Management of prostate cancer has improved over the past two decades, driven by innovations in detection of metastatic disease, biomarker characterization, and treatment. This review summarizes the latest progress in managing advanced states of this disease, spanning high risk biochemical recurrence, metastatic hormone sensitive prostate cancer (mHSPC), and metastatic castration resistant prostate cancer (mCRPC). Improved outcomes for patients have been seen with earlier use of androgen receptor pathway inhibitors in the setting of high risk biochemical recurrence and mHSPC. Meanwhile, individuals with mCRPC now represent a more diverse population, differentiated by both their previous treatments and other biological features. Advanced imaging and genomic biomarkers improve patient selection and permit more personalized therapy. Landmark clinical trials and meta-analyses have established and/or refined the role of chemotherapy, poly-ADP ribose polymerase (PARP) inhibitors, and 177Lu-PSMA-617 in this disease space. Finally, as patients with prostate cancer are living longer, the review focuses on understanding and managing potential adverse events, including cardiac and hematologic toxicity and bone health.
Layered molybdenum disulfide (MoS2) is a model transition metal dichalcogenide (TMD) whose properties can be tuned via redox-driven intercalation and phase control. In this work, we present a one-pot wet-chemical synthesis route to form MoS2 intercalation compounds using pyrenide salts with cationic potassium crown-ether complexes, K(15-crown-5)2C16H10 and K(18-crown-6)C16H10. These salts act as combined reducing and intercalating agents. Under optimised conditions in dimethyl sulfoxide at 150 °C, pyrenide affords well-ordered crystalline products, whereas more strongly reducing polycyclic aromatic hydrocarbanions yield only partially ordered phases, highlighting the role of redox potential and kinetics. X-ray powder diffraction shows an expansion of the basal spacing from 6.13 Å in pristine 2H-MoS2 to 15.05 Å and 16.05 Å, consistent with complexed [K(15-crown-5)2]+ and [K(18-crown-6)]+ cations occupying the interlayer galleries, respectively. Raman spectroscopy and atomic absorption spectroscopy confirm preservation of the 2H phase at a low to moderate reduction level (∼8-12%). Calculations using density functional theory (DFT) and a jellium model show that at such charge densities and large interlayer distances, 2H-MoS2 remains energetically favored over the 1T/1T' phase, rationalizing the coexistence of large gallery expansion with a semiconducting host lattice.
Microgravity and space radiation experienced during spaceflight have adverse effects on musculoskeletal health, yet their impact on articular cartilage has not been fully understood. In this study, we demonstrated that simulated spaceflight on Earth leads to cartilage degradation in the knees of mice. Similar changes were also observed in mice exposed to actual spaceflight. To investigate mechanisms underlying spaceflight-associated cartilage loss, human chondrocytes were encapsulated in a hydrogel scaffold and subjected to rotary culture to simulate microgravity-induced alterations. Simulated microgravity increased the expression of biomarkers related to inflammation and cellular senescence. Additionally, rotary culture decreased mitochondrial respiration and increased reactive oxygen species production. Through RNA sequencing and bioenergetic profiling, we identified NADPH oxidase 4 (NOX4) as a crucial factor driving these changes. Moreover, kaempferol, a naturally occurring flavonoid that directly binds to NOX4, was found to partially reverse the harmful effects of microgravity on chondrocytes. Finally, systemic administration of kaempferol reduced cartilage degradation in mice subjected to simulated spaceflight on the ground. These findings establish that NOX4-mediated mitochondrial dysfunction is a key mechanism underlying spaceflight-induced cartilage degradation and highlight kaempferol as a potential protective measure for joint health in space.
Asteroid impact monitoring systems search for potential collisions of near-Earth objects (NEOs) with the Earth over 100 years. A necessary condition for an impact is the intersection between the orbit of the asteroid and the orbit of the Earth. This condition is measured by the Minimum Orbit Intersection Distance (MOID), which can be computed reliably for longer periods of time to identify when an Earth impact is possible. As the orbit is propagated into the future, the uncertainty in position grows faster than the uncertainty in the MOID. If the MOID is low but the position along the orbit is unknown, we compute an analytical approximation of the frequency of close encounters for a given distance. The NEO population spreads widely in orbital uncertainty, which we consider by propagating multiple samples from the initial orbital uncertainty distribution. We demonstrate and validate the methodology for 99942 Apophis, whose MOID is secularly increasing at a slow rate that still allows for future deep encounters. We apply this methodology to the NEO population, and for a large fraction we rule out the crossing of Earth's orbit in the next 1000 years. Otherwise, we rank NEOs in terms of how long their MOID will be low, long-term frequency of close encounters, and frequency relative to the background close encounter frequency for objects of similar size. These rankings identify NEOs that should be prioritized for future tracking and orbit refinement.
Large dikes are the main mechanism of crustal extension in volcanic areas, but the processes in the underlying magma system that supply the required volumes remain unclear. We show that 1.4 cubic kilometers of magma propagated under the Ethiopian rift in December 2024 and continued for ~3 months. Geodesy and seismicity reveal that the dike was fed from a network of magma reservoirs between 6 to 12 kilometers in depth with pathways rapidly forming between them. We calculate pressure changes in the reservoirs and show that underpressure developed in the deeper portion, creating the conditions to drain large magma volumes. We find that tectonic stress and availability of magma alone are not enough to drive intrusion of massive dikes. These events will start only after magma connectivity and deep underpressure develop. Similar conditions may be important for the transfer of large magma volumes from the mantle and the formation of large igneous provinces.
Plasmon-enhanced nonlinear optical phenomena in hybrid perovskite-plasmonic systems present significant opportunities for photodetection, bioimaging, and quantum light sources. However, achieving uniform growth of luminescent materials within confined plasmonic hotspots remains challenging, as conventional surface deposition or infiltration approaches cannot fill nanocavities effectively. To resolve this, we present a vacuum-assisted capillary infiltration (VACI) strategy for delivering precursor solutions into gold (Au) nanohole (NH) arrays, enabling in situ crystallization within plasmonic cavities. This work demonstrates selective bulk-like cesium lead bromide (CsPbBr3) growth inside NHs through precise infiltration and controlled crystallization. By integrating the capillary effect with vacuum pressure, this approach ensures uniform filling beyond conventional methods. The successful integration of CsPbBr3 was confirmed through peel-off techniques and structural/chemical analyses. Electromagnetic simulations predict an average field enhancement of |E/E0| ≈2.80 at 800 nm, consistent with an experimentally observed ∼40-fold increase in two-photon absorption (TPA)-induced green emission (λ ≈526 nm). Unlike prior TPA systems employing quantum dots, rare-earth doped crystals, or organic chromophores, this approach integrates bulk-like perovskite directly into plasmonic NH cavities. This establishes a general framework for material-structure integration in plasmonics and nanophotonics, and a foundation for infrared photodetection, high-resolution nonlinear imaging, and quantum light sources.
Biological dinitrogen (N2) fixation sustains productivity in oligotrophic oceans and is now also thought to contribute substantially to the nitrogen supply in the warming Arctic. Here we demonstrate significant N2 fixation by particle-associated diazotrophs in subsurface waters of the Barents Sea. Comparing our findings with subtropical studies reveals particle-associated non-cyanobacterial diazotrophs as the primary N2 fixers in subsurface Arctic waters of the Barents Sea, contrasting with diverse communities in warmer regions. As the Arctic shifts towards oligotrophication, understanding the magnitude and controls of particle-associated N2 fixation will provide critical insights into future nitrogen supply required to sustain productivity in the rapidly changing Arctic Ocean. However, particle-associated N2 fixation may be a distinctive feature of the Barents Sea, where in contrast to other Arctic shelves the seasonal and long-term trends in nitrogen dynamics are heterogeneously determined by changes in the external Atlantic Water supply, sea-ice extent, and terrestrial inputs. In this context, the role of particle-associated N2 fixation across the wider Arctic Ocean will require further investigation.
The rare biosphere harbors immense microbial diversity, yet most low-abundance taxa remain uncultured and functionally enigmatic. Here, we isolated strain D14T from deep-sea water, and propose to classify it as a novel species, Metabolovarius oceani sp. nov., within the novel family Metabolovariaceae fam. nov. M. oceani represents the first cultivated member of the candidate family NORP267, a globally distributed but elusive alphaproteobacterial lineage known only from metagenome-assembled genomes. It possesses broad metabolic capabilities, including CO2 fixation, polyhydroxyalkanoate biosynthesis, complete denitrification and thiosulfate oxidation, and is capable of aerobic growth under both heterotrophic and autotrophic conditions and of anaerobic autotrophic denitrification via thiosulfate oxidation. Despite its versatile metabolic repertoire and global distribution, Metabolovariaceae remains consistently low in abundance across diverse habitats. The isolation of M. oceani permits direct experimental insights into the evolutionary adaptations, physiological resilience, and potential ecosystem roles of rare but metabolically versatile microorganisms within the microbial dark matter.
Aquatic birds encompass diverse ecologies and locomotion types. Some of them are flightless; others lack effective terrestrial locomotion, whereas numerous species perform well in water, on land, and in the air. Bone microanatomy provides insight into bone functional adaptations to different locomotor strategies. Previous studies on aquatic birds have relied mainly on 2D transverse sections. In this study, we aim to qualitatively and quantitatively analyze the microanatomical characteristics of limb long bones using several virtual sectional planes and whole-bone measurements to investigate in more detail the link between inner structure and locomotor abilities. In the humerus, femur, and tibiotarsus, whole bone compactness is higher in species with better diving abilities, likely reflecting adaptations to counteract buoyancy and drag. In these bones, flightless penguins exhibit the highest compactness, consistent with the release from flight-related constraints. The tarsometatarsus shows a distinct pattern and is more compact in foot-propelled and less terrestrial birds, whereas non-foot-propelled, terrestrial penguins show a lower compactness than in their other bones. Trabecular structure and orientation in the humerus appear to reflect general wing kinematics and wing-propelled locomotion, while hindlimb bones show structural traits probably related to body weight support and foot-propelled swimming. These findings contribute to a better understanding of the adaptations of the birds' skeletal system to various lifestyles and could prove useful in inferring the ecology of extinct species.
Sand mining is a poorly quantified threat to river deltas because its impacts are often confounded with those of dams and climate change. Here, we isolate its effects in the Vietnamese Mekong Delta, a global sand mining hot spot, using a long-term numerical model and observed mining data. Results show that mining exceeds natural sediment supply by 6 to 15 times, causing riverbed erosion across ~65% of channels, with mean incision rates of ~0.10 meters per year (~25 to 30% of total incision driven by all drivers). This channel deepening alters flow, reduces sediment transport, and enhances saltwater intrusion. Sand mining alone contributes ~16 to 30% of the annual salinity increase, extending intrusion up to ~1.5 kilometers further inland during the dry season. These changes demonstrate that sand mining is a major, previously underquantified driver of delta instability, affecting river morphology, flow, sediment, and salinity. This study provides a framework to quantify these impacts and support better management of sand extraction in vulnerable deltas worldwide.
Wildfire smoke is a major source of fine particulate matter (PM2.5) and may increase vulnerability to severe infectious outcomes such as sepsis, a condition responsible for an estimated 49 million cases and 11 million deaths annually. Despite this global burden, to our knowledge, no prior epidemiological study has specifically examined the association between wildfire-specific PM2.5 exposure and infectious disease-related sepsis. We conducted a multi-country time-series analysis across 1,024 communities in seven countries/territories (2000-2019). Daily hospitalizations for infectious disease-related sepsis were identified using ICD-10 codes, restricted to explicit sepsis diagnoses. Wildfire-specific PM2.5 was estimated using the GEOS-Chem chemical transport model combined with machine learning calibration and linked to hospitalization data. Associations between wildfire-specific PM2.5 and sepsis hospitalizations were estimated using quasi-Poisson regression with distributed lag non-linear models over lag 0-7 days. Community-specific estimates were pooled using random-effects meta-analysis. Across all communities, we identified 2.3 million infectious disease-related sepsis hospitalizations, with the highest burden among older adults and in Brazil. Each 10 μg/m3 increase in wildfire-specific PM2.5 was associated with a 1.5% increase in sepsis hospitalizations (Relative Risk [RR]: 1.015, 95% Confidence Interval [CI]: 1.007-1.024), nearly double the effect of non-wildfire PM2.5 (0.8%). Strongest associations were found among children aged <5 years (RR: 1.063, 95%CI: 1.029-1.097) and those aged 5-19 years (1.093, 1.050-1.138), in moderately populated communities, and in New Zealand and Brazil. Sensitivity analyses confirmed the robustness of the findings. Short-term exposure to wildfire-specific PM2.5 was associated with increased risk of hospitalization for infectious disease-related sepsis, particularly greater risks in adolescents and young children. These findings underscore the need of further research to clarify underlying mechanisms and long-term impacts.
Comparing spatial molecular distributions across mass spectrometry imaging (MSI) sections is complicated by intersection shape differences, intensity variation, and the blindness of intensity-based tests to spatial organization. Persistent homology (PH) with per-section z-score normalization and 1-Wasserstein (W1) distance between persistence diagrams provides an alignment-free framework for quantifying spatial dissimilarity. We applied this pipeline to the public positive-mode MALDI-MSI lung lipidomics data set of Stevens et al. (2025): 12 mice (6 female, 6 male; 3 saline (SFA) and 3 HDM + O3 per sex). For each sex, 1000 m/z channels were screened across 15 pairwise comparisons and prioritized by 9/9 directional consistency (all 9 cross-group distances exceeding the within-group mean). The female cohort yielded 16 PH candidates (∼15 putative species), of which 8 have strong Moran's I support (HO3/SFA Moran ratio ≥2 with absolute HO3Moran ≥0.20); the male cohort yielded 1 candidate, consistent with the expected sex-specificity. The Kolmogorov-Smirnov and Earth Mover's Distance baselines applied to the same pair structure returned 9 and 29 female candidates with zero overlap with the PH set at the main parameters (KS was a complete subset of EMD); the overlap becomes partial at coarser binning. A control analysis applying EMD to z-scored pixel distributions returned 92 female candidates, of which only 5 overlapped with PH and 3 with raw-EMD, localizing the detection-domain separation primarily to the topology/W1 step rather than to z-score preprocessing alone. Within this positive-mode data set PH acts as a detection axis partially orthogonal to intensity-based screening; candidates are reported as prioritization targets requiring targeted MS/MS for identification.
Aerosol-cloud interactions (ACIs) are fundamentally nonlinear, with their strongest climatic effects emerging where cloud properties are highly sensitive to aerosol changes-the aerosol-limited regime. Quantifying this regime's evolution is therefore critical for constraining uncertainties in climate forcing and future projections. By integrating satellite observations with climate model simulations, we map this regime globally and track its recent change. We find it expanded by 4.8% per decade over the past 20 years, primarily due to a sharp increase (∼14.7% per decade) in the Northern Hemisphere driven by anthropogenic emission reductions. Under a strong emission reduction pathway, its frequency is projected to double or triple in key ocean regions. This systematic shift pushes marine clouds into a state of heightened aerosol sensitivity, thereby amplifying the cloud-mediated radiative response to aerosol changes. Our findings underscore the need to account for this evolving sensitivity in climate projections.
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Marine biotechnology draws on one of the richest sources of biological novelty on Earth. Yet, as investment accelerates alongside new international ocean governance frameworks, marine discoveries rarely reach the market as marine production systems. Rather than translation failure, the more consequential pattern is structural displacement: value routinely migrates into land-based fermentation, chemical synthesis, or microbial production rather than remaining marine. In this marine biotechnology translation paradox, discovery succeeds while marine production is left behind. Current success metrics conflate innovations that stay marine with those that exit the domain, distorting investment and progress. The Marine Deployability Triad is proposed as an early framework to identify which innovations can remain marine at deployment, with implications for funding, evaluation, and blue economy policy.
Ice nucleation is ubiquitous in nature and technology and decisive for a wide range of fields, including biology, geochemistry and environmental science. In most cases, ice nucleation occurs heterogeneously due to the presence of an ice nucleating material. Despite its importance, we still largely fail to reliably predict the ice nucleation efficacy of a given material. A particularly puzzling example is calcite, a major constituent of rocks in the Earth's crust. Although calcite possesses a high hydrophilicity, it is basically inactive in ice nucleation. Here, we combine non-contact atomic force microscopy with temperature programmed desorption measurements to investigate water multilayer formation and ice growth on calcite's (10.4) surface in ultrahigh vacuum. Adsorption of water results in the formation of up to four water layers. Interestingly, the fourth layer is observed to be metastable, as it shrinks as soon as crystalline ice nucleates. The molecular structure of the water layers is governed by the underlying calcite lattice, highlighting the strong impact of the surface. This strong templating effect of the substrate prevents the water from adopting an ice-like structure even in the fourth layer. Our results, thus, provide an explanation for the poor ice-nucleating efficacy of calcite and underscore that ice nucleation efficacy cannot be predicted based on a single descriptor.
Sulfur is a key volatile that influences Earth's redox state, climate, and deep geochemical cycles. Subduction zones are the primary pathways carrying sulfur from the surface into the mantle, yet the global sulfur budget and recycling efficiency remain uncertain. Here, we compile a trench-by-trench inventory of subducting sulfur using sediment compositions from ocean drilling programs collected near major trenches, integrated with spatially resolved estimates of oceanic crustal and serpentinite thicknesses derived from seismic data. Our results reveal pronounced spatial heterogeneity in sulfur fluxes, driven by large variations in sedimentary sulfur contents and fundamental tectonic differences between erosive and accretionary margins. Slab-to-arc sulfur recycling efficiency averages 37% globally but varies markedly among individual subduction systems. Despite this heterogeneity, the global sulfur cycle appears balanced on the modern Earth: Sulfur input into the mantle via slab subduction (57 ± 3 Mt y-1) is matched within uncertainty by mantle output (~60 ± 14 Mt y-1) through mid-ocean ridges, volcanic arcs, and intraplate magmatism. This balance suggests that Earth's deep sulfur cycle operates in a steady state today. Sulfur isotopes reveal a systematic decoupling, with subducted sulfur carrying negative δ34S values, whereas arc sulfur output is consistently positive. The strong spatial variability in sulfur inputs and recycling efficiency underscores the individuality of Earth's subduction zones, but the balanced input-output fluxes highlight its capacity for self-regulation. These findings have important implications for atmospheric chemistry, surface environments, and the long-term evolution of the deep Earth's sulfur cycle.
Human activities related to the industrialization generated an overall rise of global temperatures with approximately 1 °C since 1880. These increases in temperatures have been accelerating since 1981, with the rate of temperature increase roughly doubling since the 1970s, the average warming rate being of approximately 0.18 °C to 0.20 °C per decade between 1970 to 2015. Even more alarmingly, recent studies indicate that this rate has accelerated to over 0.35 °C per decade since 2015, roughly the double of the previous period. The primarily contributor to the observed extensive climate change is the accumulation of greenhouse gases in the atmosphere, the effect of which is a significant rise in Earth's surface temperature. Here, we examine the interplay between global warming and climate change, emphasizing their interconnected yet distinct roles. The consequences include extreme weather events, permafrost melting, and biodiversity loss. Most importantly, climate change represents a direct threat for human health. Higher temperatures can produce metabolic imbalances and oxidative stress, that may be responsible for various levels of immunosuppression, increased susceptibility to infections, and ultimately death. Climate change is proven to be associated with increased frequency and emergence of vector-borne diseases, mainly due to significant expansion of the endemic areas for the vectors. It is also related to exacerbation of respiratory, cardiovascular, and infectious diseases and an increase in the prevalence of psychiatric disorders. Given the limitations of climate change modeling, proactive policies and adaptive strategies are imperative. Climate change and global warming should be central aspects of current education, and educational programs should be implemented at every societal level. Actions to control climate change need to be continuously adapted to the observed reality and, should the current targets be deemed as insufficient to address the main problems, new, more ambitious, goals have to be negotiated and implemented. Solving the complex challenge of climate variability will necessitate a coordinated and sustained global action, independent of political views, geographical location and individual interests to safeguard both environmental and public health.
Amazonia harbours more than 10% of the terrestrial biodiversity of the Earth1 and more than 400 Indigenous groups2. So far, however, no study has assessed how climate change and the loss of Indigenous languages may simultaneously impact its biological and cultural heritage. Here, to bridge this gap, we first assembled a database of 90,536 reports from 700 references to understand the societal benefits that native plants provide across all countries of the Amazon basin. We found that humans utilize 5,796 native plant species, which amounts to one-third of the known Amazon vascular seed plant flora. Next, analysing 8,429 species distribution models across three future climate scenarios (SSP1-2.6, SSP3-7.0 and SSP5-8.5), we show that climate change will produce a greater reduction in the ranges of utilized than of non-utilized species by 2060-2080. Locally, Indigenous cultures may lose an average of 28-34% of their utilized plant species and 18-23% of their associated services from climate change. Regionally, the loss of threatened Indigenous languages may result in a 26% reduction in the Amazonian knowledge pool. Overall, our results point to the strong climate and language vulnerability of Amazonian biocultural heritage. At the same time, these results-together with our publicly available dataset-may serve to guide biocultural restoration and reverse the growing global change effects on ecosystems and cultural traditions.
Future crewed expeditions beyond Earth will span multiple years, requiring a transition away from Earth-dependent pharmaceutical supply chains. Medications degrade more rapidly in space due to radiation exposure and storage constraints, while transporting large quantities of temperature-controlled biologics is logistically impractical. These challenges necessitate the development of self-sufficient, in-situ medical capabilities for deep space missions. This study evaluates the operational and clinical relevance (OCR) and recombinant production feasibility (RPF) of peptide therapeutics for on-demand manufacturing during long-duration spaceflight. Building on established astropharmacy databases and literature, 26 peptide-based medications relevant to spaceflight were identified and ranked using ten predefined OCR and RPF criteria. OCR criteria included regulatory status, shelf stability, storage requirements, NASA Human Research Roadmap risk/impact score, and purification requirements. RPF criteria included amino acid chain length, prior recombinant production, functional assay availability, dosing requirements, and post-translational modification complexity. All criteria were scored from 0-2 points. Teriparatide achieved the highest overall score (17/20), followed by abaloparatide and amylin (16/20). Several therapeutics, including angiotensin II, daptomycin, GLP-1 agonists, G-CSF, GM-CSF, and salmon calcitonin, also demonstrated potential (14/20). This study identifies peptide therapeutics as promising candidates for in-situ production and provides a structured framework to guide future astropharmacy development.