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CONCLUSION: LLM-derived mobility functional status assessment was associated with ED visits and hospitalization, but not with all-cause mortality after adjustment. Prospective validation and evaluation of incremental discrimination, calibration, and clinical utility are needed before clinical implementation.

Scientists discovered a population of cells that can start the process of programmed cell death, survive it, and then help rapidly rebuild damaged tissue. Their descendants become far more resistant to future damage, revealing a mechanism that could improve healing but may also help cancers return after treatment.

No abstract

Alzheimer disease (AD) is defined biologically by the presence of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain; however, these pathologies do not affect all brain regions equally. Typical AD usually presents with memory impairment, whereas atypical forms of AD, including posterior cortical atrophy, logopenic variant primary progressive aphasia, behavioural and dysexecutive AD, and corticobasal syndrome, manifest with prominent non-memory symptoms. Aβ biomarkers usually...

The ability to initiate stepping promptly and accurately is critical for safe mobility in later life. Choice stepping reaction time (CSRT) is an independent predictor of recurrent falls in older adults and is often prolonged in dementia. Although the prefrontal cortex (PFC) is crucial for rapid response execution, existing studies primarily focus on regional activation, leaving the topological reorganization of prefrontal functional networks poorly understood. In this study, twenty-six healthy...

Alzheimer's disease (AD) biomarkers may be associated with decline in non-cognitive domains of intrinsic capacity (IC), but such evidence has not been synthesized. This narrative review, based on a structured PubMed search (last search: December 31, 2025), included 119 human studies examining associations of core AD biomarkers (e.g., amyloid-beta (Aβ) and tau protein) and biomarkers of non-specific processes involved in AD pathophysiology (including neurofilament light chain (NfL), glial...

CONCLUSION: Frailty in older adults with cancer is affected by multi-dimensional, complex determinants. Targeted screening and intervention strategies can be formulated upon identification of these factors to reduce frailty incidence and improve clinical prognosis.

Although women live longer, they paradoxically face heightened susceptibility to cognitive and systemic decline emerging in midlife-an underexplored transition from resilience to vulnerability. Here, we investigate biological processes associated with this female-biased vulnerability and their molecular regulation. Senescence-associated features were preferentially elevated in middle-aged females in human brain and spleen tissues, with similar changes in mice. In female mice, epigenetic...

Microglia, the brain's resident immune cells, rely on histone modifications and chromatin remodeling to sculpt their identity across the trajectory from development through aging. Recent studies have identified enhancer rewiring and metabolic-epigenetic coupling-exemplified by histone lactylation-as central drivers of microglial plasticity. Disruption of this regulatory balance drives the transition from homeostatic microglia toward disease-associated microglia (DAM) in Alzheimer's and...

APOE gene variants encoding the apolipoprotein E (ApoE) protein are strong genetic modifiers of risk of Alzheimer's disease (AD) with the APOE ε4 allele (APOE4) associated with substantially increased disease risk, APOE ε2 allele (APOE2) associated with decreased risk and APOE ε3 allele (APOE3) considered neutral. Recently the Christchurch variant of APOE3 (APOE3CH) has been shown to protect people from familial AD. Despite this strong evidence for APOE mediating AD risk, the exact biological...

Although women live longer, they paradoxically face heightened susceptibility to cognitive and systemic decline emerging in midlife-an underexplored transition from resilience to vulnerability. Here, we investigate biological processes associated with this female-biased vulnerability and their molecular regulation. Senescence-associated features were preferentially elevated in middle-aged females in human brain and spleen tissues, with similar changes in mice. In female mice, epigenetic...

Nuclear factor I (NFI) misexpressions in humans are associated with severe brain malformations, yet the underlying mechanisms remain poorly understood. Here, we show that NFIs regulate the broad lineage progression and lifespan of radial glial progenitors (RGPs), thereby bidirectionally controlling neocortical development. Human cerebral organoids carrying patient-mimicking NFI mutations exhibit expression-level-dependent bidirectional impairments in RGP temporal development, coinciding with...

Oligodendrocytes are a specialized class of glial cells responsible for myelination, which sustains central nervous system (CNS) function. Though long considered a passive and static cell, the oligodendrocyte is now recognized to actively support axonal energy demands through metabolic provision, modify neural signaling in response to environmental stimuli through adaptive myelination, and repair or regenerate myelin following injury. However, oligodendrocytes become dysfunctional in aging and...

Microglia, the brain's resident immune cells, rely on histone modifications and chromatin remodeling to sculpt their identity across the trajectory from development through aging. Recent studies have identified enhancer rewiring and metabolic-epigenetic coupling-exemplified by histone lactylation-as central drivers of microglial plasticity. Disruption of this regulatory balance drives the transition from homeostatic microglia toward disease-associated microglia (DAM) in Alzheimer's and...

Alzheimer's disease (AD) involves complex neuroimmune dysregulation, and the role of immune checkpoint pathways in regulating neuro-glial interactions and intrinsic glial homeostasis remains unclear. In AD, glial expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) is elevated in mouse models and human patients, suggesting involvement of immune checkpoint signaling in glial function. To define the role of this pathway in the AD brain, we locally modulated PD-1/PD-L1...

Insecticide resistance poses a major challenge to global pest management, yet its cascading effects on ecological networks remain poorly understood. Here, we show that target-site-resistant herbivorous insects can accumulate unmetabolized insecticides and inadvertently function as "toxic prey," impairing the fitness of their natural enemies. Using neonicotinoid- and spinosyn-resistant Myzus persicae and genetically modified Drosophila melanogaster, we demonstrate that resistant hosts surviving...

As the most popular hole-selective materials in efficient p-i-n perovskite solar cells (PSCs), self-assembled monolayers (SAMs) still remain great challenges in long-term stability due to their frail construction and week bonding. To form a toughened donor-acceptor interface, here, we adopt an amine-rich cross-linking templates for SAM layer growth. The enhanced Coulombic interaction between polymer amines and SAMs promotes the formation of SAM growth networks, resulting in reduced...

Naïve T cells maintain quiescence yet must respond rapidly to antigens, but how they prime this capacity is unclear. We identify histone variant H2A.Z as a key regulator of an epigenetic training program that licenses quiescent naïve CD8^(+) T cells for future activation. H2A.Z deficiency disrupts naïve T cell homeostasis and effector responses. Multiomics reveals that H2A.Z is selectively deposited at oxidative phosphorylation (OXPHOS) gene promoters in quiescent naïve CD8^(+) T cells, priming...

Oxidative stress, iron dyshomeostasis, and chronic neuroinflammation are the principal mechanisms involved in the progression of central nervous system (CNS) disorders, which are a significant source of death and chronic disability worldwide. This review focuses on understanding the mechanistic relationship between ferroptosis and neuroinflammation in central nervous system (CNS) disorders, which involves the molecular mechanisms, their role in the pathogenesis of the disease, and therapeutic...

Newer blood thinners may do more than prevent strokes in people with Alzheimer’s disease and atrial fibrillation. Researchers found that patients taking NOACs experienced a slower decline in cognitive function than those using warfarin or no blood thinners. The effect was modest each year but could add up over time.