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The Nikkei 225 in Japan declined 0.51% to close at 21,086.59, with shares of index heavyweights Fast Retailing and Softbank Group slipping. The Topix index fell 0.59% to finish its trading day at 1,534.34.
In South Korea, the Kospi closed just above the flat line at 2,121.85, while Australia's slipped 0.26% to end its trading day Down Under at 6,640.50.
Mainland Chinese shares struggled for gains on the day. The Shanghai composite was down 0.19% to 2,976.28, while the Shenzhen composite was largely flat at 1,560.51. The Shenzhen component, meanwhile, rose fractionally to 9,122.43.
In Hong Kong, the Hang Seng index was slightly higher, as of its final hour of trading.
Overnight stateside, Dow Jones Industrial Average ended about 179 points lower at 26,548.22 — its biggest one-day loss since May 31. The also closed approximately 0.95% lower at 2,917.38, while the Nasdaq Composite fell 1.51% to close at around 7,884.72.
The moves on Wall Street came as Powell said the U.S. central bank is assessing whether current economic uncertainties call for lower rates. Powell noted the Fed will take a wait-and-see approach given how rapid recent economic changes have been, but added the Fed is "insulated from short-term political interests. "
One strategist said Powell's comments had left the market "none the wiser in terms of whether or not the Fed will look to embark on a new easing cycle at the end of July."
"While the word 'patience' was dropped in the (Federal Open Market Committee) statement, it seems that Powell is still on a wait and see mode noting that much will depend on the incoming data and specifically the near-term risks (which we take to mean upcoming trade discussions)," Rodrigo Catril, senior foreign exchange strategist at National Australia Bank, wrote in a note.
"We should at least end up in a situation where the U.S. and China are at least talking to each other," Manpreet Gill, head of fixed income, currencies and commodities investment strategy at Standard Chartered Private Bank, told CNBC's "Squawk Box" on Wednesday.
On the subject of a potential deal being reached, Gill said it "might be a stretch too far" given "how far apart" the two parties are at present.
"A resumption of dialogue, resumption to at least start talking about some of the more difficult issues, we think will be enough for markets to at least ... take this outcome positively," he said.
The U.S. dollar index, which tracks the greenback against a basket of its peers, was at 96.262 after rising from levels below 96.0 yesterday.
The traded at 107.42 against the dollar after touching below 107.1 in the previous session. The changed hands at $0.6975, continuing to move upward from levels below $0.685 seen last week.
Oil prices jumped in the afternoon of Asian trading hours, as the international benchmark Brent crude futures contract surged 1.68% to $66.14 per barrel and U.S. crude futures soared 2.14% to $59.07 per barrel.
The moves come as U.S.-Iran relations remain tense following the announcement of fresh sanctions by Washington on Tehran after the latter downed an unmanned American drone last week.
— CNBC's Fred Imbert contributed to this report.
— This report was updated to reflect that U.S.-Iran relations remain tense following the announcement of fresh sanctions by Washington on Tehran after the latter downed an unmanned American drone last week.