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Third seed Jessica Pegula and Wimbledon finalist Ons Jabeur suffered frustrating defeats in the fourth round at the US Open.
American Pegula, who had been one of the favourites for the title, put in an error-strewn performance in a 6-1 6-3 loss to compatriot Madison Keys.
Despite her success on the WTA Tour, the 29-year-old has yet to go beyond the quarter-finals at any Grand Slam.
Last year's runner-up Jabeur lost 6-2 6-4 to China's Zheng Qinwen.
Qinwen, 20, reached the first Grand Slam quarter-final of her career and will face Belarusian second seed Aryna Sabalenka next.
Sabalenka, a semi-finalist at Flushing Meadows in 2021 and 2022, won 6-1 6-3 against Russian 13th seed Daria Kasatkina.
The Australian Open champion, 25, will be become the new world number one at the end of the tournament following Iga Swiatek's exit in the last 16.
"I had no doubt that Iga was going to make it to the final. I was sad that she lost, but becoming number one means a lot to me," said Sabalenka.
"I've been pushing myself a lot this year to make this goal and I still can't believe it, but I didn't want to be distracted for tonight."
Jabeur was left heartbroken after losing a second Wimbledon final in July and has struggled with illness during her time in New York.
The Tunisian fifth seed has also exerted a lot of energy on the court, having won both of her previous two matches in three sets.
Jabeur was broken twice in the first set against Qinwen, rescuing one of them before handing the momentum straight back to her opponent.
She saved four match points in the second as Qinwen's nerves struck, but the Chinese 23rd seed held on to secure a place in the last eight.
"No matter what the tournament is, you always take a great lesson," said 29-year-old Jabeur.
"I know that I can dig deep. Maybe I'm tough with myself today because I couldn't get that warrior mood on. It's just disappointing."
Jessica Pegula reached the quarter-finals at last year's US Open
Keys and Pegula are good friends and the two shared a warm hug at the net following their fourth-round match, but Pegula could not hide her disappointment.
She had won the Canadian Open in the build-up to the final major of the year, registering a notable victory over Swiatek in the process.
However, she has consistently struggled to break through at the majors, having never gone beyond the last eight in six attempts.
Pegula was off-colour from the start, struggling to find her rhythm against the big-hitting Keys, who was the runner-up in 2017.
She hit just three winners in the first set, which she lost in just 28 minutes, and quickly found herself a break down in the second.
Pegula was able to take advantage of a blip from 17th seed Keys to retrieve the break for 3-3, but she lost the next three games as Keys reasserted her dominance.
Keys will now face Wimbledon champion Marketa Vondrousova, who had to fight back to see off spirited American Peyton Stearns 6-7 (3-7) 6-3 6-2.
Czech ninth seed Vondrousova, who has reached the quarter-finals in New York for the first time, appeared to be struggling with an arm injury during the match.
She took medication at the start of the second set for the issue and later said the heaviness of the tennis balls was impacting her..
"It's just from the balls. They are very heavy and the season is long, so I feel like you just have to fight through it," she said.
"I feel like the balls are not helping with everything. It's tough but I just fought through it and I'm very happy with my win".
The 24-year-old was upset later when she told doubles partner Barbora Strycova she would not be able to compete alongside her.
Fellow Czech Strycova is competing in her last tournament and the duo's withdrawal from the doubles marks the end of the end of her career.
"Of course it was a bit sad, I cried a bit when I told Barbora [she couldn't play doubles] but I had so many injuries that I don't want to play with some more," Vondrousova added.
