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Cellular senescence in neurodegenerative diseases: a bibliometric analysis and mechanistic synthesis linking translational pathways to therapeutic implications

1 day ago
CONCLUSION: Cellular senescence research in NDs (notably AD, PD) shows broad promise from mechanisms to therapy. Future priorities include elucidating tau dysregulation's core role in senescence, developing specific biomarkers and targeted interventions. Senescent microglia are new therapeutic targets. Multi-target senomorphics modulating SASP offer new mechanisms for delaying ND progression. Understanding senescence mechanisms and precise interventions may provide novel ND therapies.
Runjin Zhou

Metabolomic biomarkers enhance 10-year mortality risk calibration and clinical utility in older heart failure patients: A UK Biobank study

1 day ago
CONCLUSION: Integrating metabolic biomarkers with standard clinical characteristics significantly improves model calibration and clinical net benefit for predicting 10-year mortality in older adults with heart failure. This approach highlights underlying mechanisms, such as mitochondrial energy dysfunction and chronic systemic inflammation, providing a practical tool for personalized care planning and targeted interventions.
Xiaofeng Zeng

Astrocytic AEBP1-NPAS3-LIPA pathway coordinates cholesterol homeostasis to regulate Alzheimer's pathology

1 day ago
Astrocytes regulate brain cholesterol homeostasis, but the astrocyte-specific mechanisms disrupted in Alzheimer's disease (AD) are poorly understood. By integrating human bulk transcriptomes with single-nucleus RNA sequencing (RNA-seq), we identified adipocyte enhancer-binding protein 1 (AEBP1) as an astrocyte-enriched factor upregulated in AD. In postmortem human tissue and 5×FAD mice, astrocytic AEBP1 levels rise with age and disease progression. Astrocyte-specific AEBP1 knockdown ameliorates,...
Jialin Wu

Endogenous ATP-powered nanomotors directing neural stem cell differentiation for Parkinson's disease treatment

1 day ago
Transplantation-free neuron regeneration remains attractive yet unsolved for reversing Parkinson's disease (PD). Here, we present enzyme-driven mesoporous gold nanomotors (Apyrase@Au) that leverage endogenous biochemical energy for spatiotemporally controlled promotion of neural stem cell (NSC) differentiation, without exogenous stem cell transplantation. By catalyzing endogenous adenosine triphosphate (ATP) hydrolysis, Apyrase@Au nanomotors simultaneously generate directional propulsion and...
Miaomiao Ding

Tau catalyzes amyloid-β aggregation and toxicity in a polymorph-dependent manner

1 day ago
Interactions between amyloidogenic proteins are emerging as critical drivers of neurodegenerative diseases. Among others, in Alzheimer's disease (AD) and severe forms of chronic traumatic encephalopathy (CTE), codeposition of tau and amyloid-β (Aβ) leads to worsening of clinical outcomes and disease progression. Despite the importance of such heterotypic interactions, the underlying molecular mechanisms have proven challenging to be established. Here, we investigated the direct interaction...
Michele Mosconi

Polysaccharide-mediated aging-modulatory effects of Labisia Pumila extracts on the physiological changes in C. elegans and D. melanogaster

1 day ago
Polysaccharides are natural macromolecules with diverse bioactivities and potential health benefits. It exhibits a broad spectrum of biological effects, with extensive research supporting their antioxidative, anti-inflammatory, immunomodulatory, and anti-aging properties. The study evaluated the aging-modulatory effects of Labisia pumila polysaccharides (LPP) using Caenorhabditis elegans (C. elegans) and Drosophila melanogaster (D. melanogaster) as model organisms. LPP treatment increased the...
Yinan Wang

Distinct effects of aging and klotho deletion on the choroid plexus

1 day ago
Klotho (Kl) is an anti-aging protein primarily produced in the kidney and the choroid plexus (CP, where it regulates cerebrospinal fluid composition and exerts neuroprotective effects. Here, we investigated the age-dependent consequences of a CP-specific Kl deletion on CP structure and function using mice lacking Kl exclusively in CP epithelial cells (Kl^(ΔCP)). In control mice, aging markedly disrupted CP architecture and cilia organization both in the lateral (LV-CP) and fourth ventricle...
Zahra Fanaei-Kahrani

A conserved ethylene-triggered cell death mechanism may underlie hollow stem formation across plant species

1 day ago
Hollow stems have independently evolved multiple times across the plant kingdom and play crucial roles in plant development and various environmental adaptations. However, the mechanisms underlying stem hollowness remain poorly understood. Water spinach (Ipomoea aquatica) is one of the few hollow-stemmed plants in the Convolvulaceae family (eudicot: asterid), and its hollow stems are essential for thriving in aquatic environments. Using histochemical staining and transcriptome analysis, we found...
Mengxiao Yan

Uev1A counteracts oncogenic <em>Ras</em> stimuli in both polyploid and diploid cells

1 day ago
Oncogenic Ras is known to induce DNA replication stress, leading to cellular senescence or death. In contrast, we found that it can also trigger polyploid Drosophila ovarian nurse cells to die by inducing aberrant division stress. To explore intrinsic protective mechanisms against this specific form of cellular stress, here, we conducted a genome-wide genetic screen and identified the E2 enzyme Uev1A as a key protector. Reducing its expression levels exacerbates the nurse cell death induced by...
Qi Zhang

Suppression of pathological oscillations with transcranial focused ultrasound in Parkinson's disease

1 day ago
Transcranial ultrasound stimulation (TUS) is an emerging method for non-invasive neuromodulation of deep brain structures. However, to date, there is no evidence that TUS can directly modulate disease-related pathological oscillations in the same direction as known therapies. Inspired by clinical deep brain stimulation, in this randomised controlled cross-over study we probed the effects of pallidal TUS pulsed at 130 Hz on subthalamic beta-band activity, a biomarker in Parkinson's Disease (PD)...
John Eraifej

A high-throughput conditioned-media-based screening system identifies inhibitors of aggregation induced by iPSC-secreted amyloid β

1 day ago
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)...
Masahiro Kuragano

LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial

1 day ago
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...
Omar S Mabrouk

Transcription-dependent and -independent functions of Drosophila p53 isoforms in the induction of apoptosis and senescence-associated tumorigenesis

1 day ago
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...
Marina Pérez-Aguilera

A single-atom potential confinement strategy for stabilizing rhodium nanocatalysts in methane oxidation

1 day ago
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...
Chenxin Xu