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In early drug discovery, in vitro screening is frequently used, but selected candidates often fail in vivo. Induced pluripotent stem cell (iPSC)-based disease models offer improved physiological relevance; however, the high costs of media and differentiation procedures limit large-scale testing. Here, we develop a high-throughput conditioned-media-based screening system-the High-throughput screening technology for Aggregation Inhibitors of Diseased cell-derived Aggregative Proteins (HaiDap)...

LRRK2 (encoding leucine-rich repeat kinase 2) variants are the most common genetic cause of Parkinson's disease (PD). Lowering LRRK2 levels and/or inhibiting LRRK2 activity may modify PD-associated neuropathology. BIIB094 (ION859), an antisense oligonucleotide, targets LRRK2 mRNA for degradation. REASON was a first-in-human randomized phase 1 study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecal BIIB094 in patients with PD. In part A, 40 participants...

The tumor suppressor p53 orchestrates critical cellular responses to stress, including cell cycle arrest, DNA repair, senescence, and apoptosis. While extensive research has elucidated many aspects of p53 function, the isoform-specific mechanisms governing cell fate decisions remain incompletely understood. Here, we leverage the simplified p53 gene architecture in Drosophila to systematically dissect the apoptotic and tumorigenic potential of individual p53 isoforms, uncovering fundamental...

Operating nanometal catalysts under harsh reaction conditions often leads to their disintegration into less active single atoms or clusters, which is considered as a primary cause of catalyst deactivation and loss of active components. In the current work, our theoretical calculations on CeO₂-supported Rh catalysts first reveal that pre-filling surface vacancies with suitable single metal atoms renders the subsequent anchoring of Rh atoms on supports energetically unfavorable. Guided by this...

Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here, we combine single-cell transcriptomics with in-depth genetic and imaging analysis to investigate the role of the EGFR-Ras and Hedgehog signaling pathways in homeostasis of the Drosophila follicle stem cell lineage. We find that Hedgehog signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of the...

Advances in transcriptomic technologies have progressively transformed the questions we can ask and answer about muscle stem cells (MuSCs) during aging. Early microarray and bulk RNA sequencing studies established foundational population-level signatures of aged MuSCs, including attenuation of myogenic and metabolic programs as well as induction of inflammatory and stress-associated transcription. However, these averaged readouts obscured cell-to-cell variability and rare functional states. The...

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CONCLUSIONS: Most older Americans are concerned about access to long-term care and costs, yet remain divided on who primarily should pay for caregiving costs. Caregivers are both more concerned about long-term care access and more likely to support the government's primary responsibility for caregiving costs than noncaregivers. Policymakers should consider more options for access to affordable, high-quality long-term care, and financial supports for caregivers.

CONCLUSION: Immunosenescence plays a crucial role in IS pathogenesis and recovery, with chronic inflammation and immune dysfunction exacerbating stroke outcomes in older adults. Targeting immune markers, particularly IL-6 and the Th17/Treg imbalance, may offer new therapeutic approaches to improve stroke prognosis in aging populations. Further research is needed to develop interventions that address immunosenescence in IS.

INTRODUCTION: Sleep quality is often thought to be a key determinant of cognitive performance, particularly in older adults who experience age-related changes in sleep architecture. However, the extent to which nightly variations in sleep quality impact next-day cognitive performance remains unclear-in part because it has only recently become practical to measure sleep over multiple nights.