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Ischemic stroke represents a significant danger to human beings, especially the elderly. Interventions are only available to remove the clot, and the mechanism of neuronal death during ischemic stroke is still in debate. Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs. Here we report that the serine protease, thrombin, instigates ferroptotic signaling by promoting arachidonic acid mobilization and subsequent esterification by the ferroptotic gene, acyl-CoA synthetase long-chain family member 4 (ACSL4). An unbiased multi-omics approach identified thrombin and ACSL4 genes/proteins, and their pro-ferroptotic phosphatidylethanolamine lipid products, as prominently altered upon the middle cerebral artery occlusion in rodents. Genetically or pharmacologically inhibiting multiple points in this pathway attenuated outcomes of models of ischemia in vitro and in vivo. Therefore, the thrombin-ACSL4 axis may be a key therapeutic target to ameliorate ferroptotic neuronal injury during ischemic stroke.

Large‐scale artificial intelligence (AI) models such as ChatGPT have the potential to improve performance on many benchmarks and real‐world tasks. However, it is difficult to develop and maintain these models because of their complexity and resource requirements. As a result, they are still inaccessible to healthcare industries and clinicians. This situation might soon be changed because of advancements in graphics processing unit (GPU) programming and parallel computing. More importantly, leveraging existing large‐scale AIs such as GPT‐4 and Med‐PaLM and integrating them into multiagent models (e.g., Visual‐ChatGPT) will facilitate real‐world implementations. This review aims to raise awareness of the potential applications of these models in healthcare. We provide a general overview of several advanced large‐scale AI models, including language models, vision‐language models, graph learning models, language‐conditioned multiagent models, and multimodal embodied models. We discuss their potential medical applications in addition to the challenges and future directions. Importantly, we stress the need to align these models with human values and goals, such as using reinforcement learning from human feedback, to ensure that they provide accurate and personalized insights that support human decision‐making and improve healthcare outcomes. This review provides an overview of large‐scale AI models, including language models (e.g., ChatGPT), vision‐language models, and language‐conditioned multiagent models, and discusses their potential applications in medicine, as well as their limitations and future trends. We also propose how large‐scale AI models can be integrated into various scenarios of clinical applications.

Assembly of different metal-organic framework (MOF) building blocks into hybrid MOF-on-MOF heterostructures is promising in chemistry and materials science, however the development of ternary MOF-on-MOF heterostructures with controllable architectural and compositional complexity is challenging. Here we report the synthesis of three types of ternary MOF-on-MOF heterostructures via a multiple selective assembly strategy. This strategy relies on the choice of one host MOF with more than one facet that can arrange the growth of a guest MOF, where the arrangement is site-selective without homogenous growth of guest MOF or homogenous coating of guest on host MOF. The growth of guest MOF on a selected site of host MOF in each step provides the opportunity to further vary the combinations of arrangements in multiple steps, leading to ternary MOF-on-MOF heterostructures with tunable complexity. The developed strategy paves the way towards the rational design of intricate and unprecedented MOF-based superstructures for various applications. Assembly of MOF-on-MOF hybrids with complex structures and properties is of interest, but achieving sophisticated ternary heterostructures is challenging. Here, the authors synthesize three types of ternary MOF-on-MOF heterostructures with tunable complexity via a multiple selective assembly strategy.

Construction of two-dimensional nanosheets into three-dimensional regular structures facilitates the mass transfer and exploits the maximum potential of two-dimensional building blocks in applications such as catalysis. Here, we report the synthesis of metal-organic frameworks with an orthogonal nanosheet array. The assembly involves the epitaxial growth of single crystalline metal-organic framework nanosheets with a naturally non-preferred facet exposure as the shell on a cubic metal-organic framework as the core. The nanosheets, despite of two typical shapes and crystallographic orientations, also form a single crystalline orthogonally arrayed framework. The density and size of nanosheets in the core-shell-structured composite metal-organic frameworks can be well adjusted. Moreover, metal-organic frameworks with a single composition and hollow orthogonal nanosheet array morphology can be obtained. Benefiting from the unusual facet exposure and macroporous structure, the designed structure exhibits improved electrocatalytic oxygen evolution activity compared to conventional nanosheets. Constructing regular 3D superstructures from 2D nanosheets is a challenge. Here, the authors report the epitaxial growth of MOF nanosheets into single-crystalline orthogonal arrays with enhanced functional properties.

Dirac semimetals have attracted extensive attentions in recent years. It has been theoretically suggested that many-body interactions may drive exotic phase transitions, spontaneously generating a Dirac mass for the nominally massless Dirac electrons. So far, signature of interaction-driven transition has been lacking. In this work, we report high-magnetic-field transport measurements of the Dirac semimetal candidate ZrTe 5 . Owing to the large g factor in ZrTe 5 , the Zeeman splitting can be observed at magnetic field as low as 3 T. Most prominently, high pulsed magnetic field up to 60 T drives the system into the ultra-quantum limit, where we observe abrupt changes in the magnetoresistance, indicating field-induced phase transitions. This is interpreted as an interaction-induced spontaneous mass generation of the Dirac fermions, which bears resemblance to the dynamical mass generation of nucleons in high-energy physics. Our work establishes Dirac semimetals as ideal platforms for investigating emerging correlation effects in topological matters. It has been predicted that the presence of strong electronic correlations may generate new phases in materials with topologically non-trivial band structure. Here, the authors demonstrate the generation of Dirac mass in the correlated Dirac semimetal candidate ZrTe 5 under high magnetic fields.

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant Hla H35A from Staphylococcus aureus to form a Hla H35A -PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that Hla H35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby Hla H35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by Hla H35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that Hla H35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.

Purpose. To evaluate the wound healing effect of doxycycline and its underlying mechanisms in a rat model of corneal alkali burn. Methods. Male SD rats were administered 1.0 N NaOH in the right cornea for 25 seconds and randomly divided into the doxycycline group and the control group, with 84 rats in each group. 1.0 g·L−1 doxycycline eye drops (doxycycline group) or vehicle (control group) was topically instilled onto the rat cornea after chemical injury. Three days, 7 days, and 14 days after alkali burn, microscopy was used to observe corneal wound healing by fluorescein staining and the degree of corneal opacity. The expression of transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) was detected by RT-PCR and ELISA, alpha-smooth muscle actin (a-SMA) levels were measured by immunofluorescent staining, and Western blot assays for TGF-β1, a-SMA, and nuclear factor-kappa B (NF-κB) were also performed. Results. Corneal wound healing and corneal opacity scores were better in the doxycycline group than in the control group. Three, 7, and 14 days after corneal alkali burn, a significant increase in TGF-β1 was observed in corneas from the control group, compared with the corneas from the doxycycline group (P<0.05). The corneal levels of MMP-9 in the doxycycline group were lower than those in the control group 3 days and 7 days after alkali burn (P<0.05). In addition, doxycycline inhibited α-SMA expression and suppressed NF-κB expression. Conclusion. Doxycycline treatment promoted corneal healing and reduced corneal opacity in SD rats. Doxycycline protected the cornea from alkali burn injury by reducing TGF-β1, MMP-9, NF-κB, and α-SMA expression.

In two-dimensional (2D) systems, high mobility is typically achieved in low-carrier-density semiconductors and semimetals. Here, we discover that the nanobelts of Weyl semimetal NbAs maintain a high mobility even in the presence of a high sheet carrier density. We develop a growth scheme to synthesize single crystalline NbAs nanobelts with tunable Fermi levels. Owing to a large surface-to-bulk ratio, we argue that a 2D surface state gives rise to the high sheet carrier density, even though the bulk Fermi level is located near the Weyl nodes. A surface sheet conductance up to 5–100 S per □ is realized, exceeding that of conventional 2D electron gases, quasi-2D metal films, and topological insulator surface states. Corroborated by theory, we attribute the origin of the ultrahigh conductance to the disorder-tolerant Fermi arcs. The evidenced low-dissipation property of Fermi arcs has implications for both fundamental study and potential electronic applications.High mobility and high carrier density are found in the Weyl semimetal NbAs. This is attributed to the low dissipation of disorder-tolerant Fermi arcs.

Tin selenide (SnSe) is one of the most promising candidates to realize environmentally friendly, cost‐effective, and high‐performance thermoelectrics, derived from its outstanding electrical transport properties by appropriate bandgaps and intrinsic low lattice thermal conductivity from its anharmonic layered structure. Advanced aqueous synthesis possesses various unique advantages including convenient morphology control, exceptional high doping solubility, and distinctive vacancy engineering. Considering that there is an urgent demand for a comprehensive survey on the aqueous synthesis technique applied to thermoelectric SnSe, herein, a thorough overview of aqueous synthesis, characterization, and thermoelectric performance in SnSe is provided. New insights into the aqueous synthesis‐based strategies for improving the performance are provided, including vacancy synergy, crystallization design, solubility breakthrough, and local lattice imperfection engineering, and an attempt to build the inherent links between the aqueous synthesis‐induced structural characteristics and the excellent thermoelectric performance is presented. Furthermore, the significant advantages and potentials of an aqueous synthesis route for fabricating SnSe‐based 2D thermoelectric generators, including nanorods, nanobelts, and nanosheets, are also discussed. Finally, the controversy, strategy, and outlook toward future enhancement of SnSe‐based thermoelectric materials are also provided. This Review guides the design of thermoelectric SnSe with high performance and provides new perspectives as a reference for other thermoelectric systems. Herein, aqueous‐solution‐based synthesis, characterizations, and thermoelectric performance in SnSe thermoelectrics are thoroughly reviewed by providing new insights including vacancy synergy, crystallization design, doping limit breakthrough, local lattice imperfection engineering, and a promising flexible thermoelectric generator based on appropriate synthesis design.

The aim of this study is to assess the three-dimensional (3D) stability of the tunnel face with considering the possibility of the upper partial failure in layered rock masses. The failure characteristic of the rock material is denoted by the nonlinear Hoek–Brown failure criterion, and a multi-tangent method is introduced and adopted to determine the equivalent Mohr–Coulomb parameters. Based on the traditional 3D rotational failure model, the whole failure model and the upper partial failure model are developed with considering layered rock masses and possibility of upper partial failure at the tunnel face. The upper-bound limit analysis approach is adopted to determine the limit support pressure and failure surface. The proposed method is validated by comparison with existing solutions and numerical results. Parametrical analysis is then conducted to investigate the influence of analytical parameters on the face stability. Finally, the effect of seepage forces on the tunnel face stability is presented. The results show that, the upper partial failure is likely to happen when a soft layer in the upper section of tunnel face. This possibility increases as properties of lower layer increase, the tunnel diameter decreases, and the layered position moves down. The presence of underground water delays the occurrence of upper partial failure at the tunnel face.