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Makoto Hasebe was sent off for elbowing Uzbek captain Server Djeparov with two minutes remaining but Japan held on.
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Second-half goals from Odil Akhmedov and Server Djeparov gave Uzbekistan all three points in a match played in front of a capacity 40, 000-crowd at the Khalifa Stadium.
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And Uzbekistan secured victory in the 72nd minute when captain Djeparov made the most of a poor Ibrahim Majed back pass to fire past goalkeeper Qasem Burhan.
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The 32-year-old, who played for Russain club CSKA Moscow earlier in his career, broke the deadlock with a header from captain Server Djeparov's free-kick and then stole in at the near post to convert a low cross.
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