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Lysosomal and endoplasmic reticulum (ER) Ca^(2+) release mutually influence each other's functions. Recent work revealed that ER-located ryanodine receptor(s) (RyR(s)) Ca^(2+) release channels suppress autophagosome turnover by the lysosomes. In familial Alzheimer's disease, inhibiting RyR hyperactivity restored autophagic flux by normalizing lysosomal vacuolar H^(+)-ATPase (vATPase) levels. However, the mechanisms by which RyRs control lysosomal function and how this involves the vATPase remain...

Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these...

Biomolecular condensates are essential for cellular organization, yet their formation dynamics and molecular content exchange properties remain poorly understood. Here we show that flow cytometry provides a high-throughput, solution-based platform for analyzing condensate behavior at the single-droplet level. Using self-interacting NPM1 condensates as a model, we demonstrate that this approach quantifies phase behavior across protein and salt conditions, measures the partitioning of diverse...

Battery monitoring requires high accuracy and robustness throughout the entire lifespan to ensure safe and optimal operations. Here we introduce mechanistic leading residual learners to enhance the monitoring of battery charge and health states, as well as guide safety warnings, targeting large-scale applications. Leveraging prior knowledge from real-time filtering as primary guidance, complemented by mechanistic and statistical features, our approach significantly improves accuracy and...

Children with congenital heart defects increasingly survive to adulthood, but the non-physiological Fontan circulation imposed by current surgical palliation leads to significant sequelae and reduced lifespan. Restoring subpulmonic pumping function remains a long-standing goal, and there have been several attempts using regenerative medicine approaches. These efforts have lacked biomechanical rigor, however, and have not achieved the requisite functionality. Here, we introduce an analytically...

Defect microstructures, particularly dislocations, are pivotal in determining the functional properties of ferroelectric thin films. While their density is routinely considered, the critical role of their spatial configuration has remained largely unexplored and difficult to control. Here, we develop a controlled self-assembly strategy for dislocations in Bi(Fe,Mn)O(3) thin films on Ni-Cr that directly addresses this challenge. By employing a LaNiO(3) buffer layer, we template a...

Trained immunity, the long-term reprogramming of innate immune cells to elicit an enhanced response upon subsequent challenges, has become a key concept in understanding a wide range of pathologies, including both acute and chronic inflammatory disorders. Recent evidence suggests that trained immunity also plays a significant role in the development and progression of various neurological disorders and related comorbidities, in which brain pathology can lead to trained immunity. This review...

Trisomy 21 (T21) gives rise to Down syndrome (DS), the most commonly occurring chromosomal abnormality in humans. T21 affects nearly every organ and tissue system in the body, predisposing individuals with DS to congenital heart defects, autoimmunity, and Alzheimer's disease, among other co-occurring conditions. Here, using multi-omic analysis of plasma from more than 400 people, we report broad metabolic changes in the population with DS typified by increased bile acid levels and protein...

Astrocytes not only play a central role in orchestrating the brain's microenvironment but also are tightly connected to neurodegenerative processes. Hence, unraveling astrocytes' intercellular pathways can give important insight into disease-spreading mechanisms. Here, we describe a distinct form of actively migrating cellular vehicles, which we have named zombosomes. Zombosomes shed from astrocytes but retain their adhesive and motile properties, even though they lack nuclei. They share protein...

Hematopoietic stem cells (HSCs) are multipotent self-renewing cells that give rise to all types of blood cells. Past research has identified that long-term hematopoietic stem cells in young mice and humans produce a balanced output of lymphoid and myeloid cells, while in old age, they are largely replaced by myeloid-biased HSCs (My-HSC). It has not yet been determined whether this transition results from epigenetic changes in a single population of HSC or if two or more subsets of HSCs exist...

Low concentrations of chemicals are widespread in the environment, but exploration of the effects of their chronic exposures on animal life span in the wild is limited. Field investigations showed that fish populations of lake skygazer (Culter dabryi) with chronic low-dose chlorpyrifos loads had shortened telomeres and truncated age structures. Laboratory experiments confirmed that chronic low-dose chlorpyrifos exposure induced telomere degradation and reduced survival in a dose- and...

Harms of chlorpyrifos emerge in polluted lakes and laboratory aquarium tanks.

No abstract

BACKGROUND AND OBJECTIVES: Increasing urbanization and the aging global population highlight cities as vital environments for promoting healthy aging. However, the relationship between characteristics of urban green spaces and older adults' mental well-being remains unclear.

Science, Volume 391, Issue 6782, January 2026.

Science, Volume 391, Issue 6782, January 2026.

Science, Volume 391, Issue 6782, January 2026.