“All nations of the world should resist socialism and the misery that it brings to everyone,” Trump said in a speech at the U.N. General Assembly. “In that spirit, we ask the nations gathered here to join us in calling for the restoration of democracy in Venezuela.”

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The sanctions mark the latest of increasingly restrictive measures imposed by the Trump administration amid the Maduro government’s crackdown on political opponents, the collapse of the country’s economy and corruption that has reached into the state-run oil industry. Maduro himself was hit with sanctions in July 2017.

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“President Maduro relies on his inner circle to maintain his grip on power, as his regime systematically plunders what remains of Venezuela’s wealth,” said Treasury Secretary Steven Mnuchin. “We are continuing to designate loyalists who enable Maduro to solidify his hold on the military and the government while the Venezuelan people suffer.”

Speaking at a news conference at the United Nations on Tuesday, Foreign Minister Jorge Arreaza called the sanctions against the first lady, in particular, “an insult to the U.N. and multilateralism.”

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In televised comments in Caracas, Maduro said: “Today the U.S. government released a sanction decree, no less than against the first lady Cilia Flores. Never has something like this happened. If you want to attack, attack me, but don’t mess with my family. Don’t be cowards. Her only crime is to be my wife.”

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U.S. officials also announced $48 million in humanitarian aid for Venezuelans.

The sanctions target some of Maduro’s closest allies, including his wife, Flores, a onetime head of the National Assembly and the former lawyer of left-wing firebrand Hugo Chávez, who died in 2013 after anointing Maduro as his successor. A political figure in her own right, she is deeply linked to Maduro’s administration. Two of her nephews were convicted and sentenced in a New York court last year on drug trafficking ­charges.

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Delcy Rodríguez, Maduro’s vice president, is one of his most trusted advisers. She previously served as head of the Constituent Assembly, a body created last year that critics see as instrumental in awarding Maduro near dictatorial powers. When Rodríguez was foreign minister, she fiercely defended the government in several international venues, beating back anti-Maduro measures before the Organization of American States.

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Her brother, Communications Minister Jorge Rodríguez, was also targeted Tuesday. A trained psychiatrist, he orchestrates the country’s state media apparatus. He was also close to Chávez, serving as his vice president in 2007.

Vladimir Padrino López, the minister of defense, assumed office in 2014 and helped organize the operations that put down street protests last year in which more than 100 people were killed.

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As Maduro’s political opponents have been jailed and hyperflation has risen at a staggering rate — hundreds of thousands of percentage points — the Trump administration has tried to pressure Maduro to step aside. Last year, officials in the administration met secretly with military officials said to be interested in a coup, though U.S. officials eventually decided not to support the plotters.

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But the animosity has helped Maduro form a narrative that foreigners are waging “economic war” on his government.

The latest sanctions are unlikely to be the last.

“The United States will continue to use every available diplomatic and economic tool to support the Venezuelan people’s efforts to restore their democracy,” said a Treasury Department statement, adding that it would consider lifting sanctions on those who take steps “to restore democratic order, refuse to take part in human rights abuses, speak out against abuses committed by the government, and combat corruption in Venezuela.”

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Venezuelan opposition leaders hailed the sanctions.

“We’ve gone through all the democratic routes. Maduro has closed the doors and turned the country into worse than a dictatorship — a failed state,” said Julio Borges, a former head of the National Assembly who is living in exile in Colombia. “At this point in the crisis, Venezuelans can’t do it alone. We need the help of the international community, and the pressure, and we think all options need to be studied to liberate Venezuela.”