SYDNEY (AP) -- Top-seeded John Isner lost 6-4, 6-4 to fellow American Ryan Harrison in the second round of the Sydney International on Wednesday.
The exit of Isner, who was promoted to No. 1 seed after Jo-Wilfried Tsonga and Richard Gasquet withdrew, followed two more injury withdrawals: second-seeded and 2011 Sydney champion Giles Simon (neck) and sixth-seeded Radek Stepanek (back).
Isner, who withdrew from the Hopman Cup mixed-team competition in Perth last week with a right knee injury, lasted 71 minutes against the 64th-ranked Harrison.
The Australian Open starts Monday, leaving injured players little time to prepare for the season's first major.
In other matches, third-seeded Andreas Seppi of Italy beat John Millman of Australia 6-2, 3-6, 6-3; Australian Bernard Tomic, who beat No. 1-ranked Novak Djokovic last week at the Hopman Cup, advanced with a 7-6 (4), 6-2 win over fifth-seeded Florian Mayer of Germany; and Denis Istomin of Uzbekistan beat fourth-seeded Fernando Verdasco of Spain 6-3, 6-3.
In the women's draw, top-seeded Agnieszka Radwanska of Poland advanced to the semifinals with a 6-4, 7-5 win over Italy's Roberta Vinci and Dominika Cibulkova of Slovakia beat third-seeded Sara Errani of Italy 6-2, 6-1.
After winning the WTA event in Auckland last week, Radwanska has a seven-match winning streak.
"So far I feel good and I'm very happy that I can play good matches, already seven in a row," she said. "I think this year is the first time that I played two tournaments before (the Australian Open). I never did that before. So far it's good and I'm going to keep going."
In a night match, fourth-seeded Li Na of China beat American qualifier Madison Keys 4-6, 7-6 (2), 6-2 to advance to Thursday's semifinal against Radwanska.
Li said she was surprised by the power and big serve displayed by Keys, who Li predicted would rapidly improve on her ranking of 135.
"If she plays a level like this every match she should be soon, top 20, top 15, top 10," Li said. "I got the information she had a big serve but did not think it would be like it was today."
Li won Sydney in 2011 and was runner-up to Victoria Azarenka last year.
"Maybe it's a lucky area for me," Li said.