MASON, Ohio (AP) -- Right from the start, Rafael Nadal was running on empty.
Nadal showed the effects of his long layoff from a wrist injury Thursday, losing to Croatia's Borna Coric 6-1, 6-3 at the Western & Southern Open. The 30-year-old Spaniard has a lot of work to do before the U.S. Open.
He was sluggish and well off the mark on his shots Thursday and had a trainer visit between games to check his shoulder and elbow, which were feeling the effects of a lot of tennis at the Olympics in Rio de Janeiro and two days in Cincinnati's heat and humidity.
"Too tired," he said. "Elbow, shoulder. Two and a half months without competing and especially without practicing, and to do what I did in the Olympics and come here - too much."
The 19-year-old Coric reached the quarterfinals of a Masters tournament for the first time and ended his streak of 10 straight losses against top-10 opponents.
The upset left only one member of the Big Four still in the running. Andy Murray beat Kevin Anderson 6-3, 6-2 on Thursday night to win his career-best 20th match in a row despite a head cold.
"I picked it up in Rio and only started feeling it on the flight coming over after the match," Murray said. "I sound worse today but I feel better."
Defending champion Roger Federer and top-ranked Novak Djokovic are missing the tournament because of injuries. Murray is feeling the effects of a grueling week in Rio de Janeiro where he won the gold medal Sunday. Along with Nadal, those four have combined to win 54 of the last 58 Masters events.
Nadal missed two months because of an injured left wrist and returned to the courts in Rio, where he lost in the semifinals and won the doubles title. The lack of matches showed in Cincinnati: Nadal double faulted five times and had 27 unforced errors. Coric surged ahead 4-0 in the second set and closed it out in an hour and 11 minutes.
Murray had hoped for some rain in Cincinnati, giving him time to recoup from Rio. He got rain only two points into his match on Thursday night - a downpour forced an hour-long delay. Murray was steady throughout, committing only 11 unforced errors.
Steve Johnson also advanced to the quarterfinals Thursday and put himself in position to become the top American in the ATP rankings heading into the U.S. Open.
Johnson beat Jo-Wilfried Tsonga 6-3, 7-6 (6) and raised his index finger in celebration. He'll move into the ATP's top spot next week, knocking John Isner out of the slot that he's held every week since July 29, 2013. Isner lost in the second round in Cincinnati.
"Hasn't sunk in yet," Johnson said. "I just found out. So it's an honor, it really is. John has held that spot for a while, and I'm just glad that there are a bunch of Americans pushing toward the top."
Second-seeded Stan Wawrinka wasted a chance to take advantage of the wide-open draw on Thursday, losing to Bulgaria's Grigor Dimitrov 6-4, 6-4. Wawrinka smacked his racket on the ground as he fell behind in the first set, the start of a frustrating match overall. Tied 3-3 in the second set, Wawrinka committed two unforced forehand errors and Dimitrov got the break he needed to take control.
Wawrinka had one of those few Masters titles that wasn't claimed by the Big Four, winning in Monte Carlo in 2014.
In the women's bracket, Karolina Pliskova became the first woman to reach the quarterfinals, defeating Misaki Doi 7-5, 6-3. Doi was a "lucky loser" who replaced defending champion Serena Williams when she withdrew with an inflamed shoulder on Monday.
Second-seeded Angelique Kerber moved into the quarterfinals with a 7-6 (3), 6-4 win over Barbora Strycova. She'll end Williams' streak of 183 consecutive weeks at No. 1 if she wins the tournament.