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The ExoSloNano system facilitates nanogold probe-based labeling of specific proteins of a wide range of sizes in live cells for cryo-electron tomography and correlative light and electron microscopy studies.

Utricle, a component of the inner ear vestibular system, is essential for balance. This study maps the cells and genes in the adult human utricle. It identifies distinct non-sensory cell types and reveals early responses to damage, providing insight into potential strategies for restoring balance.

The molecular mechanisms that regulate postnatal termination of neurogenesis remain poorly described. Here authors report Prdm16 deletion leads to the retention of radial glia in adulthood and prolonged postnatal neuroblast production.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Poly-ADP-ribose polymerase 1 (PARP1) plays key roles in DNA repair, transcription, and replication. Here, the authors used a single-molecule approach to reveal how PARP1 identifies DNA single-strand breaks in nucleosomes and how PARP1 activity regulates its DNA and chromatin binding kinetics.

The mitochondrial unfolded protein response (UPR^mt) has been linked to lifespan extension in Caenorhabditis elegans. Here, Bennett et al. identify negative regulators of the UPR^mt and, surprisingly, find that the UPR^mtis neither necessary nor sufficient for lifespan extension.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

G protein-coupled receptors and their effectors can now be released directly from a lipid bilayer using infrared irradiation for proteoform-level characterization by native top-down mass spectrometry. This represents a critical development for drug discovery, as the direct role of post-translational modifications in protein–protein and protein–drug interactions can be characterized.

Ultrasound imaging with acoustic reporter genes has been limited to a single ‘tone’, restricting the types of experiments that can be achieved. This work introduces two acoustic reporter genes that enable multiplexed imaging in vitro and in mice.

Insufficient pollen reception, pollen limitation, could exacerbate the threat of extinction or be a consequence of decline in threatened plants. Here, the authors conduct a meta-analysis on pollen limitation studies to find that threatened plants show stronger pollen limitation.

Synthetic microbial consortia are collections of strains which can segregate metabolic tasks for efficient use in biomaterials, biomanufacturing, and biotherapeutics. Here, the authors present a method to maintain and tune the ratio of two co-cultured bacterial strains via growth medium manipulation.

Jin et al. discovered Atlantic grey seal milk contains 332 complex sugars, including 166 novel structures. Seal milk rivals human milk complexity, includes giant molecules up to 28 sugar units, changes during lactation, and shows immune-boosting effects.

Sequencing of 144 ancient genomes from Shimao city and its satellites presents pedigrees among tomb owners spanning up to four generations showing predominantly patrilineal descent structure across Shimao communities, and possibly sex-specific sacrificial rituals.

The full potential of tunable perovskite nanocrystals is limited by complex synthesis space. Here, authors developed a self-driving lab that autonomously discovers and produces optimal scalable nanocrystals for next-generation photonic technologies.

The genetic basis of sex differences in Alzheimer’s disease (AD) is not well characterized. Here, authors report 2,320 sex-specific gene associations with 3 AD endophenotypes using bulk RNAseq data from 3 brain regions in ROS/MAP.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

In mdx mouse fetuses, the lack of dystrophin markedly impairs secondary myogenesis due to reduced muscle stem cell polarity. AAK1 deletion restores polarity and rescues secondary myogenesis, revealing fetal onset in Duchenne muscular dystrophy.

The role of individual lipid species in Alzheimer’s disease (AD) is not fully understood. Here, the authors performed global lipidomics on post-mortem dorsolateral prefrontal cortex collected from 316 participants in the ROSMAP cohort including asymptomatic and symptomatic AD.

Breeding status shapes bite force in social African Fukomys mole-rats: strong male competition drives higher bite force in breeding males, while weaker female competition results in lower bite force in breeding females.

The drivers of melanoma brain metastases (MBM) remain poorly understood. Here, the authors identify stress-induced HDAC8 activity as the driver of a neural crest-stem cell like transcriptional state that leads to MBM, and explore the molecular mechanism that drives this transition.

How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.

The direct contribution of aberrant epithelial cells to lung fibrosis is largely unknown. The authors use murine and human systems to identify how these cells activate fibroblasts, and how reciprocal signals cause them to enter a profibrotic state.

Bennett et al. develop a statistical approach for analyzing comparative glycomics data that accounts for inherent data dependencies, yielding robust and sensitive results. This approach can identify how these molecules vary in health and disease.

Enantioconvergent reactions convert both enantiomers of a racemic starting material into a single enantioenriched product. All currently known enantioconvergent processes necessitate the loss or partial loss of the racemic substrate’s stereochemical information. Now, an alternative approach has been developed that proceeds with full retention of the racemic substrate’s configuration.

LIG3α forms a complex with XRCC1 during single strand break and base excision repair. Here, the authors show that LIG3α displays higher affinity for nicks than XRCC1 and binds with its N-terminal ZnF domain more avidly to an undamaged nucleosome.

In this study, the authors present an analysis of the malaria burden in sub-Saharan Africa between 2000 and 2015, and quantify the effects of the interventions that have been implemented to combat the disease; they find that the prevalence of Plasmodium falciparum infection has been reduced by 50% since 2000 and the incidence of clinical disease by 40%, and that interventions have averted approximately 663 million clinical cases since 2000, with insecticide-treated bed nets being the largest contributor.

Mazan-Mamczarz, Tsitsipatis and colleagues apply single-cell and spatial transcriptomics to mouse models of atherosclerosis to map senescent cells contributing to plaque instability and arterial remodeling. They define a transcriptomic signature of vascular senescence.

Bennett and colleagues find that auxin modulates water uptake in Arabidopsis roots by negatively regulating the expression of water channel aquaporins to allow lateral root emergence. The functional importance of aquaporins is supported by a mathematical model that shows delayed lateral root emergence when aquaporin levels are perturbed, as well as by the effects observed after aquaporin overexpression or mutation.

Bioenergetic capacity, the ability to maintain energy balance under stress, can be monitored using blood acylcarnitine profiles. Improving this capacity may slow Alzheimer’s disease progression.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

The next generation of managers must be fit for a net-zero, nature-positive economy.

TCR-TRANSLATE, a deep learning framework adapting machine translation to immune design, demonstrates the successful generation of a functional T cell receptor sequence for a cancer epitope from the target sequence alone.

Radiation workers need accurate monitoring of X-ray exposure, but existing solutions are either inaccessible, expensive, or provide delayed feedback. This paper presents OpenDosimeter, a low-cost and open design solution to the problem.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Research identifies MEF2C as a human-specific switch that keeps microglia in balance. Loss of MEF2C tips microglia toward inflammatory and aging-like states that link to autism and Alzheimer’s disease.

Here authors demonstrate how a 2D hybrid perovskite melts and forms glass, uncovering atomic-scale structural and dynamic evolution across the crystal–liquid–glass transition. Local structural motifs are retained, advancing understanding of amorphous hybrid materials.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Heo, Xu et al. used comprehensive plasma proteomics to identify 416 plasma proteins (294 new) associated with Alzheimer’s disease and applied machine learning to select 7 proteins that were highly predictive of Alzheimer’s disease across multiple cohorts.

Single-cell RNA sequencing and spatial transcriptomic approaches reveal major expression changes in outer root cell types when grown in soil versus gel conditions, and also uncover how root tissues communicate and adapt to contrasting soil conditions at single-cell resolution.

Here, the authors present a timeline of human influence on the ecology of the Upano Valley (Ecuador) spanning the last 2770 years. They demonstrate how Pre- and Post- Columbian of maize cultivation and changing patterns of land use have produced a distinct forest composition today.

Historical climate adaptation can give insight into the potential for adaptation to contemporary changing climates. Here Bennett et al. investigate thermal tolerance evolution across much of the tree of life and find different effects of ancestral climate on the subsequent evolution of ectotherms vs. endotherms.