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Mysterious type of static electricity has a hidden culprit
Find explains how volcanic ash plumes spark lightning and why dust in grain silos can explode
Mitochondria packaged in blood cell membranes improve disease symptoms in mice
Tiny capsules can deliver healthy organelles into animals with Parkinson’s-like and other mitochondria-linked disorders
Blood-brain barrier-penetrative lipid nanoparticles enable systemic delivery of TRIM11 mRNA to disaggregate Tau in Alzheimer's disease models
Hyperphosphorylated Tau aggregates are a central pathological hallmark of Alzheimer's disease (AD), yet no approved therapy directly targets this process. mRNA therapeutics provide a transient and non-viral option but are limited by the blood-brain barrier (BBB). TRIM11 is an ATP-independent disaggregase that dissolves pathological Tau fibrils and promotes proteasomal clearance. Here, a ligand-free lipid nanoparticle (PLNP) is developed with zwitterionic, acetylcholine-mimetic...
TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas
Treatment decisions in IDH-mutant oligodendrogliomas are shaped by tumor aggressiveness, underscoring the need for objective grading of these malignant brain tumors. We collect 302 primary and recurrent resections from oligodendrogliomas and perform Ki-67 staining, proteomics, and DNA methylation profiling. During tumor progression, DNA methylation of oligodendrogliomas changes along a continuum. This continuum is linked to increased epigenetic aging, methylation of transcription factors and...
The aging cornea: from mechanisms to clinical applications
Aging is a multifactorial process characterized by a gradual decline in function, increased susceptibility to diseases, and diminished regenerative capacity. As the primary refractive structure and barrier of the eye, the cornea undergoes significant structural and functional changes during aging, making individuals more prone to various ocular surface diseases. Key age-related corneal changes include epithelial thinning, stromal remodeling with increased collagen cross-linking, endothelial cell...
Obesity metrics and fall severity in older adults: A cross-sectional analysis of weight-adjusted waist index and conventional anthropometric measures
CONCLUSIONS: WWI was significantly associated with fall risk and severity in older adults. Further prospective studies are essential to validate its predictive value in fall risk stratification and prevention.
Exercise training improves mitochondrial oxidative energy metabolism through PGC-1α-dependent transcriptional pathway in the aged rat heart
Exercise training improves the age-induced decline in oxidative metabolic capacity in cardiac mitochondria. Nuclear respiratory factor-1 (NRF-1) signaling via peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates genes encoding mitochondrial oxidative metabolic enzymes. However, the effects of aging and subsequent exercise training on fatty acid (FA) metabolism-related gene expression via the myocardial PGC-1α-NRF-1 pathway, and the relevance of these changes to...
Aging Triggers an Intestinal Energy Crisis and HDL3 Deficiency Disrupting Gut-Liver Axis Homeostasis
During aging, decreased intestinal barrier function and its ability to synthesize metabolites are closely associated with various age-related diseases. However, the mechanism by which impaired intestinal synthesis contributes to gut-liver axis aging remains unclear. This study reveals that aging induces a mitochondrial energy crisis and defective membrane localization of ABCA1, significantly inhibiting the biosynthesis of high-density lipoprotein 3 (HDL3) in the intestine. Exogenous...
Amyloid-β as a target to suppress tonic PTH hypersecretion in hyperparathyroidism due to vitamin D deficiency
Hyperparathyroidism is an endocrine disorder linked to vitamin D deficiency. Reduced vitamin D receptor (VDR) activity promotes parathyroid hormone (PTH) hypersecretion by increasing heterodimerization of the type B γ-aminobutyric acid receptor 1 (GABA(B1)R) with the extracellular Ca^(2+)-sensing receptor (CaSR) in parathyroid cells; however, endogenous activators of the heterodimers are unknown. We uncovered increased expression of amyloid-β peptide cleaved from the amyloid-β precursor protein...
Inside Out: How Cellular Localisation Shapes cGAS Functions in Health and Disease
The function of innate immune sensors is intricately shaped by their spatial distribution within cells. cGAS (cyclic GMP-AMP synthase), a key cytosolic DNA sensor, illustrates this principle through its unexpected localisation to diverse organelles-including the nucleus, micronuclei, mitochondria, and plasma membrane. In these compartments, cGAS assumes distinct regulatory states and executes specialised functions. For instance, chromatin-bound nuclear cGAS remains inactive under homeostasis but...
Massively parallel quantification of mutational impact on IAPP amyloid formation
Amyloid fibrils formed by the islet amyloid polypeptide cause pancreatic beta-cell damage, resulting in reduced insulin secretion and type 2 diabetes. Changes in the amino acid sequence of this peptide can influence its aggregation rate, and animals expressing variants that do not form amyloids do not develop type 2 diabetes. Conversely, specific single amino acid changes can accelerate the aggregation rate of this peptide. Here, we employ deep mutational scanning to measure the ability of 1916...
Structural evolution of carbon frameworks realizes in vitro interfacial transport in metabolically reprogrammed senescent cells for senolysis
Integrating the diagnostic and therapeutic functions of drugs poses challenges due to specific structural design requirements. However, the trial-and-error dilemma in performance-driven structural evolution of nanomaterials is unsatisfactory. Here, we propose a strategy using graphene quantum dots with sp²-sp³ hybridized carbon frameworks for visualized, intelligent targeted clearance of metabolically reprogrammed senescent cells. We establish a structure-activity relationship between the...
Planar Li deposition and dissolution enable practical anode-free pouch cells
Anode-free lithium metal batteries (AFLMBs), which are manufactured without anode active material, offer great potential for high-energy-density, low-cost energy storage. However, AFLMBs face a long-standing challenge of short lifespan due to the harsh conditions of lacking excess Li-resource and an anode host^(1-8). This issue is associated with uneven Li deposition/dissolution, rooted in the micro-heterogeneity and mechanical fragility of solid electrolyte interphase (SEI)⁹. Here we report a...
CellVoyager: AI CompBio agent generates new insights by autonomously analyzing biological data
Modern biology increasingly relies on complex, high-dimensional datasets such as single-cell RNA sequencing (scRNA-seq), which present a vast space of potential hypotheses. Systematically exploring this space is often impractical, as scRNA-seq analyses are time-consuming and require substantial computational and domain expertise. To address this challenge, we introduce CellVoyager, an AI agent built on large language models that autonomously generates and implements scRNA-seq analyses within a...
Combined effects of ageing and type 2 diabetes mellitus on human dental mechanics
Dental collagen, a protein subject to essentially zero turnover, is highly susceptible to the accumulation of advanced glycation end-products (AGEs) due to elevated blood glucose in type 2 diabetes mellitus (T2DM). Progressive loss of collagen's structural stability likely increases the risk of tooth decay and fracture complicating the proper fixation of dental restorations. Our study aimed at investigating the structural and mechanical alterations in T2DM-affected teeth by measuring the...
Use of Conventional Artificial Intelligence Methods in the Identification of Frailty: A Scoping Review
CONCLUSIONS: Like the broader frailty literature, emerging AI tools lack a consistent definition of frailty, leading to design and implementation inconsistencies. The absence of knowledge user involvement may further limit the clinical relevance and equity of these technologies.