A new review from the Icahn School of Medicine at Mount Sinai and the Hospital Clínic de Barcelona provides one of the clearest roadmaps to date for understanding and treating liver cancer, one of the deadliest cancers worldwide. Published in Cell, the study, “Hallmarks of Liver Cancer: Therapeutic Implications”, applies the widely used “Hallmarks of Cancer” framework to liver tumors, linking the biology of the disease to treatment strategies, including immunotherapy and precision medicine approaches, particularly in the approximately 45% of bile duct cancers that harbor targetable mutations.
The study was led by Josep M. Llovet, MD, Ph.D., Professor of Medicine at the Icahn School of Medicine (Liver Diseases) at Mount Sinai and Director of the Liver Cancer Program at the Mount Sinai Tisch Cancer Center; and Daniela Sia, Ph.D., Associate Professor of Medicine (Liver Diseases) at the Icahn School of Medicine.
Marking the 25th anniversary of the groundbreaking “Hallmarks of Cancer” framework introduced by Douglas Hanahan, Ph.D. (Swiss Institute for Experimental Cancer Research), and Robert A. Weinberg, Ph.D. (Massachusetts Institute of Technology), the Mount Sinai-led team applies this influential model specifically to primary liver cancer, offering new insights into disease biology and treatment strategies.
As we age, our ability to maintain healthy blood and a strong immune system gradually declines, largely because hematopoietic stem cells (HSCs), the cells responsible for producing all blood cell types, begin to lose their effectiveness. Normally, HSCs can both self-renew and generate a balanced mix of blood cells, but over time they produce fewer new cells, favor certain cells such as myeloid cells over lymphoid cells, and struggle to support a robust immune response. Accumulated cellular damage, shifts in gene activity, ongoing low-level inflammation, and changes in the bone marrow environment, all appear to contribute to this decline. However, the precise mechanisms by which these diverse stresses converge to weaken HSCs have remained unclear.
Researchers from The University of Tokyo, Japan, and St. Jude Children’s Research Hospital, USA, sought to uncover a mechanism explaining how age-related stresses drive HSC functional deterioration, focusing on the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase like (MLKL) signaling axis—a pathway traditionally associated with necroptosis, or programmed cell death. The study was led by Dr. Masayuki Yamashita, an Assistant Member at St. Jude Children’s Research Hospital, who, at the time of the investigation, was an Assistant Professor at The Institute of Medical Science, The University of Tokyo. The other co-authors include Dr. Atsushi Iwama from The Institute of Medical Science, The University of Tokyo, and Dr. Yuta Yamada from St. Jude Children’s Research Hospital, who was a graduate student at The Institute of Medical Science, The University of Tokyo.
Explaining the motivation behind the study, Dr. Yamashita says, “We discovered an unexpected phenotype in HSCs of MLKL-knockout mice repeatedly treated with 5-fluorouracil, where aging-associated functional changes were markedly attenuated despite no detectable difference in HSC death, prompting us to investigate whether this pathway might induce functional changes beyond cell death.” This observation shifted the research focus toward a non-lethal role of MLKL—a concept later highlighted in their study, published in Volume 17 of the journal Nature Communications on April 6, 2026.
To investigate this, the team employed a combination of genetic mouse models, stress treatments, and functional assays. They used wild-type, MLKL-deficient, and RIPK3-deficient mice, along with specialized reporter mice capable of detecting MLKL activation through a Förster resonance energy transfer-based biosensor. Mice were exposed to stressors mimicking aging, including inflammation, replication stress, and oncogenic stress. HSC function was then assessed primarily through bone marrow transplantation, which measures the ability of stem cells to regenerate the blood system. Complementary analyses included flow cytometry, ex vivo expansion, RNA-seq, assay for transposase-accessible chromatin-seq, high-resolution microscopy, metabolic assays, and mitochondrial analyses, enabling a detailed understanding of how non-lethal MLKL activation impairs HSC function at molecular, cellular, and organelle levels.
Abstract: Nature Communications.
Non-necroptotic MLKL function damages mitochondria and promotes hematopoietic stem cell aging.
As a part of a study testing out a new type of implanted brain-computer interface (BCI), three rhesus monkeys controlled movements in a virtual reality (VR) world using only brain signals. The study, published in Science Advances, demonstrates a major step toward practical BCIs that can work outside of lab conditions.
BCIs allow direct communication between the brain and external devices, like a computer or robotic arm. This ability is thought to be extremely valuable for helping people suffering from paralysis to move objects, communicate or complete other tasks. However, there is a gap between lab-based BCI demonstrations and practical, flexible systems for real-world usage.
Previous research has explored intracortical BCIs—those implanted directly into the brain—in monkeys and humans, enabling them to control computer cursors, robotic or prosthetic arms and wheelchairs. Others have restored communication and the function of paralyzed limbs. However, real-world navigation requires adapting to unpredictable events and complex environments, which previous BCIs have struggled with, often requiring overt movement or only working in overly simple settings.
Thin films might not come up in conversation every day, but they are all around us. Take the metallic plastic films of chip bags, for example, or the anti-reflective coatings on eyeglasses. Even the coatings on pills that make them easier to swallow are thin films. Depositing extremely thin layers of materials in a consistent and uniform way is also crucial to the production of semiconductors, which are the foundation of modern electronics.
Not all materials can be easily deposited in such thin layers, such as materials with very high melting points. Now, Caltech researchers led by Austin Minnich, professor of mechanical engineering and applied physics, and deputy chair of the Division of Engineering and Applied Science, have demonstrated a laser-based method for generating thin films of materials, such as niobium. The work could directly impact superconducting electronics used in quantum computers.
The team recently described the work in a paper published in the journal Applied Physics Letters.
Now online! The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis: (Cell 188, 4567–4585.e1–e12; August 21, 2025)
Now online! (Cell 188, 4567–4585.e1–e12; August 21, 2025)
During post-publication review of our article, we, the authors, identified several errors in figure assembly and annotation affecting representative images and sample size reporting. These issues are limited to figure presentation and do not affect the underlying data, quantification, or conclusions of the study.
In Figure 2G, incorrect representative images were inadvertently used for the interferon-γ-OE and PSMB8-OE glutamate conditions. The correct images have now been inserted.
Two most common causes of dementia in older adults are Alzheimer disease dementia (ADD) and dementia with Lewy bodies (DLB).1,2 Differentiating between ADD and DLB in the clinical environment remains challenging with high rates of misdiagnosis using the current standard of care.2 Up to 50% of neuropathologically confirmed DLB, known as Lewy body disease (LBD), are correctly diagnosed antemortem, with ADD as the most common misdiagnosis.2,3 Distinguishing DLB from ADD is a vital part of patient care as DLB has a worse prognosis and requires different treatment plans compared with ADD.4 Patients with DLB are particularly sensitive to neuroleptics prescribed in dementia care, leading to worsening cognitive and motor functions.5 Further, new disease-modifying therapies are approved for ADD, but not for DLB.6,7
The National Institute on Aging and Alzheimer’s Association developed a research framework for Alzheimer disease (AD) classification using biomarkers such as amyloid, tau, and neurodegeneration.8 Amyloid positivity, as assessed using PET or biofluid assays (e.g., AB42/40, ptau217), is a core pathologic, distinguishing feature of AD. However, amyloid and Lewy body copathologies occur in over 50% of patients with LBD and can contribute to diagnostic uncertainty.2,9,10 In lieu of a DLB biomarker classification framework, current diagnostic criteria recommend combining indicative and supportive biomarkers to improve distinguishing between DLB and ADD. Indicative biomarkers include dopamine transporter scans (DaTscan), myocardial scintigraphy, and polysomnography. Supportive biomarkers are collected using MRI, PET, or SPECT scans, and EEG. Current MRI biomarkers in DLB leverage the relative sparing of the medial temporal lobe (MTL) to aid in differentiation.
If humans or animals eat something that causes them to feel unwell, they subsequently avoid this food source. Until now, it has been unclear precisely how this avoidance learning takes place. A new study shows that communication between the brain cells and fat cells could play a crucial role here. The participants from the Universities of Bonn and Tohoku (Japan) and University Hospital Bonn have revealed the previously unknown mechanism in the fruit fly Drosophila. It may also exist in a similar form in mammals and even in humans. The results have now been published in the journal Neuron.
Anyone who’s ever had an upset stomach after eating a bad meatball knows just how much this experience can put you off them. Within research, this is also known as “conditioned taste aversion”: The brain registers the immune response to the bacteria and their toxins and concludes from this that the food source should be avoided in the future.
It is not yet known how the immune system’s discovery of the pathogens leads to a change in behavior. “As this learned food avoidance can be found in all species, we investigated this question in a model organism – the fruit fly Drosophila,” explains Prof. Dr. Ilona Grunwald Kadow. “Within this model, we can clarify how the brain and body interact with each other to trigger an avoidance reaction that is vital for survival.”
As antimicrobial resistance continues to challenge traditional treatment protocols, bacteriophage therapy is emerging as a viable precision medicine alternative. Recent clinical developments demonstrate the potential of these virus-based interventions to target multi-drug resistant pathogens while preserving the host microbiome.
Growing antimicrobial resistance is prompting renewed interest in phage therapy, with preliminary data indicating improved outcomes when combined with standard antibiotics.