Topic: Healthy Aging

Health & MedicineSeptember 25, 2026

Bright monomeric fluorescent protein elite-niRFP704 for two-channel near-infrared STED nanoscopy.

The near-infrared (NIR) spectral region is attractive for live-cell imaging, due to low autofluorescence and reduced phototoxicity. Some phytochrome-derived fluorescent proteins absorb and emit fluorescence in the NIR, but have short fluorescence lifetimes and relatively low quantum yields, requiring higher laser powers thus limiting their usefulness for live-cell superresolution microscopy. Using the bacterial phytochrome miRFP703 as a template, we screened for variants with longer fluorescence

Health & MedicineSeptember 25, 2026

Quantitative nanoscale imaging shows peptide-MHC I complexes are monomeric and spatially regulated in human dendritic cells.

Major histocompatibility complex class I (MHC I) molecules present antigenic peptides to cytotoxic T cells, a process central to immune surveillance. However, the nanoscale spatial organization of peptide-MHC I (pMHC I) on human dendritic cells (DCs), key initiators of cytotoxic T cell responses, remains largely unexplored. Here, we combine high-affinity soluble T cell receptors with DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) to quantitatively map and count defi

Health & MedicineSeptember 25, 2026

Cannabinoid tolerance relies on CB 1 receptor ubiquitination by NEDD4L.

Cannabinoids, the active components of cannabis, exert numerous acute effects in the brain by engaging cannabinoid CB 1 receptors (CB 1 Rs). However, tolerance emerges rapidly after repeated drug exposure, undermining the efficacy of cannabinoid-based therapies and contributing to cannabis-associated adverse effects. Although the processes of CB 1 R short-term desensitization (i.e., receptor uncoupling and internalization) are well characterized, the mechanisms underlying CB 1 R long-term tolera

Health & MedicineSeptember 15, 2026

Integrative modeling of the genome structure and dynamics in fission yeast.

Genome organization in the nucleus is highly structured and dynamic. Recent advances in genomic technology have enabled the measurement of genome-wide architecture and locus-specific motion, yielding contact maps and live-cell trajectories. However, these outcomes are derived from different modalities and are not directly comparable, with their quantitative integration being a key challenge. Here we establish a genome-wide live-cell imaging platform in fission yeast Schizosaccharomyces pombe , t

Health & MedicineSeptember 15, 2026

Resolving cell lineages and gene functions in the developing mouse gastrointestinal tract using in utero transduction.

How diverse cell lineages emerge and are genetically regulated during organogenesis are central questions in understanding the developmental origins of disease. However, the mouse gut, including its intrinsic enteric nervous system (ENS) derived from migratory neural crest, has remained difficult to experimentally target. Here, we introduce an in utero lentiviral nano-injection strategy that enables early and efficient access to progenitor cells of all major cell types within the developing gut

Health & MedicineSeptember 15, 2026

Formin-1 maintains cochlear microtubule architecture required for hearing in humans and mice.

Formin proteins contribute to the cytoskeletal organization of multiple mammalian organ systems. Genetic defects in formins lead to neurologic, renal, reproductive, and cardiac disorders, but no human phenotype has been described for mutation of FMN1 , encoding formin-1, the first-identified formin. In an extended Palestinian kindred, autosomal recessive congenital hearing loss proved due to homozygosity for FMN1 c.2162-2A>G, which leads to aberrant splicing, nonsense mediated decay, and abse

Physical/TechSeptember 15, 2026

Imaging the Meissner effect in lanthanum hydride using diamond quantum sensors.

Lanthanum hydride has attracted significant attention in recent years due to its signatures of superconductivity at around 250 K. However, the required megabar pressures present extraordinary challenges in verifying its Meissner effect. Although nitrogen-vacancy (NV) centers in diamond offer a solution, their application has been limited by insufficient working pressures. In this work, using a gaseous pressure-transmitting medium, the working pressure of NV centers is extended to nearly 180 GPa.

Health & MedicineSeptember 11, 2026

Metax enables accurate cross-domain taxonomic profiling of metagenomes.

Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 sam

Health & MedicineSeptember 11, 2026

Joint impact of pathological burden and cognitive resilience on Alzheimer's disease risk.

Alzheimer's disease (AD) is conventionally framed as a consequence of progressive amyloid-β and tau pathology, yet substantial heterogeneity in cognitive outcome at any given level of pathological burden indicates that cognitive resilience constitutes a parallel determinant of disease risk. Here we test whether pathology and resilience function as independent and synergistic dimensions of incident AD dementia. In 3,119 older adults from the China Cognition and Aging Study, followed for a m

Health & MedicineSeptember 10, 2026

In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia.

The ciliary transition zone (TZ) regulates ciliary proteome composition, yet its molecular architecture, protein content, and contribution to motile ciliopathies remain poorly defined. We applied in situ cryo-electron tomography and subtomogram averaging to human multiciliated epithelial cells. This approach resolved TZ-specific doublet microtubules at subnanometer resolution and identified nine constituent proteins. We identified that ECT2L and DZANK1 form the major linker complexes between adj

Physical/TechSeptember 10, 2026

Noncoding transcription controls the developmental dynamics of long-range gene regulation.

The genomic regions regulating gene expression are often themselves transcribed into a variety of noncoding RNAs (ncRNAs). However, the regulatory roles of this noncoding transcription remain largely unknown. By using live imaging, we reveal that the sequential transcription of ncRNAs emanating from distinct regulatory elements underlies gene activation in Drosophila embryos. Single-allele co-visualization uncovers that optimal gene activation is achieved by only moderate levels of enhancer acti

Health & MedicineSeptember 10, 2026

Mechanism of membrane perforation in rotavirus cell entry.

Cell entry of nonenveloped animal viruses requires translocation of a macromolecular assembly across a cellular membrane. Double-stranded RNA viruses introduce into the target cell an inner capsid particle that does not uncoat further. Instead, it extrudes capped viral mRNA by virtue of polymerase and capping activities within it. As described here, we used cryogenic electron tomography to visualize the full course of rhesus rotavirus entry, from cell attachment and virion uptake to release of t

EnvironmentSeptember 8, 2026

Major role for internal variability in tropical Pacific warming pattern over satellite era.

Home to El Niño, the tropical Pacific is a key player in the global climate system. While most of the planet has warmed during the satellite era of 1982-2024, the eastern tropical Pacific surface has mysteriously cooled. What is troubling is that fully coupled global climate models mostly fail to simulate this distinctive pattern. By replacing wind stress applied to the ocean with observations, here we show that climate models successfully reproduce the La Niña-like (LN) trend pattern

EnvironmentSeptember 8, 2026

State-sponsored agenda setting: Measuring the impact of narrative laundering.

Foreign information manipulation and interference (FIMI) is an important part of the digital information ecosystem, yet its effects are poorly understood. Most research analyzing FIMI to date is descriptive, exposing efforts to erode trust, promote favorable narratives, and target specific communities. Existing work evaluating the impacts of FIMI contrasts those directly exposed to FIMI messaging (by viewing the original messages) with those who were not, finding little evidence of changes in be

Health & MedicineSeptember 8, 2026

Intratumoral injection of EpCAM BITE, IL-12, and GM-CSF mRNA-LNPs blocks the growth of local treated and distant untreated tumors.

We have previously shown that a T cell engaging bispecific humanized anti-human EpCAM-CD3 antibody efficiently kills a human EpCAM positive human xenograft in an NSG partially humanized mouse injected intravenously with human T cells when the anti-EpCAM-CD3 was delivered intratumorally as an mRNA-LNP. To extend these results we tested the effects of combining the anti-human EpCAM-CD3 with various cytokines injected into a tumor on the left side of NSG mice and an uninjected tumor on the right si

Society & CultureSeptember 8, 2026

Brain metabolic correlates of heroin addiction severity during abstinence and heroin versus social seeking: A PET study in rats.

Only a subset of heroin users develop addiction, characterized by binge-like heroin use and preference for heroin over other rewards, including social rewards. We recently established a rat model that captures these features. We trained rats to lever-press for social interaction and heroin (or saline, control) infusions and then tested heroin and social seeking and heroin-vs.-social choice. During 3 to 5 abstinence weeks, we used 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) positron emission tomograp

Health & MedicineSeptember 8, 2026

Lysine iminylation derived from ω-3 polyunsaturated fatty acids.

Protein posttranslational modifications (PTMs) play a central role for regulating protein function and cellular processes, with many PTMs arising from reactions with electrophilic metabolites. Here we extend the known landscape of PTMs with the identification of "lysine C 3 -iminylation," the conjugation of protein lysine residues with propionaldehyde. To stabilize iminylation for mass spectrometric analyses and distinguish it from other isomeric PTMs, we developed a fixation and stable-isotope

Health & MedicineSeptember 3, 2026

Longitudinal dynamics of gene expression and metabolomics in an aging population cohort.

Multiomic profiling provides a comprehensive physiological overview at the molecular level, but understanding of its spatiotemporal dynamics remains limited in human populations. We profiled longitudinal whole-blood gene expression and metabolite levels in 335 females over 8 years. Levels of 5061 genes and 181 metabolites changed over time, with individual trajectories often diverging from population-level trends. Longitudinally variable genes showed cell type specificity and enrichment for agin

Health & MedicineSeptember 3, 2026

Thalamic NRXN1-mediated input to human cortical progenitors drives excitatory neurogenesis.

The human cerebral cortex develops through coordinated signals from within the cortex and from other brain regions, including the thalamus. However, how thalamic neuronal projections influence early human cortical development remains less well-understood. In this study, we fused cortical and thalamic organoids to investigate how thalamic input shapes the maturation of human cortical cells. Using single-nuclei RNA-sequencing and cellular imaging, we found that thalamic input increases the product

Health & MedicineSeptember 3, 2026

Natural history and clinical impact of epilepsy in adults with Down syndrome: a multicentre clinical study.

As individuals with Down syndrome age, they face high risks of Alzheimer's disease and epilepsy. With symptomatic Alzheimer's disease, late-onset myoclonic epilepsy in Down syndrome (LOMEDS) often emerges. We aimed to examine how epilepsy develops in Down syndrome, its timing relative to Alzheimer's disease symptom onset, and its effect on prognosis. We conducted a multicentre, observational, longitudinal study across seven international cohorts with an aggregate observation window from Oct 24,

Artificial IntelligenceSeptember 3, 2026

Leveraging generative AI for causal inference with unstructured data

We introduce GenAI-Powered Inference (GPI), a statistical framework for causal inference using unstructured data, including text and images. GPI leverages open-source pretrained Generative AI (GenAI) models—such as large language models and diffusion models—not only to generate unstructured data at scale but also to extract low-dimensional representations that are guaranteed to capture their underlying structure. Applying machine learning to these representations, GPI enables estimation of causa

Health & MedicineSeptember 1, 2026

De novo pan-rhodamine binders for fluorescence microscopy from mammalian cells to extremophiles.

Fluorescent imaging in live cells is a cornerstone of life sciences. While natural fluorescent proteins have been engineered to enhance individual features, no existing tag combines ideal properties into a single system: high brightness, reversible binding, compact size, and stability across diverse conditions. Here, we achieve this through de novo design of rhodamine binders (Rhobin). To harness the broad repertoire of rhodamine fluorophores, we developed a generalizable design strategy for a p

Health & MedicineAugust 30, 2026

124I-Evuzamitide Positron Emission Tomography/Computed Tomography for Diagnosing Cardiac Amyloidosis: The REVEAL Nonrandomized Clinical Trial.

Diagnosing cardiac amyloidosis remains challenging because current imaging approaches are limited to transthyretin amyloidosis. A noninvasive test capable of directly imaging cardiac amyloidosis from various amyloid types and in multiple organs could address an important unmet diagnostic need. To evaluate the sensitivity and specificity of 124I-evuzamitide positron emission tomography (PET)/computed tomography (CT) for diagnosing cardiac amyloidosis. Prospective, multicenter (18 US centers), sin

Health & MedicineAugust 30, 2026

Anticoagulation Monotherapy vs Antiplatelet Monotherapy After Transcatheter Aortic Valve Implant: The ACASA-TAVI Randomized Clinical Trial.

Transcatheter aortic valve implant (TAVI) is increasingly being performed in younger and healthier patients with severe aortic valve stenosis. Antithrombotic therapy after TAVI is a key element of optimizing valve durability and clinical outcomes. To evaluate the safety and efficacy of a factor Xa inhibitor non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy strategy vs an acetylsalicylic acid (ASA) monotherapy strategy after TAVI. Between December 2021 and June 2025, 360 participants

Health & MedicineAugust 29, 2026

Digital Outreach to Improve Statin Refills in Patients With Low Statin Adherence: The ADHERE-ASCVD Randomized Clinical Trial.

Statin nonadherence is a leading, addressable driver of preventable cardiovascular events. Although health systems routinely use outreach to promote preventive care, most strategies are static and lack evidence from randomized clinical trials. To determine whether an adaptive, sequential digital outreach strategy improves short-term statin refill vs usual communication among adults with established atherosclerotic cardiovascular disease (ASCVD) or high ASCVD risk and recent nonadherence within a

Physical/TechAugust 27, 2026

Hypervision: An on-chip hyperspectral microsystem for online video-rate computational imaging.

In this work, we tackled the long-standing challenge of the massive computation for hyperspectral imaging that is required to reconstruct and process large-volume spatial-spectral data cubes. Specifically, we designed a hardware accelerator, fabricated as a neural processing unit (NPU) capable of 9.3 tera operations per second at 16-bit integer (INT16), alongside a topology-aware structured pruning strategy for a lightweight reconstruction network. Through integration with our HyperspecI sensor,

Health & MedicineAugust 25, 2026

CXCR4-targeted dual softener for inducing senescence therapy in hepatic fibrosis.

Hepatic fibrosis is a central pathological driver of chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease, which collectively impose a growing global health burden. Fibrosis is primarily mediated by persistent activation of hepatic stellate cells (aHSCs) and excessive deposition of stiff extracellular matrix (ECM). The dense and rigid ECM-aHSCs network severely hinders drug delivery and penetration, posing a major challenge

Health & MedicineAugust 25, 2026

Initiation of rotational collective migration in Drosophila through tissue geometry and mechanochemical feedback.

Collective migration of epithelial cells drives diverse tissue remodeling processes. In many cases, a free tissue edge works alone or in combination with other external cues to align the cells for collective movement, but how edge-free or closed epithelia become polarized for directed migration without these cues is unclear. Here, we use the rotational migration of the follicular epithelial cells in the Drosophila egg chamber to explore how cells in an edgeless epithelium initiate rotational col

Health & MedicineAugust 25, 2026

Human Hsp70 paralogs display selective J-domain interactions tuning proteostasis under stress.

Hsp70 chaperones are central regulators of proteostasis, mediating folding, refolding, degradation, and aggregation-prevention. Their activity is tuned by the diverse J-domain proteins (JDPs), which both recruit client proteins and stimulate Hsp70 ATP hydrolysis via interaction with a conserved J-domain. The cytosol contains four Hsp70 paralogs-the stress-inducible HSPA1A/B and HSPA6, and the constitutively expressed HSPA8. Whether these act redundantly or carry distinct cellular functions has r

Health & MedicineAugust 25, 2026

Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain.

Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibit