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Naomi Osaka had won 24 of her previous 25 matches.
Naomi Osaka is out of the Australian Open after her opponent survived two match points.
Osaka was defeated at the park.
Ashleigh Barty, the Australian top seed, will face unseeded Anisimova in the last 16.
Barty has not dropped a set this week after a victory over Italy's Camila Giorgi.
Chris O'Neil won the Australian Open for the first time in 1978 but the nation is desperate to see a home champion again.
Barty was expected to face Osaka in the last 16 when the draw put two of the game's biggest stars in the same section.
At the end of last season, Osaka took a four-month break and revealed she had been suffering from depression.
The two-time champion, who also won the title at Melbourne Park, breezed through her first two matches but faced a different challenge in the second.
When she reached the French Open semi-finals, the American said she was a potential star.
The death of her father and coach before the US Open had a devastating effect on her career.
She was able to effectively use her power against Osaka because she rediscovered her best form.
As Nadal ends Friday's session, there is live radio and text.
When she faces Barty, she will look to trouble the very best.
Barty has come up short in each of the past three years, having reached the 2020 semi-finals in between quarter-final defeats.
Tougher moments are likely to occur over the rest of the fortnight.
She has dropped only eight games in three emphatic victories.
I was able to keep my momentum going because I looked after my service games well. Barty said it was a good performance.
The way she hits the ball is incredible and I felt like I was out of my weight class. I was able to use my slice effectively.
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