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Third seed Carlos Alcaraz suffered a seismic second-round exit at the US Open with a thumping defeat by unseeded Dutchman Botic van de Zandschulp.
Alcaraz was bidding to become the third man in history after Rod Laver and Rafael Nadal to win the French Open, Wimbledon and the US Open in the same calendar year in the Open era.
But the Spaniard never recovered from a shaky start against world number 74 Van de Zandschulp, who triumphed 6-1 7-5 6-4 for the highest-ranked win of his career.
The defeat ends Alcaraz's 15-match winning run at Grand Slams.
"I think my level stayed at the same point all the match, and it wasn't enough to win the match or to give myself the chance to get into the match or try to give myself chances," said Alcaraz.
"I didn't feel well hitting the ball. I think I made a lot of mistakes. When I wanted to come back or I think I wanted to come back, it was too late."
The 21-year-old made 27 unforced errors throughout the match while Van de Zandchulp made 21.
"He didn't make a lot of mistakes that I thought he was going to do so I was confused a little bit," Alcaraz said. "I didn't know how to manage that."
Alcaraz, who won silver at the Paris Olympics after losing to Novak Djokovic on 4 August, says he needed a longer break before going to Flushing Meadows.
"I came here with not as much energy as I thought that I was going to come with. But I don't want to put that as an excuse," he said.
Earlier, world number one Jannik Sinner outclassed American Alex Michelsen 6-4 6-0 6-2 for his 50th victory of the year.
Australian Open champion Sinner is playing at his first tournament since it emerged he had been cleared of any wrongdoing after twice testing positive for a banned substance earlier this year.
The crowd on Arthur Ashe Stadium were reduced to silent disbelief when Van de Zandschulp dropped just one game en route to winning the first set.
A below-par Alcaraz seemed to have found his rhythm after breaking back early in the second set, but he lost serve again at 5-5 before his Dutch opponent doubled his advantage.
The three-time major winner looked perplexed as he headed off court for a time-out, wagging a finger towards his player's box and shaking his head.
Alcaraz found his smile again when he broke back to level the third set at 3-3, but Van de Zandschulp continued to unleash superb winners and clinched the crucial break at 5-4 before serving out the victory with a clinical love hold.
"I am a little bit lost for words, it's been an incredible evening for me," said Van de Zandschulp, who reached the quarter-finals in New York in 2021.
"I think from point one here today I believed [I had] a chance."
The 28-year-old will play British number one Jack Draper in the third round.
Sinner is through to play Australian wildcard Chris O'Connell in the third round
Sinner had wobbled against American Mackenzie McDonald in the first round on Tuesday, losing the first set before rallying to triumph 2-6 6-2 6-1 6-2 at Flushing Meadows.
Against Michelsen on Thursday he had no such trouble. After coming out on top of a first set with several trades of breaks, Sinner did not look back, wrapping up a dominant victory in one hour 39 minutes.
"[I'm] very happy," said Sinner, who beat world number 49 Michelsen in the second round of the Cincinnati Masters earlier this month.
"He's a very tough opponent. We played each other in Cincinnati a week ago. I knew what to expect, he knew what to expect a little."
The 23-year-old will play Australian Chris O'Connell in the third round in New York.
Elsewhere, Russian fifth seed Daniil Medvedev entertained the crowd on Arthur Ashe Stadium in a 6-3 6-2 7-6 (7-5) win against Hungary's Fabian Marozsan.
"The match today, I felt like I was at an Italian restaurant - it was so noisy," Medvedev said in an on-court interview at Louis Armstrong Stadium.
Meanwhile, seventh seed Hubert Hurkacz was knocked out in a 7-6 (7-2) 6-1 7-5 defeat by Australian Jordan Thompson.
It is the sixth successive year that Poland's Hurkacz has exited the US Open in the second round.
Another seed soon fell as American 16th seed Seb Korda was beaten 6-4 6-2 6-4 by Czech Tomas Machac, who will play Belgium's David Goffin in the third round.
There was also an upset for Frenchman Arthur Fils, the 24th seed, who was defeated 7-5 6-7 (3-7) 6-4 6-4 by world number 143 Gabriel Diallo of Canada.
But there was better luck for Australian 10th seed Alex de Minaur, who beat Finland's Otto Virtanen 7-5 6-1 7-6 (7-3) to set up a third-round meeting with Britain's Dan Evans.
American 14th seed Tommy Paul progressed after his Australian opponent Max Purcell retired in the third set when Paul was leading 7-5 6-0 1-0.
Russell Fuller, BBC tennis correspondent
This was a startling upset, achieved with great poise, by a Dutchman who was considering retirement as recently as this year's French Open.
That was only Van de Zandschulp's 13th tour level win of an eight-month-old season, and he was better than the world number 3 throughout.
Alcaraz was a shadow of the man who won both Roland Garros and Wimbledon. He also played in the gold medal match at the Paris Olympics, and even 21-year-olds are allowed to hit the wall.
A string of upsets in this section of the draw means someone will play in their first Grand Slam semi-final at this US Open.
The opportunity falls to Van de Zandschulp and his third round opponent Jack Draper - along with the 10th seed Alex de Minaur, Matteo Arnaldi and the unseeded Dan Evans, David Goffin, Tomas Machac and Jordan Thompson.
