Advanced Science最新文献

Partial hepatectomy (PHx) has emerged as a primary therapeutic intervention for end-stage liver pathologies. However, post-hepatectomy liver failure (PHLF), a critical complication arising from inadequate regenerative capacity of the remnant liver, underscores the clinical imperative to understand molecular mechanisms governing hepatic regeneration. Through an integrative multi-omics analysis in a murine 70% PHx model coupled with clinical correlation studies, the tRNA m⁷G methyltransferase METTL1 was identified as a pivotal regulator of post-resection hepatic recovery. METTL1 exhibited significant temporal upregulation following PHx, with its expression profile positively correlating with favorable clinical outcomes in surgical patients. Genetic ablation of METTL1 substantially attenuated hepatocyte proliferation and compromised regenerative capacity, whereas its ectopic expression potentiated liver regeneration through enhanced translational efficiency. Mechanistic investigations revealed that METTL1-mediated m⁷G tRNA modification orchestrates regenerative processes by selectively augmenting the translation of Hippo pathway effectors YAP/TAZ. Most importantly, modulation of the METTL1-YAP/TAZ signaling axis successfully promotes liver regeneration after PHx. This study elucidates a previously unrecognized translational control mechanism underlying liver regeneration, proposing METTL1 as a promising molecular target for preventing PHLF through therapeutic enhancement of hepatic regenerative potential.

Interfacial instability between different electrolyte materials is a critical challenge hindering the commercialization of CO₂ electrolysis via solid oxide electrolysis cells (SOECs). Specifically, the thermal deformation disparity at the yttria-stabilized zirconia (YSZ) and Gd-doped ceria (GDC) electrolyte interface leads to delamination during high-temperature operation, severely degrading cell performance and durability. In this study, this issue is resolved by designing a novel composite intermediate layer, fabricated through a simple dip-coating process using a mixture of YSZ and GDC powders. This composite layer effectively mitigates the thermal deformation disparity, ensuring excellent structural stability without delamination even after high-temperature sintering. Consequently, the cell incorporating the composite interlayer exhibits a significantly reduced interfacial resistance and achieves an exceptional current density of 2.14 A cm^-2 at 800 °C, which is among the highest performance levels reported for Ni-based fuel electrode-supported SOECs. Furthermore, the cell demonstrates excellent long-term stability, maintaining 91% of its initial performance after 80 h of continuous operation under a harsh 1.6 V condition. The electrolyte layer also retains robust and stable interfacial adhesion, confirming the durability of the engineered interface. This study presents an effective electrolyte interface engineering strategy for the development of high-performance and large-area SOECs for CO₂ electrolysis.

Aberrant mitosis is a hallmark of cancer, which drives chromosomal instability, gene dysregulation, tumor heterogeneity, immune evasion, and therapy resistance. In this study, it is observed that dysregulation of YAP signaling can cause supernumerary centrosome clustering, thereby triggering pseudo-bipolar/multipolar diversion during anaphase in breast cancer. Mechanistically, the YAP can accumulate and hyperactivate the super-enhancer of the spindle assembly checkpoint, AJUBA, in a phase-separation-dependent manner, thus leading to aberrant mitosis. These findings reveal a crucial biological role of YAP-mediated super enhancer activation and provide new insights into aneuploidy formation in breast cancer.

Glioblastoma (GBM) is a malignant brain tumor characterized by profound angiogenic activity and immunosuppressive features. A burgeoning body of research has focused on elucidating the functional effects of stromal cells within the tumor microenvironment (TME) and developing stroma-targeted therapeutic strategies. Notably, cancer-associated fibroblasts (CAFs), essential stromal components of the TME, have garnered significant attention for their functional orchestration in glioma progression. The proteomic landscape of human primary CAFs from GBM samples has revealed the dynamic remodeling of differential protein expression in the TME, but the functional role of glutamate-ammonia ligase (GLUL) as a novel CAF target remains elusive. This study confirms that GLUL knockdown profoundly abrogated the architectural intricacy inherent to CAF-supported vasculature in vitro and in vivo. Additionally, CAF-specific GLUL knockdown attenuates tumor growth and extends median survival in a humanized orthotopic glioma model. Furthermore, GLUL-driven activation of PI3K/AKT signaling as the central regulator of CAF-mediated vascular niche formation is delineated in glioma progression. This study highlights that targeting GLUL in CAFs is a novel stroma-focused therapeutic paradigm for GBM by disrupting pro-angiogenic signaling. Collectively, these findings elucidate key aspects of CAF biology and their regulatory functions in tumor progression, underscoring the therapeutic potential of targeting CAFs in GBM.

The demand for self-powered, broadband photodetectors is rising in fields like artificial intelligence, health monitoring, and optical communications. However, conventional perovskite photodetectors face limited visible absorption and poor ambient stability. Here, we report a high-performance integrated photodetector combining a perovskite (Cs_n.15FA_n.85PbI₃) absorber with an organic bulk-heterojunction (BHJ) structure for broadband photon harvesting up to 1000 nm. The device achieves a peak external quantum efficiency (EQE) of 84% in the visible range (400-700 nm) and 63% in the near-infrared (NIR, 700-1000 nm). Benefiting from optimized energy band alignment, the photodetector exhibits a self-powered responsivity of 0.3 A W^-1 and a fast response time of 29 µs, with a linear dynamic range (LDR) of 122 dB under 900 nm NIR illumination. The BHJ organic layer suppresses the dark current (J_D) to 6.9 × 10^-11 A cm^-2 and noise current (i_n) to 10-14 A Hz^-1/2, yielding a specific detectivity (D*) of 10¹² Jones. The polymeric BHJ also enhances flexibility, enabling a reliable 25-pixel array for uniform NIR imaging. In optical communication, the device achieves a low bit error rate with data rates of 90 kbps (λ = 665 nm) and 140 kbps (λ = 904 nm). This work establishes the perovskite/BHJ detector as a promising platform for flexible, high-speed optoelectronics.

Gene-engineered T cell therapies, particularly chimeric antigen receptor (CAR)-T cells, have demonstrated remarkable clinical success. However, concerns regarding insertional mutagenesis and other risks associated with genetic modification remain. Here, a non-genetic strategy is presented for T cell engineering using glycopolymer modification. It develops glycopolymer-modified T (G-T) cells based on antigen-specific T cells by integrating metabolic glycoengineering and click chemistry, yielding cells that retain T cell functionality while significantly enhancing tumor enrichment. The polyvalent glycopolymer-receptor interactions significantly improved the binding affinity of G-T cells to various glucose transporter 1 (GLUT1)-overexpressing tumor cells, resulting in increased cytotoxicity compared to unmodified T cells. In the tumor microenvironment, G-T cells engaged in stronger immune crosstalk with dendritic cells (DCs), upregulating interferon-gamma (IFN-γ) and interleukin-12 (IL-12) secretion and amplifying the anti-tumor immune response. Notably, despite the lower specificity of glycan-receptor interactions compared to antigen-antibody binding, the findings reveal an unexpected advantage: the "less restrictive" nature of glycan-receptor recognition enhances both tumor and immune cell interactions, triggering a potent immune cascade. This study establishes a universal, non-genetic T cell engineering strategy with broad applicability, offering a new perspective for tumor immunotherapy by merging biomedical polymer materials with immune modulation.

Anode-free lithium-sulfur (Li-S) batteries with Li₂S as the cathode offer a promising alternative to improve practical energy density but suffer from sluggish redox kinetics on the cathode side and chaotic Li plating/stripping process on the copper current collectors. In this work, phosphorus-doped porous carbon nanofibers (P-CNFs) are served both as self-standing hosts for Li₂S cathode and 3D current collectors for Li deposition. In the cathode, nanoscale Li₂S particles (less than 10 nm in size) are in situ synthesized via carbon thermal reduction of lithium sulfate which is confined within the brush layer of anionic spherical polyelectrolyte brushes. The incorporation of Li₂S nanoparticles within the void of P-CNFs (Li₂S@P-CNFs) imparts unimpeded electron/ion transport at the polar carbon matrix interface, thus enhancing the Li₂S conversion reaction kinetics and mitigating the shuttling effect of polysulfides during cycling. Moreover, the lithiophilic P-CNFs skeleton with interconnected macropores effectively homogenizes Li plating behavior, resulting in smooth and compact deposition morphology. As a result, the Li₂S@P-CNFs||P-CNFs full cell delivers a low-capacity decay of 0.051% cycle^-1 for 1000 cycles at 1 C. This work gives a unique strategy for the practicalization of anode-free Li-S batteries, with the potential to extend to other battery systems.

The role of microglia in blood-brain barrier (BBB) leakage and neovascularization after ischemic stroke remains unclear. Here, a post-stroke perivascular niche of microglia characterized by low expression of M2 markers and elevated glycolysis, oxidative phosphorylation (OXPHOS), and phagocytic activity is identified, which is termed stroke-activated vascular-associated microglia (stroke-VAM). It is found that Fkbp5 acts as a central regulator driving BBB disruption and impaired neovascularization through stroke-VAM. Single-nucleus RNA sequencing (snRNA-seq) analysis of Cx3cr1^Cre Fkbp5^flox/flox (Fkbp5 cKO) mice in the ipsilateral hemisphere reveals enhanced interactions between stroke-VAM and endothelial cells, influencing signaling pathways that maintain BBB integrity and promote neovascularization. After ischemic injury, microglia in Fkbp5 cKO mice exhibits higher M2 marker expression and reduces glycolysis, OXPHOS, and phagocytosis, resulting in decreased BBB leakage and enhanced angiogenesis. Mechanistically, unbiased snRNA-seq analysis shows that the Hippo signaling pathway is altered in Fkbp5 cKO stroke-VAM. Fkbp5 inhibits Yap1 phosphorylation, facilitating its nuclear translocation. These findings provide new insights into how the perivascular microglial niche contributes to both the degradation and regeneration of cerebral vasculature, offering potential therapeutic avenues for acute ischemic stroke.

Heavy metals and organic pollutants commonly co-exist in the industrial wastewaters, and traditional treatment processes always treat them separately. Heavy metals can be effective active sites in heterogeneous Fenton-like catalysts, and their potential for in situ utilization and enhancement for organic pollutant degradation is promising but still underexplored. Herein, the metal-free TQBQ-COF is employed with abundant pre-designed metal-2N anchoring sites for the in situ capture of Cu²⁺ ions for boosting organic pollutant degradation. The co-existing Cu²⁺ can be successfully utilized to in situ fabricate a novel single-atom catalyst (SAC) within 1 min. The coordinated Cu significantly enhances visible-light absorption and charge separation ability, thereby substantially improving the catalyst's Fenton-like performance (the k value is 240 folds higher than that in the absence of TQBQ-COF). Singlet oxygen (¹O₂) and photogenerated holes (h⁺) are identified as the main active species. In real wastewater with exceptionally high concentrations of Cu and chemical oxygen demand (COD), effective synergistic removal of organic pollutants and heavy metals can still be achieved, further demonstrating the applicability of this strategy. This work provides new insights into catalyst design and a new strategy of "treating waste with waste" for heterogeneous water-treatment technologies.

Mechanoluminescence (ML) materials with their unique stress-to-light conversion capability, have been driving the evolution of stress sensing technology from single-point detection to multi-dimensional imaging. Recent advances in material defect engineering, ion doping, and heterostructure design have significantly improved the luminosity, response kinetics, and environmental stability of ML materials. These enhancements have established a technical foundation for multimodal stress visualization across diverse application scenarios. To systematically analyse the stress response mechanism and visual behavior of materials across different spatial dimensions, this review offers in-depth discussions on material design principles, device integration methods, and application scenarios for 0D, 1D, 2D, and 3D stress sensing technologies. It further proposes targeted solutions to common challenges in multi-dimensional stress sensing, such as material performance, device integration synergy, and data processing. Finally, the development path of multi-dimensional stress visualization technology will be looked forward with higher spatial resolution in intelligent diagnosis, biomechanics, and extreme environmental monitoring, providing a theoretical framework and technical support for multi-dimensional stress visualization detection.