Aggregator

Stem-cell-based in vitro models offer promising potential to elucidate human brain cell functions and interactions, but limitations in reproducibility, maturation and cell-type diversity persist. Especially, prolonged incorporation of mature microglia and studies of neuroinflammation have proven challenging. Here, we developed a human induced pluripotent stem cell-based three-dimensional cortical brain tissue model (3BTM) containing neurons, astrocytes and microglia with high reproducibility,...

No abstract

Hypothesis generation in biomedicine is constrained by human cognitive limitations in synthesizing insights from fragmented biomedical knowledge and multimodal data sources. Here we introduce XunZi, an AI biologist that integrates logical reasoning and multimodal data fusion to autonomously generate de novo therapeutic target hypotheses with testable mechanisms. XunZi has been trained on 24.4 million publications and 613.6 TB of multisource data spanning 21,008 human genes and 5,850 diseases,...

No abstract

A specially engineered chewing gum reduced HPV by up to 93% and nearly eliminated two bacteria linked to head and neck cancer. The treatment preserved beneficial mouth bacteria, raising hopes for a safer and more affordable therapy.

Metabolic dysfunction is a defining but poorly understood feature of Alzheimer's disease. Du et al. show that a brain-penetrant GLP-1 receptor agonist rewires astrocyte-neuron metabolic coupling through lactate-driven histone lactylation, linking astrocytic glycolysis to neuronal lipid homeostasis and positioning metabolite signaling as a therapeutic axis in neurodegeneration.

Alzheimer's disease (AD), as the leading cause of dementia, poses an increasingly severe socioeconomic burden in the context of global ageing. Traditionally defined by amyloid-β and tau pathology, it's increasingly recognized as a systems disorder in which impaired glucose metabolism, mitochondrial dysfunction, and neuroinflammation interact across neural cell types and disease stages. However, the interaction among these three mechanisms, their role in promoting the classical pathology of AD,...

Metabotropic glutamate receptor subtype 5 (mGlu5) is an important regulator of excitatory neurotransmission and remains a therapeutic target for neuropsychiatric and neurological disorders, including substance use disorders, depression, Fragile X syndrome, Parkinson's disease-related dyskinesia, and other movement disorders. However, the clinical development of mGlu5 negative allosteric modulators (NAMs) has been limited by translational challenges, inconsistent efficacy, and safety concerns,...

Postural and locomotor dysfunction represent axial symptoms of Parkinson's disease (PD), which remain poorly treated by medication and deep brain stimulation. Whilst non-invasive neuromodulation of the vestibular system via the vestibular nucleus complex (VNC) offers a novel therapeutic avenue, the underlying circuits are still poorly characterized. Here we show that the mouse VNC feeds extensive Vglut2-defined projections into striato-thalamo-subthalamic and caudal medulla motor hubs and...

CONCLUSIONS AND IMPLICATIONS: Community-based implementation of the WHO ICOPE pathway within routine systems is feasible and identified substantial multidomain IC impairment among otherwise independent older adults. Variation across sites highlights the need for context-specific service planning and targeted resource allocation. Embedding IC screening within community platforms, with coordinated referral pathways, supports earlier identification and management of functional decline and advances...

Dietary protein quality, not merely quantity, shapes metabolic health and aging trajectories. Fanti et al. show that moderate methionine supplementation to a low-protein, Mediterranean-inspired diet activates a GH-GLP-1-FGF21 axis that reduces adiposity and frailty without caloric restriction; their findings provide a mechanism for why traditional plant-rich diets may promote longevity while sometimes compromising physical robustness.

The spleen harbors distinct macrophage subsets that support circulatory homeostasis and initiate immune responses, but the ontogeny and long-term dynamics of these populations remain incompletely understood. Here, we identified a transcriptionally and developmentally distinct CD163-expressing red pulp macrophage (CD163^(high) RPM) population that arose from yolk sac progenitors and occupied a vascular-associated niche. Using fate-mapping models, we showed that CD163^(-) RPMs were progressively...

Alzheimer's disease (AD), as the leading cause of dementia, poses an increasingly severe socioeconomic burden in the context of global ageing. Traditionally defined by amyloid-β and tau pathology, it's increasingly recognized as a systems disorder in which impaired glucose metabolism, mitochondrial dysfunction, and neuroinflammation interact across neural cell types and disease stages. However, the interaction among these three mechanisms, their role in promoting the classical pathology of AD,...

Bilingualism offers a powerful test case for understanding how control systems adapt to sustained, variable attentional demands. Converging evidence across behavioral, structural, functional, and clinical literatures indicates that repeated demands for selection, conflict resolution, and language switching are associated with reorganization of control architecture in ways that are consistent with predictive and reinforcement-learning mechanisms, producing two interdependent outcomes. Efficiency...

INTRODUCTION: Aging is associated with impaired skeletal muscle mass and function, often attributed to reduced sensitivity to anabolic stimuli. This study investigated whether aging influences the sensitivity of key anabolic signaling pathways to mechanical tension development in skeletal muscle.

CONCLUSION: Dual assessment of olfaction and gustation may represent a promising candidate biomarker of neurodegenerative progression compared to isolated olfactory testing. We propose the integration of standardized chemosensory protocols into routine geriatric assessments as a pragmatic strategy for early cognitive risk stratification and follow-up. This approach holds significant translational potential for monitoring neurodegenerative trajectories in older adults.