Category: 3. Business

SHANGHAI, Aug. 15 (Xinhua) — The total foreign trade value of the Yangtze River Delta in east China reached 9.59 trillion yuan (about 1.34 trillion U.S. dollars) in the first seven months of 2025, up 5.4 percent year on year, official data showed.

During the period, the economic powerhouse region’s trade value accounted for 37.3 percent of the country’s total, according to Shanghai Customs.

The region’s trade growth was 1.9 percentage points higher than the national average of 3.5 percent during the period.

The region’s exports of mechanical and electrical products reached 3.64 trillion yuan in the first seven months, up 9.4 percent year on year. The export values of electric vehicles, high-end equipment and integrated circuits increased 43.9 percent, 10.2 percent and 20.1 percent, respectively.

On the import side, the value of imported medical instruments and equipment rose 10.1 percent.

The Association of Southeast Asian Nations (ASEAN) was the Yangtze River Delta’s largest trading partner during the period, with trade volume increasing 17.5 percent year on year to 1.51 trillion yuan.

The region’s foreign trade value stemming from trade with Belt and Road partner countries reached 4.77 trillion yuan, up 10.3 percent.

Private enterprises continued to serve as a key engine of the region’s foreign trade growth, with their trade volume climbing 9.5 percent to 5.35 trillion yuan, accounting for 55.8 percent of the region’s total.  ■

The randomized phase 2 OCULE-01 trial (NCT06717126) is evaluating the efficacy of roginolisib, a novel non-ATP competitive allosteric modulator of PI3Kδ, in patients with metastatic uveal melanoma.¹

The trial builds on results from the two-part phase 1 DIONE-01 study (NCT04328844), which first assessed continuous daily dosing of roginolisib in 24 patients with pretreated solid tumors and follicular lymphoma, followed by a dose-confirmation cohort in 20 patients with uveal melanoma.²

Roginolisib was well tolerated at the recommended phase 2 dose of 80 mg, with less than 7% of grade 3/4 treatment-emergent adverse effects deemed related to the agent. No immune-mediated or dose-limiting toxicities were reported, and, unlike prior PI3Kδ inhibitors, no dose modifications were required. The agent demonstrated long-term tolerability, with treatment durations extending up to 4.5 years.

Among 29 patients with uveal melanoma enrolled across both DIONE-01 cohorts, the median overall survival (OS) was 16 months. This exceeded the 7-month median OS historically observed with second-line immunotherapy, according to the drug’s developer, iOnctura. Moreover, the median progression-free survival (PFS) was 5 months compared with less than 3 months in historical controls. Translational analyses demonstrated reductions in immune-suppressive cell populations and chemokines, decreases in circulating tumor DNA from uveal melanoma–associated clones, and suppression of PI3K-related signaling, which is consistent with a shift toward a more activated tumor immune microenvironment.

In OCULE-01, approximately 85 adults with disease progression following at least 1 prior therapy will be randomly assigned to receive either roginolisib at a dose of 80 mg or 40 mg daily, or investigator’s choice of standard therapy. The primary end point is overall survival, with secondary end points including PFS, objective response, duration of response, disease control, safety, pharmacokinetics, healthcare utilization, and quality-of-life measures.

In an interview with OncLive®, Paul Nathan MBBS PhD BA FRCP, a consultant medical oncologist at Mount Vernon Cancer Centre in England, emphasized early-phase findings validating the mechanistic rationale for targeting PI3Kδ in metastatic uveal melanoma; the need for randomized data to determine whether roginolisib can deliver clinically meaningful survival gains in this rare malignancy; and how OCULE-01 aims to address this question by directly comparing the agent with established agents in a patient population with limited treatment options.

OncLive: What was the rationale for conducting this analysis?

Nathan: This pathway is of real interest in tumors that appear to have an immunosuppressed phenotype. What we know about this pathway is that there is a rare, inherited condition that leads to an overactivation of the PI3K pathway, which results in patients being immunosuppressed. It turns out that this pathway appears activated in several tumors and may be involved in suppressing immune responses to the tumor.

We see changes in the balance of T regulatory [Treg] cells compared with cytotoxic T cells, as well as other changes in the immune microenvironment, that lead to suppressed immune responses.

What is the mechanism of action of roginolisib?

Roginolisib is a small-molecule inhibitor of PI3K-δ, which is an isoform of the PI3K enzyme. Early data show that it appears to change the immune microenvironment in cancers to be more activated and less suppressed. We see reductions in Treg infiltrate and changes in myeloid-derived suppressor cells as well.

Uveal melanoma is an area of high unmet need, high in terms of the extent of the need rather than the number of patients, because it is a relatively rare disease. For these patients, we struggle to [maintain long-term disease control], and we know that uveal melanoma tumors have an immunosuppressed microenvironment.

Early data with roginolisib in uveal melanoma [suggest an] association with reversal of Treg-to-CD8 ratios but also show early signs of clinical benefit in early-phase clinical studies, with some patients doing better than expected.

This ongoing randomized phase 2 trial is comparing roginolisib with the standard of care [SOC] in patients who have progressed after prior immunotherapy. The primary end point is overall survival, [which is] a robust end point, and we’ve just opened a number of sites in Europe,

What is the design of this phase 2 trial?

Patients are randomized to receive either roginolisib at the full 80-mg dose, a lower 40-mg dose that could be escalated to 80 mg, or the SOC. Secondary end points include clinical outcomes and translational measures, with mandated tumor biopsies at baseline and after a defined period of drug exposure to evaluate effects on the tumor microenvironment, and [hopefully] that will tell us a lot about whether this drug is doing what we want it to do in the tumor microenvironment.

References

1. Nathan PD, Maria A, Piulats JM, et al. A phase II randomised study to evaluate the antitumour activity of roginolisib, a novel non-ATP competitive and allosteric modulator inhibiting PI3Kδ, in patients with metastatic uveal melanoma (OCULE-01). J Clin Oncol. 2025;43(16_suppl).doi:10.1200/jco.2025.43.16_suppl.tps9613
2. iOnctura reaches new clinical milestones in uveal melanoma. News Release. iOnctura. November 12, 2024. Accessed August 15, 2025. https://www.synconaltd.com/news-insights/news/ionctura-reaches-new-clinical-milestones-in-uveal-melanoma/

Kory Burke, a small producer of high-quality wines in central California, never believed that tariffs on imports from France or Italy could help boost his business. But he knew for sure they would be a big hindrance as soon as Donald Trump announced late last month that he was slapping a 15% levy on all goods from the European Union.

“The first email I received was from my cork provider,” Burke recalled. “He said he’d take on 2% of the additional cost of importing corks from Europe, but I would have to absorb the other 13%. Then my barrel supplier got in touch, pushing me to put in my orders as fast as possible because every new French barrel coming across the Atlantic after the tariffs was going to come with a $100 or $150 fee.”

Every one of these messages was a gut punch for Burke’s five-year-old family-run business, Dresser Winery, which sits on an idyllic hillside outside Paso Robles and specializes in big, bold reds. Burke sent a note out to his wine club members earlier this year telling them he did not plan on increasing prices for the fall shipment, but he realized he could no longer honor the commitment.

“If we do that,” he said flatly, “we have to shut the business down.”

It turns out even US wine producers are heavily reliant on foreign components – everything from French oak barrels, which give the wine a buttery, vanilla finish in contrast to the much less appealing brown sugar taste of American oak, to glass bottles and corks and the wine-making equipment itself.

“Every single product we use, from our pumps to the de-stemmer, comes with instructions written in six languages,” Burke explained. “Could we produce some of these things here? Sure, but it would take three years to get production up and running, and that’s not the way the specialization has been.”

As another producer from Paso Robles, Paul Hoover of Still Waters Vineyards, put it: “The only thing in my bottles made in America is the wine.”

Ostensibly, Trump’s tariffs on imported goods are supposed to give a competitive boost to American entrepreneurs like Burke and Hoover. But the theory does not really apply to the wine business – not only because so many of the materials used to make California wine come from overseas, but also because people do not buy wine based on price alone.

“It is a fundamental misunderstanding of wine drinkers and the wine marketplace,” the National Association of Wine Retailers said in a blistering statement in response to the 15% tariff announcement.

“Champagne is not sparkling wine. Bordeaux is not simply cabernet sauvignon or merlot … America’s independent fine wine retailers understand better than most that when an American wine drinker asks for red Burgundy, they do not substitute Oregon pinot noir when the Burgundy is out of their price range or unavailable. They simply don’t make a purchase.”

Burke echoed this sentiment, saying he had to control his reaction recently when a Trump supporter came to his winery and told him he must be excited about the business opportunities the tariffs will create. “People aren’t buying my bottles because of tariffs on French wines, that’s for sure,” he said. “If anything, I’m competing against other Californian and American wines. With European wines, it’s not a real competition at all. They’re very different regions, very different products.”

California wines are far from the cheapest because of the high cost of land and labour in the Golden state. For that reason, many producers live or die by the quality of what they make and the sort of subtle distinctions that come from varietals grown in a particular microclimate, or in a particular soil, or aged in a particular barrel.

Price still matters, because fine wines are a discretionary spending item, and if the economy or people’s personal finances are struggling it is often one of the first things that consumers stop buying. The National Association of Wine Retailers, an industry lobby group, said it was worried about tariffs generally, not just on wine, because inflation and an uncertain business climate would hurt its members’ bottom line just as much.

“The increased costs of living that will result from the recently enacted tariffs, along with the significant increase in prices for wines … will only push down consumption further, thereby harming the American wine industry to a degree from which many of its participants will not recover,” the group said.

In Paso Robles, which has seen an explosion in the number of wineries over the past two decades to about 250 and has become a major weekend tourist hub for wine lovers from San Francisco and Los Angeles, some of the harmful effects are being felt already.

Joel Peterson, executive director of the Paso Robles Wine Country Alliance, said international orders were drying up as the reverberations from Trump’s trade war echo around the globe. “We have wine sitting in a warehouse that is specially labeled for the Canadian market that producers can’t sell,” Peterson said. “We’ve had no orders from the UK since Trump’s so-called Liberation Day in April. People are scared to order those wines.”

Domestic retailers say they have not seen significant price increases kick in yet – for either domestic or European wines – but are already starting to struggle simply because of the uncertainty created by the White House’s constantly shifting messages on where and at what rate it intends to impose tariffs.

“We’re not in a recession but it’s what I call a recess market,” said Jim Knight, co-owner of the Wine House in Los Angeles, which specializes in small-label boutique wines from the United States and around the world. “People have money, they’re just not spending it … If the president made a decision and stuck with it, we could plan for it. But we haven’t been able to plan for it.”

Knight’s business has a particular problem with high-end French wines it bought in advance years ago – right after the grapes were harvested – and presold to customers with an anticipated 10% mark-up. When tariffs on European wines were briefly at 10% earlier this year, Knight was looking at his entire profit being wiped out, since tariffs are imposed when goods arrive in the United States, not when they are purchased. Now, at 15%, he’s looking at taking a loss that might force him to lay off workers or otherwise shrink his business.

For now, he is letting the wine sit in a temperature-controlled storage unit in France and hoping Trump might still bend to pressure from the industry to create a tariff exception for wines and spirits. An industry initiative called Toasts not Tariffs has been lobbying the White House hard to do exactly that.

More broadly, Knight said he was worried that small European producers would no longer offer their limited production to the US market, and that some of the specialist importers, the ones who love the same smaller label wines he does, will go out of business. “Importers of wine from the European Union are American businesses too,” he remarked.

That helps explain why a US distributor of European wines and spirits, VOS Selections of New York, has been the lead plaintiff in a lawsuit challenging the constitutionality of Trump’s tariffs – a case that led to an initial ruling against the administration in the court of international trade at the end of May.

Ilya Somin, a law professor at George Mason University who has spearheaded the suit, said the nature of the wine business was a vivid illustration of the harm that tariffs can do. “Many of the wines our client imports simply cannot be produced in the United States because of differences in climate, soil and other factors,” he said. “We’re not benefiting American industry, we’re damaging it and hurting consumers.”

Not every wine producer sees the economic outlook as uniformly gloomy. Hoover, of Still Waters Vineyards, said the cost of storing and transporting wine was a greater burden than the price of corks or bottles – particularly for California producers who have too much inventory on their hands following a post-Covid boom-and-bust cycle. He said he was relieved at a drop in fuel prices in recent months and saw opportunities if they fell further.

He was modestly hopeful, for example, that he could tap into sales opportunities on the east coast where he was previously priced out. “Before the tariffs, a boat coming from Europe could deliver wine to the east coast more efficiently than I could getting it across the United States on a truck,” he said. “Let’s see how that looks going forward. Energy costs are the key to this. Let’s hope the tariffs don’t monkey that up.”

One of the main reasons that people in the wine business do not believe the tariffs will benefit domestic producers, as the White House is promising, is that they have seen this scenario play out before, during Trump’s first term as president.

In 2019, the administration imposed a 25% tariff on most European wines, among other products, in retaliation for European subsidies on Airbus passenger jets. Trump said at the time that the relatively low price of French wines was unfair to California producers, but no evidence emerged that the tariff did anything to redress that perceived unfairness. “It did not increase my domestic wine sales at all,” Knight said.

Our results focus on the effects of reducing demand and vehicle capacity on passenger interactions. The first part highlights the main changes in passenger behavior and differences in passenger travel patterns. The second part focuses on the epidemiological effects to identify which scenario had the most significant effect on the number of infected passengers. Finally, at the end of the result section, we identify the critical parts of the system from an epidemiological point of view.

Effects of reduced demand and vehicle capacity

As discussed in previous sections, the contact network describes the fine structure of passenger co-traveling relationships during the day. Figure 5 summarizes the changes in key network metrics of the contact network under different demand and vehicle capacity restrictions. These metrics include the number of passengers (nodes), the number of connections (edges), as well as median degree (co-travel connections of individual passengers). If a vehicle travels between stations A and B, passengers sharing the trip will form a clique (fully connected subgraph) in the network. Therefore, metrics also include median clique sizes describing the size of the co-traveling groups between stations. The results shown in the table suggest that capacity restrictions and demand-related changes effectively disrupt the formation of large high-risk clusters, potentially reducing the risk associated with infectious passengers within the transit network.

The results show a significant decrease in the overall size of the passenger contact network (as shown by the number of nodes and edges) across the different scenarios. These changes highlight the impact of the demand and vehicle capacity changes on the network structure.

The restrictions also influenced the degree distribution of the contact network. As the degree of a given node represents the number of direct contacts a passenger has during the day, the risk of exposure to infectious diseases is reduced as demand and capacities decrease. At 100% demand, the median number of passenger connections was 118. Across the different scenarios, this number dropped to 58.

Diseases tend to spread more quickly inside a community or a strongly connected cluster due to the higher number of connections among passengers. Therefore, as passenger groups grow and become more interconnected in the network, they promote the spreading process, working as super spreaders during epidemiological simulation. Consequently, clique sizes and clique size distributions are expected to strongly correlate with the final epidemiological modeling results.

Demand serving functionality of the transit system

The structure of the transit system does not always match the given structure of demand due to limitations in infrastructure. A natural example is when too many passengers attempt to reach a destination simultaneously, but only a limited number of vehicle trips are available to serve that station. If the system cannot handle individual passengers due to the infeasibility of their demand, they cannot reach their destination, and the route choice model leaves them out of the simulation and the contact network simultaneously. Therefore, for each scenario, a small portion of passengers cannot satisfy their demand due to restrictions in vehicle capacity. This enables the identification of critical parts of the system from an operability point of view, designating vehicle trips that are sensitive to reduced capacities, leaving passengers without transit options. This information can also be used to evaluate the system’s capability to serve passengers. As seen in Table 2, the number of passengers who are unable to reach their destinations increases as restrictions in vehicle capacity are introduced. Consequently, reducing demand naturally reduces the load on sensitive vehicle systems, facilitating system efficiency.

Under normal operating conditions, with 100% demand and unrestricted vehicle capacity, 4270 passengers failed to reach their destination. This serves as a baseline for comparing the effects of different scenarios. Table 2 shows that as capacity restrictions are introduced, the number of passengers with infeasible demand grows substantially. The trend worsens as capacity restrictions become more strict, reaching as many as 9203 stranded passengers at the end of the restriction range. This means that introducing only transit system-related restrictions significantly damages operability. However, even a slight decrease in demand helps ease the load on critical components, helping the system serve a larger portion of passenger demand.

The results demonstrate the necessity of balance between capacity restrictions and demand management. Combining different demands and reducing vehicle capacity can help maintain operability while protecting passengers in case of an outbreak.

Epidemiological spread analysis

This section is an overview of the epidemiological simulation results, which focus on the global rate of infected passengers and the number of highly endangered individuals. We also provide these values as a ratio compared to the network size in each scenario to compare the real epidemiological effects of restrictions.

At the beginning of each simulation process, we started with 100 infected passengers ((|A_0| =100)), selected randomly from the network, and then we simulated 5 iterations representing an infection period of 5 days. We ran the epidemic spreading process (k = 100,000) times to estimate the probability of infection. As discussed previously, we selected (tau _i) so that no nodes transitioned to the removed state, remaining infectious throughout the simulation.

The epidemiological simulation shows that reduced demand and vehicle capacities affect the global infection rate of the contact network. Figure 6 presents the expected percentage of passengers who are infected at the end of the simulation.

The baseline scenario that did not have reduced demand or restricted capacities shows an infection rate of 30.9%. As the capacity restriction becomes more strict, global infection slightly declines, reducing to 27.9%. A similar but more pronounced trend can be observed for lower demand levels. For example, a 50% reduction in demand results in 8.5% decrease in the risk of infection in the scenario where vehicle capacity is set to 90%. Results show that the reduction in infection rate is more noticeable in the case of demand change than in restricted capacities. However, implementing capacity restrictions, even without significantly reducing passenger demand, can reduce infection rates within the transit network. Furthermore, the combined effect of restrictions on the transit system and government regulations that affect demand can substantially reduce the impact of an outbreak on society. The results underscore the importance of coordinated measures in managing public health risks during pandemics.

To determine changes in the number of infected passengers in a more refined way, we collected highly endangered passengers—those with a final infection probability greater than 50%—from the different demand and capacity-reduced scenarios. The table 3 provides a different view of the results.

In the original scenario, with full capacity and demand, capacity restrictions reduced the percentage of highly endangered individuals from 23.3% to 20%. The results follow the same trend as the global infection percentage: as demand decreases and capacity restrictions are introduced, this percentage declines further. For example, when capacity restrictions increase from 0% to 50%, the percentage drops to 16.6%, reducing the proportion of endangered passengers by 7%. Furthermore, when decision-makers implement 50% capacity restrictions along with local measures that reduce demand by 50%, the proportion of individuals at a critical infection level decreases to 13.7%.

The results highlight that demand-related restrictions have a stronger effect on the infection rate. Although capacity restrictions are essential parts of containment strategies, they are not necessarily enough to minimize the negative impact of an outbreak situation. Finally, combining transit system-related measures with demand-reducing decisions can maximize the reduction in infected individuals.

Identifying critical components

Bota et al.²⁹ proposed a methodology for identifying the most critical bus trips responsible for spreading disease among passengers. Here we follow the same approach by taking the average infection probabilities for all passengers on a particular vehicle trip to estimate the likelihood of transporting infected passengers. From another perspective, this gives us an estimate of the probability of getting infected if a passenger uses that specific vehicle trip. To calculate the most critical parts of the system, we take the top 100 vehicle trips based on this metric, according to the highest infection likelihoods.

Since we are interested in measuring the impact of the scenarios on the epidemiological risk associated public transportation system components, we took a slightly different approach. Instead of focusing on individual vehicle trips, we evaluated a similar likelihood of infection at the transit route level as a whole (i.e., any vehicle traveling on a particular route within a 24-hour time-frame). In the following part of the paper, we summarize the results for the top 10 most critical bus routes identified using this approach.

Figure 7 shows the most critical bus routes and the regions they connect. As shown, these transit routes are located in different parts of the Bay Area region, and most of them connect different counties or cities. However, there are other routes, for example, cccta_206A, operated by the Central Contra Costa Transit Authority, or sf_muni_39, which operates within San Francisco. The most critical routes include the connection between Fremont and Palo Alto, Richmond and Vallejo, Vallejo and Fairfield, or Berkeley and San Leandro. If passengers use these routes, the likelihood of getting infected is higher than 90% for baseline scenario. In the rest of this section, we evaluate how the different demand and vehicle capacity-related restrictions affect these routes.

Figure 8 shows the changes in the expected likelihood of infection across varying scenarios with different vehicle capacities and reduction in travel demand. It can be seen that the probability of infection decreases with reduced transit demand for all identified routes. Among the top 10 routes, two types of patterns can be observed. The first pattern involves routes, such as in the case of sf_muni_39 or cccta_206A, where the likelihood of infection decreased slightly for the different scenarios. However, interesting trends can be observed in the rest of the routes, especially the soltrans_80 route that connects the cities of Fairfield and Vallejo, and lavta_12WBX operated by the Wheel public bus service in the Tri-Valley region. We can spot the drastic impact of vehicle capacities on the likelihood of infection for these routes. There is a 50–70% decrease in the probability of expected infection specifically due to restrictions in vehicle capacity. In some cases, demand-related changes did not impact the route-related risks. In other cases, these restrictions were effective in reducing disease-related dangers. Results show that some routes react differently to the various types of restrictions, highlighting the importance of combining multiple measures. This strategy will balance the reduction effect in the different parts of the system.

(Bloomberg) — US stocks stepped back from record highs on Friday as consumer sentiment fell for the first time since April.

The S&P 500 Index closed down 0.3% in New York, pulling back from prior levels. The Nasdaq 100 Index fell 0.5%, while the Dow Jones Industrial Average advanced 0.1%.

The preliminary sentiment index for August dropped to 58.6 from 61.7 a month earlier, according to data from the University of Michigan that signaled concern President Donald Trump’s tariffs are likely to worsen inflation. Consumers expect prices to rise at an annual rate of 4.9% over the next year, more than economists had predicted.

“The inflation expectations component of the consumer confidence data was much higher than expected,” said Miller Tabak’s Matt Maley. “When you combine this with the much lower headline number, it renews concerns about stagflation. So, it’s not a surprise that investors are taking some profits today.”

Bill Adams, chief economist at Comerica Bank, said the consumer appears “mixed” so far in the third quarter. “While the data don’t all point in the same direction, the US economy looks to be in okay shape in the third quarter,” Adams said. “What consumers do is more important to the economy than what they say.”

Earlier data showed US retail sales rose in July in a broad-based advance, boosted by car sales and major online promotions. The value of retail purchases, not adjusted for inflation, increased 0.5% after an upwardly revised 0.9% gain in June, according to Commerce Department data released Friday. Excluding cars, sales climbed 0.3%.

Following the “explosive” PPI data on Thursday, Board’s Michelle Green said the retail sales confirm that costs are being successfully passed onto consumers.

“For equities, this creates a margin compression story: consumer-facing companies may sustain top-line growth, but rising input costs will pressure profitability, particularly in goods-heavy sectors,” Green said. “With 4.2% unemployment providing no justification for rate cuts, the Fed’s higher-for-longer stance becomes increasingly likely, keeping discount rates elevated and putting sustained pressure on valuations.”

Next week, investor focus will shift from economic data to the US central bank’s annual symposium in Jackson Hole, Wyoming, where Chair Jerome Powell is scheduled to speak.

Bank of America Corp. strategists led by Michael Hartnett expect US stocks to decline in the event of dovish signals from the Fed at Jackson Hole. A dovish tone from Powell at Jackson Hole could result in stocks sliding as investors “buy rumor, sell fact,” Hartnett said in a note.

Meanwhile, President Donald Trump is set to meet Russian President Vladimir Putin in Alaska for their first summit in seven years. Both leaders have very different measures of success for the talks: the US president wants a ceasefire in Ukraine, while getting face time without making any concessions is already a win for the Russian leader.

Among single stocks, UnitedHealth Group Inc. surged 12% after funds, including Berkshire Hathaway Inc., piled into shares of the troubled insurer. The investments are a welcome reprieve for a company that had seen its stock fall 46% this year.

The stock reaction for UnitedHealth, as well as the broader managed care sector, is likely a reflection of how “beaten down” the space has been this year, according to Daniel Barasa, portfolio manager at Gabelli Funds.

“Overall, I wouldn’t say that this is a definitive signal that the sector has reached a bottom, but it does suggest we may be approaching that point,” said Barasa.

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