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A new approach to a Covid-19 nasal vaccine shows early promise | CNN

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A new approach to a Covid-19 nasal vaccine shows early promise | CNN



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Scientists in Germany say they’ve been in a position to make a nasal vaccine that may shut down a Covid-19 an infection within the nostril and throat, the place the virus will get its first foothold within the physique.

In experiments in hamsters, two doses of the vaccine – which is made with a reside however weakened type of the coronavirus that causes Covid-19 – blocked the virus from copying itself within the animals’ higher airways, attaining “sterilizing immunity” and stopping sickness, a long-sought purpose of the pandemic.

Though this vaccine has a number of extra hurdles to clear earlier than it will get to a physician’s workplace or drug retailer, different nasal vaccines are in use or are nearing the end line in medical trials.

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China and India each rolled out vaccines given by the nasal tissues final fall, although it’s not clear how effectively they could be working. Research on the effectiveness of those vaccines have but to be revealed, leaving a lot of the world to wonder if this strategy to safety actually works in folks.

The US has reached one thing of a stalemate with Covid-19. Even with the darkest days of the pandemic behind us, tons of of People are nonetheless dying day by day because the an infection continues to simmer within the background of our return to regular life.

So long as the virus continues to unfold amongst folks and animals, there’s at all times the potential for it mutate right into a extra contagious or extra damaging model of itself. And whereas Covid infections have change into manageable for many wholesome folks, they could nonetheless pose a hazard to susceptible teams such because the aged and immunocompromised.

Researchers hope next-generation Covid-19 vaccines, which purpose to close down the virus earlier than it ever will get an opportunity to make us sick and finally forestall the unfold of an infection, may make our latest resident respiratory an infection much less of a risk.

A technique scientists try to do this is by boosting mucosal immunity, beefing up immune defenses within the tissues that line the higher airways, proper the place the virus would land and start to contaminate our cells.

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It’s a bit like stationing firefighters beneath the smoke alarm in your own home, says research creator Emanuel Wyler, a scientist on the Max Delbruck Heart for Molecular Medication within the Helmholtz Affiliation in Berlin.

The immunity that’s created by photographs works all through the physique, but it surely resides primarily within the blood. Which means it could take longer to mount a response.

“If they’re already on web site, they’ll instantly remove the hearth, but when they’re like 2 miles away, they first must drive there, and by that point, one-third of the home is already in full flames,” Wyler stated.

Mucosal vaccines are additionally higher at priming a unique sort of first responder than injections do. They do a greater job of summoning IgA antibodies, which have 4 arms to seize onto invaders as a substitute of the 2 arms that the y-shaped IgG antibodies have. Some scientists assume IgA antibodies could also be much less choosy about their targets than IgG antibodies, which makes them higher outfitted to take care of new variants.

The brand new nasal vaccine takes a brand new strategy to a really outdated thought: weakening a virus so it’s not a risk after which giving it to folks so their immune techniques can study to acknowledge and battle it off. The primary vaccines utilizing this strategy date to the 1870s, towards anthrax and rabies. Again then, scientists weakened the brokers they had been utilizing with warmth and chemical substances.

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The researchers manipulated the genetic materials within the virus to make it more durable for cells to translate. This method, referred to as codon pair deoptimization, hobbles the virus so it may be proven to the immune system with out making the physique sick.

“You would think about studying a textual content … and each letter is a unique font, or each letter is a unique measurement, then the textual content is way more durable to learn. And that is principally what we do in codon pair deoptimization,” Wyler stated.

Within the hamster research, which had been revealed Monday within the journal Nature Microbiology, two doses of the reside however weakened nasal vaccine created a a lot stronger immune response than both two doses of an mRNA-based vaccine or one which makes use of an adenovirus to ferry the vaccine directions into cells.

The researchers assume the reside weakened vaccine most likely labored higher as a result of it intently mimics the method of a pure an infection.

The nasal vaccine additionally previews all the coronavirus for the physique, not simply its spike proteins like present Covid-19 vaccines do, so the hamsters had been in a position to make immune weapons towards a wider vary of targets.

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As promising as all this sounds, vaccine consultants say warning is warranted. This vaccine nonetheless has to move extra exams earlier than it’s prepared to be used, however they are saying the outcomes look encouraging.

“They did a really good job. That is clearly a reliable and considerate group that did this work, and spectacular within the scope of what they did. Now it simply must be repeated,” maybe in primates and definitely in people earlier than it may be broadly used, stated Dr. Greg Poland, who designs vaccines on the Mayo Clinic. He was not concerned within the new analysis.

The research started in 2021, earlier than the Omicron variant was round, so the vaccine examined in these experiments was made with the unique pressure of the coronavirus. Within the experiments, after they contaminated animals with Omicron, the reside however weakened nasal vaccine nonetheless carried out higher than the others, however its skill to neutralize the virus was diminished. Researchers assume it would want an replace.

It additionally must be examined in people, and Wyler says they’re engaged on that. The scientists have partnered with a Swiss firm referred to as RocketVax to begin section I medical trials.

Different vaccines are additional alongside, however the progress has been “sluggish and halting,” Poland stated. Teams engaged on these vaccines are struggling to lift the steep prices of getting a brand new vaccine to market, they usually’re doing it in a setting the place folks are likely to assume the vaccine race has been gained and performed.

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In actuality, Poland stated, we’re removed from that. All it could take is one other Omicron-level shift within the evolution of the virus, and we might be again at sq. one, with no efficient instruments towards the coronavirus.

“That’s silly. We must be growing a pan-coronavirus vaccine that does induce mucosal immunity and that’s long-lived,” he stated.

At the very least 4 nasal vaccines for Covid-19 have reached late-stage testing in folks, in accordance with the World Well being Group’s vaccine tracker.

The nasal vaccines in use in China and India depend on innocent adenoviruses to ferry their directions into cells, though effectiveness knowledge for these has not been revealed.

Two different nasal vaccines are ending human research.

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One, a recombinant vaccine that may be produced cheaply in hen eggs, the identical approach many flu vaccines are, is being put by its paces by researchers at Mount Sinai in New York Metropolis.

One other, just like the German vaccine, makes use of a reside however weakened model of the virus. It’s being developed by an organization referred to as Codagenix. Outcomes of these research, which had been carried out in South America and Africa, might come later this yr.

The German group says it’s eagerly looking forward to the Codagenix knowledge.

“They are going to be essential with a view to know the place whether or not this sort of try is principally promising or not,” Wyler stated.

They’ve purpose to fret. Respiratory infections have proved to be powerful targets for inhaled vaccines.

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FluMist, a reside however weakened type of the flu virus, works moderately effectively in youngsters however doesn’t assist adults as a lot. The reason being considered that adults have already got immune reminiscence for the flu, and when the virus is injected into the nostril, the vaccine largely boosts what’s already there.

Nonetheless, a number of the most potent vaccines such because the vaccine towards measles, mumps and rubella use reside attenuated viruses, so it’s a promising strategy.

One other consideration is that reside vaccines can’t be taken by everybody. Individuals with very compromised immunity are sometimes cautioned towards utilizing reside vaccines as a result of even these very weakened viruses could also be dangerous for them.

“Though it’s strongly attenuated, it’s nonetheless an actual virus,” Wyler stated, so it must be used rigorously.

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Ukraine turns to prisons to replenish frontline forces

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Ukraine turns to prisons to replenish frontline forces

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Ukraine is to start recruiting prisoners to fight against Russia under a new law designed to bolster its frontline forces, including with men convicted of murder or fraud.

Using a tactic Moscow has relied on to fill ranks since its full-scale invasion of Ukraine in 2022, Kyiv would begin to offer certain convicts a path to freedom if they are willing to join a combat unit.

The bill, approved on Wednesday by the Ukrainian parliament, is the latest in a series of measures aimed at mobilising more men to replace casualties and soldiers exhausted from long tours on the frontline. It still requires the signature of President Volodymyr Zelenskyy to enter into force.

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The drive to enlist convicts is expected to result in several thousand new recruits from a prison population of about 20,000, according to David Arakhamia, a senior lawmaker. That is a fraction of the hundreds of thousands of fresh soldiers Ukraine says it needs this year to hold back Moscow’s advancing forces.

The Russian army and militias deployed in Ukraine have routinely drawn manpower from prisons, irrespective of the crimes recruits have committed. Examples of convicts reoffending have been numerous, while in service or after returning to Russia, further damaging the reputation of the Russian armed forces.

Though Ukraine’s decision to turn to prisons is borne out of the same manpower needs, Kyiv has included stricter eligibility conditions to distance itself from Russia’s more reckless prison recruitment practices.

Ineligible convicts include serial murderers, drug traffickers and those guilty of sexual violence, corruption and national security crimes, according to Olena Shuliak, an MP from Zelenskyy’s party.

Men convicted of a single murder can sign up but would be automatically excluded if also found guilty of rape. Former high-ranking politicians and ministers who are serving prison terms are also not allowed to enlist.

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Shuliak acknowledged that the law had the potential to “cause a violent reaction from society”, but said that it had been crafted together with the ministries of defence and justice, as well as the armed forces.

“It is only possible to withstand the conditions of a total war against an enemy with more resources by consolidating all [our] forces. This draft law is about our struggle and preservation of Ukrainian statehood,” she wrote on social media.

Ukrainian prisoners who volunteer must undergo a physical and mental health test and have at least three years remaining of their sentence. They will serve in special units for as long as the war continues or until they are demobilised.

Failure to complete their military service or attempting to defect would be punishable by five to 10 years in prison. If they commit another crime while serving, the remainder of their previous sentence will be added on top.

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Nine Things We Learned From TikTok’s Lawsuit Against The US Government

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Nine Things We Learned From TikTok’s Lawsuit Against The US Government

Yesterday, as they promised they would, TikTok and ByteDance filed a lawsuit against the federal government challenging the constitutionality oft the Protecting Americans From Foreign Adversary Controlled Apps Act, known as PAFACA or just “The TikTok Ban Bill.”. The bill, which was passed by Congress and signed into law last month, requires ByteDance to sell TikTok’s U.S. operations by January 19, 2025 or face a ban of the app in the United States.

Most of the arguments in TikTok and ByteDance’s complaint are things that we’ve reported before — including details, acknowledged in the suit by the companies for the first time, but reported exclusively by Forbes last summer, of an ultimately unsuccessful negotiation with the interagency Committee on Foreign Investment in the United States. But here are nine things that were new or noteworthy, and suggest where this fight may be headed next.

1. RIP Project Texas?

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In the complaint, TikTok and ByteDance now allege that they have “invested” more than $2 billion in Project Texas, the legal and technological framework that formed the basis of the companies’ proposal to CFIUS through years of national security negotiations. The ultimate goal of Project Texas was to divorce ownership from control, allowing ByteDance to own TikTok and its algorithm while legally and logistically preventing it from controlling the app’s U.S. operations. But CFIUS rejected Project Texas in March 2023, and the passage of PAFACA shows that Congress, too, thinks it’s not enough.

The $2 billion figure is new, up from a claim by TikTok in early 2023 that the company would spent $1.5 billion on the initiative. Tech companies have for years sought refuge from regulation by portraying themselves as engines of the U.S. economy, and part of TikTok/ByteDance’s strategy here is to project confidence and show that things are business as usual. But continuing to invest in a proposal that the U.S. government has repeatedly rejected may amount to throwing that money away, if the courts say the ban bill can stand.

2. Ghosted By The Government: When The Deal Really Went South

TikTok/ByteDance paint a dramatic picture of CFIUS ghosting them at the negotiating table between August 2022 and March 2023, when CFIUS said that ByteDance would have to sell TikTok or face a ban in the U.S.

“From Petitioners’ perspective, all indications were that they were nearing a final agreement,” the companies write. “After August 2022, however, CFIUS without explanation stopped engaging with Petitioners in meaningful discussions about the National Security Agreement. Petitioners repeatedly asked why discussions had ended and how they might be restarted, but they did not receive a substantive response.”

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A lot happened in the months when CFIUS wasn’t talking to TikTok/ByteDance. It was during those months that Forbes revealed a plan by ByteDance’s Internal Audit and Risk Control department to surveil reporters in an effort to ferret out their sources, and ByteDance conducted an investigation showing that its employees had in fact surveilled journalists. ByteDance fired four employees as a result of what it subsequently referred to as “the misguided effort,” including its chief internal auditor and the Beijing-based executive that he reported to.

3. ByteDance’s Founder Lives In Singapore, Not China

The companies say that ByteDance founder Zhang Yiming, a Chinese citizen, is officially living in Singapore. Yiming, who prefers to go by his given name, has lived part-time on the island nation since 2022, where he rode out much of China’s most draconian COVID restrictions, but this is the first time the companies have described him as legally domiciled in a country other than China.

4. TikTok and ByteDance Finally Admit How Tightly They’re Wound Together

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TikTok/ByteDance are now leaning into a thread that we’ve reported on for years: that the TikTok app is inextricably tied to the rest of ByteDance’s systems, in a way that makes separating them effectively impossible. “Moving all TikTok source code development from ByteDance to a new TikTok owner would be impossible as a technological matter,” the companies argue, before launching into an explanation about TikTok’s “millions of lines of software code that have been painstakingly developed by thousands of engineers over multiple years.”

It’s an ironic pivot away from a prior narrative in which TikTok and ByteDance insisted they were more separate than they really are. They have claimed time and again that US-based execs are running the show, despite extensive reporting showing that this isn’t and hasn’t ever fully been the case.

The companies also say that “to keep the platform running,” TikTok engineers “would need access to ByteDance software tools, which the Act prohibits.”

To be clear: TikTok’s reliance on other, non-TikTok ByteDance tools is one of the reasons lawmakers are worried about it! The companies’ new Project Texas entity, USDS, has reduced its dependency on ByteDance systems like Lark, the company’s all-in-one office suite, and Seal, its VPN. But their acknowledgement that TikTok still needs to run through ByteDance’s pipes eliminates any doubt that TikTok is still not just owned, but very much also controlled, by ByteDance today.

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5. We Don’t Do Punishment By Legislation

PAFACA sets out conditions for how a president can designate an app as a “foreign adversary controlled application.” But it separately places TikTok — and all other ByteDance apps — in this category, without requiring the same presidential designation that is required for any other apps that might someday be covered by the law.

This structure is pretty weird! It likely came about because some lawmakers didn’t want to give the president discretion about whether to designate TikTok or not. By naming a specific app and its parent company in the bill, though, the lawmakers have opened themselves up to one of TikTok and ByteDance’s key claims: that the law is an unconstitutional Bill of Attainder — in layman’s terms, a law that seeks to punish a specific person or entity.

We don’t do punishment by legislation in the U.S.; we do it in the courts. So if TikTok can prove that the intent of this bill was to punish or ban it specifically, then the courts will likely find that the law can’t stand.

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6. The Chinese Government Will Call The Shots On A Sale

TikTok and ByteDance flatly acknowledge in their complaint that the Chinese government would prohibit ByteDance from selling its famous recommendations algorithm. We’ve heard this from nearly every expert out there, but hearing it directly from TikTok/ByteDance makes clear that the Chinese government is the ultimate arbiter of who gets access to TikTok’s secret sauce.

7. Lawmakers Will Have To Eat Their Own Anti-TikTok Rants

We wrote a few weeks back about how lawmakers’ comments about the content on TikTok might come back to bite them in court, making it harder for the government to prove that it wasn’t acting out of hostility toward the substance of the conversation on the app. Our prophecy came true: TikTok/ByteDance argued exactly this point in their complaint.

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8. About That Weird Product Review Carve Out

Lawmakers made a weird carve-out in their law for sites that host product reviews, travel reviews, and business reviews. TikTok and ByteDance say it’s unfair.

The bill is targeted at large platforms where users can create their own posts and view others’ posts — i.e. platforms that enable user-generated content, or UGC. Review apps are technically UGC apps, but they don’t have the same potential influence over discourse and culture as social apps do, so Congress exempted them from the law.

TikTok and ByteDance are now claiming that this exemption favors certain speech (reviews) over other speech (non-reviews). It seems unlikely that legislators were actually trying to privilege one topic of speech over the other, but that may not matter if the courts determine that the exemption effectively does so.

9. Everybody Has Been Gathering Evidence For This Showdown

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Both TikTok/ByteDance and the government have spent years preparing for this moment — one where TikTok/ByteDance will argue that the ban bill is ill informed and overbroad and the government will ruefully shake its head and say, “we tried, but there was no other way.”

The First Amendment will govern most of the arguments raised by TikTok and ByteDance. But the First Amendment isn’t a blanket protection for all speech all the time. The parties will fight about which level of scrutiny applies in this case: whether the government will have to show that the law is substantially related to an important government interest (intermediate scrutiny) – or whether it will have to show that the law is narrowly tailored to achieve a compelling government interest (strict scrutiny). But that legalese is all just gradations of the same basic question: was this really necessary?

TikTok and ByteDance will pull out their last four years of communications with the government to claim that it wasn’t. They will say — they do say, in the complaint — that Project Texas would’ve worked. That a national data privacy law would’ve worked. That there were plenty of narrower things Congress could’ve done and didn’t do, things that were more targeted to their actual concerns. Because Congress didn’t do those things, TikTok and ByteDance say, they didn’t even try to take the narrowest path here.

But the government has almost certainly been amassing evidence too, even if we haven’t seen it yet. Back in 2020, TikTok and ByteDance defeated President Trump’s first attempt to ban the app in part by arguing that the whole thing was rushed. After that, the Biden Administration spent years in negotiations with the company, engaging with the inner workings of TikTok and ByteDance’s systems. Its agencies also spent many months examining the companies — the FBI and DOJ in a criminal investigation and the FTC in an investigation about the companies misleading users about who could access their data.

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TikTok and ByteDance say that PAFACA was rushed just like the Trump ban attempt – from its conception largely in secret to the fact that it was quickly voted on and then appended to an omnibus foreign aid package, all before their lobbyists could get a word in edgewise.

Even if PAFACA was rushed, though, the larger government conversation about TikTok hasn’t been. Years of CFIUS negotiations and agency investigations — as well as classified intelligence — informed the closed-door briefings that members of the House and Senate received before voting on the bill. So we’ll be looking at years’ worth of evidence from both sides as the parties battle it out in Round 2.

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Mexico’s presidential frontrunner defends sweeping legal reforms

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Mexico’s presidential frontrunner defends sweeping legal reforms

The frontrunner in Mexico’s presidential election has defended a proposed constitutional overhaul as business-friendly, arguing that popular votes for top judges will enhance democracy.

Investors “have nothing to worry about”, Claudia Sheinbaum, 61, told the Financial Times while being driven between campaign rallies in the capital in a modest Chevrolet family saloon, as well-wishers pressed against the windows to offer flowers ahead of elections next month.

Proposals by leftist President Andrés Manuel López Obrador, of whom Sheinbaum is a close ally, to open up the choice of top election officials and supreme court judges to a popular vote as part of the overhaul have sparked concerns about the rule of law in Mexico.

But Sheinbaum maintained: “What we want is more democracy in the country. And their investments will be guaranteed.”

Sheinbaum, who holds a commanding lead in the polls, has pledged to continue López Obrador’s “transformation” of Mexico with the aim of bringing greater social justice, improving public services and burying a “neoliberal” economic model that she says brought “atrocious poverty and inequality”.

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The proposal to amend the constitution to let the public vote for supreme court justices and election commissioners has been one of López Obrador’s most contentious reforms, and his alliance lacked the two-thirds majority needed to pass it in the last congress. His Morena party hopes to try again after the June elections, which also include a vote for a new congress.

Only one country, socialist Bolivia, currently elects supreme court judges, according to the Federal Judicial Center.

The opposition believes the changes would destroy Mexico’s judicial independence, and investors have privately expressed concerns about risks to the rule of law. But Sheinbaum said institutional reforms were needed because the supreme court had “acted politically, not in terms of justice”.

Asked whether she believes in checks and balances, a major concern for civil rights groups and investors, she said: “I believe in freedom. I believe in democracy. And that the people should decide.”

Mexico will almost certainly elect its first female president on June 2. Most polls give Sheinbaum, who cut her teeth in student politics and later served as mayor of Mexico City, a double-digit lead over the main opposition candidate, entrepreneur-turned-politician Xóchitl Gálvez.

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Mexican President Andrés Manuel López Obrador’s party has upended Mexican politics since his landslide presidential victory in 2018 © Rashide Frias/AFP/Getty Images

A skilful communicator with an instinctive popular touch, López Obrador — who is standing down after a single six-year term in line with Mexico’s constitution — has greatly expanded welfare programmes and more than doubled the minimum wage. Those measures reduced poverty and inequality, and won him enduring support among Mexico’s less fortunate.

At the same time, the president will hand his successor Mexico’s biggest fiscal deficit since the 1980s, having abandoned austerity in his final year in office. But Sheinbaum played down the gap, projected at 5.9 per cent of GDP this year, as a temporary blip.

“This is a one-year deficit because all the president’s strategic infrastructure projects are being paid for. Next year that will reduce significantly,” she said.

Sheinbaum believes there is scope to raise revenues further through better enforcement and technology. Pressed on whether her flagship promises of better education, health and infrastructure would require higher taxation, she replied “yes” before quickly adding: “But we’re not thinking about it in the first instance. We don’t want to propose a deep fiscal reform until we’ve really looked things over when we take office.”

Mexico’s economy has been transformed over 30 years by its free trade agreement with the US and Canada, and Sheinbaum is keen not to rock the boat, especially when US companies are considering moving production from China to countries such as Mexico.

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“We need to take advantage of the opportunity the trade agreement with the United States and Canada gives us,” she said.

However, she wants the government to take a more active role in planning economic development to ensure that investment reaches poorer regions and that Mexico adds value to manufactured products rather than simply assembling components.

“You can’t just put any kind of company in any place, because different territories have different vocations, especially when it comes to natural resources like water,” she said. “We don’t think investment should just create jobs per se. We believe in well-paid jobs, and jobs with wellbeing.”

Beijing has made big inroads in Latin America this century, displacing the US as the biggest trading partner in most of South America, but Sheinbaum is clear where Mexico’s priorities lie. “We don’t have a free trade agreement with China and I don’t think we should have one,” she said.

With the US election later this year, the candidates are preparing for the possible return of former president Donald Trump, who has lambasted Mexico over trade, migration and fentanyl. Sheinbaum insisted the relationship would be “good”, even if Trump wins.

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She spoke to the Financial Times after a rally in Coyoacán, a middle-class area in the capital’s south, where she gave an assured speech in blazing midday sun.

Recalling Mexico’s defeat of the invading French army in 1862, she painted her Morena party as the heirs of the patriots who defended their country. She denounced the opposition as the corrupt heirs of the traitors who invited a foreign emperor to govern them.

Mexican army personnel in Ciudad Juarez
Mexican army personnel arrive in Ciudad Juarez to reinforce security at the airport. López Obrador has called in the armed forces to perform tasks traditionally handled by civilians, such as building train lines and running airports © Jose Luis Gonzalez/Reuters

“What does Coyoacán want? Transformation or corruption? . . . Patriotism or subservience?” she asked the crowd, who chanted “Presidenta! Presidenta!”

López Obrador’s party has upended Mexican politics since his landslide presidential victory in 2018. It now controls two-thirds of state governorships and, with its allies, holds majorities in both houses of congress. This political dominance worries opponents, who recall that Mexico was ruled by a single party for 71 years until 2000.

Juanita Goebertus, Americas director at Human Rights Watch, said Morena’s proposals threatened judicial independence. “It would make it much easier for any political party that’s in government to control the nomination of judges,” she said.

Mexico is a key exporter of cocaine and fentanyl to the US and the country has become a battleground for rival cartels. Polls show security is a top voter concern but Sheinbaum believes she can bring down violent crime by deploying methods she used as mayor in the capital.

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“We need to strengthen [the policy of] zero impunity in our country. It doesn’t matter who commits murder, murder has to be punished by the law.” She dismissed the opposition’s calls for head-on confrontation with the cartels, saying that in the past they gave security forces a “licence to kill” innocent civilians.

“Our vision is the construction of peace,” she said.

López Obrador has replaced the federal police with a new 130,000-strong National Guard run by the military, and has called in the armed forces to perform tasks traditionally handled by civilians, such as building train lines and running airports, ports and the customs service.

Sheinbaum says she is comfortable with the strategy because the military ultimately answers to the president.

“Maybe people don’t understand it from the outside, but it’s not militarisation,” she said. “The Mexican army comes from the Mexican revolution, it comes from a social revolution, it doesn’t come from the elites.”

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A climate change expert with a doctorate in environmental engineering, Sheinbaum wants to accelerate Mexico’s transition to clean energy, using minority private investment with the state in the driving seat. “I dedicated my whole life, before my public life, to climate change. So obviously when we take office we’re going to push it,” she said.

Famously disciplined, Sheinbaum is keen to make clear that while she has been a loyal disciple of López Obrador during her ascent to power, she will govern in her own style.

Although Mexico has “historically been characterised by very strong machismo”, Sheinbaum believes her probable victory is proof that this is changing.

“I think machismo is being left behind . . . Otherwise, a female president would be unthinkable.”

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