Structurally ordered metal-organic framework (MOF) membranes hold great promise for selective molecular separations in chemical and pharmaceutical industries due to their precise pore size control and strong stability in organic solvents. However, the high surface energy of MOF nanodispersions complicates their assembly, leading to nonselective grain boundaries and poor processability, which hinder

Proteolysis-targeting chimeras (PROTACs) are catalytic protein degraders with promising preclinical activity. The clinical translation of PROTACs has been limited by poor pharmacologic properties and toxicities, in part due to their “non-druglike” characteristics, including large molecular weights. We found that the vast majority of PROTACs can self-assemble into nanoparticles, yielding nanoparticle

We describe a machine-learned (ML) model, MCNet, which predicts interactions between proteins and glycans. MCNet predicted quantitative interactions between glycan-binding proteins (GBPs) and enantiomers of common glycans, which were not part of the original training datasets. l -glycans are rare in nature but are important in consideration of safety of putative mirror-image life-forms. Current ML

T cell immunogenicity, the ability of peptide fragments to elicit T cell responses, is a critical determinant of the safety and efficacy of protein therapeutics and vaccines. While deep learning shows promise for in silico prediction, the scarcity of comprehensive immunogenicity data is a major challenge. We present T cell immunogenicity scoring via cross-domain aided predictive engine (T-SCAPE), a

MINimal photon FLUXes (MINFLUX) offers nanometer localization precision, with lower fluorophore requirements than for other super-resolution microscopy (SRM) techniques. Nonetheless, low localization probabilities hamper its application, and use of less bright and photostable fluorophores, including near-infrared (NIR) fluorophores has been difficult to realize. Here, we devised strategies overcoming

Our understanding of biodiversity patterns comes primarily from described species. Here, we analyze how known biodiversity has increased across living organisms. Past research suggested that the number of new species per year peaked near 1900 and that only ~2 million species exist. We find that overall rates of species descriptions have recently accelerated, with the largest numbers of new species

Ocean-driven basal melt can thin and weaken ice shelves, reducing buttressing and causing sea level rise. However, the processes driving melt in ice shelf cavities are challenging to observe. Here we report float observations spanning the ocean cavity beneath Shackleton Ice Shelf. Warm water at depth reaches the cavity beneath the Denman Glacier, driving strong melt. Beneath the rest of the Shackleton

High-speed active metasurfaces enable spatiotemporal light control within an ultrathin device layer, offering previously unexplored possibilities for optical communication, sensing, and computing. However, a trade-off between electrical conductivity and optical loss has hindered the realization of a high-speed, low-loss device. Here, we experimentally demonstrate an active metasurface operating at

Acquired drug resistance mutations in epidermal growth factor receptor (EGFR) present a substantial clinical challenge in treating non–small cell lung cancer (NSCLC). While EGFR oligomerization plays a pivotal role in modulating receptor signaling, its relationship with resistance mutations remains unclear. Here, we investigated the real-time link between oligomerization of oncogenic and resistant

To address the challenge of extremely low drug bioavailability in osteoarthritis (OA) cartilage, we developed a self-assembled micelle-exosome system (Mic-Exo) tailored to the specific characteristics of OA cartilage. The hydrophobic lipid layer of Mic-Exo enables efficient loading of therapeutic lipids (DHA), while the incorporation of 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) reverses surface

Ciliogenesis requires an orchestrated interaction between the Golgi apparatus and centrioles via vesicle trafficking, yet this process is still poorly understood. Phosphatidylinositol 4-kinase β (PI4KB) is a conserved kinase that localizes to the Golgi for generating phosphatidylinositol 4-phosphate, an important lipid component related to cilium formation. Here, we demonstrate a previously uncharacterized

Pancreatic ductal adenocarcinoma (PDAC) is generally resistant to conventional immunotherapies due to its immunosuppressive tumor microenvironment (TME). We combine an innate cell–enriched product activated by interleukin-2 (IL-2) and zoledronic acid (ZA) (ICP IL2ZA ) with low-dose radiotherapy (RT) and monoclonal antibodies (mAbs) to overcome this immunosuppressive TME. ICP IL2ZA is composed of natural

Understanding meiotic and genomic stability in polyploid species is critical for advancing genetic discovery and breeding. Potato ( Solanum tuberosum ), the third most important food crop globally, is represented by cultivated potato, an autotetraploid with highly heterozygous genomes. Here, we revealed that cultivated potato showed different chromosomal pairing configurations and irregular chromosomal

Understanding the brain’s intrinsic mechanisms that drive the emergence of consciousness from anesthesia remains a substantial and unresolved challenge in brain research. Here, we show in mice that, when the brain is forced into a minimal responsive state by an anesthetic, a rapid activation of EphB1 receptor occurs in the ventral posteromedial nucleus (VPM) of the thalamus and contributes to promote

The blood-brain barrier (BBB) is commonly known to be distributed evenly within the central nervous system. This study elucidates previously unexplored physiological phenomena associated with the spatial heterogeneity of the BBB. We found that isoflurane facilitates hemispheric lateralization in BBB permeability, leading to different responses between the left and right hemispheres. To substantiate

Cyclones cause major damage to mangrove ecosystems globally. While this damage is projected to increase as storms intensify with climate change, the consequences of changes in cyclone attributes other than wind speed remain largely unexplored. Here, we show that shifts in cyclone travel speed may also dramatically alter the risks and mechanisms of damage. By developing an interpretable machine learning

Precise atomic-level control over interfacial charge density and lattice distortions remains a critical challenge across electromagnetism, optoelectronics, and catalysis. Here, we introduce a high-entropy strategy that leverages local compositional disorder to synergistically manipulate charge density distribution and lattice strain at anisotropic morphotropic phase boundary (MPB) interfaces. Experimental

Although genomes encode instructions for mammalian cell differentiation with rich syntactic relationships, existing methods for genetically programming cells have only modest capabilities for stepwise gene regulation. Here, we develop a sequential genetic system that transcriptionally activates endogenous genes in a preprogrammed, stepwise manner. This system uses the removal of an RNA polymerase III

Ferroelectric capacitive memory (FeCAP) holds enormous potential for low-power, high-density in-memory computing. While hafnia-based FeCAPs have attracted attention for their silicon compatibility, they suffer from limited performance, such as a narrow memory window and relatively high switching fields. In this work, an FeCAP device is developed on the basis of a single-crystalline barium titanate

Prokaryotes use polycistronic transcription (operons) to express multiple messenger RNAs (mRNAs) from a single promoter to coexpress functionally related genes. However, how do eukaryotes, which express monocistronic messages, achieve the same regulation? Previously, we demonstrated that yeast uses RNA operons, i.e., mRNAs assembled in trans (transperons), to control multiple cellular pathways such

Intratumor heterogeneity impacts disease progression and therapeutic resistance but remains poorly characterized by conventional histologic, immunophenotypic, and molecular approaches. Single-cell biophysical properties distinguish functional phenotypes complementary to these approaches, providing additional insight into cellular diversity. Here, we link both buoyant mass and stiffness to gene expression

Chronic stress disrupts skeletal homeostasis, yet central neural mechanisms remain unclear. In this study, we demonstrated that hyperactivation of locus coeruleus noradrenergic (LC NE+ ) neurons was both necessary and sufficient to drive bone loss in a mouse model of chronic social defeat stress (CSDS). Mechanistically, CSDS induced a bidirectional imbalance in the central amygdala corticotropin-releasing

The search for development strategies that yield low κ lat has become the focus of thermoelectrics and barrier coatings. Here, we propose a “forced bond ionization” strategy by integrating conflicting coordination environments (planar three coordination versus tetrahedral four coordination of Cu) to form pseudo-tetrahedral structures. This approach induces partial ionization of Cu─I bonds in Cu 5 TeS

Lithium (Li) and magnesium (Mg) are designated as critical mineral materials (CMM) due to their essential roles in clean energy technologies. However, extracting high-purity Li + from brine remains a formidable challenge owing to the presence of Mg 2+ , a physicochemical similar ion that often exists in excess. Here, we introduce a polyoxoniobate-based “Mg-PONb sponge” that enables ultraselective and

Photocatalytic therapy holds great prospects in high-performance tumor treatment owing to its advantages of noninvasiveness and oxygen nonreliance. However, there is still a lack of ideal photocatalyst materials that respond to near-infrared (NIR) light, especially with organelle-specific features. Here, a mitochondria-biomimetic organic semiconductor photocatalyst was designed for NIR-activatable

The confinement-controlled molecular interactions in living systems are fundamental for governing information conversion and transmission in metabolic processes. Artificial systems that mimic this confinement effect at the nanoscale provide valuable insights into programmable molecular information processing. Here, we introduce DNA origami framework cryptosystem (DOFC), a strategy that leverages DNA

Long-persistent luminescent (LPL) materials store photon energy as charges and emit light over extended periods via charge recombination. LPL decay typically follows a power law rather than an exponential decay, enabling confirmation of charge accumulation from emission decay characteristics. While charge generation in organic materials has been widely studied at donor-acceptor (D/A) interfaces, it

Maternal lipid levels change dynamically during gestation to support normal fetal growth. To obtain a detailed footprint of these changes and their differences in pregnancies with preterm or small-for-gestational-age (SGA) neonates, we analyzed 641 lipids and 639 metabolites in plasma from women by 24 weeks of pregnancy from three cohorts from low- and middle-income countries: Bangladesh, Zimbabwe

Aerial insects exhibit agile maneuvers such as sharp braking, saccades, and body flips under disturbances; in contrast, insect-scale aerial robots are limited to tracking smooth trajectories with small acceleration. To achieve similar flight capabilities, insect-scale robots require a robust and computationally efficient controller. Here, through designing a deep-learned robust tube model predictive

The specification of intestinal stem cells (ISCs) during development is critical for maintaining intestinal homeostasis. However, the mechanisms underlying this process remain elusive. Here, by counting and tracing ISC in Drosophila pupal midgut, we show that ISCs are specified within a narrow 12-hour developmental window, with ~150 ISCs emerging from a pool of ~6000 intestinal epithelial cells. Single-cell

Seed dormancy and germination are dynamically regulated by abscisic acid (ABA), with transcription factor ABA INSENSITIVE 5 (ABI5) serving as a key repressor of germination under stress. Here, we identify QUIRKY (QKY), a MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEIN (MCTP) in Arabidopsis , as a critical regulator of ABA signaling through posttranslational control of ABI5. QKY interacts with ABI5

Carcinogenesis in human urothelium is driven by a high burden of mutations caused by the antiviral “APOBEC3” (apolipoprotein B mRNA editing enzyme, catalytic subunit–like 3) cytosine deaminase enzymes; however, there is no established viral etiology. BK polyomavirus (BKPyV) is a ubiquitous childhood infection that persists in the kidney during adulthood and is frequently detected in urine. Chronic

Chemical and conformational changes are crucial to protein function and its pharmacological control. X-ray crystallography can reveal these changes in atomic detail, but standard analysis methods, which refine separate datasets, often overlook differences that are subtle or arise in only a subset of molecules. Direct comparison of crystallographic datasets is, in principle, more powerful, but systematic

The occurrence of seismic events can be modulated by external periodic stress perturbations, such as daily tidal stress and annual hydrological stress. Such periodic modulations are crucial for understanding earthquake triggering, yet their underlying physical mechanisms are not fully understood. Here, we find that ordinary earthquakes (OEs) and low-frequency earthquakes (LFEs) on the Central San Andreas

Memory consolidation enables animals to draw on past experiences to guide future behavior. This process involves system- and synaptic-level changes and predominantly occurs during sleep. While hippocampal-cortical circuits are well studied in this context, the contributions of other systems, including dopaminergic circuits—key players in learning-related processes—remain poorly understood. Ventral

Distinguishing between enantiomers is crucial in chemistry and pharmacology. Existing optical methods rely on enantiospecific three-photon electric-dipole transitions, requiring phase locking, three-photon resonance, and precise beam control, limiting their practicality. Here, we propose an optical method that eliminates these constraints by applying a static electric field, which breaks a symmetry

Inspired by ancient chain mail, we introduce a stealth skin constructed from topologically interlocking units that synergizes mechanical robustness with electromagnetic functionality. This architecture is lightweight, highly conformable to complex surfaces, and load-bearing without sacrificing strength. We demonstrate its application by fabricating an electromagnetic skin with an areal density of only

Ovarian cancer is the deadliest gynecological malignancy. The fluorescence-guided surgery technique provides a real-time visualization of the desired regions to guide the tumor resection. However, the fluorescent probes used in clinics suffer from the limited selectivity of ovarian tumors and short blood circulation half-lives. Here, we design an activatable trident-like fluorescent peptide probe (RMN)

Self-renewing hematopoietic stem cells (HSCs) generate all blood cells and give rise to long-term reconstitution of the hematopoietic system after transplantation, but the molecular mechanisms that specifically regulate HSCs remain poorly defined. Here, we found that HSCs displayed a distinct messenger RNA alternative splicing pattern and preferentially expressed Rbfox2 , an alternative splicing regulator

Villin is an actin filament nucleating, severing, capping and bundling protein; however, the structural basis for villin’s functions and the characteristics of the actin polymerization nucleus remain poorly understood. Here, we present the structure of vent-worm villin bound to a trimeric actin nucleus. Villin wraps around and caps the barbed end of the actin trimer. Its headpiece domain interacts

Plant cryptochromes (CRYs) are blue-light photoreceptors regulating physiological processes via oligomerization-dependent interaction with effectors. However, the structural basis for photoactivated CRY-effector assembly remains elusive. Here, we report the crystal structure of an active maize CRY1c photolyase homology region in complex with GLOSSY2 (ZmGL2), a BAHD acyltransferase family protein that

Vaccine-induced seropositivity (VISP) causes antibodies produced by HIV-1 vaccines to react with standard serological tests, complicating diagnosis and leading to false positives. To distinguish VISP from true HIV infections, we developed a rapid, multiplexed companion electrochemical assay that integrates a three-dimensional–printed device with screen-printed electrodes coated with antigen, antibody

Abdominal aortic aneurysm (AAA) is a life-threatening condition lacking effective drug interventions, and its progression is difficult to predict, complicating early clinical management. Here, we present a reactive oxygen species–responsive theranostic nanozyme for AAA early intervention and efficacy monitoring, establishing a feedback loop between treatment and diagnostics. OZn, designed by encapsulating

Metabolic disorders caused by defects in energy metabolism can lead to many life-threatening diseases; their therapy remains elusive in most cases. Conventional gene therapy relies on the “one gene for one genetic defect” strategy. Here, we demonstrate a more efficient strategy to target multiple genetic defects with a single gene intervention. Specifically, we used a bacterial lipoate protein ligase

B cell involvement in neoantigen-driven antitumor immunity remains largely unexplored because of challenges in predicting B cell responses. Here, we developed a method to identify B cell epitopes by characterizing >437,000 peptides tested for IgG binding and >370 million B cell receptor (BCR) clones. Our single-cell BCR sequencing of pre– and post–severe acute respiratory syndrome coronavirus 2 vaccination

Stimulator of IFN genes (STING) is an endoplasmic reticulum (ER) signaling receptor involved in the type I interferon response to pathogen- or self-derived cytosolic double-stranded DNA. Excessive activation of STING is associated with many diseases, but the regulatory mechanism of STING activation remains to be further elucidated. Here, we identify VAPB as a negative regulator of STING-mediated innate

Plant cuticular waxes, crucial hydrophobic barriers, are primarily composed of aliphatics derived from very-long-chain fatty acids (VLCFAs; >C28) synthesized by the endoplasmic reticulum fatty acid elongase complex. The core catalytic subunit, CER6 (KCS6), requires interaction with the BAHD protein GL2 to elongate acyl chains beyond C28. We determined the cryo–electron microscopy structure of the maize

Trapped ions constitute a promising platform for implementation of a quantum network. Recently, a dual-type qubit scheme has been realized in a quantum network node where communication qubits and memory qubits are encoded in different energy levels of the same ion species, such that the generation of ion-photon entanglement on the communication qubits has negligible cross-talk error on the preloaded

Wavefront shaping is essential for optical imaging through aberrations, but conventional methods rely on physical modulators and iterative optimization, hindering real-time applications in dynamic environments like turbulence. Inspired by quantum nonlocal aberration cancellation, we propose a modulator-free, computational wavefront shaping technique. By leveraging classical correlated illumination

Advancements in cellular immunotherapy demanded efficient immune cell delivery. To meet this need, we introduced hydrogel-based immune millirobots designed for high immune cell loading and precise tumor targeting. These ultrasoft robots, embedded with magnetic nanoparticles, exhibited adaptable locomotion: walking, rolling, climbing, and undulating, enabling navigation through complex biological environments

The ventral pallidum (VP) was defined as a basal ganglia nucleus with dense input from ventral striatum. To further investigate its regional identity, we conducted a cross-species transcriptional characterization of VP cell types. We performed single-nucleus RNA sequencing of VP tissue from mice and rats and identified 16 conserved VP neuronal subclasses, including 14 γ-aminobutyric acid–releasing

In the later stages of Parkinson’s disease, patients often manifest levodopa-induced dyskinesia (LID), compromising their quality of life. The pathophysiology underlying LID is poorly understood, and treatment options are limited. To move toward filling this treatment gap, the intrinsic and synaptic changes in striatal spiny projection neurons (SPNs) triggered by the sustained elevation of dopamine

Centrioles undergo marked transformations during spermatogenesis that are essential for sperm motility and male fertility. Despite their importance, the molecular mechanisms and ultrastructural dynamics underlying these transformations remain largely unknown. Here, we apply ultrastructure expansion microscopy and reveal previously unrecognized centriolar architectural changes in mouse male germ cells

Nonadjacent chirality is prevalent in pharmaceuticals and bioactive molecules, but prior studies primarily focused on constructing noncontiguous stereocenters. However, the construction of nonadjacent axial and flexible, acyclic central chirality often involves highly flexible transition states, posing challenges in achieving precise control over enantio- and diastereoselectivity. Here, extensive ligand

The development of cysteine (Cys)–selective bioconjugation reagents with enhanced stability remains a critical challenge for therapeutic applications such as antibody-drug conjugates (ADCs). Leveraging the modular 1,3,5-triazine scaffold, we report the design and optimization of triazine-pyridinium chemistry (TPC) reagents for selective Cys labeling. Through systematic structural modifications and

Cross-validation is a common method for evaluating machine learning models. “Leave-one-out cross-validation,” in which each data instance is used to test a model trained on all other instances, is often used in data-scarce regimes. As common metrics such as the R 2 score cannot be calculated for a single prediction, predictions are commonly aggregated across folds for performance evaluation. Here,

In normally sighted human adults, 2 hours of monocular deprivation is sufficient to transiently alter ocular dominance. Here, we show that this is associated with a reduction of functional connectivity between the pulvinar and primary visual cortex (V1), selective for the pulvinar-to-V1 directionality. Across participants, the strength of the pulvinar-to-V1 connectivity was negatively correlated with

The acquisition of a chemoresistant state underlies poor prognosis in many cancers, including neuroblastoma. We previously demonstrated that heterogeneity in apoptosis induction through c-Jun amino-terminal kinase (JNK) promotes a form of nongenetic chemoresistance in neuroblastoma observable at both patient and single-cell levels. As the maintenance of this JNK-impaired state in the relapse setting

Neural hyperexcitability and network dysfunction are neurophysiological hallmarks of Alzheimer’s disease (AD) in animal studies, but their presence and clinical relevance in humans remain poorly understood. We introduce a perturbation-based approach combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), alongside resting-state EEG (rsEEG), to investigate neurophysiological