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Synthesis of functionalized hydrosilanes via titanium-catalyzed hydroboration and hydrogenation of C(sp3)–Si bonds in silacyclobutanes
The embryo game uncovers hidden cell behaviours
YBX1 Confers immunosuppressive bone metastatic traits in non-small cell lung cancer
Abstract The spread of lung cancer to bone is a devastating complication often linked to resistance against immunotherapy, but the reasons for this connection are poorly understood. Here we show that the transcription factor YBX1 acts as a central regulator driving both bone metastasis and the formation of an immunosuppressive environment in non-small cell lung cancer (NSCLC). YBX1 achieves this by activating distinct signaling pathways (IL6 and CCL5, respectively). Mechanistically, YBX1 protein levels are controlled by glycosylation that marks it for autophagic degradation inside cells. Notably, reduced YBX1 glycosylation was observed in highly bone-metastatic NSCLC cells. Importantly, we identified a drug candidate, Icaritin, which boosts this sugar-modification, leading to YBX1 degradation. This dual action inhibits bone metastasis and re-sensitizes tumors to immune attack. Our work reveals YBX1 as a promising single target for combating bone spread and overcoming immunotherapy resistance.
Crop fields complement biodiversity in permanent grasslands across European landscapes
Abstract Temperate agricultural landscapes are experiencing unprecedented biodiversity declines. Landscape simplification is commonly identified as a driver of species loss across taxonomic groups, but the contribution of crop and non-crop habitats to farmland biodiversity conservation is surprisingly poorly known. Using 86 paired permanent grasslands and oilseed rape fields in five European countries, we assess how habitat type shaped plant, butterfly, wild bee, and carabid assemblages and whether increasing grassland amount in surrounding landscapes fosters the spillover of grassland-associated biodiversity to oilseed rape fields. We find habitat type rather than landscape-level grassland amount determines diversity and shapes species assemblages: plants and butterflies are more diverse in grasslands, while wild bees and carabids are equally or more diverse in oilseed rape fields. Increasing landscape-level grassland amount affects species assemblage composition but only reduces turnover between habitats in wild bees. Overall, both grasslands and oilseed rape fields harbour distinct sets of species, together contributing complementarily to regional diversity. Safeguarding biodiversity in agricultural landscapes therefore requires not only the conservation of permanent semi-natural habitats but also biodiversity-friendly management of disturbed habitats such as crop fields that can contribute valuable species.
Robust bulk silicon carbide polymorphs sintered from collapsed hollow mesoporous structure
Deciphering small sequence differences in T cell receptor-antigen pairing
Clonal evolution and mutational trajectories of metastatic colorectal cancer shaped by anticancer therapies
Covalently bonded polymer-metal-organic framework semiconductive membranes for flexible X-ray detection
Mid-infrared snapshot spectral imaging via nonlinear radial dispersion
The PLK4 inhibitor RP-1664 demonstrates potent efficacy in neuroblastoma preclinical models through a dual mechanism of sensitivity
Abstract It was recently shown that inhibition of polo-like kinase 4 (PLK4) induces synthetic lethality in cancers with chromosome 17q-encoded TRIM37 copy number gain due to cooperative regulation of centriole duplication and mitotic spindle nucleation. We show here that chromosome 17q/TRIM37 gain is a defining feature of high-risk neuroblastoma and renders patient-derived cell lines hypersensitive to the novel PLK4 inhibitor RP-1664. We demonstrate that centriole amplification at low doses of RP-1664 contributes to this sensitivity in a TRIM37 -independent fashion. CRISPR screens and live cell imaging reveal that upon centriole amplification, neuroblastoma cells succumb to multipolar mitoses due to an inability to cluster or inactivate supernumerary centrosomes. RP-1664 monotherapy showed robust anti-tumor activity in 14/15 human neuroblastoma-derived xenograft models, and significantly extended survival in a transgenic MYCN -driven murine model of neuroblastoma. RP-1664 combined with GD2-directed chemoimmunotherapy resulted in maintained complete responses in 6/9 mice with established MYCN -driven murine neuroblastomas. These data support clinical development of PLK4 inhibitors for high-risk neuroblastoma and other cancers with somatically acquired TRIM37 overexpression.
Generative flow model on distance geometry for predicting transition states of chemical reactions
A probabilistic forecasting framework for neighbourhood-level disaggregation of electric vehicle adoption scenarios
Abstract The rapid growth of electric vehicle (EV) adoption presents significant challenges for electricity networks, particularly at the low-voltage level, where clustered neighbourhood demand risks overloading infrastructure. Existing scenario-based planning approaches typically assume uniform EV uptake across neighbourhoods within a region, failing to capture the heterogeneity in historical EV registration data. They provide limited uncertainty quantification, despite the difficulty of predicting future adoption at fine spatial scales. This paper introduces a Gaussian process (GP)-based forecasting framework that combines granular historical EV registration data with top-down regional scenarios to generate probabilistic neighbourhood-level forecasts. The GP captures how local adoption deviates from regional trends, encoded in the GP’s mean function, ensuring consistency with broader scenarios while accounting for local variation and uncertainty. We validate the framework using ten representative local authority districts in England and Wales, covering 1,294 neighbourhoods. The framework demonstrates improved performance compared to baseline methods (scaled scenario, logistic growth, linear extrapolation) in normalised mean absolute error, with statistically significant improvements at horizons of three years and beyond. It also delivers well-calibrated prediction intervals, providing reliable uncertainty estimates. This framework offers a practical tool for network operators, policymakers, and planners to support targeted decision-making and investment.
Trial-by-trial fMRI-neurofeedback dissociates fusiform and occipital contributions to face detection and recognition
Abstract Self-regulation of specific brain regions can be achieved using neurofeedback with real-time functional magnetic resonance imaging (rt-fMRI). We leveraged this technique to dissect the role of two tightly interconnected areas implicated in face perception, by interleaving a visual task with upregulation of either the occipital (OFA) or fusiform face-responsive areas (FFA) in a trial-wise manner. Experimental participants ( N = 22) successfully enhanced their target region when compared to yoked controls ( N = 20). Regulation was face-selective, as evidenced by concomitant increases in other nodes of the face processing network. Critically, face detection was faster with enhanced FFA activity but hindered by enhanced OFA, whereas face identity recognition was optimal with concomitant increases in both FFA and OFA. These results argue against traditional face processing models assuming an information flow from posterior occipital to anterior fusiform cortex and instead support non-hierarchical models where FFA mediates initial face detection and OFA contributes to subsequent identity recognition.
Generation of ultra-broadband frequency comb in strongly bistable nonlinear magnonic resonator
Abstract Magnonic frequency combs (MFCs) offer a promising route to compact, energy-efficient platforms for on-chip coherent microwave signal generation and processing. Conventional on-chip comb generation typically relies on nonlinear resonators supporting equidistant, low-loss resonances driven by a monochromatic signal, resulting in fixed comb spacing. Here we introduce and experimentally demonstrate a distinct mechanism for ultra-broadband MFC generation using a highly nonlinear miniaturized magnonic resonator. The small resonator volume, combined with a slow-wave transducer, drives the system deep into the bistable regime where parametric excitation of propagating spin waves facilitates comb formation. Our approach yields over 350 comb lines spanning a 450 MHz bandwidth, with spacing continuously tunable via a two-tone external drive, representing an order-of-magnitude enhancement over prior reports at relatively low power. The platform is ultra-compact, scalable, and highly tunable, establishing a distinct frequency comb paradigm with transformative opportunities in microwave signal processing, neuromorphic computing, and precision sensing.
Self-assembling proteins compose the chemically resistant shell biomaterial of planktonic tintinnid ciliates
Abstract Biomaterials provide superior properties and sustainable alternatives relevant to medicine, textiles, and high-tech applications. Research has mainly focused on animal-derived proteinaceous biomaterials, which remain challenging to reproduce while retaining their remarkable properties. Here, we show that the shell biomaterial of tintinnid ciliates, a lineage of planktonic unicellular eukaryotes, is composed of self-assembling structural proteins. The shells form in sea- and freshwater, are structurally diverse, and exhibit resistance against high temperatures and the strongest chemicals. Combining single-cell transcriptomics with proteomics of the shells, we identify the amino acid sequences of the shell-forming proteins that represent a new family unique to tintinnid ciliates, which we term Tintinnidorin. The proteins are rich in aromatic residues and possess a coherent architecture with flexible, unfolded segments connecting a folded core structure of beta-sheets. These multivalent capabilities facilitate intracellular storage, extracellular self-assembly, wet adhesion, thermostability, and salt tolerance. Tintinnid ciliates and their Tintinnidorin proteins provide an accessible system to elucidate sequence-structure-material relationships and inspire biomaterial design.
The metal mixture inflammatory index has been associated with an increased prevalence of chronic obstructive pulmonary disease and higher all-cause mortality
Integrative bulk and single-cell transcriptome analyses reveals manganese metabolism-related prognostic genes in clear cell renal cell carcinoma with experimental validation
Hard-object feeding adaptations infer relative predator-prey size relationships in Devonian placoderms
Abstract Devonian placoderms exhibit exceptional diversity in jaw and dental morphology, making them an ideal system for examining early gnathostome feeding mechanisms. Here, we investigate inferognathal (mandible) function in eight eubrachythoracid arthrodire placoderms from Australia’s Late Devonian Gogo Formation. A combination of finite element analysis and quantification of dental surface complexity revealed distinct, size-dependent strategies for processing mechanically resistant materials (durophagy). Taxa with broad, flat dental surfaces experienced low strain during simulated bites, consistent with crushing armoured prey that could be engulfed whole. In contrast, the jaw of the largest taxon combined exceptional structural strength with highly complex, reinforced dentition, enabling force concentration to pierce through armour or shell, and tear apart prey items exceeding its oral capacity. Taxa of intermediate size exhibited higher strain and specialised slicing dentition, consistent with generalist diets or feeding strategies focused on shearing through softer tissues. Consumption of armoured prey in placoderms was therefore governed not by predator size alone, but by the relative size of prey to predator. Hard object feeding in arthrodire placoderms was not a result of a single mechanical solution, but involved several distinct solutions influenced by body size and prey-processing constraints.