Anthropogenic global change presents a growing threat to insect pollinators. Yet, long-term, continental-scale assessments of their population trends remain limited. Here, we leveraged a curated database of over four million occurrence records, covering 88% of extant bee and hoverfly species in Europe, to assess persistence, richness, and occupancy trends over the past century. Species persistence at the European level was relatively high, with modern records available for 87% of bee and 89% of
If [Formula: see text] and [Formula: see text] are cardinals, then the cardinal exponentiation [Formula: see text] is the set of all functions from [Formula: see text] into [Formula: see text]. The ABCD hypothesis is the statement that for all infinite cardinals [Formula: see text] and [Formula: see text], [Formula: see text] if and only if [Formula: see text] and [Formula: see text]. The Axiom of Determinacy, AD, states that every two-player infinite game on [Formula: see text] has a winning st
Adsorbate bonding at metal surfaces requires hybridization of localized molecular orbitals with delocalized electronic bands of the metal; hence, the electronic wave function involved in bonding may extend far beyond the adsorption site. We revealed the consequence of this delocalization by determining the distance over which structural variations of the metal surface influence the molecule-metal bond strength. Velocity-resolved kinetics provided adsorption energies for three molecules bound at
Altermagnetism has been recognized as a magnetic phase that bridges the properties of ferro- and antiferromagnetism. The momentum-dependent spin splitting observed in these materials reflects their distinctive symmetry characteristics, which also establish the conditions for chiral magnons to emerge. Here we provide direct experimental evidence for a chiral magnon in the altermagnetic candidate manganese telluride (MnTe) revealed by circular-dichroism resonant inelastic x-ray scattering. This mo
Glaciers populate the mountain ranges of the western conterminous United States and despite their importance to alpine hydrology, their area and volume change have never been comprehensively evaluated. Our study shows that since the mid-twentieth century about one-quarter of the glaciers have disappeared and the overall area and volume are reduced by one-third. The pattern of glacier shrinkage suggests most glaciers in the conterminous United States are largely maintained by local topographic in
Disruption describes the extent to which a scientific work overturns the prior knowledge on which it builds and leads to a new line of research. A scientist's tendency to produce disruptive work has been found recently to decline over the career. However, the disruption index captures only how strongly a paper overturns prior work and ignores whether that disruption is later accepted or overturned by subsequent research. The persistent disruption (PD) framework adds this second perspective, iden
Transboundary aquifers (TBAs) underlie 35% of global groundwater-irrigated cropland, yet few are covered by formal cooperative arrangements. Whether this limited cooperation is consequential depends in part on where groundwater is used within shared aquifers, because pumping far from international borders may generate little cross-border impact. Combining [Formula: see text]116,000 well observations with global irrigation data across all 426 known TBAs, we assess how groundwater use and depletio
Keratan sulfate (KS) is a unique and widely distributed glycosaminoglycans family implicated in diverse biological processes. KS features branched glycan architectures with diverse sialylation and sulfation patterns, encoding a vastly expanded chemical and biological space. The limited accessibility of well-defined structures has hindered precise investigations into the KS biological functions. Here we report a programmable chemoenzymatic platform for assembling a 106-membered library of KS N -g
Although international guidelines recommend intrauterine insemination (IUI) with ovarian stimulation as first-line treatment for unexplained infertility, evidence from comparisons of this method with in vitro fertilization (IVF) is limited. We conducted a sequential, multicenter, randomized, controlled trial involving couples with unexplained infertility. Stage 1 was a noninferiority comparison between IUI with ovarian stimulation (up to four cycles) and IVF (one complete cycle, with transfer of
The standard of care for patients with muscle-invasive bladder cancer continues to evolve. Whether perioperative durvalumab, with or without tremelimumab, plus neoadjuvant enfortumab vedotin is effective in such patients is unknown. In this phase 3 open-label trial, we randomly assigned, in a 1:1:1 ratio, patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy to receive neoadjuvant durvalumab-enfortumab vedotin every 3 weeks for three cycles
The combination of docetaxel, trastuzumab, and pertuzumab (THP) is an established first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. The efficacy and safety of anbenitamab, a HER2-targeted bispecific antibody, plus albumin-bound docetaxel (HB1801) in this context are unknown. In this phase 3, multicenter, open-label, randomized trial conducted in China, we randomly assigned patients with HER2-positive advanced breast cancer in a 1:1 ratio to
Endovascular thrombectomy is an established treatment for acute ischemic stroke. Whether the benefit extends to patients with salvageable brain tissue in the infarct who present more than 24 hours after symptom onset or the time when they were last known to be well is uncertain. We conducted an open-label, randomized trial with blinded outcome assessment at comprehensive stroke centers in China. Patients with acute ischemic stroke from large-vessel occlusion of the anterior circulation and imagi
Lifestyle-related type 2 diabetes and associated obesity (diabesity) affect >2.5 billion people worldwide and impose nearly $3 trillion in annual health care costs. We developed an implantable, wirelessly powered electrocatalytic closed-loop health optimization (ECHO) device containing platinum-decorated gold nanoclusters embedded in graphite felt that enabled selective, electrically tunable oxidation of blood glucose to renally cleared gluconate. In type 2 diabetic mice, wireless, low-power
The underlying mechanism of the thermal Hall effect generated by phonons in a variety of insulators is yet to be identified. In this work, we report on a sizable thermal Hall conductivity in nickel phosphorus trisulfide (NiPS 3 ), a van der Waals stack of honeycomb layers with a zigzag antiferromagnetic order. The longitudinal (κ aa ) and the transverse (κ ab ) thermal conductivities peak at the same temperature, and the thermal Hall angle, at this peak, respects a previously identified bound. T
Retatrutide, an investigational triple agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors, may be useful for treating obstructive sleep apnea (OSA). In two phase 3, double-blind, randomized, placebo-controlled trials nested within larger basket trials of once-weekly subcutaneous retatrutide, we assigned adults with moderate-to-severe OSA and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least
Abstract Large language models are enabling a new generation of health agents, yet their ability to address the diverse needs of individuals in everyday health settings remains underexplored 1,2 . Here we developed a comprehensive personal health agent that reasons over multimodal data from consumer wellness devices and medical records to provide personalized health support. Through analysis of web search and health forum queries, together with user-centred research involving end users and healt
Abstract WEE1 phosphorylates and inhibits the activity of cyclin-dependent kinases to prevent mitotic entry and establish a G2 DNA damage checkpoint 1–3 . Consequently, WEE1 inhibitors have been developed to be synthetically lethal in TP53- mutated tumours that become reliant on this WEE1-mediated checkpoint, and such inhibitors are undergoing clinical trials. However, WEE1 inhibitors also have efficacy in TP53- wild-type tumours, and many trials have been terminated owing to high levels of toxi
Abstract Moderately cold temperatures extend lifespan and promote health across species 1–3 , yet the molecular mechanisms underlying these benefits remain unclear. Here we define a metabolite-driven, multi-tissue signalling system that links cold temperature to enhanced longevity and proteostasis in Caenorhabditis elegans . Cold temperature upregulates the biopterin-synthesis enzyme CAT-4 (GCH1 in humans), increasing production of dihydrobiopterin (BH2), a transportable reservoir for the bioact
Capturing enzymes under native turnover conditions remains a grand challenge in structural biology. Here, we develop a reaction-based cryo-electron microscopy (cryo-EM) strategy that directly samples Drosophila melanogaster cytidine triphosphate synthase (CTPS) from actively catalyzing mixtures containing only natural substrates and allosteric effectors. By integrating reaction-based sampling with three-dimensional variability analysis, we resolve a continuous conformational spectrum of CTPS dur
Cytidine triphosphate (CTP), a fundamental building block of RNA, plays vital roles in diverse biological processes. CTP synthase (CTPS) is the only known enzyme for de novo synthesis of CTP. Efficient CTPS catalysis requires guanosine triphosphate (GTP) in a dose-dependent, nonconsumptive manner; however, the precise mechanism by which GTP drives CTP formation remains unclear. Here, we integrate a series of cryo-EM structures of Drosophila melanogaster CTPS captured from actively catalyzing sam
Antiferromagnetism and superconductivity are often viewed as competing orders in correlated electron systems. Here, we demonstrate that kinetic frustration in hole motion facilitates their coexistence within the square-lattice repulsive Hubbard model. Combining exact analytical solutions on tailored geometries with large-scale numerical simulations, we reveal a robust pairing mechanism: Holes on opposite sublattices behave as if they carry opposite effective charges due to spin singlet formation
Evolutionary shape changes of the vertebrate semicircular canals (SCCs) are often ascribed to evolutionary transitions in locomotion, including the origin of flight during the dinosaur-bird transition. However, the potential for transformations of braincase architecture to influence SCC shape independent of sensory-functional adaptation has generally been overlooked. We evaluate the influence of both factors using a large dataset of 146 living and recently extinct crown birds, including taxa rep
Brain network formation unfolds on a nonuniform developmental timetable, with different cortical regions generating connections at different developmental phases. Generative network models (GNMs) aim to uncover the principles underpinning the organization of connectomes by creating synthetic networks according to simple computational rules. These models capture the connectome's topology, operationalized here as the cumulative distributions of network metrics (e.g., modularity, small-worldness, r
The linear relationship between tail-beat frequency and swimming speed in fish, first described by Bainbridge in 1958, has since been confirmed in species as disparate as eels and tuna. Dimensional scaling has explained why linearity should emerge at high Reynolds numbers, but the frequency-speed relationship itself has remained empirical, with no physical framework describing its behavior across swimming regimes, and no account of what sets the two quantities that define it: the distance covere
Protein-coding transcripts are regarded as intermediates that mediate DNA-to-protein information flow, leaving their noncoding regulatory potential largely underappreciated. Genome-wide profiling of RNA–chromatin interactions in Arabidopsis has uncovered widespread associations between protein-coding transcripts and distinct genomic loci, implying that they possess regulatory functions. Here, we found that BT2 and GSL8 transcripts modulate target gene transcription independently of their protein
In two-dimensional transition-metal dichalcogenides (TMDCs), the local electrostatic field of the chalcogen p -orbitals dictates the crystal field splitting of the transition metal d -orbitals, stabilizing diverse electronic states from semiconducting and semimetallic to exotic topological phases. On-demand substitution of the lattice chalcogens is therefore an efficient route to tuning TMDC electronic phases. Here, we custom-molded van der Waals (vdW) heterostructures by layer-by-layer vapor-ph
Limited selenium (Se) accumulation in agricultural products contributes to widespread dietary Se deficiency, posing a global nutritional threat. Efficient agronomic strategies to enhance Se biofortification in crops are still lacking. Here, we reveal the synergistic effects of shading and Se nanoparticles application on Se biofortification in tea leaves. Field experiments demonstrate that shading enhances Se accumulation in tea leaves under sufficient Se supply, through activating Se metabolism
Tetrapods arose from lobe-finned fishes with a notochord-dominated axial column 1-3 . During this transition, the skull became separated from the shoulder girdle 4-6 , giving rise to a neck region. This head-shoulder separation has generated hypotheses suggesting that neck mobility increased during the origin of tetrapods, facilitating the ecological transition towards more terrestrial habitats 4,5,7-9 . However, incompletely co-ossified vertebral components 10 have posed a challenge to mod
Cryptovivipary and vivipary, referred to as (crypto)vivipary, occur across multiple angiosperm lineages and enable embryos to continue developing before dispersal. Yet, this trait raises a fundamental question: how are seed-specific abscisic acid (ABA) responses modulated to support continuous embryonic growth without compromising ABA-dependent vegetative stress tolerance? Here, integrating phylogenomic analyses of independently evolved (crypto)viviparous lineages with spatiotemporal transcripto
The Benjamini-Hochberg (BH) procedure is the standard method for controlling the false discovery rate (FDR) in large-scale studies involving testing multiple hypotheses. Whether the BH procedure controls the FDR for every correlation structure among two-sided Gaussian tests has been a long-standing question, and a positive answer has been believed. Here, we settle the question negatively, by providing examples of Gaussian factor models for which the BH method fails to control the FDR at the nomi
Understanding the structural conformation and dynamics of nucleic acids in solution is critical for the development of nucleic acid therapeutics involving antisense or mRNA therapies, where controlling stability, efficacy, and manufacturability are important. Circular dichroism (CD) spectroscopy allows rapid and nondestructive solution analysis of the spatial arrangements of nucleic acids. While widely used to analyze protein structure, the potential of CD for DNA- and RNA-based pharmaceutical a
Existing models of learning in the brain explain how given circuits learn, but not how biology could assemble those circuits in the first place. To address this gap, we formulate Self-Assembling Learning-the study of how learning systems can emerge from lower-level interactions-and introduce one example mechanism, the Self-Assembling Motif (SAM). SAM is self-assembling at two scales: The motif emerges from initially random connectivity under heterosynaptic plasticity rules, and networks of SAMs,
A growing body of preclinical research is demonstrating the therapeutic potential of chronic, continuous hypoxia (11% FIO 2 ) for rare and common diseases. However, the chronic delivery of hypoxic gas poses both practical challenges and long-term safety concerns. We previously introduced a small-molecule, "hypoxia-in-a-pill" combining a hemoglobin affinity enhancer (GBT440) to limit oxygen delivery with a HIF-2α inhibitor (PT2399) to prevent detrimental compensatory erythropoiesis. Althoug
Transposable elements (TEs) are epigenetically silenced through multiple mechanisms, including heterochromatin formation and DNA methylation. Prior studies have implicated SETDB1 and the Human Silencing Hub (HUSH) complex in heterochromatin formation-based TE repression, but precise characterization of repeat subclass and locus-specific effects for SETDB1 and related mechanisms has been limited by short-read transcriptome mapping. Here, we use long-read RNA sequencing mapped to a telomere-to-tel
Quantum Fisher information (QFI) sets the ultimate precision of optical phase measurements and can reveal multiphoton entanglement. Yet the photon-number fluctuations that encode this sensitivity are difficult to convert into an electrical signal. We theoretically predict that a photodetector utilizing the shot noise of the quantum-geometric shift current of exciton polaritons can measure photon-number statistics and, for pure states, infer the QFI. By solving the Lindblad equation, we obtain th
Polyethylene (PE) accounts for more than a quarter of all plastic produced, owing to its exceptional material properties and scalable production. 1 However, pristine PE lacks critical properties, such as adhesion, that are needed for many additional commercial applications. 2 Selective post-polymerization functionalization of PE can impart properties that are absent in the pristine polymer, but global functionalization in a uniform medium perturbs bulk properties. 3-5 Here, we demonstrate cataly
Modern slavery remains pervasive across many economic sectors. Progress toward eradicating it has been partially hindered by a lack of tested, comprehensive policy responses. Using data on millions of cattle transactions in Brazil, we evaluated how ranchers changed their selling behavior after being added to the “Dirty List,” a public registry that names and shames employers found to use modern slavery. Dirty Listed ranchers significantly reduced direct sales to slaughterhouses that signed susta
Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection 1 . However, the functions and mechanisms of many DRTs remain unknown 2 . Here we identify a new antiviral defense system, DRT10, that associates with a noncoding RNA (ncRNA) to catalyze processive, protein-primed synthesis of tandem-repeat DNA. Reverse transcription is templated by a defined ncRNA region with a characteristic sequence pattern a
Simulations of the ocean wave climate are critical for assessment of coastal processes and hazards in observation sparse regions such as the Arctic. While the multidecade wind and ice datasets necessary for driving long-term wave simulations have proven reliable for such efforts, the presence of landfast ice along shorelines at scales not represented by these data has been a persistent uncertainty impeding accurate analysis of impacts to Arctic coasts. Here, we explore this uncertainty by produc
Informal settlements are widespread and rapidly growing, often associated with high vulnerabilities. However, global-scale understanding on their spatial distribution and complexity of vulnerability is limited. Here, we delineate the informal settlements across a sample of 1,914 cities of the Global South by integrating Sentinel-2 imagery with deep learning models, and we explore the heterogeneity of vulnerability using Urban Informal Settlement Vulnerability Index that encompasses living condit
Abstract Nanocrystalline metal halide perovskites are promising light emitters for light-emitting diodes (PeLEDs) because they suppress the intrinsic problem of exciton dissociation through charge confinement within nanocrystalline domains. Although these nanostructures have enabled high-emission efficiencies, such confinement strategies typically result in significantly reduced charge transport. This limitation is attributed to numerous grain boundaries, which induce severe charge carrier scatt
Abstract Hetero-cycloaddition reactions are powerful, atom-economical strategies for the rapid construction of heterocyclic frameworks from readily available building blocks. Over the past two decades, advances in photochemistry, photocatalysis, and modern excitation strategies have driven remarkable developments in the field. By accessing electronically excited states, light enables cycloaddition pathways inaccessible under classical thermal conditions, providing access to reactive radical, ion
Systemic therapy for breast cancer has evolved rapidly since 2020, driven by the expansion of targeted therapies, antibody-drug conjugates, and immunotherapy across biologic subtypes. The integration of tumor molecular profiling and germline testing has enabled increasingly personalized, biomarker-guided treatment strategies. In hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, cyclin-dependent kinase 4 and 6 inhibitors remain foundational, whereas phos
Fast radio bursts (FRBs) are millisecond-duration radio transients from extragalactic sources. Their frequency and polarization properties are affected by plasma and magnetic fields along the line of sight to Earth. We report radio observations of FRB 20240304B and near-infrared follow-up to identify its host galaxy. The host is a low-mass, clumpy, star-forming galaxy at redshift 2.148 ± 0.0013, corresponding to 3 billion years after the Big Bang. This FRB occurred during the peak of cosmic
The generation and manipulation of entanglement with low error are essential in quantum information systems. In practice, two-qubit entangling gates constitute a dominant error source, limiting circuit depths and performance in fault-tolerant architectures. Using a neutral-atom quantum processor, we realized entangling controlled- Z gates with a high-Rabi-frequency smooth-amplitude pulse, employing state-selective readout and qubit reuse for fast calibration, and achieved a fidelity of 99.854(4)
Low-symmetry materials unlock rich Berry curvature physics and anomalous transport phenomena that are forbidden in high-symmetry quantum systems through rigorous crystalline symmetry constraints. Current approaches rely on external fields or complex heterogeneous stacking to break crystalline symmetries, which hinders scalable device integration. In this work, we demonstrate surface premelting engineering to create wafer-scale low-symmetry graphene on germanium-110 [Ge(110)]. Controlled premelti
Lupins ( Lupinus spp.) are promising protein crops that accumulate bitter and toxic quinolizidine alkaloids (QAs). The effective removal of QAs through new breeding technologies is hampered by a poor understanding of their biosynthesis. In this study, we used pathway reconstruction and mutant analysis to elucidate the full QA pathway in L. angustifolius [narrow-leafed lupin (NLL)] comprising 15 enzymatic steps. Major latex protein–like proteins play a prominent role in the pathway by acceleratin
The origin of Bronze Age tin is one of the most compelling mysteries in global archaeology. A number of studies were carried out to identify fingerprints to determine tin sources, but all failed to suit the contexts of Bronze Age China. This study provides the first comprehensive provenance analysis of the tin ore utilized during the Shang dynasty of China. Using U-Pb dating analysis on cassiterite grains surviving in various contexts including primary smelting site, metal resource hoard, and br
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that detects aberrant DNA and activates the STING-dependent innate immune response. Although cGAS is predominantly localized in the nucleus under physiological conditions, its nuclear function remains incompletely understood. Here, we identify nuclear cGAS as a transcriptional repressor that restrains inflammatory gene expression independently of STING signaling. Using macrophages challenged with lipopolysaccharide (LPS), we found that cGA
Post-transcriptional transfer RNA (tRNA) modifications dynamically regulate translational capacity, yet whether the tRNA epitranscriptome is temporally coordinated with gene expression programs during bacterial growth remains unknown. Here, we combine time-resolved nanopore tRNA sequencing, liquid chromatography-tandem mass spectrometry modification profiling, transcriptomics, and proteomics across the Pseudomonas aeruginosa PA14 growth cycle to show that tRNA-modifying enzymes, the correspondin
