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Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria

5 days 5 hours ago
In vitro models of vascular disease have focused primarily on the pathophysiology of smooth muscle cell (SMC) or endothelial cell (EC). Adventitial fibroblasts can contribute to disease progression, but their specific influence is not well understood in different disease contexts. To elucidate fibroblast's impact on vascular pathology, we developed trilayer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts. We modeled atherosclerosis in the accelerated aging disease,...
Kevin L Shores

Average performance and performance variability on a brief functional fine motor test reflect distinct behavioral constructs in aging

5 days 5 hours ago
Prior work in older adults has developed a brief functional fine motor test, which involves repeated timed trials of an upper-limb task. Performance has been associated with global and domain-specific neuropsychological tests as well as putative markers of Alzheimer's disease when scored using variability in trial time; however, the extent to which task performance depends on motor ability has not been established nor quantified. This retrospective study examined whether mean trial time and...
Chung-Fu Sun

A computational-first proof-of-concept for dual-function metal chelation and aggregate neutralization in an Aβ42 <em>Drosophila</em> model

5 days 5 hours ago
Alzheimer's disease (AD) pathology is amplified by a self-reinforcing metal-Aβ-ROS axis, in which redox-active Cu and Fe bound to Aβ N-terminal histidines catalyze Fenton-like ROS generation and accelerate aggregation. Existing single-target interventions - anti-amyloid antibodies, antioxidants, metal-protein attenuating compounds, aggregation inhibitors, and photooxygenation catalysts - each address only one node of this loop. We used a computational-first framework to evaluate a dual-function...
Edric Tsai

Deep cervical lymphovenous reconstruction in Alzheimer's disease: three target-defined interfaces with distinct mechanistic implications

5 days 5 hours ago
Age-related impairment of brain solute clearance has been implicated in Alzheimer's disease (AD), yet procedures described as deep cervical lymphovenous reconstruction do not necessarily target the same lymphatic structure. This review examines glymphatic exchange, meningeal lymphatic drainage, cervical outflow, human lymphatic imaging, lymphatic surgery, early clinical studies, registered trials, and reported harms. Three interfaces can be distinguished: lymphatic flap-vein, lymph node-vein,...
Kuisheng Sun

Scientists reprogram immune cells inside the body to fight cancer

5 days 5 hours ago
Scientists at UC San Francisco have developed a way to create cancer-fighting CAR-T cells directly inside the body, potentially avoiding the slow and extremely expensive process of removing, engineering, and reinfusing a patient’s immune cells. Using a two-particle delivery system, the researchers sent CRISPR gene-editing tools and new cancer-targeting DNA specifically into T cells, where the DNA was inserted at a precise location in the genome.