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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...

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...

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...

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...

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...

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.

Charles Bennett and Gilles Brassard share this year’s $1 million A.M. Turing Award for work on quantum information

Proteomics enables the systematic elucidation of biological mechanisms underlying frailty. Through a large proteome-wide association study of 2,911 plasma proteins from 50,506 UK Biobank participants, we identified 1,339 proteins significantly associated with frailty, highlighting collagen-containing extracellular matrix and vesicle lumen pathways. Replication in the TwinGene study confirmed partial but consistent associations. Mendelian randomization analyses identified five potentially causal...

We present TLPath, a deep learning framework that predicts bulk-tissue telomere length from tissue morphology extracted from routine histopathology images. The central thesis of TLPath is that telomere length can be determined from tissue morphology. Trained on >5,000 whole-slide images across 919 individuals and 18 organs, TLPath discovers that extracted morphological features naturally separate young, middle-aged, and elderly individuals, demonstrating that aging causes architectural changes...

Protein phosphatase 2A (PP2A) regulates Tau hyperphosphorylation in Alzheimer's disease (AD). This study hypothesized that exercise increases adiponectin levels, activating PP2A to reduce Tau hyperphosphorylation and enhance hippocampal plasticity. The study utilized adiponectin knockout (Adipo^(-/-)) and hippocampal-specific PP2A knockdown (PP2A-KD) in mice with 3-week voluntary running and/or chronic stress to assess changes in Tau phosphorylation, adult neurogenesis, and cognitive...

Analysis of published papers on eight widely studied species suggests work on them is fading, but not everyone is worried

Single-cell spatial transcriptomes have demonstrated molecular and cellular diversity in the brain, but gene regulatory mechanisms underlying transcriptomic profiles and disease pathogenesis remain largely unknown in primates. Here we performed single-nucleus Assay for Transposase-Accessible Chromatin followed by sequencing (snATAC-seq) for ~1.6 million cells from 142 cortical regions of two male cynomolgus monkeys (Macaca fascicularis), and identified distinct chromatin accessibility profiles...

Losing track of personal experiences is a defining feature of Alzheimer disease (AD), arising from the spread of AD pathology through the brain circuits that support episodic memory. In this Review, we explore strategies to improve the function of episodic memory circuits in AD by leveraging the optimized use of neural resources. We introduce the circuit utilization framework, which builds on evidence that synaptic dysfunction, maladaptive responses and deficient adaptive plasticity contribute...

Perovskite solar cells tend to degrade much faster under day-night cycling conditions. One key reason lies in the periodic strain in perovskite film under cycling mode due to its soft crystal lattice nature. Here, we propose a dynamic reversible crosslinking strategy by introducing disulfide-mediated cross-linkable additive of 2-methacryloyloxyethyl-thioctate. Combining with carbon-carbon double bond, 2-methacryloyloxyethyl-thioctate crosslinks at grain boundaries at high temperature through...

Cyclophosphamide (CTX) is a first-line chemotherapeutic agent for various cancers but is associated with a significant risk of ovarian dysfunction, which may even progress to premature ovarian failure (POF). Granulosa cell senescence is a key phenotypic manifestation of this process. Hydroxychloroquine (HCQ) exerts anti-senescence effects in age-related diseases; however, its efficacy in preventing CTX-induced ovarian damage remains elusive. We aimed to verify the protective effect of HCQ using...

Aging is a major risk factor for the onset and progression of many neurodegenerative diseases. Inflammation is the body's natural defense mechanism against harmful stimuli. A growing body of research has highlighted the intricate relationship between aging and inflammation, with chronic low-grade inflammation, often referred to as "inflammaging," being a hallmark of the aging process. Cycloneolitsol (CL) is a C-32 cycloartane-type triterpene from Taxodium ascendens which has been reported to...

The present study aimed to investigate the effect of obstructive sleep apnea (OSA) and its treatment with continuous positive airway pressure (CPAP), the gold standard treatment for OSA on changes of telomere length and its associated mechanisms. In this mechanistic pilot study of a selective patient population (middle-aged men, BMI < 35 kg/m², moderate-severe OSA), a 6-month randomized, double-blind, and sham-controlled clinical trial was conducted (Clinical Trials: NCT04872816, April 29, 2021...

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Science speaks with ecologist Stefano Mammola about the power of humor to enhance science communication