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The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decrease, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60â nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75â nm can achieve an extraordinary stability (88.6 % capacity retention over 450 cycles) with a high capacity (450â mAh g-1) and a superb rate even at an extreme temperature of 60 °C, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.
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To effectively perform the reliability analysis of the flap deflection angle, the reliability analysis framework is developed by introducing fault logic and a data-driven model. Herein, the fault logic analysis is used to study the fault mechanism and filter out the characteristic fault parameters that can be used to collect input data for data-driven modelling; the data-driven modelling is employed to establish a reliability analysis model with a small amount of input data. Under this proposed framework, the improved dung beetle optimization algorithm for back propagation (IDBO-BP) method is developed to perform the reliability modelling of the flap deflection angle. To validate the effectiveness of the proposed framework, we study the fault logic of flap symmetry and establish a surrogate model of flap deflection based on the fault parameters and the IDBO-BP algorithm. According to the predicted results of the flap deflection angle, the reliability model based on the fault mechanism can reflect the actual flap motion. At the same time, the proposed IDBO-BP algorithm has excellent modelling and simulation property by comparing with other optimization algorithms. Thus, the efforts of this study provide a new solution to the problem of reliable analysis with uncertain fault parameters. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.
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This study aimed to design an effective nanoparticle-based carrier for the oral delivery of fisetin (FST) with improved biopharmaceutical properties. FST-loaded nanoparticles were prepared with polyvinyl alcohol (PVA) and poly(lactic-co-glycolic acid) (PLGA) by the interfacial deposition method. A central composite design of two independent variables, the concentration of PVA and the amount of PLGA, was applied for the optimization of the preparative parameter. The responses, including average particle size, polydispersity index, encapsulation efficiency, and zeta potential, were assessed. The optimized formulation possessed a mean particle size of 187.9 nm, the polydispersity index of 0.121, encapsulation efficiency of 79.3%, and zeta potential of -29.2 mV. The morphological observation demonstrated a globular shape for particles. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that the encapsulated FST was presented as the amorphous state. The dissolution test indicated a 3.06-fold increase for the accumulating concentrations, and the everted gut sac test showed a 4.9-fold gain for permeability at the duodenum region. In conclusion, the optimized FST-loaded nanoparticle formulation in this work can be developed as an efficient oral delivery system of FST to improve its biopharmaceutic properties.
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Composição de Medicamentos , Flavonóis/farmacologia , Nanotecnologia , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão/métodos , Desenho de Fármacos , Concentração de Íons de Hidrogênio , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Tamanho da Partícula , Difração de Pó , Reprodutibilidade dos Testes , Análise Espectral/métodosRESUMO
OBJECTIVE: To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma (MCL) cell line Jeko-1 and its related mechanism. METHODS: The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs, respectively. CCK-8 assay was used to detect the proliferation of the cells, and Western blot was used to measure the protein expression levels of BCL-2, caspase-3, PI3K, AKT and P-AKT. RESULTS: After Jeko-1 cells were treated with chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibrutinib (3.125, 6.25, 12.5, 25, 50 µmol /L) alone for 24, 48, 72h respectively, the cell proliferation was inhibited in a time- and dose-dependent manner. Moreover, the two drugs were applied in combination at low doses (single drug inhibition rate<50%), and the results showed that the combination of two drugs had a more significant inhibitory effect (all P < 0.05). Compared with the control group, the apoptosis rate of the single drug group of chlorambucil (3.125, 6.25, 12.5, 25, 50 µmol/L) and ibutinib (3.125, 6.25, 12.5, 25, 50 µmol/L) was increased in a dose-dependent manner. The combination of the two drugs at low concentrations (3.125, 6.25, 12.5 µmol/L) could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups (all P < 0.05). Compared with control group, the protein expression levels of caspase-3 in Jeko-1 cells were upregulated, while the protein expression levels of BCL-2, PI3K, and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone. The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins, and the differences between the combination group and the single drug groups were statistically significant (all P < 0.05). CONCLUSION: Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1, and combined application of the two drugs shows a synergistic effect, the mechanism may be associated with the AKT-related signaling pathways.
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Adenina/análogos & derivados , Linfoma de Célula do Manto , Piperidinas , Humanos , Adulto , Linfoma de Célula do Manto/tratamento farmacológico , Clorambucila/farmacologia , Clorambucila/uso terapêutico , Caspase 3/metabolismo , Proteínas Proto-Oncogênicas c-akt , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fosfatidilinositol 3-QuinasesRESUMO
Carotenoids, including carotenes and xanthophylls, have been identified as bioactive ingredients in foods and are considered to possess health-promoting effects. From a biopharmaceutical perspective, several physicochemical characteristics, such as scanty water solubility, restricted dissolution, and susceptibility to oxidation may influence their oral bioavailability and eventually, their effectiveness. In this review, we have summarized various formulation approaches that deal with the modification of crystalline status for carotenoids, which may improve their physicochemical properties, oral absorption, and biological effects. The mechanisms involving crystalline alteration and the typical methods for examining crystalline states in the pharmaceutical field have been included, and representative formulation approaches are introduced to unriddle the mechanisms and effects more clearly.
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The aim of this study was to develop a nanoparticle formulation made of poly (vinyl pyrrolidone) (PVP) and poly (lactic-co-glycolic) acid (PLGA) for the oral delivery of ß-carotene (BC). The hybrid nanoparticles were prepared by the interfacial deposition method, and the physicochemical properties of this formulation were characterized in terms of its morphology, particle size, size distribution, encapsulation efficiency, dissolution, intestinal permeability, and in vivo pharmacokinetics. Our results demonstrated that BC-loaded nanoformulation and PLGA nanoparticles (PNP) significantly enhanced a release 6.1 times higher than BC suspension. The fortification of PVP into PLGA nanoparticles, named PLGA-PVP hybrid nanoparticles (PPNP), significantly reduced the particle size, as well as led to an increase 1.9 times higher in the in vitro release of BC, compared with PNP. For the ex vivo intestinal permeability assessment, PNP and PPNP-K15 significantly enhanced the intestinal permeability by 2.7 and 6.5 times at the jejunum, and 2.3 and 4.5 times at the ileum, when compared with unformulated BC. According to the pharmacokinetic study, the optimized hybrid formulation significantly increased the peak plasma concentration (Cmax) and the area under the curve (AUC0-t), and the oral relative bioavailability showed a five-fold enhancement compared with that of the BC suspension. Our results indicate that the hybrid nanoparticulate delivery system is an efficient strategy for the oral delivery of BC.
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Exposure to ultraviolet B (UVB) leads to the overproduction of reactive oxygen species (ROS), causing higher risks of skin disorders. Luteolin (Lut) is a naturally occurring antioxidant that can absorb a broad range of ultraviolet light, but its water solubility and skin permeability are limited and insufficient. The aim of the current study was to develop a Lut-loaded self-emulsifying phospholipid preconcentrate (LSEPP) for enhancing the solubility, permeability, and photoprotective activity of Lut. The designed formulations were firstly examined for their droplet size, zeta potential, dispersity, and in vitro corneum permeability after dispensing the preconcentrate to form an emulsion; the optimized formulation was further characterized for its emulsified morphology, compatibility with excipients, stability in the preconcentrate form, and photoprotective activity by the HaCaT cell model under the emulsified status. The optimized LSEPP formulation attained a smaller droplet size (140.6 ± 24.2 nm) with the addition of 1,8-cineole and increased the permeability of Lut by 7-fold. As evidenced in the cell model studies, the optimized LSEPP formulation can efficiently deliver Lut into HaCaT cells after emulsification and result in a 115% better cell viability as well as a 203% stronger ROS scavenging capability, compared with those of unformulated Lut after UVB irradiation. To sum up, we have successfully developed an LSEPP formulation, which is a safe and promising topical delivery system for enhancing the photoprotective effects of Lut.
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ETHNOPHARMACOLOGICAL RELEVANCE: Euscaphis konishii Hayata is a traditional medicinal plant in China, and its leaves are usually used to make dishes for hepatic or gastrointestinal issues by Chinese She nationality. Pharmacological analysis showed that E. konishii leaves contain high levels of flavonoids and chromones with favorable anti-hepatoma effect. AIM OF THE STUDY: The extract from E. konishii leaves was detected to evaluate its chemical composition, and the alcoholic liver injury mice model was adopted to elucidate its hepatoprotective effects. MATERIALS AND METHODS: The total leaf extract from E. konishii was separated by polyamide column to get the flavonoid and chromone-rich extract (FCE). Single compounds from FCE was purified by gel and Sephadex LH-20 chromatography and analyzed by nuclear magnetic resonance (NMR). The chemical component of FCE was confirmed and quantified by HPLC-MS. The OH·, O2-, DPPH and ABTS + free radical assays were adopted to estimate the antioxidant activity of FCE in vitro. The alcohol-fed model mice were established to assess the hepatoprotective capacity of FCE in vivo, through biochemical determination, histopathological analysis, mitochondrial function measurement, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) detection and Western blot determination. RESULTS: 8 flavonoids and 2 chromones were recognized in the FCEextract by both NMR and HPLC-MS. FCE represented strong free radicals scavenging activity in vitro. With oral administration, FCE (50, 100 and 200 mg/kg) dose-dependently decreased the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in alcohol-fed mice. FCE gradually reduced the malondialdehyde (MDA) content, increased the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the alcohol-treated liver tissues. FCE also alleviated the hepatic inflammation, inhibited the hepatocyte apoptosis and lessened the alcohol-induced histological alteration and lipid accumulation in the liver tissues. FCE administration inhibited the overexpression of endoplasmic reticulum (ER) chaperones signaling and unfolded protein response (UPR) pathways to defense the ER-induced apoptosis. Pretreatment with FCE also restored the mitochondrial membrane potentials andadenosine triphosphate (ATP) levels, which in turn suppressed the Cytochrome C release and mitochondria-induced apoptosis. CONCLUSIONS: FCE conferred great protection against alcoholic liver injury, which might be associated with its viability through suppressing reactive oxygen species (ROS) stress and hepatocyte apoptosis.
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Doença Hepática Induzida por Substâncias e Drogas , Flavonoides , Alanina Transaminase , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cromonas/farmacologia , Feminino , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Fígado , Camundongos , Estresse Oxidativo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Butachlor is the most commonly used herbicide on paddy fields in Taiwan and throughout Southeast Asia. Since paddy fields provide habitat for pond breeding amphibians, we examined growth, development, time to metamorphosis, and survival of alpine cricket frog tadpoles (Fejervarya limnocharis) exposed to environmentally realistic concentrations of butachlor. We documented negative impacts of butachlor on survival, development, and time to metamorphosis, but not on tadpole growth. The 96 h LC(50) for tadpoles was 0.87 mg/l, much lower than the 4.8 mg/l recommended dosage for application to paddy fields. Even given the rapid breakdown of butachlor, tadpoles would be exposed to concentrations in excess of their 96 h LC(50) for an estimated 126 h. We also documented DNA damage (genotoxicity) in tadpoles exposed to butachlor at concentrations an order of magnitude less than the 4.8 mg/l recommended application rate. We did not find that butachlor depressed cholinesterase activity of tadpoles, unlike most organophosphorus insecticides. We conclude that butachlor is likely to have widespread negative impacts on amphibians occupying paddy fields with traditional herbicide application.
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Acetanilidas/toxicidade , Herbicidas/toxicidade , Ranidae/fisiologia , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Agricultura , Animais , Relação Dose-Resposta a Droga , Crescimento e Desenvolvimento/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Testes de Mutagenicidade , Mutagênicos/toxicidade , Sistema Nervoso/efeitos dos fármacos , Ranidae/crescimento & desenvolvimento , Ranidae/metabolismo , Taiwan , Testes de Toxicidade Aguda , Testes de Toxicidade CrônicaRESUMO
In the fight against sports doping, the Athlete Biological Passport (ABP) system aims to indirectly unveil the doping incidents by monitoring selected biomarkers; however, several unexplored extrinsic factors may dampen a fair interpretation of ABP profiles. Chinese herbal medicine (CHM) plays a pivotal role in the health care system, and some remedies have a long history of being used to treat anaemia. In this study, we addressed the concerns of whether the CHM administration could yield a measurable effect on altering the ABP haematological variables. Forty-eight healthy volunteers were randomly assigned to receive two-week oral administration of one of the six selected CHM products that are commonly prescribed in Taiwan (eight subjects per group). Their blood variables were determined longitudinally in the phases of baseline, intervention, and recovery over 5 weeks. Blood collection and analyses were carried out in strict compliance with relevant operating guidelines. In the groups receiving Angelicae Sinensis Radix, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma, a significant increased reticulocyte percentage and decreased OFF-hr Score were manifested during the intervention, and such effects even sustained for a period of time after withdrawal. All other variables, including haemoglobin and Abnormal Blood Profile Score, did not generate statistical significance. Our results show that the use of CHM may impact the ABP haematological variables. As a consequence, we recommend athletes, particularly those who have been registered in the testing pool, should be aware of taking specific Chinese herbal-based treatment or supplementation, and document any of its usage on the anti-doping forms.
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Dopagem Esportivo , Medicamentos de Ervas Chinesas , Esportes , Atletas , Humanos , Detecção do Abuso de SubstânciasRESUMO
Higenamine is a ß2 -agonist that has been prohibited in sports by the World Anti-Doping Agency. Higenamine could potentially promote anabolism and lipolysis; however, its crucial pharmacokinetics data, particularly muscle distribution, remain unavailable. The present study aims to investigate the blood-to-muscle distribution as well as the urinary excretion of higenamine in laboratory rats. In the first experiment, the microdialysis technique was employed to continuously measure free, protein-unbound concentrations in blood and muscle for 90 min (sampling at a 5-min interval) after rats received IV infusion of higenamine. The mean half-lives of higenamine in blood and muscle were 17.9 and 19.0 min, respectively. The blood-to-muscle distribution ratio (AUCmuscle /AUCblood ) of higenamine was estimated to be 22%. In the second experiment, rats were orally administered with a single-dose higenamine, and their urine samples were profiled at a 12-h interval for up to 48 h. Results showed only a small portion of total consumption (1.44%, ranging 0.71%-2.50%) was excreted in the urine. Among these time points, about 43% cumulative amount of higenamine was eliminated within the first 12 h. Our data suggested that one-quarter of the unbound higenamine rapidly penetrates from the vessels into muscle, distributes to the interstitial fluid, then eliminates from the rat in a short span of time. The muscle tissue is likely to have a low binding affinity for higenamine, and renal excretion plays a minor role in its elimination. Together, our findings provide valuable pharmacokinetics data that may gain deeper insights into higenamine's role in skeletal muscle functions.
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Agonistas Adrenérgicos beta/farmacocinética , Alcaloides/farmacocinética , Dopagem Esportivo/prevenção & controle , Tetra-Hidroisoquinolinas/farmacocinética , Animais , Área Sob a Curva , Meia-Vida , Masculino , Microdiálise/métodos , Ratos , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
The complexes of Zn2+, Ni2+ with 4-amino-3,5-dimethyl-1,2,4-triazole and 4-amino-1,2,4-triazole were synthesized in water, respectively. By elemental analysis, coordination titration and molar conductivities studies, the compositions of the complexes were suggested as Zn3 (NCS)6 (L1)6 (NO3)2 and Ni3 (NCS)6 (L2)6 (NO3)2 respectively. The ligands and coordination compounds were studied by means of IR spectra, UV and fluorescence excitation and emission spectra. The IR spectra studies indicate that triazolate was bonded with RE (II) through nitrogen atoms in the heterocyclic ring. The fluorescence spectra showed that the fluorescence emission intensity of Ni3 (NCS)6 (L2)6 (NO3)2 was stronger than that of Zn3 (NCS)6 (L1)6 (NO3)2.
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Schiff base 4-(p-dimethylaminobenzaldehydeamino)-4H-1,2,4-triazole(L) was synthesized from 4-amino-1,2,4-triazole and p-dimethylaminobenzaldehyde using acetic acid as the catalyst. The solid complexes RE3L6(NO3)6(H2O)2 (RE = Cu, Co, Zn, Cd; x = 3-6) were synthesized with 4-(p-dimethylaminobenzaldehydeamino)-4H-1,2,4-triazole and nitrate of transition metals in ethanol and characterized by elemental analysis, infrared spectroscopy, UV spectrum, and fluorescence spectrum. Experimental results showed that the free ligand is a thermally stable material, and its ethanol solution emitted intense blue fluorescence at the peak wavelength of 416 nm. The absorption band at about 406 nm can be assigned to the intrinsic absorption of C==N. Compared with the fluorescence emission of free ligand in ethanol solution, the emission of the complex of RE3L6 (NO3)6(H2O)2 was red-shifted to 445 nm and narrow in solution. RE(II) was coordinated with N atomy of triazole in 4-(p-dimethylaminobenzaldehydeamino)-4H-1,2,4-triazole.
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The solid complex of lanthanum nitrate hydrate with 4-(p-dimethylaminobenzaldehydeamino)-4H-1,2,4-triazole (L) LaL3 (NO3)3 x (H2O)2 x (C2 H5 OH)2 was synthesized in dry N2 atmosphere and absolute alcohol. The composition of the complex was determined by chemical and elemental analyses. The crystal structure showed that La3+ was coordinated by ten oxygen atoms with three nitrate, two water and two alcohol molecules. Characterized by elemental analysis, infrared spectroscopy, and solid fluorescence, the experimental results showed that the free ligand is a thermally stable material, and emitted intensive blue fluorescence at the peak wavelength of 451 nm. Compared with the fluorescence emission of free ligand in solid-state, the emission of complex of LaL3 (NO3)3 x (H2O)2 x (C2H5 OH)2 red-shifted to 464 nm and exhibited stronger blue fluorescence.
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The structure of the inclusion complex of diferrocenylenone and beta-cyclodextrin prepared by a novel method of solid-grinding was studied by UV, FTIR and powder X-ray diffractometry. Continuous variation plot proved that 2 : 3 (DFE : beta-CD) inclusion complex has been formed. The binding constant of the inclusion compound was found to be 1.48 x 10(15) (L4 x mol(-4)) with the data of UV spectroscopy. Furthermore, the influence of different solvents and pH on the UV spectrum of DFE and beta-CD-DFE was discussed respectively. The results show that different micro-environment has apparently different effects on the electric spectra of guest and inclusion complex.
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Inclusion complex of benzoylferrocene-thiosemicarbazone (TBF) with beta-cyclodextrin (beta-CD) was prepared by using kneading method. Continuous variation plot proved that 2:3 (TBF: beta-CD) inclusion complex has been formed. The characterizations of the inclusion complex were studied by UV, FTIR and X-ray diffractometry. By using the data of UV spectroscopy, the binding constant of the inclusion compound was estimated to be 5.04 x 10(13) (L4 x (mol)(-4)), and its change in absorption with time was studied. The stability of inclusion is obviously greater than the guest molecule. Furthermore, the influences of different solvents and pH on the UV spectra of TBF and beta-CD-TBF were discussed respectively. The results show that different micro-environments have apparently different effects on electric spectra of guest and inclusion complexes.
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Inclusion complex of acetylferrocene-thiosemicarbazone(TAF) with beta-cyclodextrin(beta-CD) has been prepared by using kneading method. Elemental analysis and the solubility determination proved that 1:1 inclusion complex has been formed. Characterization of the inclusion complex was studied by UV, FTIR, and X-ray diffractometry. The association constant was calculated to be 227 L x mol(-1) from the straight portion of the phase-solubility diagram. Furthermore, the influence of different solvents and pH on UV spectrum of acetylferrocene-thiosemicarbazone and beta-CD -TAF was discussed respectively. The results show that different micro-environment has apparently different effects on electric spectra of guest and inclusion complexes.
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Compostos Ferrosos/análise , Tiossemicarbazonas/análise , beta-Ciclodextrinas/análise , Concentração de Íons de Hidrogênio , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
Potential commercial physicochemical pretreatment methods, NaOH/microwave and NaOH/ultrasound were developed, and the carbon-based sulfonated solid acid catalysts were prepared for furfural residues conversion into reducing sugars. After the two optimum pretreatments, both the content of cellulose increased (74.03%, 72.28%, respectively) and the content of hemicellulose (94.11%, 94.17% of removal rate, respectively) and lignin (91.75%, 92.09% of removal rate, respectively) decreased in furfural residues. The reducing sugar yields of furfural residues with the two physicochemical pretreatments on coal tar-based solid acid reached 33.94% and 33.13%, respectively, higher than that pretreated via NaOH alone (27%) and comparable to that pretreated via NaOH/H2O2 (35.67%). The XRD patterns, IR spectra and SEM images show microwave and ultrasound improve the pretreatment effect. The results demonstrate the carbon-based sulfonated solid acids and the physicochemical pretreatments are green, effective, low-cost for furfural residues conversion.
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Carbono/química , Fenômenos Químicos , Furaldeído/química , Hidróxido de Sódio/química , Ácidos Sulfônicos/química , Catálise , Hidrólise , Micro-Ondas , Temperatura , Fatores de Tempo , UltrassomRESUMO
The electrocatalytic oxidation of isoniazid (INH) by (ferrocenylmethyl)trimethylammonium [(FcM)TMA] at the platinum electrode in 0.10 M Na2SO4 aqueous solution was studied by cyclic voltammetry (CV). Although INH itself showed a very poor electrochemical response at the platinum electrode, the response could be greatly enhanced by using (FcM)TMA as a mediator, which enables a sensitive electrochemical determination of the substrate INH. The reaction rate constant for catalytic oxidation reaction was evaluated as (3.98+/-0.10)x10(3) M(-1) s(-1) by using chronoamperometry (CA). Experimental conditions such as supporting electrolyte and its concentration, solution pH, and the concentrations of the catalyst (FcM)TMA and the substrate INH were investigated to maximize the current efficiency of the electrocatalytic oxidation. The method can be used for the sensitive practical determination of INH, and also opens an avenue for using (FcM)TMA as a mediator in electroanalytical determination which is very simple, cheap, and rapid. Furthermore, no sample pretreatment or time-consuming extraction steps are required prior to the analysis.