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  • Breakthrough study questions longstanding STING activation approach

    Breakthrough study questions longstanding STING activation approach

    Researchers have long focused on the STING (Stimulator of Interferon Genes) pathway as a way to harness the immune system’s natural defenses against cancer. This pathway, which plays a key role in helping the body defend against potential pathogens, can be leveraged to trigger an innate immune response that targets cancer cells. However, a study published July 3 in the journal Nature Chemical Biology, led by biochemist Lingyin Li (Bluesky: @lingyinli.bsky.social), is spearheading a new school of thought.

    Historically, research on STING has overwhelmingly focused on activating the pathway to recruit immune cells that attack tumors. However, inhibiting the pathway is understudied and mounting evidence suggests that overactivation of STING may turn the immune system against healthy cells. This dual nature of activation and inhibition of STING make the pathway a powerful but complex target for drug development – one that has yet to be viable in humans.

    “Our study evaluated the effectiveness of H-151, the most advanced inhibitor of human STING, which has shown promise in reversing cognitive decline in mice but has failed to block human STING signaling in purified human blood cells,” said senior author Li, an Arc Institute Core Investigator and professor in the Biochemistry Department and ChEM-H Institute at Stanford University. “Our results show that in humans the target site of H-151 lacks a pocket that is found in mouse STING – without it, drug tailoring is incredibly challenging.” 

    H-151 is a powerful STING inhibitor because once it binds to its target, it does not let go. It also targets a section of the STING pathway that is necessary for mouse STING signalling, but not humans. This fundamental mechanistic difference explains the discrepancies in inhibitor effectiveness between the two species, highlighting the limitations of using mouse models to predict human outcomes in STING-targeted therapy development. 

    To circumvent this mismatch, Li’s team rigorously dissected the essential steps required for human STING signalling. The team found that oligomerization,the process where STING molecules assemble to trigger immune signaling, is an essential checkpoint prior to activation. Drawing inspiration from STING’s natural autoinhibitory mechanism, Li’s team proposed targeting STING by directly preventing oligomerization and developed a proof-of-concept molecule that mimics this mechanism and prevents STING from forming the large complexes necessary for immune activation in humans.

    “This work emphasizes the need to focus on developing STING inhibitors exclusively in humans,” says Xujun Cao, one of the first authors on the paper and a postdoctoral fellow in the Li Lab. “Our method for uncovering this distinct druggable pocket provides a blueprint for others seeking to identify context-independent targets that can prevent STING autoimmunity.” 

    “For STING to function, it needs to oligomerize flawlessly,” says Rebecca Chan, the paper’s other first author, a former graduate student in the Li Lab. “This discovery reveals why STING activation has such a high threshold-if it were easy to activate, our immune system would be attacking our own cells all the time. It’s an exquisitely controlled process, which is actually a good thing.“

    Looking ahead,the Li lab will explore whether this understanding of STING inhibition could expand treatment possibilities beyond cancer immunotherapy. Their research will focus on potential applications for neurodegeneration and autoimmune diseases, while simultaneously advancing the development of promising molecular candidates as human-ready STING inhibitors for future clinical trials.

    Source:

    Journal reference:

    Chan, R., et al. (2025). Cysteine allostery and autoinhibition govern human STING oligomer functionality. Nature Chemical Biology. doi.org/10.1038/s41589-025-01951-y.

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  • Quality of life, insomnia, attitudes and beliefs in women undergoing chemotherapy for breast cancer: a cross-sectional study in Amol city Northern Iran | BMC Women’s Health

    Quality of life, insomnia, attitudes and beliefs in women undergoing chemotherapy for breast cancer: a cross-sectional study in Amol city Northern Iran | BMC Women’s Health

    Study design

    The researchers conducted a cross-sectional, descriptive correlational study to investigate factors affecting women undergoing chemotherapy for breast cancer. This type of study design was chosen to capture information of the variables of interest and to determine relationships among them without manipulating any variables.

    Study setting and population

    The study was carried out among women undergoing chemotherapy for breast cancer referred to selected hospitals and outpatient oncology clinics located at the Arian Clinic, in Amol city, Mazandaran Province, northern Iran. These healthcare centers were selected based on their patient volume and accessibility to ensure a representative sample of the regional population. Data collection was conducted over a six-month period, from July to December 2024.

    Inclusion criteria

    Participants were selected based on the following inclusion criteria: (i) female patients aged 18 years and older, (ii) histologically confirmed non-metastatic breast cancer (Stages I–III), (iii) patients who were either currently receiving or scheduled to receive chemotherapy treatment, (iv) provided informed consent for participation in the study.

    Exclusion criteria

    Patients were excluded from the study if they met any of the following conditions: i: presence of significant psychiatric disorders (such as major depression, bipolar disorder, or schizophrenia), ii) diagnosis of non-cancer-related chronic conditions that could independently affect the study outcomes (e.g., severe anemia, chronic pain syndromes), iii) concurrent use of medications known to impact sleep or psychological well-being, such as sedatives, antipsychotics, or stimulants, iv) employment involving night-shift work, as such work schedules can independently disrupt circadian rhythms and sleep patterns, thus confounding the study findings.

    Sampling technique and sample size

    This study included 468 women with breast cancer undergoing chemotherapy, recruited through convenience sampling due to feasibility constraints in a single-center setting and to maximize participation during treatment visits. The required sample size was calculated using G*Power software version 3.1.9.7, based on a two-tailed test, an alpha of 0.05, a power of 0.90, and a correlation coefficient of 0.16 from a previous study [16]. The minimum sample size was determined to be 406. To account for potential dropouts or incomplete data, a 15% increase was applied, resulting in a final target of 467 participants.

    Research instruments

    The data collected included demographic information (age, marital status, occupation, place of residence, education level, economic status, family history of illness, and duration of cancer), quality of life according to the EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer), insomnia according to the Insomnia Severity Index Questionnaire (ISI), and patients’ attitudes and beliefs according to the Cancer Attitude and Belief Questionnaire.

    EORTC QLQ-C30

    The quality of life (QoL) of women undergoing chemotherapy for breast cancer was evaluated via the EORTC QLQ-C30 (version 3), which consists of 30 items across three subscales: global health status/QoL; functional scales (covering physical, role, cognitive, emotional, and social aspects); and symptom scales (covering fatigue, pain, nausea/vomiting, insomnia, etc.) [17]. The global health/QoL assessment used a 7-point Likert scale, whereas the symptom and functional items used a 4-point scale. According to the EORTC standards [18], scores were also converted from 0 to 100 and interpreted so that higher functional/global scores denoted better outcomes and higher symptom ratings denoted greater burdens. Excellent reliability was demonstrated by the validated Persian adaptation [19, 20]. In this study, the reliability of this questionnaire was assessed via the calculation of Cronbach’s alpha coefficient and was reported as 0.88 for overall quality of life.

    Insomnia severity index questionnaire (ISI)

    The Insomnia Severity Index (ISI) was used to assess the level of insomnia. The ISI questionnaire contains seven items, which include difficulty in starting sleep and problems with staying asleep (waking up at night and waking up early in the morning), satisfaction with the current sleep pattern, and interference with daily functioning. The questionnaire helps to evaluate the severity of the damage attributed to the sleep problem and the degree of confusion or worry caused by the sleep problem and is estimated on a 5-point Likert scale (0 = never and 4 = very much). The total score (0–28) of this questionnaire was categorized as follows: 0–7 = clinically significant insomnia, 14–8 = below the clinical threshold, 21–15 = moderate clinical insomnia, and 28–22 = severe clinical insomnia [21]. The validated Persian-translated version of the ISI is highly valid and reliable [22, 23]. The present study’s internal consistency with this research tool was similarly good (α = 0.80).

    Cancer attitude and belief questionnaire

    The researchers assessed attitudes and beliefs toward cancer via the questionnaire developed by Cho et al., which consists of 12 items in three domains: (a) impossibility of recovery; (b) stereotypes; and (c) discrimination, each with four questions related to the impossibility of recovery, stereotypes, and discrimination. The data were collected via a Likert scale (1 = completely disagree, 2 = disagree, 3 = agree, and 4 = completely agree). After the scores of the questions were summed, a total score between 12 and 48 was obtained. The higher the participants’ scores for each dimension are than the mean values are, the more negative the attitude toward cancer and the greater the degree of stigma [24]. In a study by Shervin Badihian, the internal consistency of the questionnaire items in the study sample was satisfactory, with Cronbach’s alpha coefficients for the impossibility of recovery, stereotypes, and discrimination of 0.67, 0.38, and 0.66, respectively [25]. In the present study, the internal consistency of this research tool was similarly good: 0.70, 0.85, and 0.72.

    Data collection procedure

    After receiving a permission letter from the research committee and head of institution, the researcher collected samples from women undergoing chemotherapy for breast cancer as the research population. The researchers used a convenient sampling method to choose participants after informed consent was obtained from the research participants. Each participant was thoroughly informed about the study’s objectives and procedures, with clear assurances regarding the protection of their anonymity and the confidentiality of their data. Additionally, they were explicitly made aware that their participation was entirely voluntary and that they could withdraw from the study at any time without any negative consequences. Following this, self-administered questionnaires were distributed to a total of 468 participants. To facilitate data collection, three trained researchers were assigned to the task. These researchers underwent comprehensive training covering the study’s objectives, methodology, inclusion and exclusion criteria, and ethical considerations. Moreover, the training sessions included instructions on how to collect data from illiterate participants data collection and these researchers assisted illiterate participants in completing questionnaires.

    Statistical analysis

    The data were analyzed with IBM SPSS (Statistical Package for the Social Sciences) version 24 statistical software. Data normality was evaluated via kurtosis, skewness and Q-Q plots. Nonparametric tests (Gamma/Cramer’s) were used for skewed data. Descriptive statistics (frequency, percentage and mean) were used for demographic variables. Gamma and Cramer’s correlation coefficients were employed to determine the relationships between variables (insomnia, QoL, and attitudes/beliefs toward cancer). The rank logistic test was used to investigate the predictors of the variables. P values less than 0.05 were regarded as statistically significant.

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  • Litigation funders get a boost in budget bill drama, court wins – Reuters

    1. Litigation funders get a boost in budget bill drama, court wins  Reuters
    2. ‘Big Beautiful Bill’ Raises Threat of Default for Litigation Asset-Backed Securities  Bloomberg
    3. Insurance industry laments loss of TPLF tax, applauds 199a, as ‘Big Beautiful Bill’ progresses in House  The Insurer
    4. Axing Lit Funding Tax Bid Relieves Industry But Fears Remain  Law360
    5. Litigation finance tax, limits on contempt power dropped from Senate’s version of budget megabill  ABA Journal

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  • FDA Greenlights New Treatment for Advanced Blood Cancer

    FDA Greenlights New Treatment for Advanced Blood Cancer

    July 3, 2025 — A new treatment has received a quick federal nod for a common blood cancer, which could affect more than 36,000 people and result in around 12,000 deaths in the U.S. this year alone. 

    The drug, known as linvoseltamab but sold under the name Lynozyfic, is for adults with multiple myeloma whose cancer has returned or isn’t responding well to treatment, especially if they’ve already tried at least four other treatments. Lynozyfic is said to offer a flexible dosing plan tailored to each patient’s needs.

    In multiple myeloma, plasma cells (a type of white blood cell that makes antibodies against diseases) multiply abnormally, leading to too much of a protein called immunoglobulin in bones and blood that crowds out healthy blood cells in the bone marrow. This damages the bones and eventually multiple organs as the disease worsens and spreads. B-cell maturation antigen (BCMA) is a protein found in high levels on multiple myeloma cells that promotes their survival and growth, making the cancer more aggressive and difficult to treat. Despite undergoing three to four therapies, many patients see their cancer return, highlighting the need for new treatments, especially those targeting BCMA.

    Lynozyfic was approved after a study with 80 people who had multiple myeloma and had already tried at least four other treatments. About 70% of them got better with Lynozyfic. Of those people, about 9 out of 10 were still doing well after nine months, and about 7 out of 10 were still doing well after a year. Scientists watched the patients for about 13 months. 

    About 45% of patients receiving Lynozyfic had no measurable sign of cancer after treatment, according to a news release from Regeneron Pharmaceuticals, the drug’s maker.

    “The FDA approval of Lynozyfic is a welcome milestone. It provides appropriate multiple myeloma patients and their care teams with a novel patient-centric treatment option that includes a dosing schedule that can be adapted based on patient response,” said Diane Moran, interim CEO and senior vice president of strategic planning at the International Myeloma Foundation. 

    Lynozyfic works by connecting special immune cells called T cells to cancer cells in the blood (multiple myeloma cells). This helps the T cells find and kill the cancer cells that usually hide from the immune system. Lynozyfic can be given quickly. It could be an option for people who can’t get a similar but stronger treatment called CAR T therapy, which is harder to make and can have serious side effects.

    Lynozyfic is given through a drip into your vein. At first, people get three small doses that get bigger each time: 5 milligrams, 25 milligrams, and then 200 milligrams. After that, they get 200 milligrams once a week for 10 weeks, then once every two weeks. If they’re doing well at week 24 and have had at least 17 doses, they can switch to once every four weeks.

    The most common side effects are bone or muscle pain, feeling tired, headache, cough, shortness of breath, weakness, diarrhea, and feeling sick to your stomach.

    Some serious side effects can happen, like a very strong immune reaction, problems from the infusion, or nerve damage. Because of these risks, patients may need to stay in the hospital for 24 hours after their first two doses. Lynozyfic is only given through a special safety program to help keep people safe.

    Other warnings include a higher chance of infections, low blood cell counts, liver problems, and harm to fetuses. People need to use birth control during treatment and for three months after their last dose. Patients should not drive, use heavy machines, or do dangerous activities for 48 hours after each first dose or if they have new nerve problems like confusion, shaking, or numbness until they feel better.

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  • OxPhos System Evolution Explored, Indicating Links Between Mutations and Disease

    OxPhos System Evolution Explored, Indicating Links Between Mutations and Disease

    Credit: wir0man/Getty Images

    Mitochondria are known as the body’s “energy factories,” and their function is essential for life. Inside mitochondria, a set of complexes called the oxidative phosphorylation (OxPhos) system represents the main site of metabolic and energy integration in the cell and acts like a biochemical assembly line, transforming oxygen and nutrients into usable energy.

    Research headed by scientists at GENOXPHOS group at the Spanish National Centre for Cardiovascular Research (CNIC) and the Biomedical Research Networking Centre in the area of Frailty and Healthy Ageing (CIBERFES) has revealed how this system evolved over millions of years—from the first vertebrates to modern humans. For their study, the team developed a tool to detect mutations that may cause mitochondrial disease and suggest their results could lead to improved diagnosis.

    Headed by research lead José Antonio Enríquez, PhD, head of the CNIC Functional Genetics of the Oxidative Phosphorylation System (GENOXPHOS) group, working in collaboration with Fátima Sánchez-Cabo, PhD, head of the CNIC Computational Systems Biomedicine group, the team analyzed the interaction between the two types of DNA that encode OxPhos proteins: nuclear DNA, which is inherited from both parents, and mitochondrial DNA, which is inherited only from the mother.

    “Understanding this evolution helps explain why some genetic mutations cause rare but serious diseases that affect the OxPhos system,” said José Luis Cabrera Alarcón, PhD, who is first author of the team’s published paper in Cell Genomics, titled “Structural diversity and evolutionary constraints of oxidative phosphorylation.” In their paper, Cabrera, together with senior author Enríquez, and colleagues, concluded, “The integration of population genetics, structural biology, and evolutionary analysis provides a comprehensive view of how this essential metabolic system has evolved and adapted across different species while maintaining functional integrity.”

    The OxPhos system comprises five large protein complexes, including four that transport electrons and one, called ATP synthase, that produces ATP, the cell’s molecular “fuel,” Enríquez explained. “The oxidative phosphorylation (OxPhos) system is central to metabolism,” the authors wrote. “Respiratory complexes (RCs) comprise subunits originating from mitochondrial DNA (mtDNA) and nuclear DNA (nDNA), with 13 mtDNA-encoded and 77 nDNA-encoded subunits across the five complexes (CI–CV)…”

    Enríquez continued, “These complexes can work individually or in combination, depending on the cell’s energy needs. Together, they are made up of 103 proteins encoded by two different genomes: nuclear and mitochondrial. While nuclear DNA changes slowly over time and gains variation through genetic mixing during reproduction, mitochondrial DNA evolves much more rapidly but is passed only through the maternal line.”

    The proteins encoded by mitochondrial DNA form the core of the respiratory complexes, explained Cabrera, “so proper function depends on precise compatibility between the nuclear and mitochondrial components.”

    For their study, the team aimed to explore how genetic evolution and variability in the Ox-Phos system are integrated in what they term a functional and structural context, to help understand adaptive forces that have shaped “mitonuclear evolutionary dynamics,” and also to better understand how evolutionary strategies have diversified from vertebrates to current human populations “…according to the different RCs or interaction between autosomal, mtDNA, or X-linked genes…” To achieve this the team examined population variability in OxPhos genes from data in the 1000 Genome Project.

    An evolutionary analysis of the OxPhos system reveals the adaptive diversity of each respiratory complex, shaped by the interaction between proteins encoded by mitochondrial and nuclear DNA [CNIC]

    “To determine how many different OxPhos complexes an individual can assemble, we analyzed the extent of individual genetic diversity of the OxPhos system subunits in all the 2,504 individualized genotypes included in the 1000 Genomes Project, considering the alleles that differ by one or more amino acids,” the team explained.

    The team introduced a new tool, ConScore, a predictive index—which they described as “a conservation-based predictor of variant impact within OxPhos proteins”—that assesses the clinical relevance of mutations in the 103 OxPhos proteins. “ConScore is based on the evolutionary divergence of these proteins across vertebrates—including primates and other mammals—and complements human population genetic data,” explained Enríquez.

    Their results, the investigators commented, define a 3D map of the relative importance of all individual amino acid residues in RCs based on evolutionary and population information embedded in RC structures. “Integrating structural, functional, and genetic data, we highlight the significance of each OxPhos protein position, expanding insights into its role in speciation and disease,” they stated. The findings revealed “unexpected genetic intra-individual variability resulting from the heterozygosity of diploid genes, while diversity at the population level is generated by variability in mtDNA.”

    The resulting map, the team further noted “…can contribute to the understanding of the portion of human variability associated with an increased risk of diseases in which the OxPhos system plays a crucial role, such as cancer, neurodegenerative diseases, and mitochondrial diseases, and can provide insights into infertility and miscarriage and enhance our understanding of the mechanism of aging.”

    The authors maintain that ConScore provides a new framework for interpreting potentially pathogenic mutations, opening the door to improved diagnosis and treatment of mitochondrial diseases. Ultimately, the researchers conclude, this study not only advances our understanding of how human cells evolved but also brings us closer to new solutions for patients with rare genetic diseases.


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  • Playstation’s third-person shooter ‘Helldivers 2’ is coming to Xbox

    Playstation’s third-person shooter ‘Helldivers 2’ is coming to Xbox

    A day after reports surfaced of mass layoffs at Microsoft and its gaming division, Xbox, Sony-published video game Helldivers 2 announced it’s coming to Xbox next month.

    Where once game publishers kept their products exclusively available to their own gaming systems — e.g., Sony games on Playstation, Microsoft games on Xbox — that wall appears to be breaking down. Helldivers 2, one of the most popular games of 2024, will be available on Xbox Series X and S starting on August 26. The game premiered on PlayStation 5 and PC in February 2024 and was an instant smash, selling tens of millions of copies, according to IGN. Helldivers 2 still remains a favorite on Steam.

    Helldivers 2 is a cooperative, third-person shooter set in the 22nd century, with human soldiers battling hordes of aliens to save Super Earth. With crossplay enabled, Xbox, PC, and PS5 players will all be able to play Helldivers 2 together.

    Mashable Top Stories

    The news of Helldivers 2‘s Xbox launch is even more surprising considering it happens the same day Microsoft releases Gears of War: Reloaded on PlayStation 5, the first time the once Xbox-exclusive series debuts on PlayStation. Meanwhile, Xbox’s The Outer Worlds 2 arrives on PlayStation in October.

    Microsoft Gaming CEO Phil Spencer elaborated on his exclusivity (or, rather, non-exclusivity) plans earlier this year.

    “We are finding that our games shipping on multiple platforms is a good thing for Xbox,” Spencer told The Destin Channel podcast. “It makes Xbox stronger…give[s] our teams the time they need, for us to invest in platform, for us to invest in hardware. I think all of this is a part of what Xbox will be, going forward.”

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  • Michael Madsen, star of Reservoir Dogs, Kill Bill and Donnie Brasco, dies aged 67 | California

    Michael Madsen, star of Reservoir Dogs, Kill Bill and Donnie Brasco, dies aged 67 | California

    The actor Michael Madsen has died aged 67 at his home in Malibu, according to authorities and his representatives. No foul play is suspected, the sheriff’s department confirmed, after deputies responded to the Los Angeles county home following a call to the emergency services on Thursday morning.

    He was pronounced dead at 8.25am. In an email, Madsen’s manager, Ron Smith, confirmed his client had died from cardiac arrest.

    A statement from Smith and another manager, Susan Ferris, along with publicist Liz Rodriguez said:

    “In the last two years Michael Madsen has been doing some incredible work with independent film including upcoming feature films Resurrection Road, Concessions and Cookbook for Southern Housewives, and was really looking forward to this next chapter in his life.

    “Michael was also preparing to release a new book called Tears for My Father: Outlaw Thoughts and Poems, currently being edited. Michael Madsen was one of Hollywood’s most iconic actors, who will be missed by many.”

    Over a four-decade career, Madsen had won acclaim for his portrayals of often enigmatic and frequently wise-cracking tough guys in films including Kill Bill: Vol. 1, Reservoir Dogs, Thelma & Louise and Donnie Brasco.

    He also features in later Tarantino films including The Hateful Eight and Once Upon a Time in Hollywood. Other credits amongst the 346 listed in IMDb include The Doors, Free Willy, Species, Die Another Day, Sin City and Scary Movie 4.

    Madsen began his career in Chicago as part of the Steppenwolf Theatre company as as apprentice to John Malkovich before debuting on the big screen in 1983 sci-fi WarGames.

    Speaking to the Hollywood Reporter in 2018, Madsen spoke about his industry typecasting, calling fame “a two-edged sword. here are a lot of blessings but also a lot of heavy things that come with it. I think it has a lot to do with the characters I’ve played. I think I’ve been more believable than I should have been. I think people really fear me. They see me and go: ‘Holy shit, there’s that guy!’

    “But I’m not that guy. I’m just an actor. I’m a father, I’ve got seven children. I’m married, I’ve been married 20 years. When I’m not making a movie, I’m home, in pyjamas, watching The Rifleman on TV, hopefully with my 12-year-old making me a cheeseburger. I sure as hell had my rabble-rousing days, but sooner or later you have to get over that and move on.”

    The brother of the actor Virginia Madsen, he was married three times and had six children, one of whom pre-deceases him.

    More to follow …

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  • Neanderthal DNA may refute 65,000-year-old date for human occupation in Australia, but not all experts are convinced

    Neanderthal DNA may refute 65,000-year-old date for human occupation in Australia, but not all experts are convinced

    Humans did not arrive in Australia 65,000 years ago, and likely didn’t reach the land down under until around 50,000 years ago, a controversial new paper reports.

    The reasoning behind the finding is that modern humans didn’t mate with Neanderthals until around 50,000 years ago, but Indigenous Australians have a small percentage of Neanderthal DNA. So, the first Australians could not have arrived until after humans mated with Neanderthals.

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  • Oscar Piastri not expecting Silverstone fight to just be with Lando Norris as he predicts ‘interesting weekend’

    Oscar Piastri not expecting Silverstone fight to just be with Lando Norris as he predicts ‘interesting weekend’

    Oscar Piastri has predicted a potential multi-team battle at the British Grand Prix, with the Australian suggesting that it will not just be a fight between himself and McLaren team mate Lando Norris.

    A race-long scrap played out between the pair last time out in Austria, in which Norris fended off the challenge from Piastri to claim his third win of the season. Piastri, however, still leads the championship standings by a margin of 15 points.

    When asked if he was ready for another battle with Norris this weekend at his team mate’s home track, Piastri smiled: “Let’s wait and see. I think it’s going to be an interesting weekend – Silverstone always is. The weather’s always a factor and it looks like it will be again this weekend.

    “Let’s wait and see, I don’t think it will just be two McLarens this time. I think Mercedes will probably be quick, Red Bull honestly you never really know but they’ve been quick here in the past, Ferrari as well looked to be a little bit stronger in Austria, so let’s see.

    “It’s a track I always enjoy, and I’m expecting it to be a good fight with whoever it is.”

    A sequence has emerged during the campaign so far in which, whenever Norris has won a race, Piastri has proven victorious at the following Grand Prix.

    In terms of whether that might be on his mind during the weekend ahead, the 24-year-old answered: “I have found the same pattern as you, but there’s nothing conscious about it. I think it’s just been coincidence.

    “I always go into every weekend, just trying to do the best that I can. I felt like maybe in China there was a bit of extra motivation but more because of how painful Melbourne was, more than anything else.

    “I just go into every weekend trying to do my best, go in with the best state of mind that I can and I think I’m always learning things about myself, about how I need the car as well, and [I’m] learning lessons all the time.”

    And given the psychological element at play in the championship fight, Piastri was also quizzed on how important it would be to beat Norris at the Briton’s home track.

    “I don’t really think so,” the seven-time race winner said. “Every driver wants to win their home race, but at the end of the day it’s only worth the same amount of points as everywhere else. Monaco is kind of a similar feeling but, yes, would I love to win this weekend? Of course.

    “So let’s see what happens. It’s a track I enjoy, a track I’ve had good success at in the past, so hopefully can be a good weekend.”

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  • Lung cells generated from mouse embryonic fibroblasts in just 7 to 10 days

    Lung cells generated from mouse embryonic fibroblasts in just 7 to 10 days

    Researchers in Japan have successfully generated lung cells similar to alveolar epithelial type 2 (AT2) cells from mouse embryonic fibroblasts without using stem cell technology. The AT2-like cells were generated in just 7 to 10 days-a significant reduction compared to the approximately one month typically required by conventional stem cell-based differentiation methods.

    This approach may pave the way for treating serious respiratory diseases, such as interstitial pneumonia and chronic obstructive pulmonary disease, which currently lack effective treatments. The study was published in npj Regenerative Medicine.

    AT2 cells are essential for maintaining lung homeostasis. They produce surfactant and serve as progenitor cells for alveolar repair. In patients with severe lung diseases, such as interstitial pneumonia, these cells are often reduced in number or functionally impaired, which highlights the therapeutic potential of regenerating AT2 cells.

    The advent of the induced pluripotent stem cell (iPSC) technology in 2006 has enabled the generation of AT2 cells in approximately one month, but this method is costly and carries risks of tumor formation and immune rejection. To overcome these disadvantages, we focused on direct reprogramming instead. The direct reprogramming approach produces AT2-like cells in just 7 to 10 days, with lower tumor risk and potential for autologous use.”


    Professor Makoto Ishii of Nagoya University Graduate School of Medicine

    Professor Ishii and colleagues, including Professor Koichi Fukunaga, Assistant Professor Takanori Asakura, and Joint Researcher Atsuho Morita from Keio University School of Medicine, conducted a study to generate AT2-like cells from fibroblasts in mice through direct reprogramming, which had never been accomplished before.

    First, the researchers selected 14 candidate genes associated with lung development. Then, they investigated the expression levels of the AT2 cell marker, surfactant protein-C (Sftpc), to determine the gene combination with the highest reprogramming efficiency. They found that a combination of four genes-Nkx2-1, Foxa1, Foxa2, and Gata6-was the most effective for reprogramming AT2 cells.

    The four genes were introduced into a three-dimensional culture made from mouse embryonic fibroblasts that express green fluorescent protein (GFP) in response to Sftpc. As a result, approximately 4% of the cells became Sftpc/GFP-positive in 7 to 10 days, showing their success in inducing AT2-like cells, called induced pulmonary epithelial-like cells (iPULs).

    The researchers analyzed iPULs after isolating GFP-positive cells by flow cytometry. These purified iPULs exhibited lamellar body-like structures, which are organelles characteristic of normal AT2 cells. In addition, transcriptomic analysis revealed that their gene expression profiles were highly similar to those of native AT2 cells.

    Next, they transplanted purified iPULs into mouse lungs with interstitial pneumonia. Forty-two days later, the transplanted cells had successfully engrafted in the alveolar region. Notably, some of the cells had differentiated into alveolar epithelial type 1 (AT1)-like cells, which are essential for lung tissue regeneration.

    Ishii concluded: “In this study, we succeeded in direct reprogramming of fibroblasts into AT2-like cells in mice. We now aim to explore the application of this technology to human cells, with the ultimate goal of developing a safe regenerative therapy using a patient’s own fibroblasts.”

    This study was funded by JSPS KAKENHI Grant Numbers JP24K02113, JP24K23468, JP22KJ2672, JP21J21344, JP21H02926, JP19K17682, JP18K19566, JP18H02821, JP15K19945, and AMED Grant Numbers JP21bm0404053, JP23wm0325031, and JP24ym0126807.

    Source:

    Journal reference:

    Morita, A., et al. (2025). Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells. npj Regenerative Medicine. doi.org/10.1038/s41536-025-00411-4.

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