Category: 3. Business

The Bank of England is poised to cut interest rates on Thursday despite a growing divide between its policymakers over the dangers to the economy from high inflation and rising unemployment.

In a development that will ease pressure on households and businesses, City forecasters expect the central bank to announce a quarter-point cut, its fifth rate reduction in a year.

Financial markets predict an almost 100% chance of a quarter-point cut from 4.25%, the same as the last reduction in May.

The chancellor, Rachel Reeves, will welcome the cut as Labour comes under pressure over its economic management and growing questions about potential tax rises at her autumn budget.

Ministers have sought to claim credit for the Bank reducing its base rate four times since August last year, arguing that it had been able to do so only after Labour had worked to “restore stability to the economy”.

Publishing research before the rate decision at midday on Thursday, the party said a family buying a typical home was now paying almost £1,000 a year less on their mortgage than in July 2024, when the Conservatives left office.

Figures from the property website Rightmove showed that a typical first-time buyer’s mortgage payment was now almost £100 a month less than a year earlier.

However, a fifth rate cut will highlight the dangers facing the economy amid a worsening slowdown, as households and businesses grapple with tax rises, stubborn inflation, and global uncertainty created by Donald Trump’s tariff war.

Analysts expect the vote on rates from the Bank’s nine-strong monetary policy committee to be split, exposing tensions at the heart of Threadneedle Street over the best course of action to keep fast-rising consumer prices in check while also safeguarding jobs and growth.

City investors are predicting a three-way split, with the external economists Alan Taylor and Swati Dhingra favouring a bigger, half-point cut amid concern about rising job losses.

Most of the MPC members, including the governor, Andrew Bailey, are expected to vote for a quarter-point reduction.

Huw Pill, the Bank’s chief economist, could split from his colleagues to join the external economist Catherine Mann in voting to keep rates unchanged owing to concerns that inflationary pressures are mounting.

Analysts believe that divisions have become more entrenched since the Bank last produced economic forecasts in May. Threadneedle Street will update its outlook on Thursday.

Michael Saunders, a former MPC member who is now at the consultancy Oxford Economics, said the committee’s split was understandable.

“You have weak growth, rising unemployment and inflation well above target; those signals go in opposite directions [for a rate decision],” he said. “Different people will put different weights on them. It is not sign that they are more argumentative than other committees [in the past], just that they face a greater disparity between growth, unemployment and inflation.”

Interest rate cuts support economic growth by lowering borrowing costs for businesses and households. However, bolstering economic activity can stoke inflationary pressures.

“Monetary policy remains quite tight. Fiscal policy is tightening, and the budget may include further tax hikes later this year. Trade policy uncertainty remains high, deterring investment and hiring.”

China diverting cheap exports from the US to the UK during Trump’s tariff war could also reinforce downward pressure on inflation, he added.

Labour has come under pressure from business leaders blaming Britain’s recent economic weakness on Reeves raising employment taxes in her first autumn budget, which firms warned would force them to cut jobs and put up prices.

Official figures show unemployment has crept higher in recent months, while the economy shrank in April and May. Inflation has risen by more than expected, reaching 3.6% in June – significantly above the Bank’s 2% target.

Business surveys this week have shown a slowdown in the service sector and a collapse in construction output.

Labour said cheaper mortgage rates available today – with the average two-year fixed rate falling to 4.52% – had saved borrowers £81.69 on average each month.

The Treasury minister James Murray said: “Labour’s urgent task when we took office was to restore stability to the economy after 14 years of Tory failure. Since we came into office, rates have been cut four times, and that’s putting more pounds in the pocket of homeowners through cheaper mortgages.”

Ham and bacon sold by supermarkets including Tesco, and Marks and Spencer still contain cancer-causing chemicals almost 10 years after the World Health Organization warned about the dangers of their use in processed meats.

Wiltshire ham is the product with the highest concentrations of nitrites, according to analysis that compared it to cooked ham and unsmoked bacon.

All of the 21 products tested in a laboratory were found to contain nitrites, which are used to preserve meat, despite the WHO in October 2015 declaring them to be unsafe.

Tesco’s Wiltshire ham contained the most nitrites – almost 33 milligrams per kilogram. That was 11 times the 2.88mg/kg in its cooked ham and almost four times the 8.64mg/kg in its unsmoked bacon. And it was also almost 18 times the 1.84mg/kg found in Morrisons’s bacon.

Other Wiltshire ham products, including those sold by M&S (28.6 mg/kg), Sainsbury’s (21.1mg/kg) and Morrisons (19.2mg/kg) also contained relatively high levels, although Asda’s version only had 8mg/kg.

Food campaigners, who want nitrites banned, said the findings were “alarming”.

Cancer charities said the widespread use of nitrites showed that people should eat as little processed meat as possible, such as ham, bacon and sausages, because consumption increases the risk of bowel cancer. Cancer Research UK estimates that 13% of the 44,100 cases of the disease diagnosed each year in Britain are linked to processed meat.

The analysis was commissioned by the Coalition Against Nitrites and undertaken by Food Science Fusion, an independent company, and the laboratory experts Rejuvetech. However, it found the levels of nitrites in all 21 products were well below the 150mg/kg legal limit.

A spokesperson for the Coalition Against Nitrites, which includes food safety experts, medical specialists and politicians from most of the UK’s major parties, said: “It’s nearly a full decade since the WHO classified nitrite-cured processed meats as a group one carcinogen and it is disappointing and alarming that we continue to see products on sale containing high levels of nitrites.”

They added: “Consumers are increasingly aware of the dangers of nitrites in processed meats, yet they continue to be exposed to their risks.”

Wiltshire ham contains such high levels of nitrites because during the production process the pork is injected with nitrates, as also happens with cooked ham. However, Wiltshire ham is then soaked in a bath of brine and nitrites, to give it its red colour and protect it from deadly bacteria. At that point a chemical reaction occurs, which turns nitrates into nitrites.

Prof Chris Elliott, the food safety expert who led the government-ordered investigation into the 2013 horsemeat scandal, said the research confirmed that nitrites remained “unnecessarily high in certain UK meat products”.

He added: “Given the mounting scientific evidence of their cancer risk, we must prioritise safer alternatives and take urgent action to remove these dangerous chemicals from our diets.”

Several food firms, including Finnebrogue and Waitrose, have responded to mounting concern about nitrites by producing bacon that is free of them.

Dr Rachel Orritt, Cancer Research UK’s health information manager, said: “Eating processed meat increases the risk of bowel cancer. Nitrites … can lead to cell damage, which is one of the ways that processed meat is linked to bowel cancer. The less processed meat you eat, the lower your risk of bowel cancer.”

Dr Giota Mitrou, the director of research and policy at the World Cancer Research Fund, said it recommended “eating as little, if any, processed meat as possible”.

A Tesco spokesperson said: “We follow all UK and EU requirements, alongside guidance from the UK Food Standards Agency, to ensure we get the right balance of improving the shelf life and safety of our products with limited use of additives.

“The nitrites levels in all of our products, including our traditionally cured Finest Wiltshire ham, fall significantly below the legal limits in the UK and EU.

“Nitrates and nitrites are an important part of the curing process for some meats and they are used to prevent the growth of harmful bacteria that cause serious food poisoning.”

Andrew Opie, the director of food and sustainability at the British Retail Consortium, which represents supermarkets, said: “Food safety is paramount to our members and they implement strict policies with their suppliers to ensure all products comply with UK food legislation.”

Any motorist who has ever waited through multiple cycles for a traffic light to turn green knows how annoying signalized intersections can be. But sitting at intersections isn’t just a drag on drivers’ patience — unproductive vehicle idling could contribute as much as 15 percent of the carbon dioxide emissions from U.S. land transportation.

A large-scale modeling study led by MIT researchers reveals that eco-driving measures, which can involve dynamically adjusting vehicle speeds to reduce stopping and excessive acceleration, could significantly reduce those CO₂ emissions.

Using a powerful artificial intelligence method called deep reinforcement learning, the researchers conducted an in-depth impact assessment of the factors affecting vehicle emissions in three major U.S. cities.

Their analysis indicates that fully adopting eco-driving measures could cut annual city-wide intersection carbon emissions by 11 to 22 percent, without slowing traffic throughput or affecting vehicle and traffic safety.

Even if only 10 percent of vehicles on the road employ eco-driving, it would result in 25 to 50 percent of the total reduction in CO2 emissions, the researchers found.

In addition, dynamically optimizing speed limits at about 20 percent of intersections provides 70 percent of the total emission benefits. This indicates that eco-driving measures could be implemented gradually while still having measurable, positive impacts on mitigating climate change and improving public health.

“Vehicle-based control strategies like eco-driving can move the needle on climate change reduction. We’ve shown here that modern machine-learning tools, like deep reinforcement learning, can accelerate the kinds of analysis that support sociotechnical decision making. This is just the tip of the iceberg,” says senior author Cathy Wu, the Thomas D. and Virginia W. Cabot Career Development Associate Professor in Civil and Environmental Engineering (CEE) and the Institute for Data, Systems, and Society (IDSS) at MIT, and a member of the Laboratory for Information and Decision Systems (LIDS).

She is joined on the paper by lead author Vindula Jayawardana, an MIT graduate student; as well as MIT graduate students Ao Qu, Cameron Hickert, and Edgar Sanchez; MIT undergraduate Catherine Tang; Baptiste Freydt, a graduate student at ETH Zurich; and Mark Taylor and Blaine Leonard of the Utah Department of Transportation. The research appears in Transportation Research Part C: Emerging Technologies.

A multi-part modeling study

Traffic control measures typically call to mind fixed infrastructure, like stop signs and traffic signals. But as vehicles become more technologically advanced, it presents an opportunity for eco-driving, which is a catch-all term for vehicle-based traffic control measures like the use of dynamic speeds to reduce energy consumption.

In the near term, eco-driving could involve speed guidance in the form of vehicle dashboards or smartphone apps. In the longer term, eco-driving could involve intelligent speed commands that directly control the acceleration of semi-autonomous and fully autonomous vehicles through vehicle-to-infrastructure communication systems.

“Most prior work has focused on how to implement eco-driving. We shifted the frame to consider the question of should we implement eco-driving. If we were to deploy this technology at scale, would it make a difference?” Wu says.

To answer that question, the researchers embarked on a multifaceted modeling study that would take the better part of four years to complete.

They began by identifying 33 factors that influence vehicle emissions, including temperature, road grade, intersection topology, age of the vehicle, traffic demand, vehicle types, driver behavior, traffic signal timing, road geometry, etc.

“One of the biggest challenges was making sure we were diligent and didn’t leave out any major factors,” Wu says.

Then they used data from open street maps, U.S. geological surveys, and other sources to create digital replicas of more than 6,000 signalized intersections in three cities — Atlanta, San Francisco, and Los Angeles — and simulated more than a million traffic scenarios.

The researchers used deep reinforcement learning to optimize each scenario for eco-driving to achieve the maximum emissions benefits.

Reinforcement learning optimizes the vehicles’ driving behavior through trial-and-error interactions with a high-fidelity traffic simulator, rewarding vehicle behaviors that are more energy-efficient while penalizing those that are not.

However, training vehicle behaviors that generalize across diverse intersection traffic scenarios was a major challenge. The researchers observed that some scenarios are more similar to one another than others, such as scenarios with the same number of lanes or the same number of traffic signal phases.

As such, the researchers trained separate reinforcement learning models for different clusters of traffic scenarios, yielding better emission benefits overall.

But even with the help of AI, analyzing citywide traffic at the network level would be so computationally intensive it could take another decade to unravel, Wu says.

Instead, they broke the problem down and solved each eco-driving scenario at the individual intersection level.

“We carefully constrained the impact of eco-driving control at each intersection on neighboring intersections. In this way, we dramatically simplified the problem, which enabled us to perform this analysis at scale, without introducing unknown network effects,” she says.

Significant emissions benefits

When they analyzed the results, the researchers found that full adoption of eco-driving could result in intersection emissions reductions of between 11 and 22 percent.

These benefits differ depending on the layout of a city’s streets. A denser city like San Francisco has less room to implement eco-driving between intersections, offering a possible explanation for reduced emission savings, while Atlanta could see greater benefits given its higher speed limits.

Even if only 10 percent of vehicles employ eco-driving, a city could still realize 25 to 50 percent of the total emissions benefit because of car-following dynamics: Non-eco-driving vehicles would follow controlled eco-driving vehicles as they optimize speed to pass smoothly through intersections, reducing their carbon emissions as well.

In some cases, eco-driving could also increase vehicle throughput by minimizing emissions. However, Wu cautions that increasing throughput could result in more drivers taking to the roads, reducing emissions benefits.

And while their analysis of widely used safety metrics known as surrogate safety measures, such as time to collision, suggest that eco-driving is as safe as human driving, it could cause unexpected behavior in human drivers. More research is needed to fully understand potential safety impacts, Wu says.

Their results also show that eco-driving could provide even greater benefits when combined with alternative transportation decarbonization solutions. For instance, 20 percent eco-driving adoption in San Francisco would cut emission levels by 7 percent, but when combined with the projected adoption of hybrid and electric vehicles, it would cut emissions by 17 percent.

“This is a first attempt to systematically quantify network-wide environmental benefits of eco-driving. This is a great research effort that will serve as a key reference for others to build on in the assessment of eco-driving systems,” says Hesham Rakha, the Samuel L. Pritchard Professor of Engineering at Virginia Tech, who was not involved with this research.

And while the researchers focus on carbon emissions, the benefits are highly correlated with improvements in fuel consumption, energy use, and air quality.

“This is almost a free intervention. We already have smartphones in our cars, and we are rapidly adopting cars with more advanced automation features. For something to scale quickly in practice, it must be relatively simple to implement and shovel-ready. Eco-driving fits that bill,” Wu says.

This work is funded, in part, by Amazon and the Utah Department of Transportation.

A joint investigation by The Guardian and +972 Magazine has revealed that Microsoft has been providing its Azure cloud computing infrastructure to Israeli military intelligence to store a vast archive of intercepted communications by Palestinians. The data stored and utilized by intelligence agents within Israel Defense Forces (IDF) Unit 8200 has facilitated deadly airstrikes and military operations in both Gaza and the West Bank.

This unprecedented integration of Microsoft with the war crimes of the Israeli military exposes the increasingly central role played by and correspondence of interests between giant global tech corporations and the strategic aims of US imperialism in the ongoing genocide and ethnic cleansing of the Palestinian people.

According to the investigative reports, the collaboration between Microsoft and Unit 8200 was brokered at the highest levels. In late 2021, a delegation from Israel’s military intelligence, led by then-commander Brigadier General Yossi Sariel, met at Microsoft’s Seattle headquarters with CEO Satya Nadella and other key executives.

Nadella personally committed Microsoft’s technological resources to the project, reportedly calling the partnership “critical” for Microsoft’s future, and approved the creation of a customized, segregated area within Azure for exclusive use by Unit 8200.

This platform, according to anonymous sources and leaked internal Microsoft documents, was not for hosting generic cloud services but was designed to meet “the most ambitious demands for mass data collection and analysis ever proposed to the company.” Within months, Unit 8200 was able to begin storing and analyzing intercepted communications on a scale that the Israeli military had previously regarded as technically impossible.

The technological infrastructure that Microsoft built and now maintains is significant in its scale and scope. The foundation of the system is Azure data centers located in the Netherlands, with additional clusters in Ireland and within Israel itself. By July 2025, at least 11,500 terabytes of Israeli military data—equivalent to about 200 million hours of audio—were being stored on Microsoft servers.

Most of the data, according to Israeli and Microsoft sources cited by the investigation, consist of recordings of phone calls by Palestinians in the West Bank and Gaza. Surveillance officers and internal documents described the ambition to “capture and store up to a million calls an hour.”

This required “collaboration on security architecture between Microsoft engineers and military staff,” with Unit 8200 alumni among the Azure development teams responsible for implementation. Internal memos reveal “a rhythm of daily, top-down and bottom-up interaction” between the company’s cloud division and its Israeli military client, with project secrecy so tight that non-essential Microsoft personnel were not permitted to refer to the “8200 project” by name.

The Israeli surveillance of Palestinians is universal. The operations described in the investigation mirror details revealed by former NSA intelligence officer Edward Snowden in 2013 about the scale and scope of US government surveillance, data storage and searching of the electronic communications of everyone in the country, if not throughout the entire world.

Having long controlled the telecommunications infrastructure in the occupied territories, Israel indiscriminately intercepts all phone calls, radio transmissions and internet traffic, gathering up the communications of millions of ordinary Palestinians.

Leaked documents show the primary purpose of this data is to generate rapid “targets for kinetic action,” that is, identify cellular phones and voices for tracking and subsequent drone strikes, air raids or ground operations. Several anonymous Israeli intelligence officers, speaking to reporters, described a machinery that “finds incriminating material to be used for anything: blackmail, mass arrests, administrative detention, or retroactive justification for killing.”

Three sources specifically confirmed the data collected and stored using Microsoft’s cloud has been pivotal in planning lethal airstrikes in Gaza, as well as sweeping military detentions in the West Bank, operations which have left thousands of Palestinians dead or disappeared since October 2023.

The source of these revelations is derived from a rare trove of leaked documents—internal emails, technical memos, contracts and meeting summaries—supplemented by extensive interviews. At least 11 current and former Microsoft and Israeli intelligence sources, some of whom participated directly in the system’s development, provided corroboration under strict anonymity due to the immense legal and career risks involved.

One well-placed official warned that a successful legal challenge to this arrangement, especially under international human rights law, would threaten both Israeli and American interests, given the “codependence of government and cloud monopolies in waging cyber and kinetic war.”

The thermal stability of 1 was assessed kinetically in aqueous solutions at different pH levels relevant to the formulation of commercial products. Andrographolide (1) is the major bioactive metabolite of A. paniculata and is thus a driver for the development of value-added products, either as a single material or as an ingredient in a standardized mixture. The use of standardized preparations of A. paniculata leaves or leaf extracts as functional ingredients for medicinal plant products is also important for commercial development. Knowledge regarding the thermal stability of 1 is therefore of significance for the development of high-quality functional products for the cosmetic and nutraceutical industries. Such standardized extracts and cosmetic products may be exposed to elevated temperatures at different pH levels, depending on the production processes, and may experience a variety of formulation, storage, and manufacturing operations where metabolite integrity could be compromised^13,27,28.

Identification of degradation products

The HPLC method for the analysis of 1 was adapted from the American Herbal Pharmacopoeia²⁹. The separation of 1 and its major degradation products from the pH-adjusted solutions in methanol (MeOH) was accomplished within a 25 min time frame. The isolates were characterized using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry and comparison with published spectroscopic data (Supplementary Tables S3 and S4, Figures S1−S10). In the acidic environment (pH 2.0), the degradation products 2^{30,31,32,33,34,35} and 3^24,36 eluted at retention times (t_R) of 4.1 min and 7.6 min, respectively (Fig. 1). Isoandrographolide (2), a white amorphous powder, possessed a molecular formula of C₂₀H₃₀O₅ as determined by (+)-LC-MS-QTOF [M + Na]⁺ at m/z 373.1976 (Supplementary Figure S11). The ¹H- and ¹³C-NMR spectra of 2 were similar to those of 1, except for a methyl group at C-17 (δ_H 1.19) and an oxymethine proton at C-12 (δ_H 4.58), instead of an exo-methylene group H-7α (δ_H 4.67) and H-7β (δ_H 4.89) and an olefinic proton H-12 (δ_H 6.85) in 1, respectively (Supplementary Table S3). The ¹³C NMR data of 2 showed two oxymethine carbons at C-8 (δ_C 83.2) and C-12 (δ_C 72.3) instead of the two resonances of olefinic carbons in 1 (Supplementary Table S4). The NMR data of 2 agree with those reported³⁵. 8,9-Didehydroandrographolide (3), white amorphous powder, C₂₀H₃₀O₅, showing (–)-LC-MS-QTOF at m/z 395.2069 ([M + HCOO]^– (Supplementary Figure S12). The ¹H- and ¹³C-NMR data were closely related to those of 1, except for an endo-olefinic group at C-8 (δ_C 129.2), C-9 (δ_C 134.9), and C-17 (δ_C 20.9) in 3, instead of an exo-methylene group in 1 (Supplementary Table S4). The NMR spectral data of 3 agreed with those previously reported²⁴.

For the pH 8.0 solution, the degradation products 4^3,24,37,38, 5³⁹, and 6^19,20,24 eluted at t_R of 5.5, 10.2, and 19.8 min, respectively. Compound 6 was not detected in strongly basic conditions (pH 10.0–12.0) (Fig. 1). 15-Seco-andrographolide (4) was isolated as a white amorphous powder, C₂₀H₃₂O₆, m/z 367.2123 ([M – H]^–) (Supplementary Figure S13). The structure of 4 was confirmed by comparison of the NMR data with 1, through the presence of an acyclic oxy-methylene group at C-15 (δ_H 3.75 and δ_H 3.61; δ_C 66.3) instead of the cyclic oxy-methylene protons (δ_H 4.16 and δ_H 4.46; δ_C 76.1) in 1 (Supplementary Table S3). The NMR data of 4 agreed with those reported²⁴. 14-Deoxy-15-methoxyandrographolide (5) was obtained as a white solid, C₂₁H₃₂O₅, m/z 365.2328 ([M + H]⁺) (Supplementary Figure S14). The NMR data were similar to those of 1, except for resonances for a methylene at C-14 (δ_H 3.09, 2.67; δ_C 33.5) and di-oxymethine at C-15 (δ_H 5.55; δ_C 104.4), instead of resonances for an oxymethine and oxymethylene in 1. The structure of 5 was confirmed by comparison of the NMR data with those reported³⁹. The structure of 11,14-dehydro-14-deoxy-andrographolide (6) was confirmed by analysis of the ¹H-NMR data with those reported²⁴. A trans-olefinic group was observed at C-11 (δ_H 6.86; δ_C 136.54) and C-12 (δ_H 6.16; δ_C 122.5). and by the resonances for an olefinic group at C-13 (δ_C 129.6) and C-14 (δ_H 7.44; δ_C 146.7) instead of an oxy methine in 1. The (+)-LC-MS-QTOF at m/z 333.2060 ([M + H]⁺) confirmed the molecular formula to be C₂₀H₂₈O₅ (Supplementary Figure S15).

The HPLC chromatograms illustrating the degradation products formed at pH 2.0, pH 6.0, and pH 8.0 are presented in Fig. 1 and Supplementary Figures S16–S18. In experiments using DMSO, the degradation product observed under acidic conditions (pH 2.0) produced similar signals as in MeOH, whereas under strongly basic conditions (pH 10.0 and pH 12.0), only 4 was formed from 1 (Supplementary Figure S19). Polarity or nucleophilicity therefore plays an important role in the degradation pathways of 1 since MeOH is a stronger nucleophile than DMSO and thus 5 could be observed in the MeOH conditions.

The persistence of the degradation products from 1 in pH 2.0 solution was evident with compounds detected for at least 7 days (Supplementary Figure S16), whereas at pH 6.0 and pH 8.0 4 was the major degradation product, and 5 and 6 were observed in small amounts under these conditions (Fig. 1 and Supplementary Figures S17 and S18). The formation of products 4, 5, and 6 was initially detected after 2 days at pH 6.0, and after 1 h at pH 8.0 (Supplementary Figures S17 and S18). These studies support the previous reports on the kinetic degradation of 1 in solution²⁴. Andrographolide (1) therefore undergoes distinctive acid and base-catalyzed degradation pathways which provides a critical insight into the degradation mechanisms of 1 and highlights the importance of pH on the stability and transformation of this bioactive compound when different pharmaceutical or cosmeceutical formulations are being considered.

Kinetics of the degradation of 1

HPLC chromatographic analysis revealed a direct relationship between the pH of the solution and the rate of the degradation reaction. Specifically, at pH 2.0 and pH 4.0, the degradation of 1 occurred at a slower rate compared to solutions at higher pH levels (pH 6.0 to pH 12.0) (Figs. 2 and 3). The HPLC chromatogram of 1 at pH 2.0 over a period of 7 days at 70 °C indicated two degradation products, 2 and 3 (Supplementary Figure S16), while no degradation was detected at pH 4.0 in the same time frame and temperature (Supplementary Figure S20). Thus, 1 exhibited greater stability in pH 4.0 buffer solution compared to pH 2.0, consistent with previous findings that noted the optimal stability of 1 within the pH range of 3–5⁴⁰. Although the degradation rates increase below pH 3.0, 1 remains largely present at pH 2.0, a typical human gastric value, and making this low pH relevant in the context of food, cosmetic, and drug processing.

The metabolite remained stable at the boiling point of MeOH (64.7 °C for 28 days), whereas in DMSO, the degradation rate of 1 depended on the temperature and the composition of the solvent²³. The rate constant for the degradation of 1 was investigated at pH 2.0, pH 6.0, and pH 8.0, and at three individualized, elevated temperatures of 70, 77, and 85 °C (Table 1). Chemical kinetic parameters and profiles for the degradation of 1 are shown in Table 2. As expected, in each case the apparent kinetic rate constant (k) increased with increasing temperature. Strong correlation coefficients (0.9800 < r² < 0.9978) from the plot of ln (C) against reaction time (day) were found (Table 1). The rate constant obtained from Eq. (1) was fitted to an Arrhenius-type equation in each kinetic model studied to determine the effect of temperature on the chemical reaction (Fig. 2). The k values indicated the decreased thermal stability of 1 as the temperature was increased. Under different conditions, the k value of solid-state andrographolide under heat-accelerating conditions was reported to be 3.8 × 10^− 6 per day¹⁷ and 6.58 × 10^− 6 per day¹⁸ while in pH-dependent solutions the k value was revealed as 6.5 × 10^− 5 per day (at pH 2.0), 2.5 × 10^− 3 per day (at pH 6.0), and 9.9 × 10^− 2 per day (at pH 8.0). Thus 1 decomposed faster in acid and basic solutions than in the solid state. This is the first report documenting the thermal degradation kinetics of 1 at specific pH conditions. These results align with earlier studies that characterized the degradation of 1 as following a first-order reaction model in solution through intermolecular interactions²³. First-order kinetics indicated that the degradation of 1 is concentration dependent, therefore the amount of 1 degrading per unit of time is not constant for the ambient pH conditions. Most drugs tend to degrade with either zero- or first-order kinetics⁴¹. On the other hand, solid state 1 decomposed through second-order degradation kinetics under accelerated conditions through intramolecular interactions^19,20. Second-order degradation occurs when the rate is influenced by the concentration of two separate or identical reactants. Therefore, the varied matrix or formulation of 1 under study may be the cause of the identified differences in degradation kinetics. The intermolecular interactions of 1 influence the rate of degradation^17,18,19,20. However, the intramolecular interactions of 1, particularly through hydrogen bonds and hydrophobic interactions are crucial for stability and function. The calculated activation energies (E_a) derived from the curves showed that the values for 1 at pH 2.0, pH 6.0, and pH 8.0 were 118.9, 82.8, and 79.4 kJ/mol¹, respectively (Table 2). A high E_a generally indicates that the reaction is less sensitive to temperature fluctuations¹⁵. Hence, the higher E_a value of 1 at pH 2.0 portends a lower sensitivity to temperature-induced degradation than in pH 6.0 and pH 8.0 solutions. The stability of 1 in acidic conditions may be due to the presence of free –OH groups causing clustering, followed by strong intermolecular hydrogen bonding. The shelf-life values for 1 at pH 2.0, pH 6.0, and pH 8.0 at 25 °C were 4.3 years, 41 days, and 1.1 days, respectively (Table 2) which is highly significant for product formulation studies.

First-order plot and Arrhenius plots of the degradation of andrographolide based on pH, (A) pH 2.0, (B) pH 6.0, and (C) pH 8.0.

First-order plot of the degradation of andrographolide (1) in MeOH between pH 2.0 and pH 4.0 at 70 °C for 35 days.

Formation of degradation products

The transformation of 1 into 2 can occur through (a) allylic rearrangement of the hydroxyl group on the lactone ring, (b) protonation of the exo-methylene group, and (c) cyclization of the tetrahydrofuran ring³⁰. The formation of 3 was visualized to occur through isomerization of the 8,17-double bond by (a) protonation of the exo-methylene moiety, and (b) abstraction of the proton at C-9[22] (Scheme 1). However, the¹³C-NMR spectrum indicated a mixture of formation olefinic isomers of 3 for which the precise configuration could not be established. Compound 4 could be produced through fragmentation of the lactone ring of 1, and 6 could arise through E2 elimination by base following abstraction of the δ-proton in 1 leading to 1,4-elimination from an allylic alcohol²⁴ (Scheme 1). The formation of 5 may occur through methoxylation at C-15 involving an enol lactone intermediate (m/z 333.2060)⁴² which may be derived from 6 (Scheme 1 and Supplementary Figure S21). However, the¹H-NMR spectrum indicated either a mixture of C-15-epimers of 5, or only one epimer for which the precise configuration could not be established. This mechanistic possibility was revealed from the HPLC analysis of 5 when 6 was treated at pH 8.0 in MeOH solution (Supplementary Figure S22). This chemical reaction supports the biogenetic pathway for 5 that is proposed to occur in plants³⁹. However, 5 could also be an artifact due to the presence of MeOH in the solution which acts as a nucleophile to react with an enol lactone intermediate (Figure 4 and Scheme 1). This analysis enumerates some of the mechanisms underlying the degradation of 1 and highlights the potential for exploring reaction opportunities towards further analogues for biological assessment while retaining their stability.

Chemical structures of 1 and its degradation products.

Reaction mechanisms for the degradation of 1 under acidic and basic conditions.

Biological activity assessments

To investigate the changes in the biological profile of the degradation products in comparison with 1, two bioassays were performed. The first assay evaluated the inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages. The results of this anti-inflammatory bioassay for 1 and its degradation products are summarized in Table 3. The presence of a newly formed tetrahydrofuran ring and an olefinic bond in 2 did not enhance the anti-inflammatory activity when compared to 1 and the other degradation products. This affirmed that the conjugated Δ¹²⁽¹³⁾-double bond and the hydroxy group at C-14 are critical structural elements for the inhibition of NO production³³. In addition, the anti-inflammatory activity of 5 and 6 was not enhanced relative to 1, 3, and 4 through the introduction of a methoxy group at C-15 in 5, and a conjugated double bond in compound 6. These results align with molecular docking studies on the nitric oxide production inhibition activity of 1 and its derivatives⁴³. The formation of a C-8 vinylic methyl group, as in 3, and 4 where the lactone ring is opened, were less active than 1. These data confirm that, since in the degradation products of 1 the strong anti-inflammatory activity is not retained, the stability of 1 in formulated medicinal products must be monitored over time to avoid diminished efficacy for the patient. In this study it was affirmed that 1 was extensively degraded under strongly basic conditions. Therefore, alkaline products of 1, such as soaps and shampoos, can be explored for other activities, recognizing that the anti-inflammatory activity of 1 will have been lost.

The cytotoxic activities of the degradation products and 1 were assessed against the SW480 human colon cancer cell line, with the resulting IC₅₀ values presented in Table 3. Compounds 2 and 6 exhibited no activity at the tested concentrations, in agreement with earlier studies across a selection of cancer cell lines^{42,43,44,45,46,47}. In this investigation, the parent compound 1 was identified as the most cytotoxic with a modest IC₅₀ value of 4.17 µM, suggesting the important role of the allylic hydroxyl lactone moiety of 1 in imparting cytotoxic effects. Compounds with a C-8 vinylic methyl group, e.g., 3, and with the lactone ring-opened, e.g., 4, demonstrated weaker cytotoxic activity compared to 1. In summary, the structural integrity of 1 is necessary for maintaining both the anti-inflammatory and cytotoxic activities in developed products.

US President Donald Trump said the tariff will not impact companies if they have already invested in US facilities.

United States President Donald Trump says he will impose a 100 percent tariff on foreign-made semiconductors, although exemptions will be made for companies that have invested in the US.

“We’ll be putting a tariff on of approximately 100 percent on chips and semiconductors, but if you’re building in the United States of America, there’s no charge, even though you’re building and you’re not producing yet,” Trump told reporters at the Oval Office on Wednesday evening.

The news came after a separate announcement that Apple would invest $600bn in the US, but it was not unexpected by US observers.

Trump told CNBC on Tuesday that he planned to unveil a new tariff on semiconductors “within the next week or so” without offering further details.

Details were also scant at the Oval Office about how and when the tariffs will go into effect, but Asia’s semiconductor powerhouses were quick to respond about the potential impact.

Taiwan, home of the world’s largest chipmaker TSMC, said that the company would be exempt from the tariff due to its existing investments in the US.

“Because Taiwan’s main exporter is TSMC, which has factories in the United States, TSMC is exempt,” National Development Council chief Liu Chin-ching told the Taiwanese legislature.

In March, TSMC – which counts Apple and Nvidia as clients – said it would increase its US investment to $165bn to expand chip making and research centres in Arizona.

South Korea was also quick to extinguish any concerns about its top chipmakers, Samsung and SK Hynix, which have also invested in facilities in Texas and Indiana.

Trade envoy Yeo Han-koo said South Korean companies would be exempt from the tariff and that Seoul already faced “favourable” tariffs after signing a trade deal with Washington earlier this year.

TSMC, Samsung and SK Hynix are just some of the foreign tech companies that have invested in the US since 2022, when then-President Joe Biden signed the bipartisan CHIPS Act offering billions of dollars in subsidies and tax credits to re-shore investment and manufacturing.

Less lucky is the Philippines, said Dan Lachica, president of Semiconductor and Electronics Industries in the Philippines Foundation.

He said the tariffs will be “devastating” because semiconductors make up 70 percent of the Philippines’ exports.

Trump’s latest round of blanket tariffs on US trade partners is due to go into effect on Thursday, but the White House has also targeted specific industries like steel, aluminium, automobiles and pharmaceuticals with separate tariffs.

The metal has gained nearly 30% this year due to expectations of rate cuts and diversification from US dollar assets.

Gold held a moderate loss, as traders looked past uncertainty created by US President Donald Trump’s latest trade moves, including threatening a 100% tariff on chip imports.

Bullion was steady around $3,370 an ounce after a 0.3% decline in the previous session. This came after Trump said he would impose a 100% levy on semiconductor imports in a bid to force companies to move production back to the US.

Meanwhile, relations with key trade partners soured, with the US leader doubling the tariff on Indian goods to 50% over the South Asian country’s continued purchases of energy from Russia. Japan may also face higher duties than agreed last month on some products, Kyodo reported.

Traders also watched for Trump’s nomination within days of a temporary Federal Reserve governor who is expected to be more aligned with his agenda to ease monetary policy. Lower rates benefit gold, which doesn’t yield interest.

The precious metal’s recent rally has been driven by rising expectation of rate cuts. Central bank buying and a broad trend of diversifying away from US dollar-denominated assets have also offered support. It’s climbed nearly 30% this year, though the bulk of its gains happened in the first four months, as geopolitical and trade tensions rattled the market.

Gold was 0.1% higher at $3,373.45 an ounce as of 8:42 a.m. in Singapore. The Bloomberg Dollar Spot Index was steady. Silver, palladium and platinum all rose.

Stay updated with US News covering politics, crime, weather, local events, and sports highlights. Get the latest on Donald Trump and American politics also realtime updates on Indonesia ferry fire.

Stay updated with US News covering politics, crime, weather, local events, and sports highlights. Get the latest on Donald Trump and American politics also realtime updates on Indonesia ferry fire.

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At the end of 2024, BBVA launched the Analytics Transformation unit, which houses the functions of advanced analytics and business analytics to accelerate the bank’s transformation to a data-driven organization. This unit includes the more than 1,000 data scientists responsible for designing and executing the AI models and algorithms the bank uses in both its internal operations and in products and services for clients. The more than 2,500 data specialists who help enhance the value of data and AI from the business areas are also part of this unit.

With the aim of making the most of these professionals’ technical knowledge, BBVA is offering them a professional development model that allows them to continue advancing in their careers from the early stages of their careers. They can choose a traditional management role leading teams (manager) or a path of advanced specialization as an expert or individual contributor (IC), which allows them to continue developing advanced AI solutions.

“Many of our professionals stand out for their command of emerging technologies and technical knowledge, which are of great value to the bank’s technological projects. However, traditional career advancement usually leads to management roles, which means that this valuable technical contribution gets lost along the way,” explained Cayetano Gea-Carrasco, Head of Analytics Transformation at BBVA. “With our professional development model for these profiles, we want to recognize and empower technical leadership as a career path parallel to management.”

Within the IC itinerary, BBVA has established three levels of specialization:

• Data Scientist Expert: internal professionals who are leaders using advanced algorithms to solve complex business challenges.
• Data Scientist Senior Expert: experts with a focus on areas like natural language processing, graphs or recommendation systems, actively participating in publications and training programs.
• Data Scientist Master Expert: highly specialized profiles with a key role in innovation, global technical standards and research initiatives.

These experts also belong to a community of practice that encourages knowledge sharing and continuous learning through mentoring, intensive technological training programs (bootcamps) and informal meetings (meetups). Each IC profile also has a personalized development plan, which includes advanced training and participation in strategic projects.

With this model, BBVA is creating an environment where technical knowledge is not only valued – it is also a real path to leadership and professional development.