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1.
Antiviral Res ; 224: 105835, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401714

RESUMO

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing. Here we report on an optimized in vivo DHBV duck model and explore several characteristics of NAP treatment. REP2139 was efficacious in reducing DHBV DNA and DHBsAg levels in approximately half of the treated ducks, whether administered intraperitoneally or subcutaneously. Intrahepatic or serum NAP concentrations did not correlate with efficacy, nor did the appearance of anti-DHBsAg antibodies. Furthermore, NAP efficacy was only observed in experimentally infected ducks, not in endogenously infected ducks (vertical transmission). REP2139 add-on to entecavir treatment induced a deeper and more sustained virological response compared to entecavir monotherapy. Destabilized REP2165 showed a different activity profile with a more homogenous antiviral response followed by a faster rebound. In conclusion, subcutaneous administration of NAPs in the DHBV duck model provides a useful tool for in vivo evaluation of NAPs. It recapitulates many aspects of this class of compound's efficacy in CHB patients, most notably the clear division between responders and non-responders.


Assuntos
Infecções por Hepadnaviridae , Vírus da Hepatite B do Pato , Hepatite B Crônica , Hepatite Viral Animal , Ácidos Nucleicos , Animais , Humanos , Vírus da Hepatite B do Pato/genética , Hepatite B Crônica/tratamento farmacológico , Antivirais/farmacologia , Ácidos Nucleicos/uso terapêutico , Polímeros/uso terapêutico , Resultado do Tratamento , Patos/genética , DNA Viral , Hepatite Viral Animal/tratamento farmacológico , Vírus da Hepatite B , Infecções por Hepadnaviridae/tratamento farmacológico , Infecções por Hepadnaviridae/veterinária , Fígado
2.
RSC Adv ; 9(22): 12615-12625, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35515842

RESUMO

Spinel Co3O4 thin films were synthesized using a sol-gel technique to study the annealing atmosphere effect on resistive switching (RS) and magnetic modulation properties. Compared with oxygen and air annealed Pt/Co3O4/Pt stacks, the nitrogen annealed Pt/Co3O4/Pt stack shows optimal switching parameters such as a lower forming voltage, uniform distribution of switching voltages, excellent cycle-to-cycle endurance (>800 cycles), and good data retention. Improvement in switching parameters is ascribed to the formation of confined conducting filaments (CFs) which are composed of oxygen vacancies. From the analysis of current-voltage characteristics and their temperature dependence, the carrier transport mechanism in the high-field region of the high resistance state was dominated by Schottky emission. Besides, temperature dependent resistance and magnetization variations revealed that the physical mechanism of RS can be explained based on the formation and rupture of oxygen vacancy based CFs. In addition, multilevel saturation magnetization under different resistance states is attributed to the variation of oxygen vacancy concentration accompanied with the changes in the valence state of cations. Results suggested that using a nitrogen annealing atmosphere to anneal the thin films is a feasible approach to improve RS parameters and enhance the magnetic properties of Co3O4 thin film, which shows promising applications to design multifunctional electro-magnetic coupling nonvolatile memory devices.

3.
ACS Appl Mater Interfaces ; 10(21): 17842-17849, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29726250

RESUMO

Piezoelectric effect, commonly known as a change in electric polarization in piezoelectric/ferroelectric materials under mechanical stress, is extensively employed as a driving force for the catalytic degradation of organic pollutants. However, the relationship between electric polarization and piezocatalytic activity is still unclear. In this work, we investigated the role of ferroelectric polarization in the piezocatalytic activity of BaTiO3 nanoparticles through annealing BaTiO3 at different temperatures or poling BaTiO3 at different electric fields. The BaTiO3 nanoparticles annealed at 800 °C exhibit effectively enhanced piezocatalytic activity compared with those annealed at other temperatures. The polycrystalline particles annealed at higher temperatures exhibit a greatly reduced catalytic activity. After poling, the piezocatalytic activity of the polycrystalline BaTiO3 particles was obviously improved. In addition, we identified the free radical species and the intermediate products of the catalytic reaction. We also well-explained the dependence of electric polarization in the BaTiO3 piezocatalyst on annealing temperature and ultrasonic vibration theoretically. Our study indicates that increasing ferroelectric polarization (but not crystallite size) can effectively enhance the piezocatalytic activity. We believe that the present work provides a clear understanding of the role of ferroelectric polarization in piezocatalysis.

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