Isner will face world No.31 Stefanos Tsitsipas, the first Greek man to first Greek man to reach the fourth round of a grand slam in the 50-year professional era, for a quarterfinal berth.
Anderson hit 34 aces to beat Andreas Seppi 6-3 6-7 (5) 6-3 6-4 and set up a third-round meeting with Philipp Kohlschreiber of Germany.
But Luke Bambridge and Katie Boulter were knocked out of the mixed doubles event at the first stage following two tie-break defeats in each set against Andrei Vasilevski and Arina Rodionova. In truth, we all want that Roger-Rafa final. "It's more hard for me to understand what's going on", said the 32-year-old Nadal after his 6-4, 6-3, 6-4 win. It was easier to play facing a deficit, Keys said - "When you're down a set and 4-0, it's a lot easier to be, like, oh, I probably should play better now and do that" - but she admitted that throughout the final set, stepping up to the baseline to serve had been nerve-wracking every time.
The world number 133 is in the third round for the first time after winning back-to-back matches on the main tour for only the second time in 2018.
Nick Kyrgios, seeded 15, unleashed 42 winners to see off Robin Haase of the Netherlands 6-3, 6-4, 7-5.
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"It's going pretty well", she said courtside in staggering understatement after beating the accomplished French player Kristina Mladenovic 7-5, 7-6 (2) in front of a Centre Court audience who had come to soak up the sun and the American's glowing brilliance on Friday afternoon.
He will face Australian teenager Alex De Minaur in the next round.
Only half of the men's top 10 seeds have made Wimbledon third round with 2017 finalist Marin Cilic joining the casualty list on day four at the All England Club.
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Dominic Inglot and Franko Skugor came through to win 6-3 4-6 7-6 (7-5) 2-6 6-2 in five sets against Fernando Gonzalez and Marcelo Demoliner.
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