Advanced Science最新文献

Black holes constitute nature's fastest quantum information scramblers, a phenomenon captured by gravitational analogue systems such as position-dependent XY spin chains. In these models, scrambling dynamics are governed exclusively by the hopping interactions profile, independent of system size. Utilizing such curved spacetime analogues as quantum batteries, how the black hole scrambling affects charging via controlled quenches of preset scrambling parameters is explored. This analysis reveals that the intentionally engineered difference between post-quench and pre-quench scrambling parameters can significantly enhance both maximum stored energy E_max and peak charging power P_max in the quench charging protocol. Furthermore, the peaks of extractable work and stored energy coincide. This is because the system's evolution under a weak perturbation remains close to the ground state, resulting in a passive state energy nearly identical to the ground state energy. The optimal charging time τ_* exhibits negligible dependence on the preset initial horizon parameter x_h0, while decreasing monotonically with increasing quench horizon parameter x_ht. This temporal compression confines high-power operation to regimes with strong post-quench scrambling x_ht > x_h0, demonstrating accelerated charging mediated by spacetime-mimicking scrambling dynamics.

Conduction of protons in solids is a cooperative process propelled by phonons, with molecular details obscured by the irregular movements in the thermal bath. It is shown that substitution with Y forms an imaginary phonon mode, instrumental for the function as proton conductor and effectively lowering the activation barrier for proton transport. To untangle the interplay in the exemplary proton conductor BaSn_0.9Y_0.1O₃, its crystallographic structure is determined with high resolution neutron diffractometry and its phonon density of states with density functional theory calculations, experimentally validated by element specific nuclear resonant vibration spectroscopy. Based on phonon analysis, a quantitative transport model is present, which predicts the activation energy and performance by the ratio of ionic radii. Rather than individual vibrational modes, it is the oxygen sub-lattice which exerts its momentum on the protons. The extent of this momentum transfer is governed by the ratio of ionic radii. This model extends the transition state theory by the phonon-phonon interaction and complements the previously proposed idea that lattice dynamics is decisive for proton transport and specifies which properties of the material exactly define the vibration properties.

NAD⁺ homeostasis is vital for neuronal health, as demonstrated by the opposing roles of nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), a NAD⁺-synthesizing enzyme, and sterile alpha and TIR motif-containing protein 1 (SARM1), a NAD⁺ hydrolase. Neurodegenerative insults that decrease NMNAT2 activate SARM1, leading to axon loss. To understand how the NMNAT2-SARM1 axis influences brain energy metabolism, multi-omics approaches are used to investigate the metabolic changes resulting from neuronal NMNAT2 loss. Loss of NMNAT2 in glutamatergic neurons leads to a significant metabolic shift in the cerebral cortex from glucose to lipid catabolism, reduced lipid abundance, and pronounced neurodegenerative phenotypes and motor behavioral deficits. These metabolic disturbances are accompanied by altered glial expression of enzymes regulating glucose and lipid metabolism, enhanced inflammatory signaling, and disrupted astrocytic transcriptomic profiles related to cholesterol synthesis and immune activation. Notably, SARM1 deletion in NMNAT2-deficient mice restored lipid metabolism, astrocyte transcriptomic profiles, and mitigated neurodegeneration and motor behaviors. These findings suggest that neuronal NAD⁺ depletion triggers maladaptive, SARM1-dependent metabolic reprogramming, shifting energy use from glucose to lipids, which in turn promotes inflammation and neurodegeneration.

The chromatin remodeler nucleosome assembly protein 1-like 4 (Nap1L4) is highly expressed in megakaryocyte-erythroid progenitors (MEPs) and erythroid cells. Mutations, deletions, and aberrant expressions of Nap1L4 are observed in diseases such as acute myeloid leukemia (AML). However, the roles of Nap1l4a in erythropoiesis and related diseases, as well as the underlying mechanisms, remain unknown. Here, it is demonstrated that zebrafish nap1l4a homozygous mutants (nap1l4a^-/-) are more sensitive to hypoxia stress during the early embryonic stage and exhibit impaired primitive erythropoiesis. Mechanistically, zebrafish Nap1l4a interacts with the erythropoietic transcription factors (TFs) Scl and Klf1, and recruits the histone variant H2A.Z. This interaction remodels the cis-regulatory element (CRE) landscape and promotes nascent RNA transcription of erythropoietic genes. Meanwhile, Nap1l4a deficiency impairs chromatin accessibility at the epigenetic regulators kdm6b and kmt2c. This results in expanded H3K27me3 and diminished H3K4me1 in erythrocytes, leading to altered histone landscapes at erythropoiesis TF loci and reduced TF expression. Moreover, Nap1l4a regulates primitive erythropoiesis by transcriptionally and epigenetically modulating the canonical WNT/β-Catenin pathway. Together, the findings reveal a lineage-selective transcription, with histone epigenomics-dependent role for nap1l4a in vertebrate primitive erythropoiesis. These findings highlight potential mechanisms underlying human blood disorders and hypoxia responses associated with Nap1l4a deficiency.

Recurrence of coronavirus outbreaks and zoonotic origins of human coronaviruses underscore the importance of developing pan-coronavirus antivirals. The highly conserved 3C-like protease (3CL^pro) in coronaviruses, together with the well-established druggability, makes it an ideal target for broad-spectrum antiviral therapeutics. Here, the inhibitory activity of approved 3CL^pro inhibitors, including nirmatrelvir, ensitrelvir, and simnotrelvir, against fifteen 3CL^pros is first reported by enzymatic assays. Despite their potent inhibition toward 3CL^pros of β-CoVs, these inhibitors show reduced potency against 3CL^pros from the other three genera, particularly against two newly identified human coronaviruses (α-CCoV-HuPn-2018 and δ-PDCoV). In this context, continued efforts in structure-based optimization of nirmatrelvir lead to the identification of compound 8 that potently inhibits a panel of 32 3CL^pros across all subgenera (IC₅₀s: 19-146 nm), with an IC₅₀ value of 61 and 81 nm against α-CCoV-HuPn-2018 and δ-PDCoV 3CL^pros, respectively. Moreover, it effectively inhibits nirmatrelvir-resistant 3CL^pro mutants and demonstrates broad-spectrum antiviral efficacy in cells. These findings suggest an important rule that a small, non-cyclic P2 segment and a P4 segment with a suitable size are preferred by the design of ultra-broad-spectrum 3CL^pro inhibitors, and provide a proof-of-concept guide for developing broad-spectrum antivirals as potential pan-CoV therapeutics.

Phase change materials (PCMs) are promising heat storage media to solve the intermittency and instability of renewable energy utilization. However, due to the spontaneous crystallization behavior and the accompanied release of latent heat upon cooling, the absorbed thermal energy can not be well stored at room temperature, which severely limits the applicability of PCMs in thermal energy storage. Herein, the long-term storage as well as switchable and controllable release of thermal energy using activated perethylated pillar[5]arene EtP5 (EtP5α) is reported for the first time. Through activation at 393 K, EtP5α can store thermal energy in the supercooled state at room temperature and release thermal energy by triggering cold crystallization at 370 K. High thermal energy storage capacity can be maintained for 20 thermal cycles and more than 365 days at room temperature, which is the PCMs that can store thermal energy for the longest time at room temperature.

Matching energy input to water supply is key to efficient solar-driven interfacial water evaporation, but conventional interfacial solar steam generators (ISSGs) fail to adapt to diurnal solar flux fluctuations, thus hindering the achievement of dynamic hydrothermal balance. Inspired by marine octopuses, a fabric-based dual-interface solar evaporator (PDMS-CFs-CFF-SF) is developed by integrating 3D knitting and electrostatic flocking, enabling adaptation to light intensity changes. When light intensity exceeds the upper interface's water supply capacity and heat accumulates, hydrophobic spacer yarns facilitate the directional transfer of excess heat to the lower interface, thereby triggering dual-interface evaporation. The lower interface, leveraging its large-pore structure, regulates moisture content to match the transferred excess heat. Moreover, the octopus-inspired structure increases the evaporation area, enriches vapor escape channels, enhances thermal insulation performance, and adapts to sunlight incident at different angles. Under 1 kW m^-2 irradiation, the evaporator achieves an evaporation rate of 3.14 kg m^-2 h^-1 and an efficiency of 129.32%. This work provides a novel structural strategy for developing ISSGs with dynamic hydrothermal balance capabilities.

Type I photosensitizers (PSs), which operate effectively under low-oxygen conditions, offer a promising approach to overcome hypoxia-associated challenges in solid tumor therapy. However, their design remains challenging due to the limited number of reported molecules with diverse structures, as well as insufficient understanding of the underlying mechanisms. Herein, a closed-loop hybrid discovery system is developed that combines molecular excited-state calculations with machine learning (ML) to rationally design and predict high-performance Type I PSs for hypoxic tumor therapy. Through a support vector machine (SVM) classification model, 664 potential Type I PSs are identified from a molecular space based on donor-acceptor (D-A) and donor-acceptor-donor (D-A-D) structures. Among these, two candidates, M1 and M2, are synthesized and experimentally verified as Type I PSs, exhibiting aggregate-induced enhancement of Type I reactive oxygen species (ROS) generation. Both in vitro and in vivo studies demonstrated their ability to induce intracellular Type I ROS generation and effectively suppress tumor growth. The work highlights the potential of ML in the design and prediction of Type I PSs for hypoxic tumor therapy.

Cerebral edema and hypoperfusion, hallmark pathologies of both hemorrhagic and ischemic stroke, critically compromise clinical outcomes. Astrocytic aquaporin-4 (AQP4) not only drives post-stroke brain edema progression but also maintains the protective clearance function of the glymphatic system. Herein, systemic AQP4 inhibition using TGN-020 (TGN) paradoxically exacerbates global glymphatic dysfunction despite alleviating cerebral edema and microcirculatory dysfunction following subarachnoid hemorrhage (SAH). To overcome this therapeutic dilemma, an angiopep-2-functionalized lipid nanoparticle (A-LNP) platform enabling lesion-targeted TGN delivery is engineered. This system reverses the detrimental effects of TGN on the post-SAH glymphatic system while enhancing the therapeutic benefits of TGN in mitigating cerebral edema and microcirculatory dysfunction. Remarkably, TGN demonstrates multimodal efficacy in ischemic stroke by mitigating the no-reflow phenomenon, alleviating blood-brain barrier disruption, and suppressing neuroinflammation. The A-LNP system retains the protective effects of TGN without compromising global glymphatic function, leading to enhanced therapeutic efficacy. These findings confirm the feasibility of using functional nanoparticles to enhance the protective effects of AQP4 inhibition while minimizing adverse effects on the glymphatic system, offering a promising therapeutic strategy for both stroke subtypes.

Developing elastocaloric materials that combine a large adiabatic temperature change with high superelastic stress and large recovery strain is crucial for the commercialization of solid-state refrigeration. In this study, a scalable manufacturing route is introduced by integrating simulations with experiments to investigate the orientation-dependent phase transformation behavior, producing NiTi alloys with performance surpassing that of all reported elastic metals in terms of superelasticity and elastocaloricity. Microstructural characterization confirmed that the preferred (001) grain orientation facilitates the generation of (001) compound twins in the [100](001) slip system, promoting the formation of low-index reversible martensite and thereby enhancing the reversibility of the phase transformation. These results establish a direct link between crystallographic texture, variant selection, and functional performance, providing a scalable material solution for next-generation solid-state cooling devices.