In Geneva, Secretary of State John Kerry was once more locked in talks with Russian counterpart Sergei Lavrov but US officials warned talks could not go on forever without a breakthrough.
The two powers back opposite sides in the five-year conflict, with Moscow supporting the regime of President Bashar al-Assad and the US behind a coalition of rebel groups it regards as moderate.
Senior officials travelling with Kerry said he would not have flown out once again to new face-to-face talks with Lavrov unless he thought there was a chance of progress.
The ministers met in the familiar confines of a hotel on the shore of Lake Geneva and made brief remarks to reporters about North Korea's latest nuclear test before beginning closed-door talks on Syria.
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UN envoy on Syria, Staffan de Mistura, said a successful outcome from the talks could provide a major boost towards resolving the conflict that has killed 290,000 people.
Washington wants concrete steps from Russia to force Assad to stop bombing his own people, respect a ceasefire and lift the siege of Aleppo.
"We need to see a situation where it's clear within whatever is being agreed with the Russians that there won't be a siege of Aleppo," a senior US official told reporters.
Pro-regime forces have taken back a strategically important district on Aleppo's southern outskirts, rolling back nearly every gain from a major month-long rebel offensive there, the Syrian Observatory for Human Rights said Thursday.
Meanwhile, the top military commander of the Army of Conquest, the largest rebel alliance, was killed in an air strike during a meeting of the leaders of the anti-government group, Islamist sources said Thursday.
The former Al-Nusra Front, an Al-Qaeda affiliate recently renamed Fateh al-Sham Front, announced "the martyrdom" of commander Abu Omar Sarakeb on Twitter, in the biggest blow to the group since its formation early last year.
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