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Microglia modulate Abeta-dependent astrocyte reactivity in Alzheimer's disease
Experimental evidence suggests that activated microglia induce astrocyte reactivity in neurodegenerative disorders, such as Alzheimer's disease (AD). In this study, we investigated the association between microglial activation and amyloid-β (Aβ) with reactive astrogliosis in individuals across the AD spectrum. We examined 101 individuals using positron emission tomography radiotracers to assess Aβ deposition ([^(18)F]AZD4694), tau aggregation ([^(18)F]MK-6240) and microglial activation...
Age-related auditory nerve deficits propagate central gain throughout the auditory system: Associations with cortical microstructure and speech recognition
There is growing evidence that perceptual difficulties associated with age-related hearing loss are not solely due to cochlear damage and are exacerbated by central nervous system changes. We examined electrophysiological (EEG) responses to clicks and diffusion kurtosis imaging in 49 older (29 female) and 26 younger (20 female) adults to determine the extent to which auditory nerve (AN) deficits in older adults contributed to functional and structural changes throughout the auditory system....
Trilaciclib triggers a neutrophil-related immune response and sensitizes non-small cell lung cancer to anti-PD-1 therapy
Immunotherapy-based combination approaches have improved treatment efficacy in advanced non-small cell lung cancer (NSCLC), but progressive disease remains a challenge. Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor approved for myelopreservation in extensive-stage small cell lung cancer (ES-SCLC). Our results demonstrate that trilaciclib has antitumor potential in NSCLC without significant toxicity. It reprograms the tumor immune microenvironment by primarily increasing antitumor...
NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
No abstract
Gut microbiota composition and long-term physical activity in healthy older adults at high and low performance levels
Aging is associated with significant alterations in the composition of the gut microbiota, including decreased microbial diversity. These changes are accelerated by lifestyle factors, such as sedentary behavior, which tends to increase with age. Although the role of physical activity in preventing age-related functional decline has been widely recognized in recent years, its long-term influence at different intensity levels on gut microbial composition in older adults remains unclear. In this...
Scattering approach to diffusion quantifies axonal damage in brain injury
Early diagnosis and noninvasive monitoring of neurological disorders require sensitivity to elusive cellular-level alterations that occur much earlier than volumetric changes observable with the millimeter-resolution of medical imaging modalities. Morphological changes in axons, such as axonal varicosities or beadings, are observed in neurological disorders, as well as in development and aging. Here, we reveal the sensitivity of time-dependent diffusion MRI (dMRI) to the structurally disordered...
Fluorescence lifetime clocks quantify senescence and aging
Epigenetic and omics-based clocks have provided invaluable tools to quantify aging, yet these clocks do not provide direct readouts of aging in real-time in living systems. As methylation changes in nucleolar ribosomal DNA are reliably associated with aging and cellular senescence, we hypothesized that shifts in rRNA species could be leveraged to generate image-based clocks using selective dyes. Here we engineer sensitive and photostable hybrid polymethine dyes selective for rRNA. We present a...
How are chronic diseases related to depressive symptoms in older adults? The role of life satisfaction and multidimensional intergenerational relationships
CONCLUSIONS: These findings enhance our understanding of the association between chronic diseases and depressive symptoms and provide important insights that can guide policy-makers and practitioners in addressing the psychological challenges faced by older adults with chronic diseases.
Homogenized chlorine distribution for >27% power conversion efficiency in perovskite solar cells
The spatial heterogeneity of halogen distribution in perovskite thin films represents a critical factor currently limiting both the power conversion efficiency and stability of solar cells. We identified pronounced through-film inhomogeneity in chlorine distribution in formamidinium lead iodide films, with the generally used additive methylammonium chloride. We demonstrated that incorporating alkali metal oxalates could effectively homogenize the chlorine distribution. These compounds underwent...
HIV-1 Vif and Vpr cooperatively modulate the cell cycle to maximize per-cell virion production
The HIV type 1 (HIV-1) accessory proteins Virion Infectivity Factor (Vif) and Viral Protein R (Vpr) are essential for efficient virus replication in vivo. Vif mediates degradation of host restriction factor APOBEC3G, while Vpr modulates the host cell proteome in ways that promote virion infectivity and viral gene expression. In cycling cells including CD4+ T cells, Vif and Vpr also severely impact cell cycle progression for reasons that remain unknown. Here, we combined live-cell imaging with...
Sarcopenic obesity and risk of falls: findings in Middle-aged and older Chinese population from CHARLS
CONCLUSION: Sarcopenic obesity is associated with an increased risk of falls among middle-aged and older adults, especially in longitudinal analyses. Age-stratified results suggest that the impact of SO on falls may be more pronounced in the middle-aged group. Our findings support the need for early identification and targeted interventions for individuals with SO to mitigate fall-related risks in aging populations.
Age-Related Alterations in Hippocampal Microstructure Quantified Using High-Gradient Diffusion MRI (dMRI) in an Unfolded Hippocampal Space
The hippocampus, a brain region critical for memory, undergoes significant age-related changes at both the macroscopic and microstructural levels. This study investigates these changes using high-gradient diffusion MRI (dMRI) data analyzed in an unfolded hippocampal space. We applied the Soma and Neurite Density Imaging (SANDI) model to quantify microstructural alterations in 72 cognitively healthy participants aged 19-85 years, scanned on a 3 T Connectome MRI scanner with a maximum gradient...
AI drives dramatic expansion of Chan Zuckerberg Initiative’s funding to end all diseases
Entering its second decade, philanthropy with Facebook fortune has shed social causes and now focuses on ambitious science dream