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New drugs take aim at one of cancer’s deadliest mutations
‘Net zero’ isn’t madness: the staggering economic costs of climate change
Scientists invented a fake disease. AI told people it was real
Your brain on drugs: different psychedelics work in surprisingly similar ways
When page-renumbering causes outrage
This method to reverse cellular ageing is about to be tested in humans
How DNA forensics is transforming studies of ancient manuscripts
Don’t rush use of lymphatic surgery in Alzheimer’s disease
Representation without power in science isn’t equity
AI and the human mind: only one is a black box
Department of Energy’s AI push squeezes funding for research grants
Tapping already strained budgets, Genesis Mission gives scientists just weeks to apply for first awards
Artemis II captures an ‘Earthset’ and stunning views of the Moon
First crewed Moon mission since 1972 caught extraordinary glimpses of lunar terrain
The hidden math behind satisfying can-crushing videos
Fluid-filled soda cans confirm a long-untested theory of pattern formation
As Japan warms, cherry blossom displays are fading
Some trees in southern Japan are already failing to reach peak bloom—a trend researchers predict will move north in the coming decades
Effects of high-load, velocity-intentional variable resistance training combined with creatine supplementation on neuroplasticity, oxidative stress, inflammation, physical function, cognitive performance and quality of life in older adults: A randomized,…
CONCLUSIONS: High-load, velocity-intentional resistance training-on land or in water-effectively improves neurocognition, oxidative balance, inflammation, strength, function, and quality of life in older adults. Aquatic training is particularly effective for attenuating oxidative stress and inflammation. Creatine supplementation confers complementary, modality-specific benefits and supports their use in combination to high-speed resistance exercise to promote healthy aging.
Non-necroptotic MLKL function damages mitochondria and promotes hematopoietic stem cell aging
Hematopoietic stem cells (HSCs) survive many types of cellular stress but often lose their regenerative and lymphopoietic capacities as a result. Such functional decline also occurs with age, and dysfunctional HSCs with impaired mitochondria accumulate during aging. However, the molecular link between HSC stress response and age-related functional decline remains poorly understood. Here we show that multiple stress responses converge on the RIPK3-MLKL axis to induce age-related changes in HSCs....
HCCaging: a liver physiological aging-related biomarker for hepatocellular carcinoma diagnosis based on transcriptome data
Aging is a fundamental biological process that influences cancer development in a context-dependent manner; however, how aging-related programs manifest in hepatocellular carcinoma (HCC) remains incompletely understood. Here, we systematically characterized aging-associated features in HCC by establishing a liver cancer-specific aging signature, termed HCCaging, across more than 2,000 tumor samples from 16 independent cohorts. We comprehensively evaluated its heterogeneity and associations with...
Genetic architecture of lumbar spinal stenosis
Lumbar spinal stenosis (LSS) affects over 100 million people globally, with an increasing incidence due to an ageing population. While LSS is known to be heritable, its genetic basis remains poorly understood. We conduct a genome-wide meta-analysis of LSS in 40,303 cases and 741,469 controls. We identify 73 previously unreported loci in addition to 15 known loci, and highlight spinal degeneration as a key pathogenic mechanism. In 12,784 surgically treated cases, we discover five loci...
ASO therapy rescues NOTCH2NLC GGC repeat expansion-induced genomic damage, 3D chromatin structural abnormalities, and senescence
Neuronal intranuclear inclusion disease is caused by abnormal GGC repeat expansion in the NOTCH2NLC gene, though its pathogenic mechanism remains incompletely understood. This study shows that the abnormally expanded polyG-uN2C protein, encoded by the repeat sequence, contains intrinsically disordered regions and forms aggregates, leading to mislocalization of nucleophosmin and downregulation of fibrillarin. PolyG aggregates interact with nucleophosmin and rRNA, disrupting ribosomal homeostasis....
The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer
The E3 ubiquitin ligase HUWE1 modifies a diverse network of substrate proteins by ubiquitination, through which it regulates various intracellular processes and contributes to both oncogenic and tumour suppressor mechanisms in different cancer contexts. Here, by analysing human lung adenocarcinoma (LUAD) patient samples, we reveal that HUWE1 protein expression is commonly upregulated in LUAD tumours compared to normal adjacent lung tissue and that this increase is associated with tumour stage....