npj Microgravity

The transcriptomic interaction between altered gravity and innate immunity remains largely unexplored. In this study, we established a novel dual-stress model combining 3g hypergravity with lipopolysaccharide (LPS) immune challenge in 5 days post-fertilization (dpf) zebrafish (Danio rerio) larvae. RNA sequencing revealed that exposure to hypergravity alone induced no differentially expressed genes (DEGs), indicating a remarkable transcriptional resilience. In contrast, the addition of an immune challenge under hypergravity conditions triggered a substantial transcriptomic response involving 2,706 DEGs. Functional enrichment analyses identified significant alterations in pathways related to immune function, development, and circadian regulation. Targeted qPCR analyses further validated the expression patterns of selected genes. These findings suggest that while zebrafish larvae can effectively tolerate hypergravity alone, the combination of gravitational and immune stressors elicits profound molecular responses. This study provides new insights into the interplay between altered gravity and innate immunity using an animal model, contributing to future strategies aimed at safeguarding astronaut health and supporting space-based aquaculture systems.

Background: Commercial spaceflight now carries civilians on short missions, yet their stress-axis physiology is poorly described. Earlier shuttle data suggest that sympathetic responses predominate after short flights and glucocorticoid responses after long ones. The neutrophil-to-lymphocyte ratio (NLR) is a low-cost readout of both. Methods: Preregistered secondary analysis of open clinical laboratory data (NASA Open Science Data Repository OSD-569 and OSD-575) from the four Inspiration4 crew members, each sampled seven times: three draws before launch, one the day after return (R+1) and three during recovery (R+45 to R+194). Log-transformed NLR was modelled with a linear mixed model with a random intercept per crew member and Kenward-Roger inference. Lymphocyte and eosinophil counts and C-reactive protein were secondary outcomes with false discovery rate correction. Results: All 28 draws were analysed. NLR at R+1 did not differ from pre-flight (fold change 1.04; 95% CI 0.81 to 1.34; p = 0.73); two crew members increased (+25% and +46%) and two decreased (-27% and -11%). During recovery NLR was 23% lower than pre-flight (fold change 0.77; 95% CI 0.64 to 0.92; p = 0.005). No secondary outcome changed after correction; lymphocytes were 18% lower at R+1 (95% CI -35% to +4%; q = 0.31). Between-person differences explained 58% of the variance. An ordinary regression ignoring repeated measures missed the recovery effect (p = 0.08). Conclusions: A 3-day orbital flight produced no consistent leukocyte stress signature one day after return. The lower NLR during recovery suggests that pre-flight values, not recovery values, deviate from the resting state, which has implications for how baselines are defined in short-duration spaceflight studies.

To reduce health risks for human space exploration, it is important to model the effects of deep-space radiation on biological systems. The budding yeast Saccharomyces cerevisiae is a common model organism in space radiobiology, but little is known about how radiation damage to individual cells translates into the population-level effects that experiments measure. The Agent-Based Model for Microbial Populations Exposed to Radiation (AMMPER) is a spatially explicit agent-based model that simulates the effects of ionizing radiation on S. cerevisiae cells and produces population-level results. Its goal is to improve experiment design and data interpretation. AMMPER-1 demonstrated that agent-based simulations can qualitatively reproduce the effects of proton radiation on the growth rate of wild-type and DNA-repair mutant yeast. Here, we present AMMPER-2, which addresses limitations of the first model and expands its capabilities. AMMPER-2 incorporates the dynamics of the redox dye alamarBlue, a data type commonly generated in spaceflight microbiology experiments, and models the fate of reactive oxygen species in more detail. It also adds an improved graphical interface and runs faster. AMMPER-2 remains easy to execute in Python on a standard personal laptop, providing space biologists a tool to explore experimental conditions, generate hypotheses, and interpret data from microbial space radiation experiments.

Simulated microgravity provides a controlled perturbation for testing how loss of mechanical load affects human tissues. After 24 hours in rotating-wall vessels, neural, cardiac and tonsil organoids developed tissue-specific transcriptional responses that overlapped published spaceflight datasets, accompanied by higher transcriptomic-age estimates in neural and cardiac models, altered cardiac-organoid contraction dynamics and modified tonsil-organoid antiviral gene-expression signatures. These findings establish a multi-organoid framework for studying acute responses to gravitational unloading.

Meteorite impact structures on earth represent unique terrestrial analogues of extreme planetary environments where fractured lithologies, hydrothermal alteration, elevated concentrations of radionuclides, and prolonged water-rock interactions create ecological niches for specialized microbial communities. The Palaeoproterozoic Dhala impact structure in north-central India is characterized by uranium-bearing impactites and possesses a very high concentration of Uranium (up to 99.5 ppm) that makes it a unique natural laboratory to investigate microbial adaptation to radioactive and metal-rich geological environments. In addition, the Dhala structure harbors specialized radiotoxic hydrothermal mineral phases such as coffinite and pitchblende, which show a globally distinct and biologically unexplored niche. The present investigation is the first in-depth, whole-genome metagenomic study of soil and water samples of uranium-rich sites from the Dhala structure, exploring the whole microbial community (Bacteria, Archaea, Eukaryotes, and Viruses) up to the species level present in the samples. The cross-domain metagenomics analysis identified a highly unique and resilient microbiome that consists of bacteria, archaea, eukaryotes, and viruses, coevolved under prolonged radiological and multiple metal stress. Functional metagenomic analysis revealed numerous metabolic adaptations responsible for their survival, homeostasis, and biomineralization in situ. The deep sequencing method further enabled the identification of 58 functional genes directly involved in uranium bioremediation. Furthermore, this study revealed important pathways for radionuclide reduction, cellular efflux, and biotransformation. Novel findings of the present study point out the in-depth evolutionary relations of biosphere-geosphere interaction within an ancient hypervelocity impact-generated ecosystem. In a nutshell, the Dhala extremophiles with novel genetic makeup present an untapped and promising reservoir for the development of eco-friendly, next-generation microbial bioremediation strategies to efficiently tackle the global anthropogenic contamination of uranium and the challenges of nuclear waste management. Thus, the present study establishes Dhala structure as an unparalleled site for environmental geomicrobiology, microbial evolution, and astrobiology.

Despite being a topic of early experimental studies, the effects of immersion-emersion cycles and temperature on the heart rate of intertidal Mytilus mussels have not been fully characterized. Using a recently released intertidal chamber paired with our own software package, we conducted a multiday experiment and continuously monitored the heart rate of the blue mussel Mytilus edulis. Under normal conditions, we detected a subtle spike in heart rate upon emersion before the eventual decline, as well as an overshoot upon reimmersion. Additionally, heart rate was sensitive to temperature changes during immersion but less responsive during emersion. These patterns were markedly altered following an unintended prolonged emersion event, which led to the loss of the emersion spike, an extended reimmersion overshoot, and heightened thermal sensitivity on top of an overall elevation in heart rate. However, the heart rate gradually returned to the pre-event baseline over the following days, demonstrating the significant resilience of the mussels. Our study highlights the potential of high-resolution physiological data in assessing the effects of environmental stressors on coastal ecosystems.

Known for their rapid water surface locomotion, whirligig beetles (Gyrinidae) are also fast divers. They can transition from the surface to underwater swimming in under 100 ms. Diving requires them to generate sufficient hydrodynamic torque to break the water surface and reorient the body. However, the mechanism by which whirligigs create the necessary pitch-down torque is unknown. Here, we show that their diving is achieved by bending the abdomen. The inertial hydrodynamic pressure on the flexed abdomen generates the torque necessary for surface breaking and body rotation. The torque is maximized at an abdominal angle of 45{degrees}, whereas for effective diving, whirligigs display a preferential abdominal angle of around 28{degrees}, closely aligning with the angle that maximizes the torque-to-drag ratio. This abdominal angle is optimized by balancing torque generation with the drag penalty. Our findings inspire a mechanism for surface-to-underwater transition, offering design principles for multimodal robots capable of locomotion across the air-water interface.

Traumatic brain injury (TBI) is a leading cause of long-term neurological disability, affecting 50-60 million people annually. Cascading secondary injury mechanisms, including oxidative stress and neuroinflammation, impair motor and cognitive function, while current therapies often manage symptoms rather than restore lost neurological function. This study investigated an ultrasound-activated piezoelectric hydrogel scaffold composed of barium titanate nanoparticles (BTNPs), sodium alginate (SA), and polyethylene oxide (PEO). The hypothesis was that TBI flies receiving the scaffold and ultrasound would display a higher climbing assay pass rate than TBI flies receiving no treatment or BTNPs alone. TBI was induced in Drosophila melanogaster with a high-impact trauma (HIT) apparatus. Treatments were applied by opening and resealing the fly head cuticle, followed by ultrasound stimulation. Motor recovery was quantified with a climbing assay across four groups (N=10 flies per group), which measured the percentage of flies that could cross a 5 cm mark within 30 seconds. Assay validity was supported by a statistically significant difference between flies without TBI and those with TBI using Mann-Whitney U testing (p=0.0035). Although TBI treatment groups did not differ significantly (p>0.05), median pass rates increased from injury control (35%) to BTNPs (45%) to scaffold (50%). However, high inter-trial variation, a 45.2% procedural mortality rate, and small sample size limited statistical power. These results suggest that piezoelectric electrospun hydrogel scaffolds may be a pathway for safer and more biocompatible restoration after TBI, but provide insufficient evidence to conclude that the scaffold significantly improved motor recovery.

Antifreeze proteins and peptides adhere to ice crystals and inhibit their growth, resulting in freezing point depression. AFP6 is an abundant antifreeze peptide in the blood serum of winter flounder (Pseudopleuronectes americanus). This 37-residue peptide forms an amphiphilic -helix with a hydrophobic ice-binding surface. In this study, prediction of the peptide structure suggested the formation of an antiparallel dimer burying the hydrophobic surfaces of both subunits. The oligomerisation of AFP6 was therefore examined in aqueous solutions using size-exclusion chromatography and chemical crosslinking along with ice-binding evaluation. Crosslinking of non-amidated AFP6, followed by denaturing electrophoresis, revealed bands consistent with monomers and dimers, whereas results for the amidated form and a recombinant mutant suggested additional larger forms. Bands consistent with the presence of monomers and dimers were also predominant following non-amidated AFP6 crosslinking under a variety of solution conditions, with smaller proportions of peptide assembled up to tetrameric sizes; however, the larger oligomers appeared to be absent from AFP6 treated with sodium bicarbonate. Isolated oligomers of non-amidated AFP6 produced ice crystal morphologies and thermal hysteresis comparable to those for the unfractionated peptide suggesting similar interaction with ice. Oligomerisation of AFP6 may allow greater solubility of this amphiphilic -helical peptide in aqueous solutions.

Identification of early microfossils relies on morphological and chemical criteria assumed to be unique to life, but whether abiotic microstructures can satisfy these criteria has not been rigorously tested. Hydrothermal environments preserve microfossils but are also efficient geochemical reactors for abiotic reactions. Protocells form in hydrothermal conditions and represent a plausible abiotic analogue to early microfossils. Here we show that protocells form from simple organic molecules in low-temperature, alkaline hydrothermal conditions in the presence of silica and produce spheres, filaments, and lenticular structures that strongly resemble the morphology of purported microfossils in Archaean silica cherts. FTIR spectroscopy provides overlapping chemical signatures across protocells, microorganisms, and geologic microstructures. In addition, the FTIR R3/2 ratio, a chemometric index often used to discriminate domains and determine biogenicity, identifies eight different protocell systems as either bacterial, archaeal, or eukaryotic. These data suggest that protocells preserved in ancient hydrothermal deposits can satisfy current biogenicity criteria, undermining the reliability of interpretations of the early fossil record. As life detection is the primary objective for current space exploration endeavours, robust biogenicity protocols that account for abiotic signatures are essential.

Biofilm mechanics depend strongly on growth history, hydration, nutrient availability, and interfacial attachment, yet conventional rheology requires harvesting and transfer that can perturb the as-grown structure. Here, we introduce bioRheoFlow, a 3D-printed rheometer-mounted platform for cultivation and mechanical characterization without sample transfer. The platform combines evaporation compensation with static or axial nutrient flow, and benchmark measurements validate its rheometric performance. Applied to Pseudomonas putida and Pantoea sp., bioRheoFlow reveals that biofilms cultivated in situ under axial flow exhibit substantially higher elastic moduli than conventionally grown and scraped samples. Despite similar linear-viscoelastic stress ranges, the species show distinct nonlinear responses: P. putida exhibits a lower crossover stress and more abrupt failure, whereas Pantoea sp. sustains larger stresses and deformations. Creep suggests contributions from bulk deformation and biofilm-substrate interactions. bioRheoFlow provides a controlled framework for probing growth-conditioned mechanics in living biofilms.

Chronic intermittent hypobaric hypoxia is an occupational exposure experienced by workers who alternate between high-altitude worksites and lower-altitude resting locations. Its effects on cardiac autonomic modulation and electrocardiographic parameters remain insufficiently characterized in Andean workers. This study aimed to compare heart rate variability and electrocardiographic parameters between workers exposed to chronic intermittent hypobaric hypoxia and controls working permanently at lower altitude in Arequipa, Peru. An observational cross-sectional study was conducted in 96 male workers aged 20-60 years. The exposed group included 53 workers performing rotational shifts at altitudes [&ge;]3,000 m above sea level with rest periods at <2,500 m, while the control group included 43 workers working permanently at <2,500 m. Heart rate variability was assessed during the morning rest period in Arequipa, at approximately 2,300 25 m above sea level, using a Polar(R) H10 heart rate sensor after 15 minutes of rest. Participants also underwent standard 12-lead electrocardiography. Vital signs were clinically similar between groups. No statistically significant differences were observed in PR interval, corrected QT interval, time-domain heart rate variability parameters, or frequency-domain heart rate variability parameters. In this sample of apparently healthy male workers evaluated during their rest period at moderate altitude, exposure to chronic intermittent hypobaric hypoxia was not associated with significant differences in resting heart rate variability or standard electrocardiographic parameters.

Stressful events are associated with long-term adverse health impacts, but the causal mechanisms linking these exposures to subsequent disease remain poorly understood. One plausible mechanism is persistent changes to hormonal signaling that regulate metabolic homeostasis. Here, we examine the long-term impacts of stress associated with exposure to the 2004 Indian Ocean tsunami on levels of free triiodothyronine (FT3), a circulating measure of biologically active thyroid hormone, using data from the Study of Tsunami Aftermath and Recovery. We measure biomarkers 20 years after the tsunami in a population-representative sample age 35y+ in 2024 who, at the time of the tsunami, were living along the coast of Aceh, Indonesia, the most affected part of the Indian Ocean Basin. Because respondents were first interviewed before the tsunami and subsequently tracked regardless of migration, the sample avoids a major source of selection bias common in long-term disaster studies. We identify the causal effect of tsunami exposure using variation in community-level tsunami mortality, comparing communities within the same sub-district. We find that greater tsunami exposure reduced levels of FT3 20 years later. Exposure also altered relationships between FT3, body composition, and cortisol and increased cardiometabolic risk. These findings identify persistent alteration of thyroid hormone physiology as a potential pathway linking severe stressful exposures to long-term cardiometabolic disease risk.

Environmental microplastics and nanoplastics (MNPs) are emerging contaminants that accumulate in human tissues, including the brain, yet their mechanistic impact on the nervous system remains poorly understood. Converging postmortem evidence indicates increased MNP burden in brains from individuals with dementia, suggesting a potential link between plastic accumulation and disorders of the nervous system. However, whether MNPs directly contribute to brain aging and ensuing neurodegenerative processes, or disrupt neurodevelopment, is unknown. Here, we show that exposure to environmentally relevant MNPs induces cellular senescence and innate immune transcriptional programs in human brain organoids. Using region-specific cortical organoids, we demonstrate that synthetic polystyrene (PS), polyethylene terephthalate (PET), low-density polyethylene (LDPE), and high-density polyethylene (HDPE), as well as environmental ocean-derived MNPs (eMNPs) isolated from the coast of Hawaii, elicit a robust neuroinflammatory response. Transcriptomic analyses revealed activation of senescence-associated secretory phenotype (SASP) pathways. MNP exposure further disrupted neurodevelopmental trajectories, impairing neuroectodermal differentiation and redirecting lineage commitment toward mesoderm-like states, with concomitant enrichment of choroid plexus-like populations and a marked imbalance in neuronal and glial differentiation. These developmental alterations occurred in parallel with a pro-inflammatory and senescent microenvironment, suggesting coordinated disruption of developmental and aging programs. Importantly, high-density multielectrode array recordings revealed that MNP exposure altered electrophysiological activity and neuronal network dynamics, demonstrating that MNP-driven perturbations translate into dysfunctional neurological outcomes. Collectively, our findings identify MNPs as potent disruptors of human neurophysiology, linking plastic exposure to altered developmental trajectories, cellular senescence, neuroinflammation, and impaired neuronal network activity, providing mechanistic insights into how plastic accumulation may contribute to impaired brain dynamics.

Background: Head acceleration events (HAEs) are common in contact sports, but season-long exposure and its relationship with cognitive performance in amateur British American football remain poorly characterised. Methods: Thirty male players were recruited from three British American football teams. Cognitive performance was assessed pre-season, mid-season, and post-season using the Sport Concussion Assessment Tool 6 and computerised Stroop, 2-back, Go/No-go, and visual-search tasks. Seasonal cognitive analyses included 23 participants with available data. HAEs were quantified using helmet-mounted accelerometers; exposure-linked analyses were restricted to 19 participants who provided sufficiently complete sensor recordings across contact training sessions and competitive matches. Seasonal cognitive changes were assessed using mixed-effects models. Associations of in-season HAE metrics and previous contact-sport seasons with global cognitive change were examined using simple linear regression and elastic-net regression. Results: In the 19-participant exposure-linked cohort, prior contact-sport exposure showed the strongest nominal univariate association with worse global cognitive change (r squared = 0.337, p = 0.009), although this did not remain significant after correction for multiple comparisons (Benjamini-Hochberg-adjusted p = 0.055). Corrected nested cross-validation indicated little out-of-sample performance for the multivariable elastic-net model (r = 0.144, predictive R squared = -0.008). Although previous contact-sport seasons had the largest standardised coefficient in the final full-cohort fit, predictor retention varied substantially across resamples. Conclusion: Prior contact-sport exposure showed the strongest exploratory association with relatively worse global cognitive change, whereas in-season HAE metrics showed weaker associations. However, the multivariable model did not demonstrate useful out-of-sample predictive performance, and the small exposure-linked cohort precludes firm conclusions regarding the relative importance of individual predictors.

Nanoplastic contamination is increasingly recognized as a biochemical stressor, yet the molecular determinants governing how polymer fragment size dictates protein-level interactions remain poorly understood. Here, we combine molecular docking and all-atom molecular dynamics simulations to characterize the interaction of polyethylene (PE) oligomers of increasing length (n = 3, 5, 7, and 14 repeat units) with human catalase, a tetrameric heme enzyme central to cellular antioxidant defense. Single-chain simulations reveal that short PE fragments (3-, 5-, and 7-mer) migrate from an initial domain-connector pose toward a heme-proximal, previously characterized inhibitor-binding site, whereas the 14-mer remains kinetically confined to a peripheral surface site, implicating short-chain PE as a potential catalase inhibitor. In multichain corona systems, backbone dynamics show a non-monotonic, chain-length-dependent destabilization, with the 3- and 5-mer inducing the greatest structural perturbation and the 14-mer best preserving native-like dynamics despite forming an extensive, percolating surface network across all four subunits. MM-PBSA free energy decomposition identifies van der Waals interactions as the dominant thermodynamic driver of binding, while electrostatic surface mapping indicates that cationic surface patches instead govern long-range spatial targeting of PE chains. These findings establish a framework linking nanoplastic fragment size to protein-level toxicity, with direct implications for assessing the biochemical risk of environmentally weathered polyethylene.

Infection following high-energy open fractures remains a major challenge. Open fractures are exposed to environmental and skin pathogens, which, along with traumatized tissue and implanted hardware, create a favorable environment for infection. 24-83% of open fractures yield positive culture results. Despite culture-positive wounds being at higher risk for infection, culture data are rarely used in clinical decision-making. Culture-positivity in open fractures is believed to indicate higher wound bioburden, but this hypothesis remains unconfirmed. This study aimed to correlate culture positivity and quantitative wound bioburden using next-generation sequencing (NGS) and to characterize patterns of bioburden and bacterial diversity amongst patients with open fracture and Fracture Related Infection. We hypothesized that higher wound bioburden would be associated with culture positivity. This secondary analysis of the METRC Bioburden Study included 78 patients with severe open tibia fractures who underwent standardized tissue sampling at definitive wound closure and at later fracture site revision surgery. DNA extracted from intraoperative tissue was analyzed via 16S rRNA gene amplicon sequencing. Quantitative bioburden metrics included bacterial read percentage and bacteria-to-human read ratio (BHR). Associations between sequencing-based bioburden, culture results, and clinical infection (CDC-defined) were evaluated using Mann-Whitney U tests, McNemars chi-squared tests, and unsupervised clustering analyses. Culture-positive samples exhibited significantly higher bacterial read percentages and higher log(BHR) values than culture-negative samples. Optimal thresholds yielded high sensitivity and specificity for both bacterial reads and BHR for predicting culture positivity. Neither baseline culture nor NGS positivity predicted later infection. However, follow-up samples from patients with established infection showed significantly higher bioburden and distinct microbiome structures. Clustering analyses identified two infection-associated microbial profiles: one with high bioburden and high diversity (polymicrobial infection) and one with low bioburden and low diversity (single-dominant pathogen). Culture positivity in open fractures correlates strongly with increased bacterial bioburden, indicating that positive cultures may primarily reflect microbial load rather than specific pathogens. Quantitative NGS-based measures, including bacterial read proportion and BHR, may offer a biologically grounded approach to assess wound contamination and may inform infection risk. Distinct bioburden-diversity patterns suggest heterogeneous infection phenotypes that may require tailored surgical and antimicrobial strategies.

Electromicrobial production (EMP) technologies aim to combine renewable electricity, CO2, and engineered microbes to make energy-dense molecules at efficiencies exceeding photosynthesis. CO2 can be electrochemically reduced to formate, which is far easier to handle at the bench than H2 or an electrode, but formate carries only two electrons per carbon against the six in a biofuel. The remaining electrons must come from oxidizing additional formate, from H2 oxidation, or from extracellular electron uptake (EEU), and no rigorous comparison of these options coupled to the choice of carbon assimilation pathway currently exists. We calculate upper-limit efficiencies for butanol production by six carbon assimilation pathways, each paired with all three electron delivery mechanisms, using electrochemical parameters drawn from a survey of the recent literature. Electrical to butanol energy conversion efficiencies range from 35.5 to 51.7%, corresponding to solar-to-fuel efficiencies of 11.7 to 17%, so even the least efficient route exceeds the 8% theoretical ceiling of algal photosynthesis. The serine variant of the reductive glycine pathway reaches an electrical energy conversion efficiency of when using H2 oxidation, within 1.9 points of the most efficient pathway, and is the only high-efficiency option that tolerates O2. This makes an EMP system that combines electron delivery by formate coupled with the serine variant of reductive glycine pathway highly attractive, as it presents few barriers to rapid, iterative engineering in the lab, and a high theoretical ceiling. Drawing both carbon and electrons from formate costs 6.2 points against H2 at a state-of-the-art whole-cell voltage (2.2 V). However, this small penalty is amplified three-fold by any rise in the CO2-to-formate cell voltage, and reaches 13.5 points at the highest whole-cell voltages reported for scaled-up CO2-to-formate electrolyzers, where formate-only operation falls to 11.2 electrical-to-fuel and 3.7% solar-to-fuel efficiency, below the ceiling of photosynthesis, against 24.7 and 8.1% for H2 (only just above algal photosynthesis). Our choice between a formate-only system and one coupled to H2 oxidation or EEU therefore depends on our belief about the trajectory of CO2 reduction technology. If whole-cell voltages continue to fall at the rate of the past decade, formate alone is the right target, and the simplicity of its workflow is bought at low cost. However, if that improvement plateaus, the electron delivery mechanism must be swappable, and a system should be designed from the outset so that it can be. At the US Department of Energy SunShot target of 2 cents per kilowatt hour, the electricity to make a US gallon of butanol costs $1.40 for a formate-only system at the state of the art, rising to $5.45 at the highest scaled-up electrolyzer voltage reported, against $1.23 and $2.47 for formate and H2 system.

Coal-fired power plants remain a major source of fine particulate matter (PM2.5) exposure and mortality in the United States. Announced retirement dates mark when those burdens are expected to end, but rising electricity demand, partly from data centers supporting cloud computing and artificial intelligence, has led utilities and regulators to revisit them. Of 50 coal plants scheduled in January 2024 to retire before 2035, 20 had later or removed dates by January 2026. Projecting coal PM2.5 and mortality among Medicare beneficiaries from the 20 plants for 2026-2035, we estimate the revised schedule would result in 1,256 additional deaths (1,136 to 1,376), raising mortality to 3.1 times the original burden. Eighteen plants operate in balancing authorities with hyperscale data-center demand, and federal orders and utility filings supporting several plants' operation cited data-center growth. Retirement schedules are revised faster than health consequences are assessed, and those delays carry a measurable mortality cost.

Even though osteoarthritis is considered a disease of the whole joint, integrated analysis of articular calcified cartilage (ACC) behaviour with adjacent tissues remains a persistent limitation. Herein, we performed synchrotron X-ray computed tomography in intact loaded joints and coupled anatomical analysis with digital volume correlation to examine whether microarchitectural ACC features serve as predictive mechano-biomarkers of osteoarthritis. We reveal that male osteoarthritis-prone STR/Ort mice have thicker yet more porous ACC that contains larger but less spherical chondrocyte lacunae than their healthy parental-control CBA mice. This was linked to asymmetrical distribution of tensile and compressive strains generated under physiological loads in the ACC and underlying subchondral bone in tibial epiphyses of STR/Ort mice. Together these data suggest that murine ACC microarchitecture has a mechano-predictive role in age-related osteoarthritis.