Browse Articles

A mild and practical approach to N-CF3 secondary amines via oxidative fluorination of isocyanides

FOXA2 promotes metastatic competence in small cell lung cancer

Abstract Small cell lung cancer (SCLC) is known for its high metastatic potential, with most patients demonstrating clinically evident metastases in multiple organs at diagnosis. The factors contributing to this exceptional metastatic capacity have not been defined. To bridge this gap, we compare gene expression in SCLC patient samples who never experienced metastasis or relapse throughout their clinical course, versus primary SCLC patient samples from more typical patients who had metastatic disease at diagnosis. This analysis identifies FOXA2 as a transcription factor strongly associated with SCLC metastasis. Subsequent analyses in experimental models demonstrates that FOXA2 induces a fetal neuroendocrine gene expression program and promotes multi-site metastasis. Moreover, we identify ASCL1, a transcription factor known for its initiating role in SCLC tumorigenesis, as a direct binder of the FOXA2 promoter and regulator of FOXA2 expression. Taken together, these data define the ASCL1-FOXA2 axis as a critical driver of multiorgan SCLC metastasis.

LucaPCycle: Illuminating microbial phosphorus cycling in deep-sea cold seep sediments using protein language models

Provoking tumor disulfidptosis by single-atom nanozyme via regulating cellular energy supply and reducing power

Multifunctional interface engineering enables efficient and stable inverted organic photovoltaics

Cortical circuits for cross-modal generalization

Abstract Adapting goal-directed behaviors to changing sensory conditions is a fundamental aspect of intelligence. The brain uses abstract representations of the environment to generalize learned associations across sensory modalities. The circuit organization that mediates such cross-modal generalizations remains, however, unknown. Here, we demonstrate that mice can bidirectionally generalize sensorimotor task rules between touch and vision by using abstract representations of peri-personal space within the cortex. Using large-scale mapping in the dorsal cortex at single-cell resolution, we discovered multimodal neurons with congruent spatial representations within multiple associative areas of the dorsal and ventral streams. Optogenetic sensory substitution and systematic silencing of these associative areas revealed that a single area in the dorsal stream is necessary and sufficient for cross-modal generalization. Our results identify and comprehensively describe a cortical circuit organization that underlies an essential cognitive function, providing a structural and functional basis for abstract reasoning in the mammalian brain.

High‐Entropy Deep Eutectic Solvent Achieves Ultra‐Low Polarization Zinc Anode Chemistry

Abstract Deep eutectic solvents (DESs), a new class of green solvents, have emerged as promising candidates for electrolytes due to their exceptional electrochemical stability. However, the DES always exhibits unacceptable polarization of cells due to its high viscosity and low ionic conductivity, which limit its practical application in batteries. In this work, the cell polarization of DES is effectively reduced to a level comparable to that of pure aqueous electrolytes by increasing the entropy of DES via the disorder‐making strategy of solvation structure. Theoretically, constructing the high‐entropy deep eutectic solvent (HEDES) promotes the formation of more aggregates with high disorder, which accelerates mass transfer kinetics. As a result, the proposed HEDES (configuration entropy 17 times higher than traditional electrolyte) can achieve durable zinc plating/stripping behavior for more than 2000 h with low polarization and still maintain good stability even in extreme environments. The cylindrical zinc‐ion capacitor under gram‐level loading can achieve a high discharge current up to 3 A, providing ideas for the design of electrolytes for zinc‐based energy storage devices.

Boosted charge and proton transfer over ternary Co/Co3O4/CoB for electrochemical nitric oxide reduction to ammonia

Abstract The electrochemical nitric oxide reduction reaction (NORR) holds a great potential for removing environmental pollutant NO and meanwhile generating high value-added ammonia (NH3). Herein, we tactfully design and synthesize a ternary Co/Co3O4/CoB heterostructure that displays a high NH3 Faradaic efficiency of 98.8% in NORR with an NH3 yield rate of 462.18 µmol cm−2 h−1 (2.31 mol h−1 gcat −1) at −0.5 V versus reversible hydrogen electrode, outperforming most of the reported NORR electrocatalysts to date. The superior NORR performance is attributed to the enhanced charge and proton transfer over the ternary Co/Co3O4/CoB heterostructure. The charge transfer between CoB and Co/Co3O4 yields electron-deficient Co and electron-rich Co3O4. The electron-deficient Co sites boost H2O dissociation to generate *H while the electron-rich low-coordination Co3O4 sites promote NO adsorption. The *H formed on electron-deficient Co sites is more favorable to transfer to electron-rich Co3O4 sites adsorbed with NO, facilitating the selective hydrogenation of NO. This study paves the way for designing and developing highly efficient electrocatalysts for electrochemical reduction of NO to NH3.

An in-situ assembled cobweb-like adhesive with high processability

A multi-hospital, clinician-initiated bacterial genomics programme to investigate treatment failure in severe Staphylococcus aureus infections

Abstract Bacterial genomics is increasingly used for infectious diseases surveillance, outbreak detection and prediction of antibiotic resistance. With expanding availability of rapid whole-genome sequencing, bacterial genomics data could become a valuable tool for clinicians managing bacterial infections, driving precision medicine strategies. Here, we present a clinician-driven bacterial genomics framework that applies within-patient evolutionary analysis to identify in real-time microbial genetic changes that have an impact on treatment outcomes of severe Staphylococcus aureus infections, a strategy that is increasingly used in cancer genomics. Our approach uses a combination of bacterial genomics and antibiotic susceptibility testing to identify and track bacterial adaptive mutations that underlie microbiologically documented treatment failure (i.e. ongoing positive cultures [persistent infection] or new positive cultures after initial response [recurrent infection]). We show the potential added value of our approach to clinicians and propose a roadmap for the use of bacterial genomics to advance the management of severe bacterial infections.

One‐Component Ionizable Amphiphilic Janus Dendrimers for Targeted mRNA Delivery

Abstract mRNA nanomedicine represents a new generation of therapeutics. However, how to deliver mRNA to the desired organs and cells effectively remains challenging. Common mRNA delivery vectors include viral and nonviral types such as four‐component lipid nanoparticles (LNPs), polymer‐based nanoparticles, lipid‐polymer hybrid nanoparticles, and so on. One‐component ionizable amphiphilic Janus dendrimers (IAJDs), are an emerging type of mRNA delivery vehicle displaying good stability and high delivery efficiency. In this review, we comprehensively present the design, synthesis, and mRNA delivery properties of IAJDs, with particular focus on the relationship between their molecular structures and organ targeted delivery properties. Other representative types of dendrimers for RNA delivery are also reviewed. Overall, this review summarizes the recent research progress on IAJDs systematically, aiming to guide the development of more efficient mRNA delivery platforms and next‐generation mRNA nanomedicines.

High-speed atomic force microscopy and 3D modeling reveal the structural dynamics of ADAR1 complexes

HMGA2 and protein leucine methylation drive pancreatic cancer lineage plasticity

An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing

Proteome-wide ligandability maps of drugs with diverse cysteine-reactive chemotypes

Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk

Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer’s disease and a cumulative effects model for risk liability

Structural basis of ubiquitin ligase Nedd4-2 autoinhibition and regulation by calcium and 14-3-3 proteins

The global spectrum of tree crown architecture

Abstract Trees can differ enormously in their crown architectural traits, such as the scaling relationships between tree height, crown width and stem diameter. Yet despite the importance of crown architecture in shaping the structure and function of terrestrial ecosystems, we lack a complete picture of what drives this incredible diversity in crown shapes. Using data from 374,888 globally distributed trees, we explore how climate, disturbance, competition, functional traits, and evolutionary history constrain the height and crown width scaling relationships of 1914 tree species. We find that variation in height–diameter scaling relationships is primarily controlled by water availability and light competition. Conversely, crown width is predominantly shaped by exposure to wind and fire, while also covarying with functional traits related to mechanical stability and photosynthesis. Additionally, we identify several plant lineages with highly distinctive stem and crown forms, such as the exceedingly slender dipterocarps of Southeast Asia, or the extremely wide crowns of legume trees in African savannas. Our study charts the global spectrum of tree crown architecture and pinpoints the processes that shape the 3D structure of woody ecosystems.

Spatiotemporal development of expanding bacterial colonies driven by emergent mechanical constraints and nutrient gradients

Abstract Bacterial colonies growing on solid surfaces can exhibit robust expansion kinetics, with constant radial growth and saturating vertical expansion, suggesting a common developmental program. Here, we study this process for Escherichia coli cells using a combination of modeling and experiments. We show that linear radial colony expansion is set by the verticalization of interior cells due to mechanical constraints rather than radial nutrient gradients as commonly assumed. In contrast, vertical expansion slows down from an initial linear regime even while radial expansion continues linearly. This vertical slowdown is due to limitation of cell growth caused by vertical nutrient gradients, exacerbated by concurrent oxygen depletion. Starvation in the colony interior results in a distinct death zone which sets in as vertical expansion slows down, with the death zone increasing in size along with the expanding colony. Thus, our study reveals complex heterogeneity within simple monoclonal bacterial colonies, especially along the vertical dimension. The intricate dynamics of such emergent behavior can be understood quantitatively from an interplay of mechanical constraints and nutrient gradients arising from obligatory metabolic processes.