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Accurate diagnosis of early Parkinson's disease requires platforms suitable for detecting minute amounts of neuronally derived biomarkers in the massive protein excess of easily accessible biofluids such as blood. Here, we describe an on-chip droplet-confined fluorescence reporting assay that identified α-synuclein on the membrane of L1CAM+ extracellular vesicles (EVs) immunocaptured from human serum and corroborate this finding by super-resolution direct stochastic optical reconstruction...

Chronic inflammation and a decline in mitochondrial function are hallmarks of aging. Here, we show that the two mechanisms may be linked. We found that interleukin-6 (IL6) suppresses mitochondrial function in settings where PGC1 (both PGC1α and PGC1β) expression is low. This suppression is mediated by the JAK1/STAT1/3 axis, which activates HIF1α through non-canonical mechanisms involving upregulation of HIF1A and ERRα transcription, and subsequent stabilization of the HIF1A protein by ERRα....

Excessive activation of effector-triggered immunity (ETI) in plants inhibits plant growth and activates cell death. ETI mediated by intracellular Toll/interleukin-1 receptor/resistance protein (TIR) nucleotide-binding, leucine-rich repeat receptors (NLRs) involves two partially redundant signaling nodes in Arabidopsis, ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-ACTIVATED DISEASE RESISTANCE 1 (EDS1-PAD4-ADR1) and EDS1-SENESCENCE-ASSOCIATED GENE 101-N REQUIREMENT GENE 1...

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CONCLUSIONS: This study demonstrated that higher levels of certain PUFAs were associated with a reduction in PhenoAge acceleration either individually or in combination, with DHA having the most prominent effect in mixed effects. The SII mediated these relationships, suggesting that PUFAs may slow biological aging by reducing inflammation. These findings highlighted the potential role of PUFAs in mitigating accelerated aging and their implications for aging-related health interventions.

Countries are urged to advance the energy transition in a just, orderly, and equitable manner, yet the appropriate pathway remains unclear. Using a provincial-level, hourly-dispatched power system model of China that incorporates intertemporal decisions on early retirement and carbon capture retrofitting, our study reveals that for coal-rich but gas-poor economies, repositioning coal power from a baseload resource to a flexibility provider can accelerate net-zero transition of the power system...

The internationally sourced metal may have helped a predemocratic tyrant rise to power

In 2020, a case report described autologous transplantation of iPSC-derived dopamine (DA) neurons in a Parkinson's disease (PD) patient.¹ The team now follows up with the pre-clinical safety and efficacy data of autologous iPSC-derived DA neurons, forming the basis for regulatory approval of a phase 1 clinical trial involving 8 patients.².

Sleep loss is often regarded as an early manifestation of neurodegenerative diseases given its common occurrence and link to cognitive dysfunction. However, the precise mechanisms by which sleep disturbances contribute to neurodegeneration are not fully understood, nor is it clear why some individuals are more susceptible to these effects than others. This review addresses critical unanswered questions in the field, including whether sleep disturbances precede or result from neurodegenerative...

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CONCLUSION: Lower oral microbiome diversity is associated with higher frailty and mortality. The number of teeth partially mediates this link, emphasizing the importance of oral health in mitigating frailty and promoting healthy aging.

Stem cells possess an extraordinary ability for self-renewal and differentiation, making them essential for tissue repair, regeneration, and anti-aging. RNA methylation is crucial in regulating stem cell fate by modulating gene expression. This review synthesizes current research on RNA methylation modifications, such as m⁶A, m⁷G, m⁵C, and m¹A, and their impact on adult stem cell fate. It provides a comprehensive overview of the molecular machinery involved in RNA methylation, emphasizes the...

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Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient...

CONCLUSIONS: The blunting of sex differences in antibody response observed following the primary series by the 1st booster dose underscores the importance of booster vaccination in this population.

CONCLUSIONS: These findings imply that most field tests are responsive to age-related declines in physical and/or muscle function after 60. In younger age groups, field tests that evaluate lower-limb power and have minimal ceiling effects, such as SCP and CMJ, should be prioritized.

Uncovering early gene network changes of human hematopoietic stem cells (HSCs) leading to differentiation induction is of utmost importance for therapeutic manipulation. We employed single cell proteo-transcriptomic sequencing to FACS-enriched bone marrow hematopoietic stem and progenitor cells (HSPCs) from 15 healthy donors. Pseudotime analysis reveals four major differentiation trajectories, which remain consistent upon aging, with an early branching point into megakaryocyte-erythroid...

Human GWAS have shown that obesogenic FTO polymorphisms correlate with lean mass, but the mechanisms have remained unclear. It is counterintuitive because lean mass is inversely correlated with obesity and metabolic diseases. Here, we use CRISPR to knock-in FTO^(rs9939609-A) into hESC-derived tissue models, to elucidate potentially hidden roles of FTO during development. We find that among human tissues, FTO^(rs9939609-A) most robustly affect human muscle progenitors' proliferation,...

The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments with senolytics enhances remyelination in young and middle-aged mice but not aged mice. In young mice, we...