Physics

Delineation of matter into solid and fluid (liquid and gas) phases is grounded in the contrasting localization and mobility of atomic/molecular aggregates, with the fluid phase distinguished by connected pathways for these entities. Here, we demonstrate that CuInP₂S₆, a layered material, manifests as a unique system differing from both solid and fluid: It is solid but contains disconnected pathways of highly mobile Cu species. Each pathway comprises two main docking sites, facilitating rapid intersite hopping of Cu that disrupts lattice waves of the immobilized sulfur sublattice, thereby inducing strong phonon anharmonicity. The Cu⁺ ions, ordered at low temperatures, become highly activated and dynamically disordered even at room temperature. This suppresses the virial contribution, a dominant heat conduction mechanism in conventional solids, while inducing a moderate liquid-like convective mode of heat transfer. Identifying analogous systems featuring disconnected pathways and dynamical disordering states offers a promising route for increased anharmonicity.

The intrinsic drug resistance of <i>Mycobacterium tuberculosis</i> (Mtb) is a major barrier to effective tuberculosis (TB) treatment and is largely due to its complex, impermeable cell envelope. We identified a periplasmic protein complex comprising FecB and Rv3035 that is essential for maintaining envelope integrity and mediating intrinsic multidrug resistance in Mtb. FecB interacts with Rv3035, forming a stable heterodimer that associates with the cell envelope biosynthesis protein AftB. We report the structures of Rv3035 alone and in complex with FecB and identify critical residues for complex formation and function. Coessentiality and genetic interaction analyses support a functional link between FecB, Rv3035, and AftB, an arabinofuranosyltransferase that synthesizes arabinogalactan and lipoarabinomannan. Loss of FecB or Rv3035 disrupted AftB-mediated arabinan synthesis, suggesting that these proteins support AftB's enzymatic activity. FecB is required for Mtb virulence in mice, underscoring its physiological relevance. These findings highlight FecB, Rv3035, and AftB as promising therapeutic targets.

Pathogens can spread via multiple transmission routes. The epidemiology of such pathogens exhibits rich complexity and produces counterintuitive dynamics.

Chronic diabetic wounds affect millions and often fail to heal due to infection, inflammation, and poor angiogenesis, leading to high rates of amputation. Current treatments offer limited control over the wound microenvironment. Here, this work develops GPP@ZnBG hydrogels that can respond to elevated glucose and oxidative stress in diabetic wounds to release therapeutic ions in a self-pH-regulated and sequential manner. At an early stage, this hydrogel initiates a release of zinc ions under alkaline conditions, providing antibacterial activity while avoiding toxicity from excessive dosing. During the late stage, the hydrogel degrades, and it steadily releases zinc, calcium, and silicate ions that support angiogenesis, reduce inflammation, and promote tissue repair. In diabetic mice, GPP@ZnBG hydrogels improve neovascularization and enhance collagen deposition, leading to enhanced wound closure. Single-cell RNA sequencing results indicate that the hydrogel modulates fibroblast behavior, specifically fine-tuning NF-κB signaling to reduce detrimental inflammation and promote wound repair. A pilot clinical study demonstrates that topical GPP@ZnBG application showed a 94.57% relative reduction in a wound surface area within 4 weeks, with no adverse events reported. These findings establish a self-pH-driven ion delivery strategy that targets both infection and tissue regeneration, offering a promising therapeutic platform for chronic diabetic wound care.

The underlying immunopathogenesis of inflammatory arthritis (IA) immune-related adverse event (irAE) remains obscure. Unlike rheumatoid arthritis (RA), where autoantibodies and B cell dysfunction are central features, the contribution of humoral immunity to IA-irAE is unclear. Here, we performed immunophenotyping of peripheral blood from patients with IA-irAE and compared them with patients with seronegative RA, immune checkpoint inhibition-treated patients without irAE, and healthy controls. IA-irAE was marked with increased cytotoxic gene expression and metabolic activation in T cells and reduced CXCR3 and CCR6 expression in CD4⁺ T cells. Contrary to seronegative RA, patients with IA-irAE displayed no substantial elevation in autoantibody levels or atypical CD11c⁺CD21^- B cells. IA-irAE was further characterized by elevated levels of interleukin-6 (IL-6), IL-12, and type I interferon, which correlated with the T cell activation phenotypes. Together, our findings define IA-irAE as a disease with certain immunological features distinctive from RA, representing a potentially T cell-driven, autoantibody-independent autoimmunity. These results offer insights into immune tolerance breakdown and therapeutic targeting in irAEs.

Stomatin is a ubiquitous and highly expressed protein in erythrocytes, which associates with cholesterol-rich microdomains in the plasma membrane and is known to regulate the activity of multiple ion channels and transporters, but the structural basis of association with stomatin targets remains unknown. Here, we describe high-resolution structures of multiple stomatin complexes with endogenous binding partners isolated from human erythrocyte membranes, revealing that stomatin specifically associates with two membrane proteins involved in water transport and cell volume regulation, aquaporin-1 and the urea transporter SLC14A1. Together, our results reveal the structural basis of stomatin oligomerization, membrane association, and target recruitment and identify a putative role for stomatin in the regulation of osmotic balance in the erythrocyte.

Progress in science and technology is punctuated by disruptive innovation and breakthroughs. To understand disruptive innovations and their drivers, the ability to operationalize and estimate "disruptiveness" is critical. Yet, this task remains difficult because scientific influence propagates through both direct and indirect citation paths, and discoveries are often fragmented across multiple papers. Here, we introduce an embedding-based metric of disruptiveness. When applied to large-scale publication data, the measure not only reliably identifies canonical breakthroughs, such as Nobel Prize-winning papers, but also finds simultaneous disruptions that eluded standard approaches. By enabling more robust identification of disruptive innovations and simultaneous discoveries, our method facilitates more accurate attribution of transformative contributions while providing insights into the mechanisms driving scientific breakthroughs.

Bacteriophage auxiliary metabolic genes (AMGs) alter host metabolism by hijacking reactions, but previous studies mostly inferred their roles from annotations, ignoring system-wide impacts and phage production. Here we integrate AMGs and phage assembly into a genome-scale metabolic model of <i>Prochloroccocus marinus</i> MED4 infected by P-HM2. We show that 17 directly hijacked reactions substantially affect more than 30% of the reactions in MED4 metabolism, including carbon fixation, photosynthesis, and nucleotide synthesis, distinguishing these AMGs as either phage aligned-shifting feasible reaction velocities in accordance with maximal phage production-or phage antialigned. Pareto optimization reveals that phage-aligned reactions alter phage-host growth trade-offs, while phage-antialigned reactions do not. We experimentally validate our predictions of system-level AMG impacts by measuring the N-dependent effect of P-HM2 <i>cp12</i> expression on growth in a model relative of the genetically intractable MED4, <i>Synechococcus elongatus</i>. We also show that AMGs' indirect impacts are synergistically and antagonistically coupled, providing systems-level insight into AMG perturbations and highlighting how nontrivial cascading effects shape host metabolism.

The cycling of volatiles through subduction zones fundamentally shapes Earth's chemical evolution, yet how fluorine (F) and chlorine (Cl) are processed in the deep mantle remains enigmatic. Here, we use high-pressure experiments (5 to 11 gigapascals and 850° to 1200°C) on altered oceanic crust analogs to track deep halogen behavior. We show that phengite remains stable to 11 gigapascals and 1050°C, efficiently transporting F and Cl to ~330-kilometer depth. Upon breakdown or melting, phengite strongly fractionates these halogens: Cl is released into fluids or melts, while F is sequestered in residual phases such as KMgF₃. The Cl-rich fluids produced (9.6 to 19.9 wt % Cl) closely match high-density fluid inclusions in diamonds, implicating them as key agents of cratonic metasomatism. Our findings establish phengite as a critical carrier mediating postarc fluxes of F (1.7 × 10¹² to 2.6 × 10¹² grams per year) and Cl (0.52 × 10¹² to 1.1 × 10¹² grams per year), providing a major pathway for replenishing deep mantle halogen reservoirs.

Mucosal melanoma (MM), an aggressive melanoma subtype arising in mucosal tissues, displays resistance to therapies effective in cutaneous melanoma. To understand how mucosal microenvironment contributes to treatment nonresponsiveness, we performed integrative analysis of single-cell and bulk messenger RNA sequencing data derived from oral mucosa-originated melanoma and revealed that mucosa-specific inflammation induces enrichment of low-pigmented neural crest-like cancer cell, mediated by COX2⁺ macrophages and their secretome. Maintenance of this inflammation-induced neural crest-like state in cancer cells depends on HER2 and HER3 activation. Inhibition of HER2/3 by pan-HER inhibitors blocks cell state plasticity and overcomes chemoresistance in primary MM cell lines and patient-derived xenograft (PDX) models. These findings provide insights into how the tissue of origin determines cancer aggressiveness, highlight the role of mucosal inflammation in driving melanoma stemness and chemoresistance, and advance the identification of effective treatment options currently lacking for patients with MM.

Cytoskeleton-tethered mechanosensitive channels (MSCs) use compliant gating springs to convert mechanical stimuli into electrical signals for sensations like sound and touch. The mechanical properties of these gating springs are poorly understood. We investigated the homotetrameric NompC channel, which contains long ankyrin-repeat domains (ARDs), using a toehold-mediated strand displacement method to tether single membrane proteins. This method allowed precise force application and extension measurement with optical tweezers. Our results show that a single NompC complex has a low stiffness of ~0.7 piconewtons per nanometer when pulled from one ARD, with stepwise unfolding beginning at ~7 piconewtons, leading to nonlinear stiffness. ARD truncation indicates strong lateral interactions between ARDs. Computational analyses suggest that this nonlinear, low stiffness may regulate NompC's sensitivity, dynamic range, and kinetics in detecting mechanical stimuli. Our findings highlight the role of a compliant, unfolding-refolding gating spring in facilitating a graded response in MSC ion transduction across diverse mechanical stimuli.

Electron microscopy (EM) reveals atomic-scale structures that underpin catalysis, energy storage, and semiconductor reliability, yet current workflows remain fragmented across segmentation, crystallographic reconstruction, property modeling, and literature review, often requiring weeks of expert effort. Although recent artificial intelligence models have assisted individual steps, the diversity of EM modalities and tasks means existing approaches remain siloed and perform poorly in complex multistage workflows. We present EMSeek, a modular, provenance-tracked multiagent platform that connects EM to materials insight through five key units: reference-guided one-for-all segmentation, mask-aware reconstruction of crystal structures from EM data, a gated mixture of experts property predictor with uncertainty calibration, literature retrieval with citation anchoring, and physical consistency checks with audit-ready reporting. These units are orchestrated by large language models (LLMs) that automatically plan, invoke, and execute tools, minimizing human intervention. On 20 material systems and five tasks, EMSeek delivers segmentation about twice as fast as Segment Anything with higher accuracy, achieves more than 90% structural similarity on STEM2Mat, and, with about 2% labeled calibration, matches or surpasses strong single experts on three out-of-distribution property benchmarks. A complete query runs in 2 to 5 minutes per image, roughly 50 times faster than expert workflows. Case studies on two-dimensional lattices and nanoparticles validate EMSeek's ability to automate complex workflows, with integrated uncertainty calibration and audit signals that provide scientists with rigorous yet actionable guidance to accelerate materials discovery.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and restricted repetitive behaviors, yet the contribution of trace elements remains poorly defined. We profiled 21 trace elements in individuals with ASD and identified significantly reduced copper levels, which negatively correlated with social symptom severity. Magnetic resonance imaging revealed decreased white matter volume in ASD, which also correlated with social impairment. To explore the mechanisms, we generated a copper-deficient mouse model that displayed ASD-like behaviors and impaired oligodendrocyte (OL) development. Copper deficiency disrupted hypoxia-inducible factor 1α (HIF1α)-dependent angiogenesis and metabolic regulation in the embryonic brain, leading to oxidative stress, mitochondrial dysfunction, and BCL2 interacting protein 3 (BNIP3)-mediated mitophagy in oligodendrocyte progenitor cells. These processes suppressed mechanistic target of rapamycin kinase (mTOR) signaling, reduced OL-lineage cells, and caused hypomyelination. Restoring mTOR activity rescued OL maturation and improved social behavior in copper-deficient mice. These findings identify a copper-HIF1α-BNIP3-mTOR signaling axis that links trace element imbalance to glial dysfunction and ASD-relevant behavioral phenotypes, providing mechanistic insight into neurodevelopment.

The shared processing technologies of perovskite and organic semiconductors make them ideal partners for constructing perovskite-organic tandem solar cells. However, the different crystallization rates of bromide and iodide ions lead to inhomogeneous vertical halide distribution within wide-bandgap (WBG) perovskite films, causing notable open-circuit voltage (<i>V</i>_OC) loss. In this study, we developed an approach to blade-coat halide-compositionally homogeneous WBG perovskite films by introducing a hydrogen-bonding donor solvent (formamide). The formamide effectively modulates crystallization kinetics via balancing the differential hydrogen-bonding interactions of formamide with bromide and iodide ions. The resultant WBG perovskite solar cells achieved a power conversion efficiency of 18.9% with an exceptional <i>V</i>_OC of 1.41 volts. Last, a perovskite-organic tandem solar cell was fabricated, achieving a high efficiency of 26.3% (certified as 25.6%) and retaining 92% of its initial efficiency after being illuminated for 1000 hours. This work provides an approach for the large-area fabrication of halide-compositionally homogeneous WBG perovskite films, paving the way for the industrialization of tandem devices.

A central challenge in developing practical quantum processors is maintaining low control complexity while scaling to large numbers of qubits. Trapped-ion systems excel in small-scale operations and support rapid qubit scaling via long-chain architectures. However, their performance in larger systems is hindered by spectral crowding in radial motional modes, a problem that forces reliance on intricate pulse-shaping techniques to maintain gate fidelities. Here, we overcome this challenge by developing a trapped-ion processor with an individual-addressing system that generates steerable Hermite-Gaussian beam arrays. The transversal gradient of these beams couples qubits selectively to sparse axial motional modes, enabling to isolate a single or few modes as entanglement mediator. Leveraging this capability, we demonstrate addressable two-qubit entangling gates in chains up to six ions, with Bell-state preparation fidelities consistently around 0.97, achieved without complex pulse shaping. Our method substantially reduces control overhead while preserving scalability, providing a crucial advance toward practical large-scale trapped-ion quantum computing.

The protection of high-value cell lines (assets) relies on physical security by limiting access to samples. We present a cybersecurity-inspired platform that protects biological assets at the genetic level. This technology uses a permutation lock design where an asset can only be decrypted using an authentication code <i>r</i> from a search space composed of <i>n</i> objects on a defined keypad. Here, the genetic asset is designed as a scrambled DNA sequence, and the code is a temporal pattern of small molecules that regulate sets of recombinases that can unscramble a DNA sequence into the desired final sequence. In this work, a "blue team" designed and built an encrypted (scrambled) DNA sequence, and a "red team" sought to break the code through an ethical hacking exercise. Two iterations of testing revealed a 0.2% (2 in 990) chance of gaining access to the asset by random search, which is on par with the theoretical goal of 0.1% (1 in 990).

Violent ice fracture events often trigger rapid climatic or geomorphic changes, including Antarctic ice shelf collapse, glacial outbursts, and frost quakes. Existing models of sequential crack propagation inadequately explain the sudden, explosive nature observed in natural events. Here, we uncover a previously unidentified eruptive fracture of ice adhered to solid surfaces upon quasistatic cooling, which can even cause the underlying substrate fragmentation. This explosive ice instability depends on the threshold internal grain size of the ice. Above this threshold, fracture proceeds in a progressive, energy-dominated mode, whereas below it the ice undergoes an abrupt, strain-dominated fracture. We found that the apparent tensile strength of adhered ice ranges from 39 to 58 megapascals, over an order of magnitude higher than the typical value of ice (0.7 to 3.1 megapascals). This work provides a mechanistic framework for understanding and predicting abrupt cryospheric fracture events and points toward rational strategies for designing self-actuating deicing systems that exploit thermomechanical instabilities.

Psychedelic indolethylamines with therapeutic potential are naturally produced in plants, fungi, and animals. Here, we elucidated the complete <i>N</i>,<i>N</i>-dimethyltryptamine (DMT) biosynthetic pathway in hallucinogenic plant species traditionally used in shamanic rituals for spiritual healing. Leveraging the similarities in their chemical structures, we reconstructed in one plant assay the full biosynthetic pathways of five renowned natural psychedelics; psilocin and psilocybin found in mushrooms, DMT from plants, and bufotenin and 5-methoxy-DMT secreted by the Sonoran Desert toad. We further engineered halogenated analogs of these molecules, which do not naturally occur in plants and exhibit prospective therapeutic potential for psychiatric conditions. Blending catalytic functions across the tree of life, coupled with metabolic engineering guided by rational protein design of mutant enzymes, enabled substantially more efficient in planta production of the indolethylamine components. This work establishes a versatile platform for concurrent biosynthesis and diversification of psychoactive indolethylamines, paving the way for their production in plants.

Extensive wildfire profoundly influences Earth system feedback and can drive major ecosystem disturbances, yet its timing and role in the Late Devonian Frasnian-Famennian (F-F) mass extinction remain unclear. To determine whether wildfires were a driver or consequence of contemporaneous oceanic anoxic events (OAEs), we present a high temporal resolution multiproxy record (biomarkers, microfossils, and trace metals) from the Chattanooga Shale in the southeastern United States. Pyrogenic PAHs and inertinite macerals increased after peaks in δ¹³C_org and redox-sensitive proxies, indicating that wildfire activity intensified in response to post-OAEs oxygen rise rather than triggering anoxia. Modeling of global δ¹³C records reveals that the lag between OAEs/organic carbon burial and wildfire onset reflects the time required for atmospheric oxygen to accumulate to levels sustaining widespread combustion. Together, these results provide the first high-resolution dataset capable of resolving the temporal sequence between OAEs and wildfire activity, enabling the establishment of their causal linkage during the catastrophic F-F environmental disruptions.

DNA logic circuits have great potential for biocompatible and programmable computations; however, current designs require reset processes, which restrict real-time data processing and memory functionality. This study proposes a reset-free approach on the basis of toehold-mediated chain reaction (TCR), which enables continuous and reversible strand migration within dual-rail units. By localizing TCR components on two-dimensional DNA origami templates, various combinational logic gates (e.g., AND and OR gates) and memory elements were implemented, including set-reset and data latches, as well as advanced cascaded registers. These circuits consistently processed new inputs and retained outputs over multiple sequential operations. The proposed reset-free TCR framework offers a mechanism most analogous to electronic circuit operation and demonstrates considerable potential for practical applications in biosensing, diagnostics, and synthetic biology.