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1.
Small ; 18(19): e2200627, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35411712

RESUMO

Layered Ni-rich lithium transition metal oxides are promising cathode materials for high-energy-density lithium-ion batteries. These cathodes, however, suffer from rapid performance decay under high-voltage operation. In this work, the electrochemical properties and structural evolution of the LiNi0.8 Mn0.1 Co0.1 O2 (NMC811) cathode upon high-voltage cycling are investigated. The results show that the NMC811 cathode not only experiences surface evolution with the formation of Li-deficient rock-salt layers, but also suffers from drastic intragranular structural changes inside bulk grains after high-voltage cycling. Direct evidence for the formation of transition-metal/Li disordering domains with uneven Li content and lattice plane distortion at the internal grains of 4.6 V-cycled NMC811 are provided with their atomic ordering and spatial distribution clearly resolved. The complex intragranular structural changes impede Li+ diffusion inside bulk material, resulting in kinetic limitation and capacity loss. The results demonstrate that the high-voltage cycling would induce severe structural degradation at the grain interior of the cathode material beyond surface evolution, which contributes significantly to the rapid performance decay of the NMC811 cathode. The findings provide new insights for developing effective countermeasures to mitigate this degradation pathway.

2.
Int J Pharm ; 572: 118796, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678389

RESUMO

We report preparation of theranostic nanocarriers loaded with up to 50 wt% of the anticancer drug doxorubicin that contain magnetic nanoparticles which enable Magnetic Particle Imaging (MPI), an emerging technology for quantitative and unambiguous imaging of the nanocarriers. The nanocarriers, coated with poly(ethylene glycol)-block-poly(lactic acid) (PEG4.9kD-b-PLA6kD) block copolymer for colloidal stability, are composed of a hydrophobic core of precipitated hydrolysable doxorubicin prodrug (proDox) and magnetic nanoparticles. Transmission electron microscopy (TEM) shows evidence of precipitated proDox for nanocarriers with high drug loading of up to 50 wt%. MPI measurements show that the nanocarriers can be quantitatively imaged. The nanocarriers are internalized by MDA-MB-231 cells and their IC50 value via metabolic assay is 1.1 µM, compared to 0.21 µM for free doxorubicin. The release rate from the nanocarriers was dependent on environmental pH. These nanocarriers with high drug loading and quantitative imaging are promising candidates for future applications.


Assuntos
Antibióticos Antineoplásicos/química , Meios de Contraste/química , Doxorrubicina/química , Portadores de Fármacos , Magnetismo , Nanopartículas de Magnetita/química , Imagem Molecular/métodos , Tecnologia Farmacêutica/métodos , Nanomedicina Teranóstica , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Lactatos/química , Polietilenoglicóis/química
3.
J Invest Dermatol ; 138(12): 2578-2588, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29913133

RESUMO

Variants in IRF6 can lead to Van der Woude syndrome and popliteal pterygium syndrome. Furthermore, genes upstream and downstream of IRF6, including GRHL3 and TP63, are also associated with orofacial clefting. Additionally, a variant in an enhancer (MCS9.7) that regulates IRF6 is associated with risk for isolated orofacial clefting. This variant (rs642961) abrogates AP2A protein binding at MCS9.7. Here, we found that AP2A protein regulates MCS9.7 enhancer activity in vivo and IRF6 protein expression in epidermal development. In addition, loss of IRF6 leads to supra-basal expression of AP2A protein. Finally, using an IRF6 allelic series, we found that either increasing or decreasing IRF6 protein expression can destabilize AP2A protein expression in vivo. These data suggest that IRF6 regulates AP2A protein level in epidermal development. Therefore, we conclude that IRF6 and TFAP2A are part of a genetic regulatory network that is critical in epithelial development, with implications for both orofacial and cutaneous tissues. Our work provides in vivo, functional data to explain the relationship between AP2A protein binding and the MCS9.7 enhancer in orofacial clefting. This work is important because the MCS9.7 enhancer element contains a variant that abrogates AP2A protein binding and increases risk for orofacial clefting worldwide.


Assuntos
Anormalidades Múltiplas/genética , Complexo 2 de Proteínas Adaptadoras/metabolismo , Subunidades alfa do Complexo de Proteínas Adaptadoras/metabolismo , Fenda Labial/genética , Fissura Palatina/genética , Cistos/genética , Elementos Facilitadores Genéticos/genética , Epiderme/fisiologia , Anormalidades do Olho/genética , Dedos/anormalidades , Fatores Reguladores de Interferon/genética , Articulação do Joelho/anormalidades , Lábio/anormalidades , Deformidades Congênitas das Extremidades Inferiores/genética , Sindactilia/genética , Anormalidades Urogenitais/genética , Complexo 2 de Proteínas Adaptadoras/genética , Subunidades alfa do Complexo de Proteínas Adaptadoras/genética , Alelos , Animais , Células Cultivadas , Redes Reguladoras de Genes , Humanos , Camundongos , Camundongos Transgênicos , Organogênese/genética , Polimorfismo de Nucleotídeo Único , Ligação Proteica , Estabilidade Proteica
4.
J Shoulder Elbow Surg ; 24(5): 804-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25487899

RESUMO

BACKGROUND: Infection after shoulder surgery can have devastating consequences. Recent literature has implicated Propionibacterium acnes as a causative agent for postoperative shoulder infections. Axillary hair removal has been suggested as a method for infection prevention, although data quantifying its effect on the bacterial load around the shoulder are lacking. METHODS: We clipped one randomly selected axilla in 85 healthy male volunteers with commercially available surgical clippers. Aerobic and anaerobic culture specimens were taken from the clipped and unclipped axillae. Each shoulder was then prepared with 2% chlorhexidine gluconate and 70% isopropyl alcohol. Repeated culture specimens were then taken from both axillae. Cultures were held for 14 days and recorded with a semiquantitative system (0-4 points). Results were compared by the Wilcoxon signed rank test. RESULTS: There was no difference in the burden of P. acnes between the clipped and unclipped axillae before or after surgical preparation (P = .109, P = .344, respectively). There was a significantly greater bacterial burden in the clipped shoulder compared with the unclipped shoulder before preparation (P < .001) but not after preparation (P = .285). There was a significant reduction in total bacterial load and P. acnes load for both axillae after surgical preparation (P < .001 for all). CONCLUSIONS: Removal of axillary hair has no effect on the burden of P. acnes in the axilla. Clipped axillae had a higher total bacterial burden. A 2% chlorhexidine gluconate surgical preparation is effective at removal of all bacteria and specifically P. acnes from the axilla.


Assuntos
Antissepsia , Axila/microbiologia , Cabelo , Cuidados Pré-Operatórios/métodos , Propionibacterium acnes/isolamento & purificação , Ombro/microbiologia , Pele/microbiologia , 2-Propanol/administração & dosagem , Adulto , Anti-Infecciosos Locais/administração & dosagem , Carga Bacteriana , Clorexidina/administração & dosagem , Clorexidina/análogos & derivados , Remoção de Cabelo , Humanos , Masculino , Pessoa de Meia-Idade , Ombro/cirurgia , Articulação do Ombro/cirurgia , Adulto Jovem
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