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U.S. military funds AI tools to speed modeling of viral outbreaks
DARPA program could yield models of disease spread in days instead of weeks
Replenishing sapped groundwater could trigger small earthquakes
A boom in aquifer injection projects could unlock long-quiet faults
What an FDA veteran thinks a controversial vaccine email gets right—and wrong
Phil Krause applauds call by top agency official Vinay Prasad for better data, but says his approach is “destructive”
Integrated primary care for home-dwelling older adults with mild cognitive impairment in China: a hybrid effectiveness-implementation trial protocol
BACKGROUND: With China’s rapidly aging population, addressing the health management of mild cognitive impairment (MCI) in community settings has become crucial for dementia prevention. This study focuses on developing an integrated primary care intervention (IPC) within primary care system to support home-dwelling older adults with MCI and explore the underlying barriers based on the Consolidated Framework for Implementation Research (CFIR) to the implementation and further scale up of the IPC...
Multimodal mass spectrometry imaging for plaque- and region-specific neurolipidomics in Alzheimer's disease mouse models
The progressive accumulation of amyloid beta (Aβ) plaques is a hallmark of Alzheimer's disease (AD). However, the biochemical mechanisms of their formation and the consequences associated with plaque formation remain elusive. In female 5xFAD and APP^(NL-G-F) mice, we map region-specific, plaque-associated lipids with large molecular coverage including isomers. We describe a multimodal framework that integrates matrix assisted laser desorption/ionization with laser-induced postionization...
Prime editing of the beta(1) adrenoceptor in the brain restores physiological REM sleep in a mouse model of Alzheimer's disease
Prime editing offers versatile genome modifications with therapeutic potential; yet its use to modulate neural circuitry remains underexplored. Here, we used adeno-associated viral vectors to deliver prime editors into the mouse brain and introduced the naturally occurring Adrb1^(A187V) variant of the β1-adrenergic receptor, linked to short sleep in humans and mice. Editing reached up to 28.1% in the cortex six months after intracerebroventricular injection and increased excitability of...
White matter hyperintensity regression: Fact or artifact?
White matter hyperintensities (WMH) are an MRI-based biomarker associated with aging, Alzheimer's disease, and vascular dementia. Although the volume of WMH typically increases over time (growth) for individuals, WMH volume in some cases can also decrease (regress). This suggests the presence of active brain injury recovery mechanisms. Whether WMH regression reflects a true biological phenomenon or results from imaging artifacts or measurement errors, however, remains controversial. Here, we...
Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models
Sinus node dysfunction, a prevalent arrhythmia in aging populations, is characterized by fibrosis and loss of pacemaker activity, necessitating pacemaker implantation. Current therapies fail to reverse the underlying pathology. Small extracellular vesicles derived from human induced pluripotent stem cells possess regenerative potential but lack targeted delivery. Here, we engineer platelet membrane-fused vesicles that synergistically combine collagen targeting for ischemic injury homing with...
Inhibiting the formation of neutrophil extracellular traps to prevent the recurrence of post-operative glioblastoma
Glioblastoma (GBM) is a highly malignant tumor with a high postoperative recurrence rate. It is crucial to develop innovative and effective approaches to prevent its recurrence. Herein, we focus on the important roles of neutrophil extracellular traps (NETs) in the progression of GBM in mice and patients. Neutrophils accumulate around the surgical cavity and release NETs to promote the proliferation and migration of postoperative residual GBM cells. Injection of a hydrogel loaded with copper...
Predicting the demand of elderly care beds by a novel recursive grey Gompertz model: case studies of Jiangsu and Shanghai, China
CONCLUSIONS: The RGGM model introduces a memory factor into its objective function, which assigns a greater weight to newer observations. This mechanism ensures the priority of new information during the modeling process, enhancing the model's adaptability. Furthermore, the model's structural parameters are solved recursively with each new observation, allowing the parameters to inherit information from previous data points. This recursive approach effectively improves prediction accuracy....
The expectations and influencing factors to choose institutional elder care for older person in the context of future disability: an empirical analysis in China based on Anderson's health behavior model
CONCLUSION: Affected by a variety of factors, the older person's low acceptance of institutional care remains consistent even when future disability is considered. This situation provides the background and ideas for China's current research on promoting social care services. For example, the nursing institutions should consider factors such as the age, education leveland income of the older person when designing elderly care services. The government can lower the threshold for the older person...
Hospitalizations for cardiovascular events and risk for all cause and cardiovascular mortality in elderly patients with atrial fibrillation treated with oral anticoagulants: beyond preventing thromboembolism
CONCLUSIONS: Hospitalizations for CVEs in elderly AF/AFL OAC treated patients increased the risk for all cause and CV mortality within 12 months from admission for AF/AFL. Hospitalization for HF bared the highest risk, but the residual stroke/TIA/SE risk was noteworthy.
Molecular mechanisms underlying p62-dependent secretion of the Alzheimer-associated ubiquitin variant UBB(+1)
UBB^(+1), a ubiquitin variant protein resulting from a frameshift in the ubiquitin-B gene, is a pathological hallmark of Alzheimer disease (AD). At the cellular level, UBB^(+1) disrupts the ubiquitin-proteasome system while inducing autophagy. Notably, UBB^(+1) itself is secreted via autophagosome-like vesicles. Here, we demonstrate that UBB^(+1) can be removed from the cell by degradative and secretory autophagy. Sequestosome 1 (SQSTM1)/p62 functions as a pivotal ubiquitin receptor for...
IL-27 promotes Treg cell expression of CD122 and fitness at homeostasis
Regulatory T (Treg) cells express high levels of the IL-27R, and in the setting of infection and autoimmunity, the cytokine IL-27 promotes Treg cell activities that mitigate tissue pathology. However, IL-27 appears dispensable for Treg cell development and maintenance as lineage-specific depletion of the IL-27R on Treg cells does not impact these populations at steady state. In contrast, when mice were generated in which the Treg compartment comprised a mix of IL-27R-sufficient and -deficient...
Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer's Disease Progression
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal cell death, brain atrophy, and cognitive decline. Aggregation of Tau protein in neurons is a critical factor in the pathogenesis of AD. Tau aggregates increase as the disease progresses and contribute to neuronal cell death. This study investigated the role of ubiquitin-specific protease 10 (USP10) in Tau pathology and neuronal viability in AD. We found that the expression of USP10 was reduced in the...
Changing chronomics of clock, immune and Parkinson's disease-associated genes in SCN and SN with aging in male Wistar rats: ketogenic diet intervention
The hypothalamic suprachiasmatic nucleus (SCN) functions as the central circadian pacemaker, synchronizing peripheral clocks through oscillations in core clock genes and proteins. Circadian disruption contributes to immunosenescence, aging, and neurodegenerative disorders such as Parkinson's disease (PD). Previous work from our group demonstrated age-related changes in circadian rhythms of clock genes, protein levels, and serotonin metabolism in the SCN and substantia nigra (SN) of male Wistar...
Atavistic Genetic Expression Dissociation (AGED) During Aging: Meta-Phylostratigraphic Evidence of Cellular and Tissue-Level Phylogenetic Dissociation
Aging is commonly attributed to accumulated damage, or evolved antagonistic genetic trade-offs, which lead to an accumulation of damage causing misexpression of genes necessary for longevity. We propose an atavistic dysregulation of gene expression at cellular and tissue levels during aging, framing aging as a gradual regression toward ancestral cellular states. Similarly to the atavistic model of cancer, in which cells revert to unicellular-like behavior, aging may result from the breakdown of...
Machine learning algorithms to predict frailty in older adults in China: a cross-sectional study
CONCLUSION: ML algorithms can effectively predict the occurrence of frailty in Chinese elderly and identify significant factors associated with frailty. For datasets with complex feature interactions, LightGBM is preferable, while Random Forest offers improved stability and variance control. These findings support ML-based frailty screening and intervention strategies for aging populations.
beta-Hydroxybutyrate Acts as an Exercise Mimetic to Protect the Aging Liver
Liver aging is characterized by pathological features including lipid deposition, exacerbated chronic inflammation, and increased cell death. Although exercise intervention has been proven effective in delaying liver aging, its fundamental biochemical mechanism remains unclear. This study utilized a naturally aged mouse model and an in vitro cellular senescence system to reveal, for the first time, the cascade mechanism by which β-hydroxybutyrate (β-HB), a core protective mediator induced by...