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Size-tailored nanoparticle-antibody conjugates overcome hepatic sequestration in Alzheimer's disease treatment

1 month 2 weeks ago
Antibody-based immunotherapy targeting amyloid-β (Aβ) is a promising approach for Alzheimer's disease (AD). However, its efficacy is limited by rapid hepatic sequestration, complement activation, and liver dysfunction. In this study, we synthesized low-immunogenic 450-nm functionalized mesoporous silica nanoparticles (PEG-MSN-1F12) by conjugating the anti-Aβ(42) monoclonal antibody 1F12 to polyethylene glycol-modified mesoporous silica nanoparticles to address these challenges. In APP/PS1 mice,...
Xuewei Du

LAPTM5 correlates with RPE senescence and subretinal fibrosis through the LAPTM5-WWP2-OPTN mitophagy cascade and cGAS/STING activation in a D-galactose-induced aging model

1 month 2 weeks ago
Retinal pigment epithelium (RPE) senescence acts as a core driver of subretinal fibrosis, a major irreversible pathological feature that exacerbates age-related macular degeneration (AMD). Mitophagy is essential for maintaining RPE homeostasis during aging. However, the upstream molecular mechanisms underlying mitophagy impairment in senescent RPE remain poorly defined. Here, we show that lysosomal-associated transmembrane protein 5 (LAPTM5) is significantly upregulated in human AMD specimens...
Xiaowei Yang

eIF5A and polyamines restrict mRNA levels in response to ribosome stalls

1 month 2 weeks ago
Obstacles to translation elongation stall ribosomes and allow deleterious proteins to accumulate, which threatens cellular health. Cells recognize and clear stalled ribosomes via several interrelated pathways, although the mechanisms by which cells distinguish stalled from normally elongating ribosomes and mount an appropriate response are incompletely understood. While recent work highlights how ribosome collisions help cells to recognize stalled ribosomes, how other factors contribute to...
Chloe M Wohlenberg

Epicenter mapping of cortical morphological dedifferentiation in type 2 diabetes mellitus using morphometric inverse divergence

1 month 2 weeks ago
CONCLUSION: The group-level spatial map showed exploratory correspondence with selected normative functional connectivity (FC)- and structural connectivity (SC)-based candidate profiles. Individualized profiles showed greater cross- sectional correspondence with the selected SC-based profile than with the FC-based profile, providing a network-informed description of diabetic brain alterations.
Taipeng Zeng

Muscle-Specific Upregulation of Timeless Mediates Exercise-Induced Amelioration of Age-Related Circadian Rhythm Disruption and Cardiac Dysfunction in Drosophila

1 month 2 weeks ago
The core genes of the circadian pathway, such as Timeless(Tim), not only participate in the regulation of biological rhythms, but also play significant roles in DNA damage repair, chronic inflammation, and cellular metabolism. However, it remains unclear whether exercise can delay the age-related phenotypic degeneration by regulating the muscle Tim gene. In here, we first carried out the expression regulation of the muscle Tim gene in the Drosophila by constructing the Mhc-gal4/Tim-UAS system,...
Deng-Tai Wen

Early statin use linked to 15% lower dementia risk

1 month 2 weeks ago
Starting statins soon after a type 2 diabetes diagnosis may do more than protect the heart. In a nationwide Danish study of more than 132,000 people, those who began statin treatment within a year of diagnosis had a 15% lower relative risk of developing dementia over 10 years compared with those who did not start statins.