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Patient-derived model capturing hypoxia and extracellular matrix remodelling of immunologically cold high-grade serous tumours
Abstract High-grade serous carcinoma tumours present poor survival rates, often associated with immunologically excluded environments driven by hypoxia and extensive extracellular matrix remodelling that disrupt tumour-stromal-immune interactions. Current experimental models fail to fully capture these microenvironmental features, limiting understanding of tumour-immune dynamics and drug development. Here, we present bioengineered patient-derived tumour-immune models to mimic physiologically relevant oxygen levels and extracellular matrix remodelling. Cancer cells are co-cultured with cancer-associated fibroblasts within human plasma-3D matrices or grown on decellularized human ovaries. Immune cells are either included within the 3D constructs to study multi-cellular interactions or challenged to infiltrate the matrices. We demonstrate that intratumoural hypoxia acts as a friend and a foe enhancing the activation and cytotoxicity of CD8 + T cells while inducing stromal/matrix dysregulation associated with impaired immune infiltration. Targeting TGF-β signalling attenuates the hypoxia-driven stromal-mediated immune exclusion. These relevant models may aid the development of targeted therapies to transform immunologically cold tumours into immunogenic to benefit female patients.
The traffic concentration effects of urban navigation services
Abstract The collective impact of navigation services remains unclear: while often beneficial to individual drivers, they can unintentionally reshape urban traffic patterns. We simulate their impact in Florence, Milan, and Rome (Italy), integrating GPS data, road networks, and route recommendations from leading providers. We identify a concentration effect: as adoption increases, route diversity declines, and traffic and emissions converge onto fewer roads. At full adoption, route diversity decreases by up to 14% compared to a baseline where recommendations are ignored. Moreover, navigation services reduce CO 2 emissions at low adoption levels, but these benefits diminish, disappear, or even reverse beyond a city- and service-specific threshold. We replicate our experiments in an abstract setting, obtaining results consistent with those observed in real-world cities.
Super-resolution atlas of SARS-CoV-2 infection reveals protease-dependent organelle maturation, dsRNA landscapes, and intracellular structural proteins
Real-time estimation of pathogen transmission dynamics from wastewater
Abstract Wastewater monitoring proved effective for tracking SARS-CoV-2 transmission during the COVID-19 pandemic. However, estimating transmission parameters for other pathogens remains difficult due to lower concentrations in sewage, uncertain shedding kinetics, and limited clinical validation data. Here we present EpiSewer, a Bayesian semi-mechanistic wastewater model that jointly accounts for infection dynamics, pathogen shedding, and measurement noise, including outliers and non-detects. This enables direct inference of the effective reproduction number ( R t ) and epidemic growth rate ( r t ) from raw concentration and flow data, eliminating the need for prior smoothing, imputation, or outlier removal. We assessed EpiSewer across three seasons of multi-pathogen wastewater surveillance (Nov 2022 – May 2025) at 6–14 treatment plants in Switzerland, tracking SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV) transmission in real time. R t estimates were consistent and robust to measurement noise, even with IAV and RSV concentrations 10–50 times lower than SARS-CoV-2. The model provided well-calibrated fourteen-day concentration forecasts, with minimal bias across epidemic phases. Under reduced sampling frequencies, EpiSewer maintained unbiased forecasts while accurately reflecting uncertainty. Our approach enables robust inference of transmission dynamics for lower-abundance pathogens with limited clinical surveillance, using only a few wastewater samples per week.
Canopy structural diversity mediates the effect of climate on primary productivity in forests
Abstract Canopy structural diversity varies systematically with climate and species diversity across boreal, temperate, and tropical biomes. Yet, how this latitudinal variation affects forest productivity—particularly the role of structural diversity in mediating effects of climate on productivity across biomes—remains unresolved. By synthesizing airborne laser scanning data and ground-based forest inventories spanning boreal to tropical forests, we show that beyond its direct effects on forest productivity, climate influences productivity indirectly by regulating canopy structural diversity—a significant, yet previously underappreciated mechanism whose precise magnitude is challenging to isolate. Notably, we observe a pronounced latitudinal congruence between hotspots of structural diversity and productivity. This positions structural diversity not only as a complementary indicator of productivity but also as a critical mediator of the influence of climate and species diversity, essential for improved forecasting.
Structural basis of Mlc-mediated transcriptional regulation of carbohydrate metabolism
Abstract The global transcriptional repressor Mlc of Escherichia coli regulates genes involved in carbohydrate transport and metabolism, particularly glucose uptake via the glucose-specific phosphotransferase system (PTS). Unlike conventional repressors, Mlc exemplifies a system in which interactions with diverse macromolecules govern its activity. Here, we present cryo-electron microscopy structures of Mlc alone and in complexes with regulatory partners, including the glucose-specific PTS transporter IICB Glc , a cognate DNA operator and the anti-repressor MtfA, capturing multiple assemblies central to transcription control. These structures reveal the molecular architecture of Mlc and its interactions with binding partners. Together with molecular dynamics simulations, they provide insights into the structural dynamics of these complexes. Our findings establish the structural basis of membrane-transporter involvement in transcriptional regulation, the mechanism of anti-repressor action and DNA recognition. This work provides a structural framework for understanding bacterial transcriptional regulation across diverse systems.
Microbubble elevator induced buoyancy oscillations of reacting droplets
Generalised quantum computational spectroscopy on a quantum chip
Abstract Spectroscopy underpins modern scientific discovery across diverse disciplines. While experimental spectroscopy probes material properties through scattering or radiation measurements, computational spectroscopy combines theoretical models with experimental data to predict spectral properties, essential for advancements in physics, chemistry, and materials science. However, quantum systems present unique challenges for computational spectroscopy due to their inherent complexity, and current quantum algorithms remain largely limited to static and closed quantum systems. Here, we present and demonstrate a generalised quantum computational spectroscopy that lifts these limitations by reconstructing the quantum autocorrelation function via an ancilla-assisted Hadamard test quantum circuit. Our method is applicable to a broad range of quantum systems, including closed, open, and time-dependent driven quantum systems. We experimentally validate this approach, which leverages arbitrary controlled quantum dynamics and efficient classical noise-mitigation strategy, on a programmable silicon-photonic quantum processing chip, capable of high-fidelity time-evolution simulations. The versatility of our method is demonstrated through spectroscopic computations for diverse quantum systems, revealing novel phenomena such as parity-time symmetry breaking and topological holonomy that are inaccessible to conventional spectroscopy or quantum eigenstate algorithms. This work establishes a noise-robust methodology for quantum spectral analysis.
Stable real-space invariants and topology beyond symmetry indicators
Mesoscale ordered assembly of Er3+-doped quantum dots enables efficient 1.55 µm electroluminescence
Precision meets speed through an FPGA-based natively sparse Ising machine for combinatorial optimization
Conformational hijacking of lipoprotein transporter LolDF enables precision antimicrobial activity against Acinetobacter baumannii
The landscape of plasma proteomic links to human organ imaging
Structural basis of cotranslational protein N-terminal acetylation by NatB in human cells
Abstract Cotranslational N-terminal acetylation is a widespread modification that shapes protein stability, localization, and function in eukaryotic cells. The essential human NatB complex (NAA25-NAA20) acetylates the initiator methionine of a substantial fraction of the proteome, yet how NatB engages translating ribosomes has remained unclear. Here we define the cotranslational mechanism underlying NatB function. NatB is recruited by the nascent polypeptide-associated complex (NAC) through a high-affinity interaction between the NACα UBA domain and the auxiliary subunit NAA25, while both NatB subunits form additional contacts with the ribosomal surface near the tunnel exit. Together, these interactions position the NatB active site directly adjacent to the emerging nascent chain, enabling efficient modification of newly synthesized proteins. Structural comparisons reveal a conserved ribosome-binding architecture shared with other N-acetyltransferases, including NatA/E and NatD, implying mutually exclusive ribosome occupancy. Together with prior work, these findings establish NAC as a central organizer of cotranslational N-terminal processing.
Previous prescribed burns saved thousands of ancient sequoias during historically unprecedented wildfires
Abstract Wildfires in California’s Sierra Nevada during 2020–2021 killed giant sequoias ( Sequoiadendron giganteum ) at rates unseen for millennia, underscoring the vulnerability of highly fire-adapted trees to ongoing environmental change. Following a century of fire exclusion and fuel accumulation, the effectiveness of prescribed burns in reducing giant sequoia mortality from wildfire remained poorly quantified. Here we estimate mortality outcomes for 26,403 giant sequoias across 19 groves in Sequoia and Kings Canyon national parks following the Castle (2020) and KNP Complex (2021) wildfires using a Bayesian framework. We map tree mortality using a deep learning classifier integrating 3 m PlanetScope imagery, airborne lidar, and field observations. From an estimated 7,974 sequoia deaths (95% Bayesian credible interval (CI): 7,555–8,430), corresponding to 30.2% mortality (CI: 28.6–31.9%), we find previous prescribed burns (≤10 years prior) reduced mortality odds by 77% (CI: 69–83%), making treated trees nearly four times more likely to survive. Counterfactual simulations suggest that prescribed burns prevented at least 1,888 (CI: 1,487–2,302) deaths, and universal treatment would have saved an additional 3,888 (CI: 3,236–4,580) giant sequoias. These results show that prescribed burns substantially improve survival during extreme wildfires, offering guidance for conserving long-lived, fire-adapted forests under intensifying fire regimes.
Gapless fracton quantum spin liquid and emergent photons in a 2D spin-1 model
Abstract Gapless fracton quantum spin liquids are exotic phases of matter described by higher-rank U(1) gauge theories, which host gapped and immobile fracton matter excitations as well as gapless photons. Despite well-known field theories, no spin models beyond purely classical systems have been identified to realize these phases. Using error-controlled Green function Monte Carlo, here we investigate a square lattice spin-1 model that shows precise signatures of a fracton quantum spin liquid without indications of conventional ordering. Specifically, the magnetic response exhibits characteristic patterns of suppressed pinch points that accurately match the prediction of a rank-2 U(1) field theory and reveals the existence of emergent photon excitations in 2+1 spacetime dimensions. Remarkably, this type of fracton quantum spin liquid is not only identified in the system’s ground state but also in generic low-energy sectors of a strongly fragmented Hilbert space.
Pervasive summertime nitrous oxide undersaturation in U.S. lakes and reservoirs
Abstract Lakes and reservoirs are estimated to be globally important sources of nitrous oxide (N 2 O) to the atmosphere but recent evidence of N 2 O uptake across a broad range of lakes have called the accuracy of emission estimates into question. Here, we use a new national-scale dataset of dissolved N 2 O concentration and a Bayesian hierarchical model to predict summertime N 2 O concentration and emission rates in 465,896 waterbodies in the conterminous U.S. (CONUS). We found that N 2 O undersaturation was pervasive throughout the CONUS during the summer of 2017, with an estimated 72.9% (95% credible interval: 68.9–76.6%) of lakes functioning as N 2 O sinks. The model predicts dissolved N 2 O concentrations reasonably well based partly on interactions between nitrate concentration, waterbody surface area, and water temperature. Despite working with the largest aquatic N 2 O dataset to date, our national-scale estimate of summertime N 2 O emissions from CONUS lakes is poorly constrained, with a 95% credible interval ranging from net uptake to net emission (−282 − 482 metric tons N 2 O summer −1 ). Pervasive N 2 O undersaturation in CONUS waterbodies during the summer highlights the need to revisit N 2 O models which presume surface waters are a N 2 O source.
Phage portal proteins counteract stringent-response–mediated restriction
Abstract Bacteria restrict viral replication not only through dedicated defense systems but also by entering physiological states that limit cellular resources, yet how phages overcome such host-imposed barriers remains unclear. The stringent response, driven by the alarmone nucleotides ppGpp and pppGpp, can impose a growth-restrictive state that hinders phage infection in specific phage–host contexts. Here, we show that alarmone signaling constrains bacteriophage T7 infection and that the portal protein Gp8 counteracts this barrier by engaging RelA and SpoT, inhibiting their synthetase activities and suppressing alarmone accumulation. Portal mutations that disrupt this interaction sustain alarmone elevation, delay lysis and impair replication in a manner relieved in alarmone-deficient hosts. Portal proteins from representative coliphages share related stringent-response-linked features, indicating that essential virion components can moonlight as antagonists of host stress physiology and that this mechanism is not unique to T7 and may extend to additional coliphages.