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.

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.

Neural progenitor cells exhibit developmental plasticity as they can commit to distinct developmental trajectories. The male-specific lethal complex (MSLc) is linked to multiple developmental disorders, suggesting a role in neural fate commitment. To dissect MSLc function, we used a multipronged approach combining chronic and acute depletion models. Knockout of the MSLc scaffolding component MSL1 caused embryonic lethality by E10.5 (embryonic day 10.5), and single-cell multiomics revealed altered cell population composition across multiple germ layer-derived lineages, including neuroectoderm. Two-dimensional directed differentiation models showed that the MSLc facilitates accessibility at regulatory elements during early stages of neurogenesis. Neurodevelopmental genes displayed reduced enhancer-promoter contacts and failed to reach appropriate expression levels when the MSLc was absent early in neural differentiation. In contrast, MSLc loss at later stages did not recapitulate this phenotype, indicating that MSLc-mediated gene priming is a key mechanism enabling timely activation of lineage-specifying transcriptional programs.

During the embryonic development of vertebrates, initially, symmetric embryos develop asymmetrically arranged organs. The asymmetry initiates with the formation of a small fluid-filled cavity on the embryo called the embryonic node, which contains motile cilia that generate specific flow patterns. The mechanism by which this nodal flow is sensed and causes asymmetry development has remained elusive despite major experimental and computational efforts. Existing hypotheses focus on either mechanical or chemical signaling processes. We report an experimental artificial embryonic node that, combined with numerical simulations, enables in-depth investigation of nodal flow and its role in left-right asymmetry development. Dissimilar fluid velocity profiles develop around primary cilia on the left and right nodal sides, producing distinct cilium bending. Also, the distribution of signaling particles with specific diffusivities exhibits spatial and temporal asymmetry. Together, our results support both mechanical and chemical sensing hypotheses and suggest a potential synergy between the two sensing mechanisms for the enhanced robustness of left-right asymmetry development.

Mitochondrial dysfunction and dysregulated proteolysis drive Huntington's disease (HD), tauopathy, and related neurodegenerative disorders. Calpain-2, a Ca2+-activated protease restrained by calpastatin (CAST), is pathologically overactivated, yet no therapies directly target this axis. We identify A36, a brain-penetrant small molecule derived from CHIR99021 that selectively stabilizes the CAST-calpain-2 complex without inhibiting GSK3. A36 acts as a protein-protein interaction stabilizer, enhancing CAST-calpain-2 binding, preventing CAST degradation, and thereby limiting calpain-2 activation and mitochondrial damage. In patients with HD induced pluripotent stem cell-derived neurons and mutant mouse striatal neurons, A36 normalized mitochondrial morphology and membrane potential, reduced oxidative stress, and improved survival. In vivo, A36 displayed favorable pharmacokinetics and central nervous system exposure; treatment reduced striatal neurodegeneration, mutant huntingtin aggregation, and motor deficits in HD R6/2 mice, and lowered phosphorylated tau, neuroinflammation, and cognitive decline in tauopathy PS19 mice. These findings establish pharmacological stabilization of CAST-calpain-2 as a therapeutic strategy and position A36 as a mechanism-selective modulator with broad neurodegenerative disease potential.

We introduce a complementary metal-oxide semiconductor (CMOS) Ising machine (CIM) composed entirely of silicon-based metal-oxide semiconductor field-effect transistors (MOSFETs). Instead of adhering to the conventional functions of MOSFETs as switches or amplifiers, CIM adopts an unprecedented approach that uses the dual characteristics of MOSFETs to function as both oscillators and couplers, enabling the coupling strength between oscillators to be tuned through gate biasing. These dual behaviors facilitate effective synchronization within the CIM, while the use of MOSFETs ensures full compatibility with standard CMOS fabrication technology and provides a pathway toward scalable hardware implementation. We also address the challenge of frequency variability, a critical issue in a large-scale CIM, by finely tuning the gate voltage of the oscillating transistors. This strategy notably enhances the stability and reliability of the CIM, achieving a level of control that is difficult to attain in other Ising machines using heterotypic device architectures. This CIM was applied to solve a MaxCUT problem. The demonstrated advantages of our CIM, including its compact cell size, high scalability, and robust operation, represent a promising direction for the advancement of future large-scale and energy-efficient Ising machines.

Arctic precipitation has increased in recent decades (hereafter, Arctic wetting), but the drivers remain uncertain. Using observations, reanalyses, and single-model initial-condition large ensembles (SMILEs), we show that enhanced evaporation due to sea ice loss has been the primary driver of Arctic wetting during 1979–2024, especially in the Atlantic sector. However, the externally forced component in most SMILEs explains only ~69% of sea ice loss and 75% of wetting in the observations and reanalyses. Further analysis reveals that the observed transition of one of the Northern Hemisphere’s interdecadal internal variability—Atlantic multidecadal variability (AMV)—from a negative to a positive phase substantially enhanced Arctic sea ice loss, thereby accelerating wetting by about 31%. Under SSP3-7.0, if the AMV switches phase in the near future from the current +1 to a −1 standard deviation anomaly, then the rates of Arctic sea ice loss and wetting would slow by nearly 29 and 33%, respectively, relative to the externally forced response alone. These results underscore the pivotal role of AMV in modulating Arctic sea ice loss and wetting and highlight the need to account for AMV phase changes in near-term Arctic climate projections.

High-profile cases of police violence have given rise to contentious debates, yet scholars know little about why individuals interpret violent police encounters differently. We fielded a survey experiment in Germany designed to probe whether the victim’s identity matters to public opinion (N = 15,941). Our design approximates the way news events unfold sequentially over time, allowing us to measure whether eventual discriminatory beliefs persist even in the face of mounting evidence. We show that respondents are less likely to consider the actions of the police to constitute misconduct when the victim has an immigrant name compared to a traditionally German name. Discriminatory beliefs remain even when respondents are informed about evidence confirming that misconduct occurred. Our analysis shows that these results are driven by right-wing respondents, with both moderates and extremists exhibiting discriminatory beliefs and a resistance to updating. These findings help illuminate why debates over policing are so intractable.

(Ag,Cu)2(S,Se,Te) alloys, as rare examples of p-type inorganic ductile semiconductors, have emerged as promising candidates for wearable electronics because of their mechanical flexibility and favorable processability. However, the multicomponent nature of this system introduces diverse microstructures and intricate defect landscapes that complicate the optimization of thermoelectric performance. Here, we reveal the presence of compositionally inhomogeneous yet structurally coherent nanoscale chemical fluctuations within this alloy system. These fluctuations, together with abundant dislocations and twin boundaries, serve as efficient phonon scattering centers to suppress the lattice thermal conductivity to approach glass-like levels. Concurrently, tuning the cation ratios and vacancies allows for precise control over the carrier concentration and thereby leads to enhanced power factors. Last, a peak zT of 0.98 at 360 kelvins is achieved, marking a record for Ag-based ductile thermoelectrics. This study highlights the essential role of chemical fluctuations in modulating phonon and charge transports and offers valuable insight into the microstructure-defect–property interplay in ductile materials.

Urban areas are major sources of population-driven methane with high potential for mitigation, but emission quantification and sectoral attribution remain uncertain. Using satellite observations and a high-resolution (12 kilometers by 12 kilometers) atmospheric inversion framework, we find that emissions from 12 major US urban areas are 80% higher than the US Environmental Protection Agency Greenhouse Gas Inventory (EPA GHGI), with up to four times higher emissions in Houston but 32 to 37% lower emissions in Los Angeles and Cincinnati. Landfills are the principal cause of inventory underestimates, with city-level management practices driving large variations in per capita emissions. Examination of individual landfills with gas collection systems shows gas collection efficiencies averaging 38% (range: 5 to 90%), much lower than their reported average of 70% (range: 40 to 87%). An exception is Los Angeles, where we find landfill gas collection averaging 85%, suggesting large urban methane mitigation potential through improved landfill management.