Physics

Quantum simulators allow the experimental exploration of nonequilibrium quantum many-body dynamics, which have traditionally been characterized through expectation values or entanglement measures, based on density matrices of the system. Recently, a more general framework for studying quantum many-body systems based on projected ensembles has been introduced, revealing quantum phenomena, such as deep thermalization in chaotic systems. Here, we experimentally investigate a chaotic quantum many-body system using projected ensembles on a three-dimensional–integrated frequency-tunable superconducting processor, enabling both high-fidelity control and scalable architecture. Our results provide direct evidence of deep thermalization by observing a Haar-distributed projected ensemble for the steady states within a charge-conserved sector. Moreover, by introducing an ensemble-averaged entropy as a metric, we establish a benchmark for many-body information leakage from the system to its environment. Our work paves the way for studying quantum many-body dynamics using projected ensembles, and the scalability of our benchmark method represents a notable advance toward quantum computation and simulation.

There have been rapid advances in nucleoside-modified messenger RNA–based vaccines, particularly during the SARS-CoV-2 pandemic, demonstrating a rapid and cost-effective approach for addressing infectious diseases. A major challenge remains in developing a delivery system that protects mRNA from degradation and facilitates its passage through tissue and cellular barriers. Current four-component lipid nanoparticles enable efficient endosomal escape and are a pivotal technology for the delivery of mRNA vaccines. However, challenges such as stability, availability, durability, and adverse effects persist. We have developed a self-assembling one-component ionizable amphiphilic Janus dendrimers (IAJD) delivery system with naturally occurring amino heads, capable of efficiently delivering mRNA to the spleen and lymph nodes. This single-component system simplifies synthesis, reduces development complexity, and enables rapid global distribution of mRNA vaccines during pandemics. As a proof of concept, one-component IAJD97, formulated with mRNA encoding norovirus mRNA capsid protein, demonstrates the potential of IAJDs as efficient delivery platform for mRNA vaccines, advancing their effectiveness and expanding applications to improve public health outcomes.

Cancer immunotherapy remains limited by insufficient antigen presentation and immunosuppressive tumor microenvironment. Here, we present a vaccine strategy based on cold atmospheric plasma (CAP)–engineered tumor cell–derived immune reprogramming nanovesicles (CAPTURE) that integrates spatiotemporal sequential immunization to potentiate antitumor immunity. CAPTURE is engineered from tumor cells pretreated with CAP, which up-regulates major histocompatibility complex class I expression via p62-mediated autophagy to promote full-spectrum epitope antigen presentation, and surface-functionalized anti-CD28 (αCD28) on CAPTURE provides costimulatory signals to directly activate T cells through αCD28-CD28, bypassing B7-CTLA-4–mediated T cell inhibition. Under spatiotemporal sequential immunity, CAPTURE exhibits homologous tumor targeting and lymph node accumulation, enhancing antigen presentation for CD8 + T cell activation and tumor immunogenic remodeling. In mouse models, CAPTURE achieved near-complete tumor suppression, driven by amplified cytotoxic T cell responses, increased T cell clonal diversity, and CXCR3-mediated tumor infiltration. This study presents a universal biomimetic nanovaccine strategy that can reshape both T cells’ immunity and tumor cells’ immunogenicity, induce broad-spectrum immune responses to overcome immune evasion, and offer unique insights and innovative technologies for precision cancer immunotherapy.

Na 3 V 2 (PO 4 ) 2 F 3 (NVPF) is regarded as a highly promising cathode material for sodium-ion batteries. Here, we propose a general strategy for modulating the local electronic structure of vanadium (V) by introducing low-valence metal ions, such as Cu 2+ , Cd 2+ , and Ag + . This approach microscopically shortens the length of the suspended V─F2 bonds within the NVPF framework, effectively mitigating the loss of fluorine and the formation of undesirable Na 3 V 2 (PO 4 ) 3 (NVP). Consequently, this intervention indirectly enhances the overall working voltage and energy density of the battery. Density functional theory (DFT) is used to verify and deeply investigate the intrinsic mechanism of fluorine stabilization in the NVPF system. The experimental results show that NVPF with 2.5% of doped Cu exhibits a higher mid-working voltage (3.69 volts), higher energy density (447.7 watt-hours per kilogram), and excellent cycling stability (83.3% capacity retention at 20 C after 10,000 cycles).

The stereochemical diversity of Aβ42 in the brains of patients with Alzheimer’s disease (AD) is a clinically recognized but poorly understood phenomenon. A critical gap in our knowledge is how the complex mixture of these stereoisomers collectively influences the aggregation pathway and neurotoxicity of Aβ42 at the molecular level. Drawing from stereoproteome data from AD patient brain tissues and previous studies, we engineered a panel of stereoisomers to more simply simulate the stereochemical diversity of the AD marker Aβ42. We found that the coexistence of L-Aβ42 with specific D-isomers initiates a potent antagonistic effect, suppressing the formation of toxic fibrils. This stereochemically driven antagonism conferred notable neuroprotection, suggesting an endogenous protective mechanism. This proof-of-concept work elucidates at the molecular level that by regulating the stereochemical composition of Aβ, its inherent cellular protective antagonistic effect can be activated, providing unprecedented molecular basis for understanding the disease mechanism and subsequent possible clinical research.

Monkeypox virus (MPXV) infection-associated intestinal manifestations, including diarrhea and proctitis, have been frequently reported during mpox outbreaks. Here, we present clinical evidence that MPXV can directly infect the human intestine and induce lesions. Intriguingly, primary organoids cultured from human ileum and rectum support productive infections by MPXV strains from clade IIb, Ia, and Ib, which are responsible for the 2022–2023 global outbreak and concurrent outbreaks in Africa. Given that primary intestinal organoids can be rapidly expanded at large scale, we were able to screen a broad-spectrum antiviral drug library. We identified 12 leading candidates of safe-in-human agents, including clinically used drugs such as clofarabine. We extensively validated the anti-MPXV activity of clofarabine in human intestinal and skin organoids, consistently demonstrating potent antiviral activity against clade Ia, Ib, and IIb strains. These findings are important for better understanding the clinical manifestations of mpox. Primary intestinal organoid-based infection models and the established antiviral drug discovery pipeline bear major implications for responding to the current mpox global health emergency and sustaining epidemic poxvirus preparedness.

The actin cytoskeleton forms a dynamic network composed of filaments that remain flexible when bundled up, leading to complex filamentous structures in plant cells. Understanding the properties of these filamentous structures under different conditions and in different cell types can provide insight into their function. Yet, despite developments in the study of the plant actin cytoskeleton, it remains challenging to segment and identify actin filamentous structures, preventing quantification of their spatiotemporal properties. To address this problem, we devised a network-based approach termed Graph of Filaments over Time (GraFT) to trace and track filamentous structures in cytoskeleton networks extracted from two-dimensional time series imaging data. Our comparative analyses using both synthetic test cases and real-world actin cytoskeleton networks of Arabidopsis thaliana hypocotyls exposed to different treatments demonstrated that GraFT accurately traces and tracks actin filamentous structures. Moreover, GraFT facilitates automated quantification of properties for filamentous structures, providing fine-grained insights of effects of different treatments on the level of individual structures. Therefore, GraFT offers a substantial step toward an automated framework facilitating robust spatiotemporal studies of the plant actin cytoskeleton.

AMD1 encodes adenosylmethionine decarboxylase 1 (AMD1), a key enzyme in polyamine biosynthesis. A subset of ribosomes translating the AMD1 coding sequence read through the stop codon and pause at a second in-frame stop 384 nucleotides downstream, producing a conserved C-terminal extension (C-tail). Despite growing evidence that such cis-acting elements regulate translation of their genes, the molecular mechanism by which the C-tail mediates ribosome stalling remains unclear. Here, we determined the structure of the ribosome nascent chain complex paused by the AMD1 C-tail which traps eukaryotic release factor 1 (eRF1) with the ATP-binding cassette subfamily E member 1 (ABCE1). The nascent chain forms a molecular clamp that positions an arginine hook in the peptidyl-transferase center, occluding the accommodation of the eRF1 GGQ motif thereby hampering translation termination. Analysis of aggregated ribosome profiling data revealed several genes with a pattern of stop codon readthrough followed by ribosome stalling at a specific location, suggesting that regulatory readthrough-stall mechanisms may not be limited to AMD1 .

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.

Charge carrier recombination represents a fundamental constraint in semiconductor photocatalysis. Combining heterostructure design with deliberate defect engineering to facilitate hydrogen intermediate (*H) adsorption is a viable strategy for boosting photocatalytic hydrogen evolution reaction (HER). Herein, we design defective MBene via controlled etching and perform in situ hydrothermal assembly to develop a tailored MoBT x /CdS heterostructure. Incorporating a mere 0.5 wt % two-dimensional MoBT x MBene leads to a fourfold enhancement in HER activity over bare CdS. The established MoBT x /CdS catalyst achieves a remarkable HER of 10.2 millimoles per gram per hour under ambient conditions with 23.2% apparent quantum yield and sustains 90.2% activity after 24 hours of continued operation. Outstanding environmental adaptability is demonstrated through a consistent HER value of 7.1 millimoles per gram per hour in tap water and 5.7 millimoles per gram per hour in seawater. The temperature-dependent performance demonstrates notable robustness, reaching 11.1 millimoles per gram per hour at 35°C while preserving 40% functionality at harsh 5°C. Integrated photoelectrochemical and computational analyses elucidate that Mo vacancies create band alignment–optimizing electron traps and reduced *H adsorption barriers, enhancing fast carrier separation. Concurrently, interfacial covalent Mo─S bonds establish atomic-level charge-transfer pathways and enable rapid electron migration. This work establishes a previously unidentified paradigm for advanced photocatalyst design through concerted defect-interface modulation.

Single photon–level imaging at 1550 nanometers is a key driver for crucial advancements in the next-generation laser detection technology. This cutting-edge approach plays a vital role in space ranging, target recognition, and three-dimensional remote sensing. However, it has faced severe challenges such as insufficient noise-tolerant performance. Here, we introduced noise-tolerant correlated coincidence imaging (CCI) based on supercorrelated light (SCL). The light source, generated through nonlinear interaction between a pulsed laser and a photonic crystal fiber, exhibits a broader power-law photon number probability distribution and extremely strong photon correlation [with second-order correlation function g (2) (0) up to 18,166]. Our noise-tolerant CCI can resist random environmental noise up to 100,000 times stronger than the echo signal photons. SCL offers an exceptionally strong noise tolerance for single photon–level imaging in extreme environments with intense noise, paving the way for the future development of extremely sensitive light detection.

Protein function often depends on dynamic transitions between conformations rather than just static structures. However, our current ability to characterize or predict such dynamics lags behind recent advances in protein structure prediction. Enhanced sampling methods can speed up molecular dynamics simulations to study protein conformational transitions but require prior knowledge of key collective motions involved. Here, we demonstrate for a series of proteins of varying complexity that the required information is encoded in anharmonic low-frequency vibrations. Using recently developed methods, we show that this information can be easily extracted from short dynamics simulations without requiring prior knowledge. Combined with enhanced sampling, we correctly predict conformational transitions in all test proteins and generate highly reproducible free energy landscapes. This allows for the rapid generation of accurate protein conformational ensembles, which is critical to unravel the complex relationship between protein sequence, structure, and dynamics.

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.

Understanding how bacteria rapidly adapt to recently introduced antibiotics increasingly demands experimental models that move beyond classical evolution systems. We developed a microbial evolution hanging-droplet system (MEHS) that uses gravity-driven flow to sustain continuous exponential growth, doubling daily reproduction rate. Using this MEHS, Klebsiella pneumoniae rapidly adapted to fluctuating cefiderocol (CFDC) exposure. However, resistant clones comprised only a minor fraction of the evolved populations. Many mutations overlapped with variants previously observed in clinical practice, including alterations in EnvZ/OmpR two-component system that reprogrammed siderophore biosynthesis. These changes promoted cross-protection of susceptible subpopulations, alleviating the fitness costs typically associated with resistance and facilitating population-level adaptation. Moreover, the detection of similar variants in clinical isolates collected before CFDC use highlights their latent potential to evolve under selective pressure. Our findings establish MEHS as a powerful platform for resolving clinically relevant resistance trajectories and point to regulatory nodes as potential targets for disrupting cooperative behaviors that undermine antibiotic efficacy.

Exosomes, despite their promise as drug carriers for crossing biological barriers, remain underexplored for noninvasive posterior ocular delivery. Here, we demonstrate that semen-derived exosomes (SEVs) penetrate ocular barriers effectively, owing to their epidermal growth factor expression, which mediates reversible tight-junction disruption. SEVs reach the posterior segment via dual corneal and conjunctival routes. Using this, we engineered FA-SEVs@CMG eye drops, where SEVs are modified with folic acid (FA) and loaded with a nanozyme system (CMG) composed of carbon dots, manganese dioxide, and glucose oxidase. This eye drop leverages SEVs’ excellent penetration ability and FA’s targeting effect to enhance drug delivery to retinoblastoma (RB) cells. Internalized CMG induces intense oxidative stress, disrupts the autophagy-apoptosis balance, and triggers RB cell self-destruction. In vivo, FA-SEVs@CMG effectively inhibits RB growth while preserving retinal function. This work establishes the first SEV-based platform for noninvasive posterior segment delivery, offering a transformative strategy for treating posterior ocular diseases.

ABSTRACT Achieving selective and energy‐efficient urea oxidation is a key challenge in urea‐assisted water electrolysis due to sluggish activation of nickel sites and their limited active potential range. Here, we construct Ni 2 P/MoP embedded in conductive carbon nanofibers (Ni 2 P/MoP/CNFs) that couple precise interfacial charge redistribution with synergistic electronic modulation to accelerate high‐valent Ni 3+ sites formation (50 vs. 140 mV of Ni 2 P) and expand urea oxidation potential window (290 vs. 150 mV of Ni 2 P). Electronic coupling shifts the Ni d‐band center, promoting rapid Ni 2+ /Ni 3+ transformation and optimizing intermediate adsorption–desorption. In situ Raman and FTIR analyses identify NiOOH as the active phase that facilitates early‐stage C─N bond cleavage and suppresses oxygen evolution up to 110 mV beyond its onset in the pure Ni 2 P system. Supported by density functional theory calculations, this interfacial modulation reduces the energy barrier for urea oxidation from 1.84 to 1.76 eV. Benefiting from this unique electronic structure, Ni 2 P/MoP/CNFs achieve a current density of 141.2 mA cm −2 at 1.54 V, 2.9 times that of the Ni 2 P/CNFs; and it also shows good stability in the urea electrolysis for hydrogen generation over 100 h. This work advances efficient hydrogen production via urea electrolysis by bridging Ni activation kinetics and oxidation selectivity.

ABSTRACT The pursuit of high performance dielectric capacitors necessitates a deep understanding of the atomic‐scale mechanism governing their polarization response. Entropy engineering is an effective strategy for tuning polarization properties. In particular, introducing specific elements into medium/high‐entropy systems can induce an antiferroelectric‐like polarization‐electric field ( P‐E ) hysteresis loop, which is highly desirable for high energy storage performance due to its high maximum polarization and low remnant polarization. However, their atomic‐scale origin remains unclear. Herein, atomic‐scale transmission electron microscopy (TEM) analyses reveal that this distinctive behavior originates from the synergistic effect of dislocation pinning and oxygen octahedral tilting mode transition. The pinning effect inhibits polarization switching, causing a non‐overlapping P‐E loop, while oxygen octahedral tilting directly contributes to the pinched loop. The a 0 a 0 c – oxygen octahedral tilting mode stabilizes a relaxor state with low remnant polarization. In situ TEM characterization under an electric field demonstrates an electric field‐induced transformation of the oxygen octahedral tilting mode from a 0 a 0 c – to a 0 a 0 a 0 , directly correlating structural evolution with antiferroelectric‐like behavior. These findings deliver atomic‐scale insights that defect pinning and oxygen octahedral tilting induce antiferroelectric‐like behavior, offering a novel strategy for designing energy storage ceramics.

ABSTRACT Metal halide perovskite solar cells have been developed as a front runner in next generation photovoltaic technology. However, such rapid development is hampered by complex relationships among material compositions, process routes, device architectures, and environmental conditions. The fabrication system is strongly coupled with many variables, which implies that existing empirical optimization methods are less capable to explore design space in high dimensions. Additionally, perovskite materials have sensitive intrinsic properties to environmental factors hence facilitating reproducible optimization across the composition space is notoriously difficult. Now, in this coupled system, artificial intelligence and machine learning have driven progress toward the understanding of the nonlinear composition–process–property relationships. But their predictive reliability is limited by patchy data and low reproducibility in manual experiments. Therefore, controlling lab environments and generating reproducible data with help from autonomous laboratories is paramount to accelerate predictive design. This review highlights recent progress in data driven materials discovery and closed loop experiments in perovskite research. We also report that AI guided process optimization is capable of identifying reproducible manufacturing windows. In parallel, robotic manipulation, high throughput synthesis with in situ monitoring and autonomous characterization are enabling systematic exploration of the multi‐dimensional process space.