous rhEPO rescued the emotional and spatial cognitive defects without any influence on locomotive activity. These results illustrated that exogenous rhEPO improves brain dysfunction by reducing neuronal apoptosis, and AKT/mTOR signaling is likely to be involved in this process. Application of rhEPO may serve as a potential therapy for the treatment of SAE.
Assuntos
Eritropoetina/uso terapêutico , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Ceco/patologia , Cognição/efeitos dos fármacos , Emoções/efeitos dos fármacos , Epoetina alfa , Eritropoetina/administração & dosagem , Eritropoetina/farmacologia , Humanos , Ligadura , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fosforilação/efeitos dos fármacos , Punções , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Sepse/patologia , Sepse/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
PURPOSE: To report a modified reconstructive technique for Wassel type IV-D thumb duplication that preserves and transfers the flexor pollicis longus (FPL) from the removed radial portion. METHODS: We analyzed the hands of 16 patients (average age, 2 y) with Wassel IV-D thumb duplication. Patients were treated with ablation of the radial thumb and reconstruction of the ulnar thumb by a series of soft tissue procedures, including FPL rebalancing. The postoperative range of motion and the alignment at the metacarpophalangeal and interphalangeal joints of the affected thumbs were compared with the preoperative measurements. RESULTS: Of 16 cases, 14 were observed for an average of 29 months. Motion at the interphalangeal joint and alignment at metacarpophalangeal and interphalangeal joints showed improvement after surgery. According to the Japanese Society for Surgery of the Hand scoring system, the results were excellent in 2 cases, good in 11, and fair in 1. A disadvantage of this technique proved to be restricted interphalangeal joint motion with an extension lag that averaged 14°. CONCLUSIONS: The FPL rebalancing technique with soft tissue stabilization of the metacarpophalangeal and interphalangeal joints can establish dynamic rebalance of the bifurcated FPL tendon in Wassel IV-D duplicated thumb. It shows excellent results in alignment and joint stability. The long-term results are under evaluation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.