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The Ruddlesden-Popper (R-P) bilayer nickelate, La3Ni2O7, was recently found to show signatures of high-temperature superconductivity (HTSC) at pressures above 14 GPa (ref. 1). Subsequent investigations achieved zero resistance in single-crystalline and polycrystalline samples under hydrostatic pressure conditions2-4. Yet, obvious diamagnetic signals, the other hallmark of superconductors, are still lacking owing to the filamentary nature with low superconducting volume fraction2,4,5. The presence of a new 1313 polymorph and competing R-P phases obscured proper identification of the phase for HTSC6-9. Thus, achieving bulk HTSC and identifying the phase at play are the most prominent tasks. Here we address these issues in the praseodymium (Pr)-doped La2PrNi2O7 polycrystalline samples. We find that substitutions of Pr for La effectively inhibit the intergrowth of different R-P phases, resulting in a nearly pure bilayer structure. For La2PrNi2O7, pressure-induced orthorhombic to tetragonal structural transition takes place at Pc ≈ 11 GPa, above which HTSC emerges gradually on further compression. The superconducting transition temperatures at 18-20 GPa reach T c onset = 82.5 K and T c zero = 60 K , which are the highest values, to our knowledge, among known nickelate superconductors. Importantly, bulk HTSC was testified by detecting clear diamagnetic signals below about 75 K with appreciable superconducting shielding volume fractions at a pressure of above 15 GPa. Our results not only resolve the existing controversies but also provide directions for exploring bulk HTSC in the bilayer nickelates.
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Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.
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In recent years, cationic polymer vectors have been viewed as a promising method for delivering nucleic acids. With the advancement of synthetic polymer chemistry, we can control chemical structures and properties to enhance the efficacy of gene delivery. Herein, a facile, cost-effective, and scalable method was developed to synthesize PEGylated PDMAEMA polymers (PEO-PDMAEMA-PEO), where PEGylation could enable prolonged polyplexes circulation time in the blood stream. Two polymers of different molecular weights were synthesized, and polymer/eGFP polyplexes were prepared and characterized. The correlation between polymers' molecular weight and physicochemical properties (size and zeta potential) of polyplexes was investigated. Lipofectamine 2000, a commercial non-viral transfection reagent, was used as a standard control. PEO-PDMAEMA-PEO with higher molecular weight exhibited slightly better transfection efficiency than Lipofectamine 2000, and the cytotoxicity study proved that it could function as a safe gene vector. We believe that PEO-PDMAEMA-PEO could serve as a model to investigate more potential in the gene delivery area.
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Técnicas de Transferência de Genes , Nylons , Polietilenoglicóis , Transfecção , Polietilenoglicóis/química , Humanos , Nylons/química , Nylons/síntese química , Transfecção/métodos , Metacrilatos/química , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Lipídeos/química , Sobrevivência Celular/efeitos dos fármacosRESUMO
Nitric oxide (NO)-releasing coating is promising to enhance the biocompatibility of medical devices. In this study, polyurethane (PU) and S-nitrosated keratin (KSNO) were dissolved with dimethyl sulfoxide (DMSO) and tetrahydrofuran (THF) to prepare a coating solution. This solution is facile to form a porous coating on various substrates based on solvent-evaporation-induced phase separation (SEIPS). The coating could continuously release NO up to 200 h in the presence of ascorbic acid (Asc). In addition, the coating could accelerate endothelialization by promoting the viability of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation of human umbilical artery smooth muscle cells (HUASMCs). Furthermore, the coating had good antibacterial activity and blood compatibility. Taken together, this universal coating provides wider potential applications in the field of cardiovascular implants.
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Antibacterianos , Óxido Nítrico , Humanos , Óxido Nítrico/farmacologia , Porosidade , Células Endoteliais da Veia Umbilical Humana , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologiaRESUMO
The passivation of the defects derived from rapid-crystallization with electron-donating molecules is always a prerequisite to obtain desirable perovskite films for efficient and stable solar cells, thus, the in-depth understanding on the correlations between molecular structure and passivation capacity is of great importance for screening passivators. Here, we introduce the double-ended amide molecule into perovskite precursor solution to modulate crystallization process and passivate defects. By regulating the intermediate bridging skeletons with alkyl, alkenyl and benzene groups, the results show the passivation strength highly depends on the spin-state electronic structure that serves as an intrinsic descriptor to determine the intramolecular charge distribution by controlling orbital electron transfer from the donor segment to acceptor segment. Upon careful optimization, the benzene-bridged amide molecule demonstrates superior efficacy on improving perovskite film quality. As a physical proof-of-concept, the carbon-based, all-inorganic CsPbI2Br solar cell delivers a significantly increased efficiency of 15.51 % with a remarkably improved stability. Based on the same principle, a champion efficiency of 24.20 % is further obtained on the inverted (Cs0.05MA0.05FA0.9)Pb(I0.93Br0.07)3 solar cell. These findings provide new fundamental insights into the influence of spin-state modulation on effective perovskite solar cells.
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Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75â mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one-step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure-activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale.
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Antineoplásicos , Depsipeptídeos , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/metabolismo , Depsipeptídeos/farmacologia , Antineoplásicos/farmacologia , Relação Estrutura-AtividadeRESUMO
Geohazards, such as landslides, rock avalanches, debris flow, ground fissures, and ground subsidence, pose significant threats to people's lives and property [...].
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Perovskite solar cells (PSCs) have become a promising candidate for the next-generation photovoltaic technologies. As an essential element for high-efficiency PSCs however, the heavy metal Pb is soluble in water, causing a serious threat to the environment and human health. Due to the weak ionic bonding in three-dimensional (3D) perovskites, drastic structure decomposition occurs when immersing the perovskite film in water, which accelerates the Pb leakage. By introducing the chemically stable Dion-Jacobson (DJ) 2D perovskite at the 3D perovskite surface, the film dissolution is significantly slowed down, which retards lead leakage. As a result, the Pb contamination is dramatically reduced under various extreme conditions. In addition, the PSCs device deliver a power conversion efficiency (PCE) of 23.6 % and retain over 95 % of their initial PCE after the maximum power point tracking for over 1100â h.
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In this study, an extended model for describing the temporal evolution of a characteristic floc size of cohesive sediment particles when the flocculation system is subject to a piecewise varied turbulent shear rate was derived by the probability methods based on the Shannon entropy theory following Zhu (2018). This model only contained three important parameters: initial and steady-state values of floc size, and a parameter characterizing the maximum capacity for floc size increase (or decay), and it can be adopted to capture well a monotonic pattern in which floc size increases (or decays) with flocculation time. Comparison with 13 literature experimental data sets regarding floc size variation to a varied shear rate showed the validity of the entropic model with a high correlation coefficient and few errors. Furthermore, for the case of tapered shear flocculation, it was found that there was a power decay of the capacity parameter with the shear rate, which is similar to the dependence of the steady-state floc size on the shear rate. The entropic model was further parameterized by introducing these two empirical relations into it, and the finally obtained model was found to be more sensitive to two empirical coefficients that have been incorporated into the capacity parameter than those in the steady-state floc size. The proposed entropic model could have the potential, as an addition to existing flocculation models, to be coupled into present mature hydrodynamic models to model the cohesive sediment transport in estuarine and coastal regions.
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Helicobacter pylori (H. pylori) infection is highly prevalent, and has developed antimicrobial resistance to virtually all existing antibiotics. Currently, treatment of H. pylori infection (involving proton pump inhibitors and broad-spectrum antibiotics) is suboptimal, with high failure rates. Thus, there is a pressing need to develop new anti-H. pylori therapies. Cbf-K16, a cathelicidin-like antimicrobial peptide, presented broad antimicrobial activity during our previous research. This study further evaluated the therapeutic potential and the mode of action underlying Cbf-K16 against clarithromycin- and amoxicillin-resistant H. pylori SS1. The MIC and MBC of Cbf-K16 against the tested H. pylori were 16 and 32⯵g/ml, respectively, and its killing kinetics was time-dependent, reflecting the thorough elimination of drug-resistant bacteria within 24â¯h. This peptide also protected H. pylori-infected gastric epithelial cells (GES-1) from death by reducing the cell supernatant and intracellular bacterial counts by 1.9 and 2.9-log10 units, respectively. These data indicated the powerful antimicrobial effects of Cbf-K16in vitro. Meanwhile, notable antimicrobial activity in the mouse gastritis model was observed, with decreasing bacterial counts by 3.9-log10 units in stomach tissues and Cbf-K16 could effectively suppress the secretion of inflammatory cytokine IL-8. For its mode of action, Cbf-K16 not only neutralized the negative potential and increased the membrane uptake of NPN and PI by 78.5% and 85.1%, respectively, but also bound to genomic DNA, which in turn downregulated the expression of adhesion genes (alpA and alpB) and virulence gene (cagA), indicating its effective activities on membrane disruption, DNA-binding and gene expression. The data above demonstrated that Cbf-K16 possessed effective antimicrobial and anti-inflammatory activities and downregulated the expression of adhesion- and cytotoxin-associated genes of drug-resistant H. pylori SS1, making it a potential candidate for anti-infective therapy.
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Adesinas Bacterianas/efeitos dos fármacos , Catelicidinas/farmacologia , Infecções por Helicobacter , Helicobacter pylori/efeitos dos fármacos , Interleucina-8/efeitos dos fármacos , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antígenos de Bactérias/efeitos dos fármacos , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/efeitos dos fármacos , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Farmacorresistência Bacteriana , Genes Bacterianos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Humanos , Interleucina-8/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Virulência/efeitos dos fármacos , Virulência/genéticaRESUMO
Tissue-engineered vascular graft (TEVG) is a promising alternative to meet the clinical demand of organ shortages. Herein, human hair keratin was extracted by the reduction method, followed by modification with zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) through thiol-Michael addition to improve blood clotting nature. Then, phosphobetainized keratin (PK) was coelectrospun with poly(ε-caprolactone) (PCL) to afford PCL/PK mats with a ratio of 7:3. The surface morphology, chemical structure, and wettability of these mats were characterized. The biocomposite mats selectively enhanced adhesion, migration, and growth of endothelial cells (ECs) while suppressed proliferation of smooth muscle cells (SMCs) in the presence of glutathione (GSH) and GSNO due to the catalytic generation of NO. In addition, these mats exhibited good blood anticoagulant activity by reducing platelet adhesion, prolonging blood clotting time, and inhibiting hemolysis. Taken together, these NO-generating PCL/PK mats have potential applications as a scaffold for vascular tissue engineering with rapid endothelialization and reduced SMC proliferation.
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Materiais Biocompatíveis/química , Queratinas/química , Óxido Nítrico/farmacologia , Poliésteres/química , Alicerces Teciduais/química , Catálise , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cabelo/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Metacrilatos/química , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Adesividade Plaquetária/efeitos dos fármacos , Engenharia TecidualRESUMO
Drug-loaded micelles with long circulation time in blood and stimuli-responsiveness under the tumor micro-environment can significantly enhance therapeutic efficacy. In this report, human hair keratin was extracted with a reduction method and then conjugated with zwitterionic poly(2-methacryloxyethyl phosphatidylcholine, MPC) via thiol chain transfer polymerization (thiol CTP). Subsequently, keratin-polyMPC conjugates (KPC) were prepared into micelles and loaded with doxorubicin (DOX) by self-assembly. These micelles exhibited pH, glutathione (GSH), and enzyme triple-responsiveness as well as charge reversibility under the tumor micro-environment. In addition, these micelles showed high toxicity against A549 cells while low toxicity to normal cells. In vivo anticancer efficacy results revealed that these micelles showed better therapeutic efficiency than free DOX. Furthermore, these carriers exhibited prolonged circulation time, good stability, and no hemolysis in blood. Based on the results, these drug delivery systems of micelles were proper candidates as drug carriers.
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Sistemas de Liberação de Medicamentos , Queratinas , Micelas , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de HidrogênioRESUMO
The velocity profile of an open channel is an important research topic in the context of open channel hydraulics; in particular, the velocity-dip position has drawn the attention of hydraulic scientists. In this study, analytical expressions for the velocity-dip position over the entire cross section and at the centerline of a rectangular open channel are derived by adopting probability methods based on the Tsallis and general index entropy theories. Two kinds of derived entropy-based expressions have the same mathematical form as a function of the lateral distance from the sidewall of the channel or of the aspect ratio of the channel. Furthermore, for the velocity-dip position over the entire cross section of the rectangular open channel, the derived expressions are compared with each other, as well as with two existing deterministic models and the existing Shannon entropy-based expression, using fifteen experimental datasets from the literature. An error analysis shows that the model of Yang et al. and the Tsallis entropy-based expression predict the lateral distribution of the velocity-dip position better than the other proposed models. For the velocity-dip position at the centerline of the rectangular open channel, six existing conventional models, the derived Tsallis and general index entropy-based expressions, and the existing Shannon entropy-based models are tested against twenty-one experimental datasets from the literature. The results show that the model of Kundu and the Shannon entropy-based expression have superior prediction accuracy with respect to experimental data compared with other models. With the exception of these models, the Tsallis entropy-based expression has the highest correlation coefficient value and the lowest root mean square error value for experimental data among the other models. This study indicates that the Tsallis entropy could be a good addition to existing deterministic models for predicting the lateral distribution of the velocity-dip position of rectangular open channel flow. This work also shows the potential of entropy-based expressions, the Shannon entropy and the Tsallis entropy in particular, to predict the velocity-dip position at the centerline of both narrow and wide rectangular open channels.
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The coupled localized plasmon modes generated by a metal plasmonic nanoparticle (NP) dimer induces a stronger plasmon enhanced electromagnetic field as well as a stronger optical response compared to that of a single NP. Owing to the small Drude damping factor, however, the absorption bandwidth of noble metallic NPs is insufficiently broad. Herein, the near-field wide band coupling absorption for 25 nm diameter TiN nanospheres is investigated in a homo-dimer arrangement for various separation distances using the finite element method. An enhancement of the wide band coupling absorption and a red-shift is found, which can be explained by an uncomplicated dipole-dipole coupling model at interparticle distances greater than 5 nm. At short separation distances, the coupling absorption of the TiN dimer exhibits a tremendous change, which is diametrically opposite the results found for a Au dimer. This unexpected change phenomenon is shown by calculation and analysis to be owing to the change of the charge distribution approach at short separation distances, which is demonstrated to play a key role in the wide band coupling characteristic variation. With decreasing separation gap, a new coupling mechanism caused by surface charge properties is responsible for the decline in coupling absorption as well as the break in the ruler equations for both plasmon shift and temperature enhancement.
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The bathymetry of nearshore coastal environments and lakes is constantly reworking because of the change in the patterns of energy dispersal and related sediment transport pathways. Therefore, updated and accurate bathymetric models are a crucial component in providing necessary information for scientific, managerial, and geographical studies. Recent advances in satellite technology revolutionized the acquisition of bathymetric profiles, offering new vistas in mapping. This contribution analyzed the suitability of Sentinel-2 and Landsat-8 images for bathymetric mapping of coastal and lake environments. The bathymetric algorithm was developed using an empirical approach and a random forest (RF) model based on the available high-resolution LiDAR bathymetric data for Mobile Bay, Tampa Bay, and Lake Huron regions obtained from the National Oceanic and Atmospheric Administration (NOAA) National Geophysical Data Center (NGDC). Our results demonstrate that the satellite-derived bathymetry is efficient for retrieving depths up to 10 m for coastal regions and up to 30 m for the lake environment. While using the empirical approach, the root-mean-square error (RMSE) varied between 1.99 m and 4.74 m for the three regions. The RF model, on the other hand, provided an improved bathymetric model with RMSE between 1.13 m and 1.95 m. The comparative assessment suggests that Sentinel-2 has a slight edge over Landsat-8 images while employing the empirical approach. On the other hand, the RF model shows that Landsat-8 retrieves a better bathymetric model than Sentinel-2. Our work demonstrated that the freely available Sentinel-2 and Landsat-8 imageries proved to be reliable data for acquiring updated bathymetric information for large areas in a short period.
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The currently available drugs against influenza A virus primarily target neuraminidase (NA) or the matrix protein 2 (M2) ion channel. The emergence of drug-resistant viruses requires the development of new antiviral chemicals. Our study applied a cell-based approach to evaluate the antiviral activity of a series of newly synthesized benzoic acid derivatives, and 4-(2,2-Bis(hydroxymethyl)-5-oxopyrrolidin-l-yl)-3-(5-cyclohexyl-4H-1,2,4-triazol-3-yl)amino). benzoic acid, termed NC-5, was found to possess antiviral activity. NC-5 inhibited influenza A viruses A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) in a dose-dependent manner. The 50% effective concentrations (EC50) for H1N1 and H1N1-H275Y were 33.6 µM and 32.8 µM, respectively, which showed that NC-5 had a great advantage over oseltamivir in drug-resistant virus infections. The 50% cytotoxic concentration (CC50) of NC-5 was greater than 640 µM. Orally administered NC-5 protected mice infected with H1N1 and H1N1-H275Y, conferring 80% and 60% survival at 100 mg/kg/d, reducing body weight loss, and alleviating virus-induced lung injury. NC-5 could suppress NP and M1 protein expression levels during the late stages of viral biosynthesis and inhibit NA activity, which may influence virus release. Our study proved that NC-5 has potent anti-influenza activity in vivo and in vitro, meaning that it could be regarded as a promising drug candidate to treat infection with influenza viruses, including oseltamivir-resistant viruses.
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Antivirais/farmacologia , Ácido Benzoico/farmacologia , Inibidores Enzimáticos/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Neuraminidase/antagonistas & inibidores , Proteínas Virais/antagonistas & inibidores , Animais , Antivirais/síntese química , Antivirais/química , Ácido Benzoico/síntese química , Ácido Benzoico/química , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Replicação Viral/efeitos dos fármacosRESUMO
The settling velocity of a sediment particle is an important parameter needed for modelling the vertical flux in rivers, estuaries, deltas and the marine environment. It has been observed that a particle settles more slowly in the presence of other particles in the fluid than in a clear fluid, and this phenomenon has been termed 'hindered settling'. The Richardson and Zaki equation has been a widely used expression for relating the hindered settling velocity of a particle with that in a clear fluid in terms of a concentration function and the power of the concentration function, and the power index is known as the exponent of reduction of the settling velocity. This study attempts to formulate the model for the exponent of reduction of the settling velocity by using the probability method based on the Tsallis entropy theory. The derived expression is a function of the volumetric concentration of the suspended particle, the relative mass density of the particle and the particle's Reynolds number. This model is tested against experimental data collected from the literature and against five existing deterministic models, and this model shows good agreement with the experimental data and gives better prediction accuracy than the other deterministic models. The derived Tsallis entropy-based model is also compared with the existing Shannon entropy-based model for experimental data, and the Tsallis entropy-based model is comparable to the Shannon entropy-based model for predicting the hindered settling velocity of a falling particle in a particle-fluid mixture. This study shows the potential of using the Tsallis entropy together with the principle of maximum entropy to predict the hindered settling velocity of a falling particle in a particle-fluid mixture.
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In the context of river dynamics, some experimental results have shown that particle velocity is different from fluid velocity along the stream-wise direction for uniform sediment-laden open-channel flows; this velocity difference has been termed velocity lag in the literature. In this study, an analytical expression for estimating the velocity lag in open-channel flows was derived based on the Tsallis entropy theory together with the principle of maximum entropy. The derived expression represents the velocity lag as a function of a non-dimensional entropy parameter depending on the average and maximum values of velocity lag from experimental measurements. The derived expression was tested against twenty-two experimental datasets collected from the literature with three deterministic models and the developed Shannon entropy-based model. The Tsallis entropy-based model agreed better with the experimental datasets than the deterministic models for eighteen out of the twenty-two total real cases, and the prediction accuracy for the eighteen experimental datasets was comparable to that of the developed Shannon entropy-based model (the Tsallis entropy-based expression agreed slightly better than the Shannon entropy-based model for twelve out of eighteen test cases, whereas for the other six test cases, the Shannon entropy-based model had a slightly higher prediction accuracy). Finally, the effects of the friction velocity of the flow, the particle diameter, and the particles' specific gravity on the velocity lag were analyzed based on the Tsallis entropy-based model. This study shows the potential of the Tsallis entropy theory together with the principle of maximum entropy to predict the stream-wise velocity lag between a particle and the surrounding fluid in sediment-laden open-channel flows.
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Cbf-14 (RLLRKFFRKLKKSV), a designed peptide derived from cathelicidin family AMP, has proven to be potent against drug-resistant bacteria. In the present study, we investigated the anti-cryptococcal activity of Cbf-14 in vitro and in a pulmonary infection mouse model. Sensitivity test indicated that Cbf-14 possessed effective antifungal activity against Cryptococcus neoformans with an MIC of 4-16⯵g/ml, and killing experiments showed that fungicidal activity was achieved after only 4â¯h treatment with Cbf-14 at 4× MIC concentrations in vitro. Meanwhile, Cbf-14 was effective at prolonging the survival of infected mice when compared with controls, and significantly inhibited the secretion of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6, suggesting its anti-inflammatory activity against fungal infections. As a positively charged peptide, Cbf-14 was proven to neutralize the negative zeta potential of the fungal cell surface, disrupt the capsule polysaccharide of fungi, and further damage cell membrane integrity. These results were confirmed by flow cytometry analysis of the fluorescence intensity after PI staining, while cell membrane damage could be clearly observed by transmission electron microscopy after Cbf-14 (4× MIC) treatment for 1â¯h. In addition, Cbf-14 increased the IL-10 levels in cultured RAW 264.7 cells, which were stimulated by C. neoformans infection. The obtained data demonstrated that Cbf-14 could rapidly kill C. neoformans cells in vitro, effectively inhibit C. neoformans induced-infection in mice, and inhibit inflammation in vitro / vivo. Therefore, Cbf-14 could potentially be used for the treatment of fungal infections clinically.
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Criptococose/tratamento farmacológico , Cryptococcus neoformans/patogenicidade , Peptídeos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antifúngicos/uso terapêutico , Criptococose/metabolismo , Cryptococcus neoformans/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In this study, Couette flow experiments were performed to estimate the temporal evolution of the 2D and perimeter-based fractal dimension values of kaolinite flocs during flocculation. The fractal dimensions were calculated based on the projected surface area, perimeter length and length of the longest axis of the flocs as determined by sampling observation and an image-processing system. The 2D fractal dimension, which relates the longest axis length and projected surface area of flocs, was found to decrease with the flocculation time, corresponding to the production of some porous flocs from the flow shear. This fractal dimension finally reached a steady state, which resulted from a dynamic equilibrium among the floc growth, floc breakage and floc restructuring. The perimeter-based fractal dimension, which characterizes the relationship between the projected surface area and the perimeter of flocs, increases with flocculation time because the flow shear increases the collisions among the primary particles, and some irregular flocs are formed. The perimeter-based fractal dimension reaches a steady level because of the balance among floc aggregation, breakage and restructuring. In addition, a stronger turbulent flow shear makes the steady state of fractal dimensions occur early during flocculation.