Aggregator

Microglia are key players in Alzheimer's disease, but the transcriptional control of their phagocytic function remains unclear. Kim et al. show that mouse microglial Spi1 deletion worsens amyloid pathology by impairing Aβ clearance through Syk, Lyn, and Fcgr1, providing new insight into PU.1-dependent regulatory networks and microglial functions in neurodegeneration.

Increasing evidence indicates that shifts in brain polysaccharide metabolism can influence the progression of multiple neurodegenerative diseases. Here, we profile corpora amylacea (CA) in 230 postmortem human brains, revealing significantly higher densities in Alzheimer's disease (AD) patients when compared with patients with other or no neurodegenerative diseases and a tight correlation of CA density with neurofibrillary tangle (NFT) pathology. Immunohistochemical profiling using an...

Alzheimer's disease (AD) exhibits substantial clinical and pathological heterogeneity that is not fully explained by amyloid-β and tau pathology alone. TAR DNA-binding protein 43 (TDP-43) is increasingly recognized as a frequent copathology in AD, particularly in limbic regions, where its presence is associated with accelerated cognitive decline. Disruption of mitochondrial homeostasis is also an early and consistent feature of AD and contributes to neuronal vulnerability. In this review, we...

In recent decades, there has been active research into how ionizing radiation at low doses, an inevitable factor in human activity, affects aging processes and which molecular genetic mechanisms underlie this influence. This study investigates the effects of mutations in PIWI subfamily genes (piwi and aub), which regulate transposable elements, on the lifespan of Drosophila melanogaster under conditions of genome instability induced by hobo transposons and chronic low-intensity irradiation (20...

Progressive aging of bone marrow hematopoietic stem cells (HSCs) underlies clonal hematopoiesis and age-associated hematologic disorders. Defining early molecular events driving HSC functional decline is essential for rejuvenation strategies. Here, we identify P-selectin (Selp) as a surface marker that stratifies HSCs into conserved functional and transcriptional states during organismal aging in humans and mice. P-selectin expression increases early during aging and remains elevated in old...

We investigated how patients with Parkinson's disease (PD) manage the explore-exploit trade-off in a structured reward-learning task. Patients were tested either on (n = 34) or off (n = 34) dopaminergic medication (levodopa), with age-matched polyneuropathy patients serving as controls (n = 35). Behaviorally, patients off medication showed marked learning and decision-making deficits, characterized by overexploration (excessive sampling of novel options) and insufficient exploitation...

Lifestyle habits, cognitive reserve, and affective reserve (secure attachment, extraversion, psychological resilience) predict resilience in the oldest-old, though the underlying biological mechanisms remain unclear. This study explored relationships between these protective factors, 120 + NULISA CNS blood biomarkers, and multidimensional health outcomes (global cognition, mental health, walking speed) in 401 dementia-free participants (age 83-87) from the InveCe.Ab study. Using sparse partial...

CONCLUSION: These findings indicate that endurance training is associated with more favorable renal biomarker profiles in the context of chronic opioid exposure.

Robots increasingly share spaces with people, supporting delivery services and mobility for the aging populations, yet their ability to share space comfortably lacks understanding and benchmarks for designers and policy-makers. We compared human-robot (HRI) and human-human (HHI) interactions across four real-world crowd datasets spanning Europe, North America, and Asia, using a unified pipeline to detect interactions, stratify by crowd density, and model pedestrian behavior. Local motion...

Neutrophils are increasingly recognized as key orchestrators of the immunosuppressive tumor microenvironment, yet their intrinsic plasticity, short lifespan and resistance to genetic manipulation have impeded therapeutic targeting. Here, we report a non-pharmacological, biophysical immunomodulatory strategy based on cold atmospheric plasma (CAP) to reprogram tumor-associated neutrophils and restore antitumor immunity. We show that CAP simultaneously delivers reactive oxygen species and redox...

Stem-cell-based in vitro models offer promising potential to elucidate human brain cell functions and interactions, but limitations in reproducibility, maturation and cell-type diversity persist. Especially, prolonged incorporation of mature microglia and studies of neuroinflammation have proven challenging. Here, we developed a human induced pluripotent stem cell-based three-dimensional cortical brain tissue model (3BTM) containing neurons, astrocytes and microglia with high reproducibility,...

No abstract

Hypothesis generation in biomedicine is constrained by human cognitive limitations in synthesizing insights from fragmented biomedical knowledge and multimodal data sources. Here we introduce XunZi, an AI biologist that integrates logical reasoning and multimodal data fusion to autonomously generate de novo therapeutic target hypotheses with testable mechanisms. XunZi has been trained on 24.4 million publications and 613.6 TB of multisource data spanning 21,008 human genes and 5,850 diseases,...

No abstract