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CONCLUSION: Trajectories of total depressive symptoms marked by escalation, instability, or sustained elevation exhibited significantly elevated stroke risk. In contrast, individuals displaying decreasing depressive symptoms exhibit stroke risk comparable to those maintaining consistently low levels. Specifically, an ascending trajectory of cognitive-affective symptoms, alongside unstable and persistently elevated trajectories of somatic symptoms, are linked to increased stroke risk. These...

CONCLUSION: This study provides the first integrative single-cell transcriptomic map of microglial-myeloid interactions after TBI across multiple tissues and time points, linking microglial signaling to mitochondrial dysfunction and neuroinflammation. These findings lay the foundation for therapeutic strategies targeting myeloid-driven immune regulation in TBI.

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are among the most significant health challenges of aging, characterized by progressive cognitive and motor decline. Increasing evidence suggests that these conditions are not inevitable outcomes of aging but may instead be driven by preventable mechanisms involving oxidative stress, chronic inflammation, and disruptions in homeostasis. This manuscript proposes a preventive framework that integrates...

Neuronal aging and neurodegenerative diseases are accompanied by proteostasis collapse, while the cellular factors that trigger it have not been identified. Impaired mitochondrial transport in the axon is another feature of aging and neurodegenerative diseases. Using Drosophila, we found that genetic depletion of axonal mitochondria causes dysregulation of protein degradation. Axons with mitochondrial depletion showed abnormal protein accumulation and autophagic defects. Lowering neuronal ATP...

A Science analysis reveals how many were fired, retired, or quit across 14 agencies

Light pollution from green hydrogen plant would have threatened world’s largest telescopes

Branches sharpened 400,000 years ago shine light on humans’ early toolmaking

Waves of molten rock could be confounding observations of atmospheres on distant planets

Deep beneath the South Pole, two seismometers will monitor the planet’s interior and the movement of Antarctic ice

Although upregulation of toll-like receptor 2 (TLR2) excessively activates pro-inflammatory microglia through Aβ peptides, it remains unclear whether TLR2 regulates neuronal pyroptosis via the NF-κB/NLRP3 pathway in Alzheimer's disease (AD). We assessed TLR2 expression in peripheral blood from clinical samples and employed SH-SY5Y cells for initial screening. AD pathology was simulated by Aβ(1-42) stimulation, and pathway regulatory relationships were dissected through TLR2 knockdown, NF-κB...

White matter degeneration in aging drives cognitive and motor decline. Oligodendrocytes (OLs) and their precursors are central to this process. Their intrinsic aging, marked by differentiation failure, metabolic and mitochondrial deficits, and transcriptional epigenetic dysregulation, causes myelin thinning and axonal support loss. Degeneration is amplified by dysfunctional crosstalk: microglia clear debris poorly and turn inflammatory; astrocytes disrupt lipid balance and secrete inflammatory...

Lysosomes are responsible for clearing cellular waste and facilitating material recycling, thus playing a crucial role in maintaining cellular homeostasis and even in resisting the development of various diseases. Lysosomes are highly dynamic organelles. While typically exhibiting a vesicular morphology, lysosomes can remodel into tubular structures under specific conditions; this morphological plasticity underpins their functional complexity. Aging triggers significant lysosomal morphological...