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Amyloid-β as a target to suppress tonic PTH hypersecretion in hyperparathyroidism due to vitamin D deficiency

19 hours 58 minutes ago
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...
Chia-Ling Tu

Inside Out: How Cellular Localisation Shapes cGAS Functions in Health and Disease

19 hours 58 minutes ago
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...
Jiaqi Wu

Massively parallel quantification of mutational impact on IAPP amyloid formation

19 hours 58 minutes ago
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...
Marta Badia

Structural evolution of carbon frameworks realizes in vitro interfacial transport in metabolically reprogrammed senescent cells for senolysis

19 hours 58 minutes ago
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...
Xuelian Wang

Planar Li deposition and dissolution enable practical anode-free pouch cells

19 hours 58 minutes ago
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...
Lei Liu

CellVoyager: AI CompBio agent generates new insights by autonomously analyzing biological data

19 hours 58 minutes ago
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...
Samuel Alber

Combined effects of ageing and type 2 diabetes mellitus on human dental mechanics

19 hours 58 minutes ago
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...
Sarolta Antal