RESUMO
Lignin, a natural pol2ymer with a complex structure that is difficult to separate, is prone to C-C bond condensation during the separation process. To reduce the condensation of lignin, here, a novel method is proposed for separating the components by using a combination of maleic acid (MA)/ozone (O3) to co-treat wheat straw. The removal of lignin, glucan, and xylan was 38.07 ± 0.2%, 31.44 ± 0.1%, and 71.98 ± 0.1%, respectively, under the conditions of ball-milling of wheat straw for 6 h, reaction temperature of 60 °C, and O3 holding time of 9 min. Lignin-rich solutions were collected to extract the dissolved lignin (DL) after washing the treated samples. The DL obtained under MA/O3 conditions had a carboxyl group (-COOH) content of 2.96 mmol/g. The carboxyl group of MA underwent esterification with the hydroxyl group (-OH) at the γ position of lignin and O3 reacted on the positions of the lignin side chain or the phenolic ring, resulting in a break in the side chain and the opening of the phenolic ring to introduce the carboxyl group. The 2D-HSQC-NMR results revealed that the phenolic ring-opening reaction of lignin in the presence of O3 was essentially free of ß-ß and ß-5 condensation bonds.
Assuntos
Biomassa , Lignina , Maleatos , Ozônio , Triticum , Lignina/química , Triticum/química , Ozônio/química , Maleatos/químicaRESUMO
Xanthine oxidase (XO) is a crucial target for the treatment of hyperuricemia and gout. A series of derivatives based on natural 3,4-dihydroxychalcone, obtained from Carthamus tinctorious and Licorice, were designed and synthesized. Nine derivatives (9a-e, 10b,c, and 15a,b) exhibited apparent XO inhibitory activity in vitro (IC50 values varied from 0.121 to 7.086 µM), 15b presented the most potent inhibitory activity (IC50 = 0.121 µM), which was 27.47-fold higher than that of allopurinol (IC50 = 3.324 µM). The SAR analysis indicated that introducing hydroxyl groups at 3'/4'/5'-position on ring A was more beneficial to the inhibition of XO than at 2'/6'-position; the removal of 3hydroxyl group on ring B could weaken the inhibitory potency of hydroxychalcones on XO, but it was beneficial to the XO inhibitory potency of methoxychalcones. Molecule modeling studies afforded insights into the binding mode of 15b with XO and supported the findings of SAR analysis. Additionally, kinetics studies demonstrated that 15b presented a reversible and competitive XO inhibitor, which spontaneously combined with XO through hydrophobic force, and finally changed the secondary conformation of XO. Furthermore, the acute hyperuricemia model was employed to investigate the hypouricemic effect of 15b, which could effectively reduce the serum uric acid levels of rats at an oral dose of 10 mg/kg. ADMET prediction suggested that compound 15b possessed good pharmacokinetic properties. Briefly, compound 15b emerges as an interesting XO inhibitor for the treatment of hyperuricemia and gout with beneficial effects on serum uric acid levels regulating. Meanwhile, the XO inhibitors with chalcone skeleton will deserve further attention and discussion.
Assuntos
Chalcona , Chalconas , Gota , Hiperuricemia , Ratos , Animais , Relação Estrutura-Atividade , Ácido Úrico , Chalconas/farmacologia , Chalconas/uso terapêutico , Xantina Oxidase , Chalcona/farmacologia , Chalcona/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Inibidores Enzimáticos/química , Gota/tratamento farmacológicoRESUMO
A recently developed blood typing diagnostic based on a polyester thread substrate has shown great promise for use in medical emergencies and in impoverished regions. The device is easy to use and transport, while also being inexpensive, accurate, and rapid. This study used a fluorescent confocal microscope to delve deeper into how red blood cells were behaving within the polyester thread-based diagnostic at the cellular level, and how plasma separation could be made to visibly occur on the thread, making it possible to identify blood type in a single step. Red blood cells were stained and the plasma phase dyed with fluorescent compounds to enable them to be visualised under the confocal microscope at high magnification. The mechanisms uncovered were in surprising contrast with those found for a similar, paper-based method. Red blood cell aggregates did not flow over each other within the thread substrate as expected, but suffered from a restriction to their flow which resulted in the chromatographic separation of the RBCs from the liquid phase of the blood. It is hoped that these results will lead to the optimisation of the method to enable more accurate and sensitive detection, increasing the range of blood systems that can be detected.
Assuntos
Tipagem e Reações Cruzadas Sanguíneas/instrumentação , Eritrócitos/citologia , Imunofluorescência/métodos , Imunoensaio/instrumentação , Poliésteres/química , Tipagem e Reações Cruzadas Sanguíneas/métodos , Eritrócitos/imunologia , Humanos , Imunoensaio/métodosRESUMO
We report the use of bioactive paper for typing of secondary human blood groups. Our recent work on using bioactive paper for human blood typing has led to the discovery of a new method for identifying haemagglutination of red blood cells. The primary human blood groups, i.e., ABO and RhD groups, have been successfully typed with this method. Clinically, however, many secondary blood groups can also cause fatal blood transfusion accidents, despite the fact that the haemagglutination reactions of secondary blood groups are generally weaker than those of the primary blood groups. We describe the design of a user-friendly sensor for rapid typing of secondary blood groups using bioactive paper. We also present mechanistic insights into interactions between secondary blood group antibodies and red blood cells obtained using confocal microscopy. Haemagglutination patterns under different conditions are revealed for optimization of the assay conditions.
Assuntos
Análise Química do Sangue/instrumentação , Antígenos de Grupos Sanguíneos/análise , Tipagem e Reações Cruzadas Sanguíneas/instrumentação , Papel , Bioensaio/economia , Bioensaio/instrumentação , Análise Química do Sangue/economia , Tipagem e Reações Cruzadas Sanguíneas/economia , Humanos , Limite de Detecção , Fatores de TempoRESUMO
Herein, a series of lignin-based porous carbons (LC) were prepared from sulfonated lignin through a simple and environmentally-friendly one-pot activated carbonization together with various potassium compounds as activators, and used for malachite green (MG) adsorption. The results showed that the prepared biochar, especially after K2CO3 activation, exhibited a honeycomb profile with large surface area (2107.6 m2/g) and high total pore volume (1.1591 cm3/g), having excellent efficiency for MG adsorption, and the biggest adsorption capacity was 2970.0 mg/g. The kinetic study together with thermodynamic analysis indicated that the adsorption of MG by LC-K2CO3 conformed to pseudo-second-order model and the adsorption process was spontaneous, feasible, and endothermic. Moreover, LC-K2CO3 also displayed good stability and selectivity, and can selective separate the cationic dye from binary-dye system. Furthermore, the adsorption mechanism proposed in this work manifested that the high-efficient MG adsorption by LC-K2CO3 was a result of multiple actions including hydrogen bonding, electrostatic attraction, π-π interaction and n-π interaction as well as physical absorption. The work not only provide a fundamental theory for dye removal from wastewater, but offered a new insight for lignin valorization.
RESUMO
Xanthine oxidase (XO) is a crucial target for hyperuricemia treatment(s). Naturally occurred XO inhibitors with minimal toxicity and high efficacy have attracted researchers' attention. With the goal of quickly identifying natural XO inhibitors, an integrated computational screening strategy was constructed by molecular docking and calculating the free energy of binding. Twenty-seven hits were achieved from a database containing 19,377 natural molecules. This includes fourteen known XO inhibitors and four firstly-reported inhibitors (isolicoflavonol, 5,7-dihydroxycoumarin, parvifolol D and clauszoline M, IC50 < 40 µM). Iolicoflavonol (hit 8, IC50 = 8.45 ± 0.68 µM) and 5,7-dihydroxycoumarin (hit 25, IC50 = 10.91 ± 0.71 µM) displayed the great potency as mixed-type inhibitors. Docking study and molecular dynamics simulation revealed that both hits could interact with XO's primarily active site residues ARG880, MOS1328, and ASN768 of XO. Fluorescence spectroscopy studies showed that hit 8 bound to the active cavity region of XO, causing changes in XO's conformation and hydrophobicity. Hits 8 and 25 exhibit favorable Absorption, Distribution, Metabolism, and Excretion (ADME) properties. Additionally, no cytotoxicity against human liver cells was observed at their median inhibition concentrations against XO. Therefore, the present study offers isolicoflavonol and 5,7-dihydroxycoumarin with the potential to be disease-modifying agents for hyperuricemia.
Assuntos
Hiperuricemia , Xantina Oxidase , Humanos , Simulação de Acoplamento Molecular , Hiperuricemia/tratamento farmacológico , Inibidores Enzimáticos/química , Domínio Catalítico , Relação Estrutura-AtividadeRESUMO
Recent research on the use of bioactive paper for human blood typing has led to the discovery of a new method for identifying the haemagglutination of red blood cells (RBCs). When a blood sample is introduced onto paper treated with the grouping antibodies, RBCs undergo haemagglutination with the corresponding grouping antibodies, forming agglutinated cell aggregates in the paper. A subsequent washing of the paper with saline buffer could not remove these aggregates from the paper; this phenomenon provides a new method for rapid, visual identification of the antibody-specific haemagglutination reactions and thus the determination of the blood type. This study aims to understand the mechanism of RBC immobilization inside the paper which follows haemagglutination reactions. Confocal microscopy is used to observe the morphology of the free and agglutinated RBCs that are labelled with FITC. Chromatographic elution patterns of both agglutinated and non-agglutinated RBCs are studied to gain insight into the transport behaviour of free RBCs and agglutinated aggregates. This work provides new information about RBC haemagglutination inside the fibre network of paper on a microscopic level, which is important for the future design of paper-based blood typing devices with high sensitivity and assaying speed.
Assuntos
Tipagem e Reações Cruzadas Sanguíneas/instrumentação , Movimento Celular , Eritrócitos/citologia , Microscopia Confocal , Papel , Adulto , Anticorpos/imunologia , Tipagem e Reações Cruzadas Sanguíneas/economia , Células Imobilizadas/citologia , Células Imobilizadas/imunologia , Células Imobilizadas/metabolismo , Eritrócitos/imunologia , Eritrócitos/metabolismo , Fluoresceína-5-Isotiocianato/metabolismo , Hemaglutinação , Humanos , Coloração e RotulagemRESUMO
Alzheimer's disease (AD) is the most common type of age-related dementia. Inhibition of butyrylcholinesterase (BChE) emerge as an effective therapeutic target for AD. A series of new substituted acetamide derivatives were designed, synthesized and evaluated for their ability to inhibit BChE. The bioassay results revealed that several compounds displayed attractive inhibition against BChE). Among them, compound 8c exhibited the highest BChE inhibition with IC50 values of 3.94 µM. Lineweaver Burk plot indicated that 8c acted as a mixed-type BChE inhibitor. In addition, docking studies confirmed the results obtained through in vitro experiments, and showed that 8c bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE active site. Meanwhile, its ADME parameters were approximated using in silico method. Molecular dynamics simulation studies on the complex of 8c-BChE were performed, RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds were calculated as well. These results implied that 8c could serve as appropriate lead molecule for the development of BChE inhibitor.
Assuntos
Doença de Alzheimer , Butirilcolinesterase , Humanos , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Simulação de Acoplamento Molecular , Inibidores da Colinesterase/química , Doença de Alzheimer/tratamento farmacológico , Amidas/uso terapêutico , Acetamidas/farmacologia , Acetamidas/uso terapêutico , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
A low-cost and portable paper-based analytical device has been developed for high throughput and on-site monitoring TC residue in milk through visualized colorimetric reaction. The filtration and concentration effect induced by the porous nature of paper contribute to strengthen the color intensity, leading to quantitative and sensitive detection of tetracycline reaching 1 ppm detection limit, with the linear range of 1-100 ppm both in water and milk samples. The applicability was demonstrated by detection of TC in 18 different types of real milk samples with good recovery ranging from 88% to 113%. Furthermore, the dynamic degradation behavior of tetracycline was monitored through the device. To the best of our knowledge, this is the first report of colorimetric detection of tetracycline in milk using the paper-based device. This simple, fast, cost-effective (~$0.50 per device) and equipment-free paper-based platform provides a promising tool for future application in food and environmental safety.
Assuntos
Antibacterianos/análise , Análise de Alimentos/instrumentação , Contaminação de Alimentos/análise , Leite/química , Papel , Tetraciclina/análise , Animais , Colorimetria/instrumentação , Limite de Detecção , Água/químicaRESUMO
In this work, we investigated the influence of paper structure on the performance of paper-based analytical devices that are used for blood analysis. The question that we aimed to answer is how the fiber type (i.e., softwood and hardwood fibers) influences the fiber network structure of the paper, which affects the transport of red blood cells (RBCs) in paper. In the experimental design, we isolated the influence of fiber types on the paper structure from all other possible influencing factors by removing the fines from the pulps and not using any additives. Mercury porosimetry was employed to characterize the pore structures of the paper sheets. The results show that papers with a low basis weight that are made with short hardwood fibers have a higher porosity (i.e., void fraction) and simpler pore structures compared with papers made with long softwood fibers. RBC transport in paper carried by saline solution was investigated in two modes: lateral chromatographic elution and vertical flow-through. The results showed that the complexity of the paper's internal pore structure has a dominant influence on the transport of RBCs in paper. Hardwood fiber sheets with a low basis weight have a simple internal pore structure and allow for the easy transport of RBCs. Blood-typing sensors built with low basis weight hardwood fibers deliver high-clarity assays. Softwood fiber papers are found to have a more complex pore structure, which makes RBC transport more difficult, leading to blood-typing results of low clarity. This study provides the principle of paper sheet design for paper-based blood analysis sensors.
Assuntos
Técnicas Biossensoriais , Tipagem e Reações Cruzadas Sanguíneas/métodos , Eritrócitos , Papel , Humanos , Mercúrio/química , PorosidadeRESUMO
This study presents a new application of superhydrophobic surfaces in conducting biological assays for human blood typing using a liquid drop micro reactor. The superhydrophobic substrate was fabricated by a simple printing technique with Teflon powder. The non-wetting and weak hysteresis characteristics of superhydrophobic surfaces enable the blood and antibody droplets to have a near-spherical shape, making it easy for the haemagglutination reaction inside the droplet to be photographed or recorded by a digital camera and then analyzed by image analysis software. This novel blood typing method requires only a small amount of blood sample. The evaluation of assay results using image analysis techniques offers potential to develop high throughput operations of rapid blood typing assays for pathological laboratories. With the capability of identifying detailed red blood cell agglutination patterns and intensities, this method is also useful for confirming blood samples that have weak red blood cell antigens.
Assuntos
Bioensaio , Tipagem e Reações Cruzadas Sanguíneas , Humanos , Interações Hidrofóbicas e Hidrofílicas , Propriedades de SuperfícieRESUMO
A liquid marble micro- bioreactor is used to conduct blood typing as a typical biological assay. This study portrays the potential of using such microreactors for biochemical and biological analysis.
Assuntos
Reatores Biológicos , Tipagem e Reações Cruzadas Sanguíneas/instrumentação , Tipagem e Reações Cruzadas Sanguíneas/métodos , Eritrócitos/imunologia , Imunoensaio/instrumentação , Imunoensaio/métodos , Microfluídica/instrumentação , Microfluídica/métodos , Células Cultivadas , Humanos , Microesferas , SoluçõesRESUMO
This paper reports a potential method that can restore the wettability of bioactive paper-based sensors while maintaining their bioactivity. This study is driven by the need to increase the wettability of the antibody-loaded blood typing paper devices in order to increase the blood typing assaying speed using such paper devices. Plasma treatment is used to improve the wettability of bioactive paper; the protective effect of bovine serum albumin (BSA) to biomolecules against plasma deactivation is investigated. In the first stage, horseradish peroxidase (HRP) was used as a model biomolecule, because of the convenience of its quantifiable colorimetric reaction with a substrate. By using this protection approach, the inactivation of biomolecules on paper during the plasma treatment is significantly slowed down. This approach enables plasma treatment to be used for fabricating paper-based bioactive sensors to achieve strong wettability for rapid penetration of liquid samples or reagents. Finally, we demonstrate the use of plasma treatment to increase the wettability of antibody treated blood typing paper. After the treatment, the blood typing paper becomes highly wettable; it allows much faster penetration of blood samples into the plasma treated testing paper. Antibodies on the paper are still sufficiently active for blood typing and can report patients' blood type accurately.