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1.
Materials (Basel) ; 17(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38473582

RESUMO

Cathodic protection is widely used to protect structural steel from corrosion in marine environments. However, an inappropriate cathodic potential may lead to hydrogen embrittlement (HE). Therefore, this study investigates the relationship between cathodic protection potential, structure and composition of calcareous deposits, and hydrogen embrittlement susceptibility of Q460 steel. The slow strain rate test results and fracture analysis reveal that Q460 steel had the smallest HE susceptibility when covered with the calcareous deposits formed under -1.1 VSCE. The deposits have a relatively thin calcium-rich inner layer and a condensed magnesium-rich outer layer, which can significantly inhibit hydrogen entry. A sustained deposition reaction during slow strain rate testing (SSRT) in artificial seawater can also decrease the HE susceptibility of Q460 steel.

2.
J Med Chem ; 63(18): 10380-10395, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32816483

RESUMO

Chronic hepatitis C (CHC) is a major liver disease caused by the hepatitis C virus. The current standard of care for CHC can achieve cure rates above 95%; however, the drugs in current use are administered for a period of 8-16 weeks. A combination of safe and effective drugs with a shorter treatment period is highly desirable. We report synthesis and biological evaluation of a series of 2',3'- and 2',4'-substituted guanosine nucleotide analogues. Their triphosphates exhibited potent inhibition of the HCV NS5B polymerase with IC50 as low as 0.13 µM. In the HCV replicon assay, the phosphoramidate prodrugs of these analogues demonstrated excellent activity with EC50 values as low as 5 nM. A lead compound AL-611 showed high levels of the nucleoside 5'-triphosphate in vitro in primary human hepatocytes and in vivo in dog liver following oral administration.


Assuntos
Antivirais/farmacologia , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Nucleotídeos de Guanina/farmacologia , Hepacivirus/efeitos dos fármacos , Pró-Fármacos/farmacologia , Animais , Antivirais/síntese química , Antivirais/toxicidade , Cães , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/toxicidade , Feminino , Nucleotídeos de Guanina/síntese química , Nucleotídeos de Guanina/toxicidade , Humanos , Masculino , Pró-Fármacos/síntese química , Pró-Fármacos/toxicidade , Proteínas não Estruturais Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos
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