Category: 3. Business

TOKYO, Nov 4 (Reuters) – Japan’s manufacturing activity shrank in October at the fastest pace in 19 months, hit by slumping demand in the key automotive and semiconductor sectors, a private-sector survey showed on Tuesday.

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The headline index has remained below the 50.0 mark that separates growth from contraction for four consecutive months.

New orders dropped at the quickest pace in 20 months, driven by constrained client budgets and weak demand, the survey found. Export orders continued to fall for a 44th month, particularly from Asia, Europe and the United States, but the rate of contraction was the slowest since March.

“Demand weakness, particularly in the automotive and semiconductor sectors, weighed on the Japanese manufacturing industry,” said Pollyanna De Lima, Economics Associate Director at S&P Global Market Intelligence.

Despite reduced demand, the drop in production output was less severe than in September, as manufacturers adjusted to shortages in new work, according to the survey.

Input cost inflation accelerated to a four-month high, driven by rising expenses in labour, materials and transportation. Firms’ output prices rose to a three-month high as they rushed to protect profit margins in response.

Manufacturers’ outlook for output turned more optimistic in October, supported by hopes for new products, growing AI adoption and auto and semiconductor sector recoveries as global trade conditions normalise, the PMI survey showed.

“They generally hope that new product releases will be successful and that the detrimental impact of U.S. tariffs will fade,” De Lima noted.

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A month of Urolithin A supplementation restored youthful energy metabolism in immune cells, hinting at a safe nutritional strategy to counter immune aging and improve resilience to infections.

Study: Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial. Image Credit: CI Photos / Shutterstock

In a recent study published in Nature Aging, researchers evaluated whether oral Urolithin A (UA), a mitophagy-inducing postbiotic, can remodel immune cell phenotypes and metabolism in healthy middle-aged adults compared with placebo.

How Aging Impacts Immunity and Mitochondrial Function

By age 50, many people notice slower recovery, weaker vaccine responses, and lingering infections, signs of immune aging. This process involves a decline in naïve T cells and persistent low-grade inflammation (“inflammaging”).

Mitochondria, the body’s primary energy generators, and mitophagy, their quality control process, play key roles in maintaining immune balance. When mitophagy falters, immune cells lean toward exhaustion and inflammation. Scientists have hypothesized that safe, food-derived molecules that improve mitochondrial quality could strengthen immunity and enhance vaccine effectiveness, but targeted interventions require further study.

Randomized Trial Design and Participant Overview

The trial was randomized, double-blind, and placebo-controlled, enrolling 50 healthy adults aged 45–70 years. Participants received either 1,000 mg of oral UA daily or placebo for 28 days. Assessments occurred at baseline, day 7, and day 28.

Primary outcomes included changes in CD3⁺ T-cell subsets and immune metabolic remodeling. Secondary endpoints assessed included cytokine levels (IL-6, TNF, IL-1β, IL-10, and IL-2), immune population shifts, mitochondrial measures, and functional assays. PBMCs were analyzed using spectral flow cytometry.

Measuring Cellular Energy and Mitochondrial Activity

Single-cell energetic metabolism profiling (SCENITH) evaluated energy pathway use under translational blockade, assessing oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and amino acid oxidation (AAO).

Mitochondrial content and activity were measured via MitoTracker dyes and PGC-1α, a key regulator of mitochondrial biogenesis. Safety labs and adverse events were tracked throughout, in accordance with CONSORT guidelines, with Institutional Review Board approval.

Urolithin A Reprograms CD8⁺ T-Cell Function

UA supplementation reshaped the CD8⁺ T-cell profile toward a “ready-to-respond” state. Compared with placebo, UA increased naïve-like CD8⁺ T cells and Ki-67 expression (linked to proliferation and reinvigoration) while reducing TOX, a transcription factor associated with exhaustion. PD-1 expression was unchanged, and CD4⁺ subsets remained stable, indicating selective CD8⁺ rejuvenation without global activation.

Quantitatively, UA increased naïve-like CD8⁺ cells by 0.50 percentage points (95% CI 0.16–0.83; P = 0.0437) and boosted FAO/AAO capacity by 14.72 percentage points (95% CI 6.46–22.99; P = 0.0061).

Enhanced Metabolic Efficiency and Energy Flexibility

SCENITH analysis revealed that UA reduced glucose dependence and enhanced fatty acid and amino acid oxidation in CD8⁺ T cells, particularly in naïve cells, thereby favoring a durable, oxidative energy profile. NK cells displayed similar metabolic gains, while monocytes stayed glycolytic and CD4⁺ T cells were largely unchanged.

These changes indicate improved mitochondrial efficiency, characteristic of youthful immune energy management and sustained cellular readiness.

Broader Immune Remodeling Beyond T Cells

UA’s effects extended to other immune compartments. Circulating CD56^dim CD16^bright NK cells and nonclassical monocytes (CD14^lo CD16^hi) increased, whereas classical monocytes showed fewer HLA-DR^hi cells, suggesting reduced inflammatory priming. B-cell and dendritic-cell totals remained stable.

In CD8⁺ T cells, PGC-1α expression rose, indicating mitochondrial biogenesis balanced by ongoing mitophagy. Despite these shifts, senescence markers (p16, p21, KLRG1, CD57) remained unchanged, suggesting rejuvenation without reversal of senescence.

Systemic and Cytokine-Level Immune Effects

At the systemic level, plasma IL-2 decreased without unwanted increases in pro-inflammatory cytokines. Upon ex vivo stimulation, UA-treated CD8⁺ T cells produced more TNF but not IL-4, signifying a stronger type-1 immune response without type-2 skewing.

Monocytes from UA recipients demonstrated greater phagocytosis of E. coli, suggesting improved bacterial clearance potential. Cytokine analyses involved approximately 15–20 matched samples per cytokine and were exploratory in scope.

Transcriptomic Insights from Single-Cell RNA Sequencing

Single-cell RNA sequencing (scRNA-seq) revealed that UA upregulated TCF7, LEF1, and IL7R (genes linked to T-cell stemness and memory) while downregulating exhaustion-associated genes NR4A2 and CREM.

Pathway analyses revealed the activation of TCR signaling and the suppression of GPCR–Gαs–PKA inhibitory checkpoints, consistent with enhanced T-cell motility and responsiveness. Across NK cells, monocytes, and B cells, UA reduced inflammatory transcriptional programs and upregulated cytoskeletal and adhesion pathways.

Monocytes also increased NAMPT expression, part of the NAD salvage pathway associated with anti-inflammatory states. These exploratory transcriptomic findings (from five post-randomization participants) warrant cautious interpretation.

Safety, Tolerability, and Study Limitations

UA was bioavailable and well-tolerated, with adverse events comparable to those of the placebo over 28 days. While the study detected cellular and molecular rejuvenation signatures, it was limited by small sample size, short duration, and absence of infection or vaccine-response outcomes.

Conclusions: Urolithin A as a Potential Immune Rejuvenator

In healthy middle-aged adults, a 28-day UA regimen shifted CD8⁺ T cells toward a youthful, less exhausted phenotype, reprogrammed metabolism toward mitochondrial oxidation, expanded beneficial NK subsets, and enhanced monocyte bacterial clearance.

These molecular and metabolic improvements suggest better mitochondrial quality control and reduced inhibitory signaling, potentially translating to stronger immune defenses with age. Larger, longer trials are necessary to assess clinical benefits, optimize dosing, and evaluate synergy with vaccines or immunotherapies.

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Experts have found weaknesses, some serious, in hundreds of tests used to check the safety and effectiveness of new artificial intelligence models being released into the world.

Computer scientists from the British government’s AI Security Institute, and experts at universities including Stanford, Berkeley and Oxford, examined more than 440 benchmarks that provide an important safety net.

They found flaws that “undermine the validity of the resulting claims”, that “almost all … have weaknesses in at least one area”, and resulting scores might be “irrelevant or even misleading”.

Many of the benchmarks are used to evaluate the latest AI models released by the big technology companies, said the study’s lead author, Andrew Bean, a researcher at the Oxford Internet Institute.

In the absence of nationwide AI regulation in the UK and US, benchmarks are used to check if new AIs are safe, align to human interests and achieve their claimed capabilities in reasoning, maths and coding.

The investigation into the tests comes amid rising concern over the safety and effectiveness of AIs, which are being released at a high pace by competing technology companies. Some have recently been forced to withdraw or tighten restrictions on AIs after they contributed to harms ranging from character defamation to suicide.

“Benchmarks underpin nearly all claims about advances in AI,” Bean said. “But without shared definitions and sound measurement, it becomes hard to know whether models are genuinely improving or just appearing to.”

Google this weekend withdrew one of its latest AIs, Gemma, after it made up unfounded allegations about a US senator having a non-consensual sexual relationship with a state trooper including fake links to news stories.

“There has never been such an accusation, there is no such individual, and there are no such new stories,” Marsha Blackburn, a Republican senator from Tennessee, told Sundar Pichai, Google’s chief executive, in a letter.

“This is not a harmless hallucination. It is an act of defamation produced and distributed by a Google-owned AI model. A publicly accessible tool that invents false criminal allegations about a sitting US senator represents a catastrophic failure of oversight and ethical responsibility.”

Google said its Gemma models were built for AI developers and researchers, not for factual assistance or for consumers. It withdrew them from its AI Studio platform after what it described as “reports of non-developers trying to use them”.

“Hallucinations – where models simply make things up about all types of things – and sycophancy – where models tell users what they want to hear – are challenges across the AI industry, particularly smaller open models like Gemma,” it said. “We remain committed to minimising hallucinations and continually improving all our models.”

Last week, Character.ai, the popular chatbot startup, banned teenagers from engaging in open-ended conversations with its AI chatbots. It followed a series of controversies, including a 14-year-old killing himself in Florida after becoming obsessed with an AI-powered chatbot that his mother claimed had manipulated him into taking his own life, and a US lawsuit from the family of a teenager who claimed a chatbot manipulated him to self-harm and encouraged him to murder his parents.

The research examined widely available benchmarks but leading AI companies also have their own internal benchmarks that were not examined.

It concluded there was a “pressing need for shared standards and best practices”.

Bean said a “shocking” finding was that only a small minority (16%) of the benchmarks used uncertainty estimates or statistical tests to show how likely a benchmark was to be accurate. In other cases where benchmarks set out to evaluate an AI’s characteristics – for example its “harmlessness” – the definition of the concept being examined was contested or ill-defined, rendering the benchmark less useful.

By Frances Yue

Still, the long-term momentum points to the upside, one technical analyst says

Bitcoin fell below its 200-day moving average on Monday.

Bitcoin has broken below an important technical level, which could signal further downside for the cryptocurrency, according to Katie Stockton, founder and managing partner at Fairlead Strategies.

Bitcoin (BTCUSD) has fallen below its 200-day moving average at $109,800, Stockton wrote in a Monday note. The 200-day moving average is one of the most widely followed indicators that may be used to define a long-term trend, and also acts as a support level for bitcoin in this case.

“We assume the corrective phase will keep hold of bitcoin for another few weeks,” based on technical indicators, Stockton wrote. Bitcoin’s next support level stands at around $94,200, she said.

Still, the long-term momentum of bitcoin remains positive, she noted, eyeing a potential price target at $134,500 in the long term if the technical trend is complete.

Bitcoin fell 3.9% on Monday to trade at around $106,400, as some large bitcoin holders sold part of their holdings, based on blockchain data.

It is unclear what triggered the move lower, analysts at crypto trading firm QCP said. “Recent selloffs, including today’s, came with no clear macro catalyst,” they wrote.

-Frances Yue

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  11-03-25 1839ET
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Community and environmental advocates recently won two legal challenges against fossil fuel polluters in South Africa. These resounding victories show that despite setbacks in places like the United States, international leadership and common sense can still prevail in the global fight to curb climate change.  

Earthjustice partnered with Natural Justice and the Green Connection on behalf of coastal communities fighting a plan from Total Energy and Shell to drill multiple oil and gas exploration wells off the West Coast of South Africa, roughly between Cape Town and Cape Agulhas. This region’s unique, ecologically rich, and diverse marine and coastal ecosystems not only provide habitat for numerous species but also support the cultural traditions and livelihoods of the many communities living along the coast. These communities are deeply concerned about the risks of oil spills from the exploration wells, which could reach the shoreline in as little as half a day, depending on weather conditions and the season. 

In a landmark decision in August, the Western Cape High Court set aside the project’s environmental authorization, effectively halting the project and protecting 10,000 square-kilometers (3,861 square-mi) of open ocean from the risk of catastrophic oil spills and habitat destruction that would devastate marine species.  This case has had an immediate impact because the Minister paused consideration of all other oil and gas projects until the government’s appeal of this case is decided, which could take up to six to eight months.  And if this case is upheld on appeal, it is likely that it will send all the pending oil and gas applications back to the drawing board. 

The court’s decision was a powerful rebuke to the companies and the government. First, it found that the project proposal failed to assess the cultural and economic impacts of a catastrophic oil spill on communities, which violated South Africa’s environmental review law and regulations. The court also ruled that the company’s proposal failed to consider transboundary impacts on Namibia from an oil spill.  

And importantly, the Court held that only considering the climate impacts of exploratory drilling, without considering the impacts of full-scale production drilling, was unlawful. The court agreed with our partners that exploration and production are inherently intertwined, noting, “[t]here would be no point in conducting an exploration activity unless an entity hoped to proceed to the next phase of production.”  

Another decision took the government to task for failing to adequately account for the harms caused by fossil fuels: the Supreme Court of Appeal of South Africa, the country’s second highest court, handed our partners Natural Justice, South Durban Community Environmental Alliance, and groundWork a critical victory rejecting a proposal to build a massive 3000 MW gas power plant in Richards Bay. In South Africa’s first ever legal challenge against a gas power plant, the court set aside the power plant’s environmental permit. This requires Eskom, South Africa’s state-run utility monopoly, to start from scratch if it wants to advance this ill-conceived project.  

The court found that the government and Eskom should have considered renewable energy alternatives to the proposed power plant and that “the preferred alternative must be the final choice after comparing the social, environmental, technical, and economic impacts of all the considered options” with sustainable development remaining the goal. The court also found that the government and Eskom failed to assess the cumulative impacts of extraction and transportation of the gas supplying the power plant, and that the public was denied adequate opportunities to participate in the environmental authorization process.  

This case could not have come at a more opportune time, as there are more than a dozen gas plants proposed across South Africa, and we plan to support our partners to hold the government and Eskom accountable the impacts of this gas build-out. 

Earthjustice proudly supported our partners in developing their legal arguments and look forward to continuing our work together to guarantee the right to a healthy and safe environment in South Africa, including the right to safe, clean, and affordable energy.

By Emily Bary

Third Point looked overseas to find a cheaper way to play the memory-chip boom

Third Point cheered SK Hynix’s market-leading status.

Daniel Loeb’s Third Point LLC made a bet on SK Hynix in the third quarter as it saw a way to play the artificial-intelligence trade in a cheaper way than U.S. options afforded.

His third-quarter investor letter mentioned new investments in SK Hynix (KR:000660), a South Korean memory player, and Ebara (JP:6361), a Japanese maker of semiconductor-production equipment. “We believe both companies are leaders in their respective industries, significant beneficiaries of the AI buildout, and trade at undemanding absolute valuations and meaningful discounts to their U.S. peers,” he wrote.

See also: 10 stocks that let you invest like Nvidia in the next hot AI trade

Loeb continues to see opportunities for SK Hynix, which has seen its stock surge more than 250% so far this year. The company competes against Micron Technology (MU) and Samsung Electronics (KR:005930) in the oligopolistic memory market that’s “in the early innings of de-commoditization.”

“AI workloads have been driving substantial growth in high bandwidth memory…where Hynix is the market leader with over 50% market share,” he wrote. And high-bandwidth memory confers various benefits, such as “design stickiness,” that Loeb thinks can reduce earnings volatility in the traditionally cyclical memory industry.

See also: The surprising stocks leading the tech sector this year thanks to an AI renaissance

He noted that SK Hynix is trading “at a mere 7x” estimated 2026 earnings, whereas Micron commands a 10x multiple and Samsung has a 12x multiple. Loeb also invested in SK Square (KR:402340), a “related holding company,” which has a 20% stake in SK Hynix and thereby lets investors “buy SK Hynix at a nearly 60% discount.”

Loeb also discussed the investment in Ebara, which makes chip-production equipment. The company is “a major beneficiary of the advanced packaging structures critical in AI semiconductors across both logic and memory,” he wrote, but he noted that shares trade at a “substantial discount” to rivals.

That discount reflects “an overextended cost structure as well as unnecessarily discounted pricing,” which Loeb said has hurt margins, but Third Point is “in active dialogue with Ebara’s new management team.”

U.S. artificial-intelligence investments served Third Point well in the third quarter, according to the letter, as Taiwan Semiconductor Manufacturing (TSM) (TW:2330) and Nvidia (NVDA) were its two biggest winners.

Loeb commented that OpenAI is expanding its computing capacity at a scale “difficult to comprehend” – but one nonetheless emphasizing “a compute-constrained world…that has benefited our existing investments in TSMC and Nvidia as two integral pieces in this buildout.”

Third Point’s flagship Offshore Fund returned 3.2% in the third quarter, trailing the S&P 500’s SPX 8.1% return and the MSCI World Index’s XX:990100 7.4% return.

“Our performance for the quarter and year has been below our expectations due to the weak performance of several of our largest event-driven positions including Kenvue,” the letter noted.

That stock stands to be less of a detractor in the fourth quarter, as Kimberly-Clark (KMB) announced Monday plans to purchase Kenvue (KVUE) at a 46% premium to the stock’s Friday close.

See: Could Huggies and Tylenol be a good fit? Kimberly-Clark is buying Kenvue for $48 billion

-Emily Bary

This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal.

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The lawsuit, filed on Friday, alleges the lithium-ion battery pack in the Model S caused the electronic door systems to fail.

Electric Vehicle company Tesla has been sued over a fiery crash in the United States that killed all five occupants of a Model S, who were allegedly trapped inside because of a design flaw that prevented them from opening the sedan’s doors.

Jeffrey Bauer, 54, and Michelle Bauer, 55, of Crandon, Wisconsin, were passengers in a Model S when the car went off the road and struck a tree in Verona, Wisconsin, a suburb of Madison, on November 1, 2024. They died the next day.

According to a complaint filed on Friday by four of the Bauers’ children, the couple’s fate was sealed because the Model S’s lithium-ion battery pack caused the electronic door systems to fail.

The children said that Tesla knew this could happen based on earlier fires, yet made a “conscious departure from known, feasible safety practices”.

Tesla, based in Austin, Texas, and led by Elon Musk, did not immediately respond to requests for comment on Monday by the Reuters news agency.

The automaker has also been sued by families of two college students killed in a Cybertruck crash last November in a San Francisco suburb, after allegedly being locked in the burning vehicle because of its door handle design.

In September, the National Highway Traffic Safety Administration disclosed a probe into the possible defects on some Tesla doors, following reports that handles could fail.

The Bauer children said that Model S rear seat passengers, like Michelle Bauer, were particularly vulnerable in the event of a crash, because they would have to lift carpeting to find a metal tab allowing their escape, which is not intuitive.

A nearby homeowner told 911 that she heard screaming from within the Bauers’ vehicle, the complaint said.

“Tesla’s design choices created a highly foreseeable risk: that occupants who survived a crash would remain trapped inside a burning vehicle,” according to the complaint.

Other defendants include the estate of the car’s driver, whom the Bauer children accused of negligent driving.

On Wall Street, Tesla’s stock finished the day up 2.5 percent.