(Vienna, 12 August 2026) For more than 70 years, the drug 6-thioguanine (6-TG) has been used to treat leukemia. Although its clinical effects have been studied extensively, scientists are still uncovering the molecular mechanisms that determine whether cells succumb to the drug or survive its attack.

Now, researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, together with collaborators at the University of Oxford, the Weizmann Institute of Science and the University of Dundee, have identified an unexpected player in this process: the protein NUDT5.

The discovery builds directly on a recent breakthrough from the Kubicek and Huber laboratories (Science, 2025). In that work, researchers showed that NUDT5 performs a critical cellular function independently of its enzymatic activity. Instead of acting primarily as a catalyst, NUDT5 was found to serve as a molecular scaffold that helps organize cellular metabolism. This unusual behavior has direct consequences for the action of the important cancer drug.

“We initially expected that NUDT5 would influence 6-TG through its enzymatic activity,” says co-first author Tuan-Anh Nguyen from CeMM. “Instead, we found that inhibiting the enzyme had little effect. What mattered was whether the protein itself was present.”

When inhibition is not enough

Most drugs that target enzymes work by blocking their catalytic activity. To investigate whether this was also true for NUDT5, the researchers turned to an emerging technology known as targeted protein degradation. Rather than inhibiting a protein, this approach removes it entirely from the cell.

“We developed a cell-based platform to accelerate the discovery of NUDT5 degraders. This platform helped guide the medicinal chemistry efforts that ultimately produced dNUDT5, our most active degrader.”, said Anne-Sophie Marques, a first author of the paper whose work at Oxford contributed to the findings.

In a dedicated medicinal chemistry effort led by the Huber laboratory at the University of Oxford, the team designed, synthesised and optimised a NUDT5 degrader toolkit: highly selective molecules that remove NUDT5 from cells, together with matched control compounds that bind NUDT5 but do not trigger its degradation, and compared their effects with conventional NUDT5 inhibitors. The outcome was striking: while inhibition of NUDT5 failed to alter cellular responses to 6-TG, degradation of the protein itself protected cells from the drug’s toxic effects. Genetic experiments produced the same result.

“Chemical degraders give us a way to separate what a protein does as an enzyme from what it does as a physical presence in the cell,” says Professor Kilian Huber, Centre for Medicines Discovery at the University of Oxford and co-corresponding author of the study. “In this case, that distinction was decisive: removing NUDT5 revealed biology that conventional inhibitors missed.”

These findings revealed that NUDT5 influences thiopurine sensitivity through a non-enzymatic mechanism – one that cannot be detected by studying catalytic activity alone.

“As the results came in, it became immediately clear that the dNUDT5 was protecting cells from 6-thioguanine toxicity in a dose-dependent manner. That was an incredibly exciting moment.” said Ludwig Bauer, a first author of the paper.

An unexpected counterpart

The work also uncovered a surprising relationship between NUDT5 and NUDT15, another protein already known to influence patient responses to thiopurine drugs.

Whereas loss of NUDT15 increases sensitivity to 6-TG, depletion of NUDT5 has the opposite effect, making cells more resistant to treatment. The results suggest that the two proteins operate through distinct and, in some respects, opposing mechanisms.

“Our results show that proteins can have important biological functions that are completely independent of their enzymatic activity,” says corresponding author Stefan Kubicek, Principal Investigator at CeMM. “By removing NUDT5 rather than simply inhibiting it, we were able to uncover a hidden layer of biology that helps determine how cells respond to a clinically important drug.”

Although the findings do not immediately point to a new therapy, they reveal an unexpected mechanism that influences the activity of a widely used leukemia drug. By showing that NUDT5 affects 6-TG response through a non-catalytic function, the study opens new avenues for understanding why patients respond differently to thiopurine treatment and demonstrates the unique power of targeted protein degradation to uncover hidden biological functions.

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The Study “Targeted Protein Degradation of NUDT5 Dissociates Catalytic Inhibition from Protein Loss in 6-Thioguanine Response” was published as a pre-print in Nature Communications on 30 June 2026, the final peer-reviewed version was published on 12 August, 2026. DOI: 10.1038/s41467-026-74489-9

Authors: Anne-Sophie M. C. Marques, Ludwig G. Bauer, Tuan-Anh Nguyen, Alejandro Gonzalez Orta, Jan-Lennart Venne, Carol Cheng, Esra Balıkçı, Yusi Liu, Barr Tivon, Alena Kroupova, Alessio Ciulli, Nir London, Stefan Kubicek & Kilian V. M. Huber.

Funding: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, the Austrian Science Fund (FWF), the Vienna Science and Technology Fund (WWTF), the Marie Skłodowska-Curie Actions Postdoctoral Fellowships programme, the Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU), the Wellcome Trust, Merck Sharp & Dohme Corp. and Janssen Pharmaceutica NV.

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The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is an international, independent and interdisciplinary research institution for molecular medicine under the scientific direction of Maria Rescigno. CeMM is oriented towards medical needs and integrates basic research and clinical expertise to develop innovative diagnostic and therapeutic approaches for precision medicine. Research focuses on cancer, inflammation, metabolic and immune disorders, rare diseases and aging. The institute’s research building is located on the campus of the Medical University and the Vienna General Hospital.

www.cemm.at

We use artificial intelligence (AI) tools for proofreading and translation purposes. All AI-generated output is reviewed and edited by humans before publication.

For further information please contact:

Wolfgang Däuble
Media Relations Manager / Science Writer
Phone +43-1/40160-70092
wdaeuble@cemm.at
 

CeMM
Research Center for Molecular Medicine
of the Austrian Academy of Sciences
Lazarettgasse 14, AKH BT 25.3
1090 Vienna, Austria
www.cemm.at

Journal

Nature Communications

DOI

10.1038/s41467-026-74489-9

With over 450 active clinical trials involving 8,700 participants, Ochsner has solidified its position as a regional leader in medical research innovation. Among these, 181 trials focus specifically on oncology, reflecting a robust effort to develop novel therapeutic interventions for cancer patients. Integral to this network is Ochsner’s strategic clinical integration with UT MD Anderson Cancer Center, providing access to state-of-the-art treatments and early-phase clinical trials across eight cancer centers in South Louisiana. This partnership amplifies the reach of personalized medicine approaches that are transforming cancer care paradigms through genomic sequencing, biomarker identification, and targeted therapy development.

The Alton Ochsner Award Relating Smoking and Disease lectures, a distinguished element of Research Week, honored pioneering studies that delve into tobacco-related pathologies. Award recipients, Dr. Robin Mermelstein and Dr. Li-Shiun Chin, have contributed significant advancements in understanding nicotine dependence and cessation methodologies. Their research underscores the vital interface between behavioral science and molecular medicine, exemplifying how translational research can directly influence public health policies and smoking-related disease prevention strategies.

Dr. Leonardo Seoane, Ochsner’s executive vice president and chief academic officer, emphasized the historical and contemporary significance of research at the institution. Since its inception in 1942, Ochsner has embedded clinical investigation within its practice model, facilitating access to groundbreaking therapies throughout the Gulf South. Research Week serves as a platform to bridge academic inquiry with patient-centered care, advancing innovative treatments that resonate within the diverse communities it serves.

The event featured a diverse slate of presentations spanning graduate and medical students, residents, fellows, and seasoned researchers who brought insights from translational science, clinical therapeutics, pharmacy research, and health outcomes analysis. This multidisciplinary engagement highlights Ochsner’s commitment to fostering an academic ecosystem that nurtures emerging talent while advancing rigorous scientific inquiry across multiple domains.

Among the featured talks, Dr. Jonathan Mizrahi’s keynote presentation on colorectal cancer evolution shed light on the dynamic changes in tumor biology that influence treatment resistance and disease progression. By leveraging serial biopsies and circulating tumor DNA analyses, Dr. Mizrahi’s research aims to refine adaptive therapeutic strategies that respond to the molecular complexity of cancer over time, paving the way for more durable treatment responses.

Dr. Marc R. Matrana expanded on the transformative potential of precision oncology through next-generation sequencing technologies. His work elucidates how molecular profiling uncovers actionable mutations, enabling clinicians to tailor treatments that maximize efficacy while minimizing off-target effects. This approach represents the vanguard of personalized medicine, where genomic data drives therapeutic decision-making and clinical trial matching.

In the realm of gynecologic oncology, Dr. Katrina Wade highlighted antibody-drug conjugates (ADCs) as an emerging class of targeted therapies for ovarian, endometrial, and cervical cancers. ADCs combine the specificity of monoclonal antibodies with potent cytotoxic agents, offering a dual mechanism to selectively eradicate malignant cells while sparing healthy tissues. This modality exemplifies a paradigm shift towards more precise and less toxic oncologic treatments.

Historical perspectives were provided by Dr. Justin Barr, who traced scientific discovery’s evolution throughout the 19th and 20th centuries. His analysis underscored the persistent role of inquiry, skepticism, and evidence-based practices in shaping modern medicine. This reflective approach enriches the research discourse, reminding clinicians and scientists alike of the enduring principles that guide innovation.

The competitive scientific environment at Research Week was exemplified by the submission of 153 abstracts, with 20 selected for oral presentations and 96 featured in the poster session. This robust participation evidences the depth of Ochsner’s investigative pipeline and the vibrant culture of academic excellence promoting rigorous research methodologies.

Mentorship remains a cornerstone of Ochsner’s research framework, as demonstrated by awards honoring clinicians who have distinguished themselves in training the next generation of investigators. Recipients included Dr. Rohith Arcot, a urologic oncologist; Dr. Craig Sable, a pediatric cardiologist; and Dr. Lawrence Haber, a pediatric orthopedic surgeon. Their leadership ensures sustained scientific vitality and innovation within the institution.

The week’s concluding Research Day lecture series synthesized insights across the spectrum of Ochsner’s clinical and research expertise, reaffirming the institution’s mission to integrate discovery with patient care. This holistic approach not only accelerates translational science but also ensures that novel findings lead to tangible improvements in population health outcomes.

Looking forward, Ochsner Health continues to push boundaries in biomedical research, with a portfolio that spans oncology, precision medicine, pharmacy, health outcomes, and population health. By fostering collaboration and leveraging advanced technologies, Ochsner provides its patients with access to novel therapies that are often unavailable elsewhere in the region. This commitment positions the organization as a beacon of medical innovation, dedicated to improving lives across the Gulf South and beyond.

Subject of Research: Biomedical research and clinical trials in oncology, precision medicine, tobacco-related diseases, and health outcomes within an academic healthcare system.

Article Title: Ochsner Health’s 23rd Annual Research Week Highlights Innovative Clinical Trials and Precision Medicine Advances

News Publication Date: May 2026

Web References:
– https://research.ochsner.org/opportunities/research-week/
– https://research.ochsner.org/opportunities/research-awards/the-alton-ochsner-award-relating-smoking-and-disease/
– https://www.ochsner.org/services/cancer-care/cancer-services/
– https://www.ochsner.org/doctors/jonathan-mizrahi/
– https://www.ochsner.org/doctors/marc-matrana/
– https://www.ochsner.org/doctors/katrina-wade/
– https://www.ochsner.org/doctors/justin-barr-md/
– https://news.ochsner.org/news-releases/2025-alton-ochsner-award-for-smoking-cessation-research-winners-announced/
– https://www.ochsner.org/

Image Credits: Ochsner Health, Beth Burris

Keywords: Ochsner Health, clinical trials, biomedical research, precision medicine, oncology, antibody-drug conjugates, tobacco-related disease, Alton Ochsner Award, cancer evolution, next-generation sequencing, personalized medicine, translational research

Dr. Papagiannakopoulos’s research is pioneering in its examination of how cancer cells adapt metabolically to stressful environments, rewiring nutrient and energy utilization pathways to survive and evade immune destruction. His laboratory employs sophisticated genome editing tools and functional genetic screens in living models, an approach that allows precise dissection of the molecular drivers of tumor progression. This methodology is crucial in distinguishing which genetic aberrations are cancer’s true vulnerabilities, offering promising avenues for the development of targeted therapies.

What sets Dr. Papagiannakopoulos apart is his integrative focus that spans metabolism and immunology, fields traditionally studied in isolation. His work elucidates how metabolic rewiring in tumor cells not only supports survival but actively shapes the immune milieu within and beyond the tumor microenvironment. By understanding these dynamic interactions, his research opens the door to manipulating tumor metabolism and immune responses concurrently, a strategy that could revolutionize anti-cancer treatments.

A novel dimension of his research investigates the crosstalk between tumors and the nervous system. Dr. Papagiannakopoulos and his team explore how cancer cells influence brain and peripheral nerve functions to modulate tumor growth, metabolic pathways, and immune system behavior. These interactions have significant clinical implications as they contribute to the cachexia syndrome frequently observed in cancer patients—manifesting as fatigue, anorexia, and severe weight loss—and currently represent a major therapeutic challenge.

Dr. Papagiannakopoulos’s involvement in the InteroCANCEption project, backed by a prestigious Cancer Grand Challenges grant, aims to decode the mechanisms by which the nervous system senses and responds to cancer throughout the body. This systemic approach to cancer biology underscores the emerging paradigm that cancer should be understood not only as a cellular and genetic disease but also as a complex disorder modulated by whole-body physiological networks.

Commenting on the appointment, Salk Institute President Gerald Joyce highlighted Dr. Papagiannakopoulos’s talent for bridging fundamental cancer biology with innovative, interdisciplinary strategies. Joyce emphasized that this alignment with Salk’s culture of curiosity-driven research and collaboration exemplifies the Institute’s mission to pioneer foundational science with the potential to yield transformative clinical breakthroughs.

Dr. Papagiannakopoulos expressed enthusiasm about joining the Salk Institute, citing its unique environment where high-risk, high-reward science thrives. He underscored the significance of integrating his expertise with the existing strengths in cancer immunobiology, metabolism, and neurobiology at Salk, particularly collaboration opportunities with the NOMIS Center and neuroscientists focusing on how cancer intersects with systemic physiology.

Among his groundbreaking contributions, Dr. Papagiannakopoulos’s recent publications in Nature unveiled therapeutic potentials by targeting proteins involved in ferroptosis resistance and immune evasion in lung and pancreatic cancer models. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, represents an Achilles’ heel for certain tumors—disabling mechanisms that prevent ferroptosis can trigger cancer cell death. Similarly, inhibiting proteins that suppress anti-tumor immune responses unveils new immunotherapeutic strategies that could complement existing treatments, broadening the arsenal against aggressive cancers.

Dr. Papagiannakopoulos’s academic journey is distinguished by rigorous training, beginning with a Bachelor’s degree in Molecular Genetics from the University of Sussex, followed by a PhD in Molecular and Cellular Biology at the University of California, Santa Barbara. His postdoctoral work at MIT sharpened his expertise in genome engineering techniques and in vivo cancer modeling. Throughout his career, his innovative research has attracted significant funding from federal and philanthropic sources, including the National Institutes of Health and the American Cancer Society.

At the Salk Institute, Dr. Papagiannakopoulos aims to establish a multidisciplinary research program that emphasizes integrative cancer biology, emphasizing the complex interplay between genetic mutations, cellular metabolism, immune surveillance, and neural regulation. His work will further energize Salk’s Conquering Cancer Initiative, which coordinates researchers across diverse fields to develop innovative strategies targeting lethal cancers, with a focus on lung cancer among others.

Reuben Shaw, PhD, director of Salk’s NCI-Designated Cancer Center, praised Dr. Papagiannakopoulos’s rare blend of experimental prowess and biological insight. Shaw highlighted how his innovative use of in vivo genetic modeling combined with deep knowledge of tumor metabolism and immune responses, along with a novel focus on cancer’s brain-body interactions, will greatly enhance the Center’s mission to identify new cancer vulnerabilities. Beyond research, Papagiannakopoulos is also recognized as a dedicated mentor, poised to inspire the next generation of cancer scientists at Salk.

This appointment signals a bold expansion of Salk’s cancer research capabilities, poised to unravel the multifaceted nature of cancer biology. By converging metabolism, immunology, and neurobiology, Dr. Papagiannakopoulos’s interdisciplinary vision promises not only to accelerate basic scientific understanding but also to accelerate the translation of discoveries into novel, effective therapies, potentially transforming cancer treatment paradigms.

The Salk Institute itself, founded in 1960 by Jonas Salk—the developer of the first safe polio vaccine—continues its mission of pioneering foundational and high-impact biological research. Its commitment to risk-taking, curiosity-driven science remains a beacon for innovation, addressing some of society’s most urgent health challenges, including cancer. Dr. Papagiannakopoulos’s recruitment exemplifies the Institute’s ongoing leadership in marrying foundational science with translational prospects that can change medicine globally.

As Dr. Papagiannakopoulos embarks on this next chapter at Salk, the scientific community eagerly anticipates the groundbreaking discoveries that will emerge from his integrative and visionary approach to cancer biology. These efforts not only deepen our molecular understanding of cancer but also pave pathways toward innovative therapeutic interventions that may one day cure or effectively manage certain cancers that currently pose formidable clinical challenges.

Subject of Research: Cancer biology, tumor metabolism, cancer immunology, tumor-host interactions, cancer neuroscience

Article Title: Salk Institute Welcomes Dr. Thales Papagiannakopoulos to Advance Cancer Research Frontier

News Publication Date: April 2, 2026

Web References:

• Salk Institute: www.salk.edu
• InteroCANCEption Project: Cancer Grand Challenges

References:

• Papagiannakopoulos et al., Nature, recent studies on ferroptosis and anti-tumor immunity (specific citations not provided in source text)

Image Credits: Sim Singh

Keywords: Cancer metabolism, immunology, tumor microenvironment, ferroptosis, genome engineering, nervous system and cancer, tumor-host interactions, Salk Institute, lung cancer, pancreatic cancer, cancer neuroscience, cancer therapy

The groundbreaking study, spearheaded by Nakano, K., Oki, E., Yamazaki, M., and collaborators, meticulously captures the complex cellular state of residual cancer cells—those that survive initial therapeutic onslaught and drive tumor relapse. By leveraging cell line-derived organoids, small three-dimensional cellular cultures that simulate the structural and functional attributes of original tumors, the research uncovers vital mechanisms underpinning treatment resistance and tumor regeneration. This research fills a significant void, as current preclinical models inadequately emulate the dynamic adaptation and stemness of residual cells post-therapy, impeding the development of targeted interventions.

Organoids have surfaced as a transformative platform bridging the gap between two-dimensional cell cultures and in vivo tumor biology. Unlike traditional monolayer cultures, organoids sustain cellular heterogeneity and niche interactions, vital for modeling tumor behavior accurately. This study’s organoids retain not only the genetic makeup of the parental colorectal cancer cells but also exhibit robust self-renewal and differentiation capacities intrinsic to cancer stem cells. These properties are paramount in mirroring the persistent subpopulation responsible for disease recurrence, thus presenting a versatile and scalable model for exploring therapeutic vulnerabilities.

Central to the investigation was the application of neoadjuvant chemotherapy, a preoperative regimen designed to shrink tumors, followed by close analysis of the surviving cancer cell fractions. The organoid system encapsulated the so-called "regrowing state," a transitional phase wherein residual cells activate stemness programs to initiate tumor resurgence. Detailed molecular profiling revealed elevated expression of canonical stem cell markers and signaling pathways implicated in cell survival, proliferation, and metastasis. Such insights illuminate the adaptive reprogramming that equips these cells to endure recent cytotoxic stress.

Furthermore, the research delineated critical molecular circuits, including enhanced Wnt/β-catenin and Notch signaling, which are pivotal in maintaining the self-renewing population within the organoids. These pathways have long been implicated in the regulation of normal intestinal stem cells and colorectal carcinogenesis, and their activation in residual cells underscores a shared survival strategy exploited by cancerous tissues. By dissecting these signaling networks, the model paves the way for therapeutic interventions that selectively ablate stem-like cancer cells while sparing normal tissue.

One of the transformative aspects of this research is its potential to inform personalized medicine approaches. The organoid model, derived from specific colorectal cancer cell lines, can be tailored to represent patient-specific tumor genotypes and phenotypes. This capacity could allow oncologists to simulate neoadjuvant chemotherapy effects ex vivo, directly testing drug susceptibilities and resistance mechanisms, thus optimizing therapeutic regimens on an individual basis. Such predictive modeling heralds a new era of precision oncology focused on minimizing relapse rates and improving long-term survival.

The current preclinical tools, including xenograft models and conventional cell lines, have suffered from limited reproducibility and failure to capture the nuanced biology of residual disease. The cell line-derived organoid system addresses these gaps by maintaining a balance between experimental accessibility and biological relevance. It also facilitates high-throughput drug screening under conditions that closely mimic the post-chemotherapy tumor microenvironment. This innovation significantly accelerates the identification of candidate compounds targeting the regenerative potential of residual cancer cells.

Beyond therapeutic implications, the study raises fundamental questions about cancer dormancy and the microenvironmental cues that govern the switch from dormancy to active proliferation. The organoid platform enabled the researchers to observe dynamic changes in cellular phenotypes and gene expression profiles, suggesting that residual cells exist in a poised state capable of rapid adaptation. Understanding these transitions could unlock new strategies to prevent relapse by sustaining dormancy or forcing differentiation into less aggressive cell types.

In their comprehensive analysis, the authors also investigated epigenetic modifications accompanying the regrowing state. These changes influence chromatin remodeling and gene accessibility, enabling plasticity within the residual tumor cell population. The epigenetic landscape’s flexibility appears crucial for evading chemotherapy-induced apoptosis and might be exploited therapeutically through epigenetic drugs that disrupt cancer stem cell maintenance. This typifies the multi-layered control governing residual disease and underscores the importance of integrative molecular approaches.

The study importantly highlights the heterogeneity within the regrowing cell populations, emphasizing that not all residual cells share identical stem-like features. This heterogeneity has profound clinical implications, as it suggests a need for combinatorial therapies targeting multiple subpopulations simultaneously. The organoid model’s capacity to preserve this diversity offers a powerful experimental context to unravel intercellular interactions and resistance hierarchies in colorectal cancer.

Moreover, the technological advances demonstrated by Nakano and colleagues set a precedent for similar models in other cancer types. Given the universal challenge of residual disease across oncology, the conceptual framework and methodological blueprint could inform the development of organoid systems from various malignancies, facilitating a broader translational impact. Such cross-cancer applicability amplifies the significance of this work and positions it at the forefront of cancer research innovation.

Importantly, the researchers also addressed the potential limitations of their model. While organoids recapitulate many essential features of the tumor microenvironment, they inherently lack components such as immune cells and vasculature, which modulate therapy responses in vivo. Future iterations could incorporate co-culture systems or microfluidic platforms to enhance physiological relevance. Acknowledging these constraints reflects a balanced perspective and guides subsequent refinements aimed at bridging experimental models closer to clinical reality.

In summary, this cell line-derived organoid model with stem cell properties marks a significant stride forward in decoding the biology of residual colorectal cancer cells post-neoadjuvant chemotherapy. By faithfully capturing the regrowing state, the study provides a robust, versatile tool to dissect mechanisms of chemoresistance, trace tumor evolution, and identify novel therapeutic targets. The translational potential is immense, offering hope for strategies that effectively eradicate residual disease and reduce relapse rates in colorectal cancer patients.

As colorectal cancer continues to impose a heavy clinical burden globally, innovations like this reshape the landscape of cancer research and treatment. This integrative approach, combining advanced organoid technology with detailed molecular characterization, exemplifies the cutting-edge efforts needed to overcome persistent challenges in oncology. Future research building upon these findings will be instrumental in translating laboratory discoveries into tangible clinical benefits, ultimately improving patient outcomes and survival.

The path forged by Nakano, Oki, Yamazaki, and their team epitomizes the fusion of scientific rigor and clinical ambition. Their work not only advances our understanding of colorectal cancer biology but also serves as a clarion call for greater investment in sophisticated preclinical models that mirror the complexities of human cancers. The promise held by these organoid systems reaffirms the potential of personalized and precision medicine to transform cancer care in the coming decades.

Subject of Research: Colorectal cancer, residual cancer cells, neoadjuvant chemotherapy, organoid models with stem cell properties

Article Title: Colorectal cancer cell line-derived organoid model with stem cell properties captures the regrowing state of residual cancer cells after neoadjuvant chemotherapy

Article References:
Nakano, K., Oki, E., Yamazaki, M. et al. Colorectal cancer cell line-derived organoid model with stem cell properties captures the regrowing state of residual cancer cells after neoadjuvant chemotherapy. Cell Death Discov. 11, 282 (2025). https://doi.org/10.1038/s41420-025-02567-w

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41420-025-02567-w