Advanced Science最新文献

Chemiresistive gas sensors based on semiconducting metal oxides for toxic gas detection are widely explored for terrestrial applications under ambient environments, but their potential in extraterrestrial applications remains underexplored. Herein, we developed porous Cu-doped SnO₂ microspheres, enabling high sensitivity and selectivity toward hydrogen sulfide (H₂S), from the ambient air (25°C, 10⁵ Pa) to extreme conditions (-40°C, ∼10^{- 4} Pa) designed to simulate the space-like oxygen defects and cryogenic environments. Hierarchical porosity enables efficient gas diffusion across pressure regimes, and Cu^{2 +} doping and oxygen vacancies thus enable oxygen-independent chemisorption. Moreover, in situ-formed chemical adsorption promotes interfacial charge transfer, which exhibits partial reversibility. The semi-quantitative framework represented by a CuS kinetic proxy, combining numerical simulations based on Wolkenstein adsorption theory, finite element methods, and experimental results, reveals a dual-mechanism paradigm. At ambient conditions, the oxygen-adsorption-driven redox reaction is dominant. In contrast, under a vacuum around 10^-4 Pa, direct chemisorption and interfacial charge transfer primarily govern the gas adsorption responses. This study offers a generalized metal-oxide platform for gas detection for future space exploration and life-support monitoring systems.

Organic ferroelectric field-effect transistors (OFeFETs) are promising candidates for next-generation wearable electronics and non-volatile memory technologies owing to their bistable switching, low power consumption, and mechanical flexibility. Here, room-temperature organic chiral multiferroic FETs are demonstrated, in which both gate field and chiral field dependence of charge-spin conversion are studied. Remarkably, the chiral FET presents tens of micrometer chiral signal transport. This long-range chiral transport provides an ideal platform for probing the interaction between charge and chirality-induced polarized spin. The interfacial dipoles in the ferroelectric layer could impact the degree of charge carrier localization to further modulate spin polarization, presenting a charge-spin conversion-dependent magnetoelectric coupling. Conversely, polarized spin in the organic chiral layer could modify saturated ferroelectric polarization and ferroelectric hysteresis loop, apparently. In addition, when an external magnetic field is applied parallel (antiparallel) to the chiral axis, the OFET shows an enhanced (weakened) chiral magneto-chiral current, which can also be modulated by remanent polarization.

Microwave ablation (MWA) represents a highly effective and clinically significant therapeutic modality for the treatment of liver metastases. The proliferation of disseminated tumor cells within the peri-necrotic transition zone (TZ) is a critical factor contributing to the postablative recurrence; to date, no effective method has been identified to specifically target and eliminate these cells. Here, based on an experimental liver metastases model, we leverage single-cell RNA sequencing and flow cytometry analysis, which reveals that TZ exhibits a VEGF-mediated immunosuppressive microenvironment, characterized by a significant increase of CD155⁺ myeloid cells. We further report the development of engineered cell membrane vesicles encapsulating Bevacizumab, which are fused with TIGIT-expressing membranes and platelet membranes (referred to as Bev@TPNVs). The Bev@TPNVs can specifically target the liver and the TZ, inhibit neovascularization, and restore the anti-tumor functionality of CD8⁺ T cells. Our findings demonstrate that Bev@TPNVs can effectively suppress liver metastasis after MWA. The intrahepatic metastasis burden is reduced by approximately 10-fold compared with the control group, and the survival rate of mice within 70 days reaches 50%. This work has the potential to establish a novel standard treatment paradigm that could revolutionize combined immunotherapy following liver metastasis ablation.

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with a dismal prognosis, and pronounced interpatient heterogeneity severely limits the efficacy of systemic therapies, underscoring the need for rapid and accurate functional platforms to guide individualized drug selection. Here, we develop a clinically oriented, patient-derived, 3D bioprinted in vitro model for personalized drug sensitivity assessment in ICC. Using a compositionally defined and cost-effective GelMA/HAMA composite hydrogel, we reconstruct a tumor microenvironment that supports rapid self-organization and sustained viability of primary ICC cells. Histological analyses, marker expression profiling, and bright-field imaging demonstrate close similarity to matched patient tumor tissues. Genomic and transcriptomic fidelity are further confirmed by whole-exome and RNA sequencing, revealing preserved driver mutations and transcriptional programs. Drug sensitivity testing was performed on tumor samples from 21 ICC patients using clinically relevant agents. Notably, in patients receiving neoadjuvant therapy, in vitro drug responses were fully consistent with clinical outcomes. Longitudinal follow-up further showed that recurrence occurred exclusively in patients who did not receive the predicted sensitive therapies. Importantly, clinically actionable drug response profiles were generated within 10 days. Collectively, this platform provides a rapid, reproducible, and patient-specific functional drug testing strategy with strong potential for clinical translation.

Under soil drought conditions, plant roots sense stress and transmit signals to the shoots, leading to coordinated whole-plant responses to the stress. While several root-to-shoot signals have been identified, the existence and significance of shoot-to-root signals in this process remain unclear. Here, we identify a two-step, CLE peptide-mediated root-shoot-root signaling relay underpinning drought adaptation in common bean. We show that PvCLE16, a gene predominantly expressed in leaves under well-watered conditions, was specifically upregulated in leaves, but not roots, under moderate drought. This spatially restricted transcriptional activation was driven by the leaf-preferentially expressed transcription factor PvTCP10. Accumulated PvCLE16 in leaves promoted stomatal closure and also translocated to the roots, where it suppressed primary root elongation and stimulated lateral root development, adaptations that collectively enhance drought resilience. PvBAM3 was identified as the primary receptor for PvCLE16. Upstream of this module, we found that drought-induced expression of PvCLE16 in leaves requires PvCLE11b, a root-derived CLE peptide that moved acropetally under drought. Together, our findings reveal a novel root-shoot-root signaling relay, wherein root-derived PvCLE11b functions as the upward signal to induce PvCLE16 in leaves, which subsequently acts both locally and systemically by translocating to the roots to coordinate whole-plant drought adaptation responses.

Background: Spatial proteogenomics marks a paradigm shift in oncology by integrating molecular analysis with spatial information from both spatial proteomics and other data modalities (e.g., spatial transcriptomics), thereby unveiling tumor heterogeneity and dynamic changes in the microenvironment.

Methods: We systematically reviewed the evolution of spatial proteogenomics, from single-modality profiling to integration with transcriptomics and metabolomics, from the detection of abundant proteins to exploration of "dark proteome" with low abundance or stability, and from analytic software based on traditional machine learning algorithms to advanced artificial intelligence-driven analytical frameworks.

Results: Key advances of sub-fields of spatial proteogenomics include: RNA-protein co-localization: Spatial CITE-seq, enabling RNA-protein co-localization to reveal immune microenvironmental patterns and neoantigen distribution. Spatial Proteomics + Spatial Metabolomics: Matrix-assisted laser desorption/ionization imaging (MALDI), overcoming protein detection bottlenecks and capturing metabolic reprogramming. Deep visual proteomics (DVP): achieving unbiased spatial analysis via AI-guided microdissection. Spatial-aware multiplex dark proteome approaches: Examples are nanodroplet processing in one pot for trace samples (NanoPOTS) and proteoform imaging mass spectrometry (PiMS). Multimodal foundation AI models: Examples are KRONOS and HEIST, which integrate multiple data modalities and significantly improve diagnostic precision and therapeutic prediction.

Conclusions and future directions: Despite challenges of resolution, standardization, and data complexity, spatial proteomics is advancing rapidly. Together with frontier technologies such as quantum computing, live imaging, and organoid integration, it is driving breakthroughs in cancer diagnosis, personalized immunotherapy, and drug development.

Immune checkpoint blockade (ICB) efficacy is limited by tumor-intrinsic immune escape mechanisms. This study identifies the transcription factor ZBTB21 as a central orchestrator of dual immunosuppressive programs. ZBTB21 epigenetically silences gasdermin D (GSDMD)-dependent pyroptosis by restricting STAT1-mediated chromatin accessibility via H3K27ac modulation at the GSDMD locus. Simultaneously, it represses MHC-I antigen presentation by attenuating IRF1 expression and its transactivation capacity. Genetic ablation of ZBTB21 unleashes pyroptotic cell death and enhances tumor antigen presentation, establishing a self-reinforcing cycle that recruits and activates CD8⁺ T cells. This dual activation overcomes ICB resistance in murine models, while B2M deletion ablates efficacy, confirming MHC-I dependency. Pharmacological inhibition of ZBTB21 with dobutamine disrupts its DNA-binding domain, which triggers pyroptotic inflammation and MHC-I upregulation to synergize with anti-PD-1 therapy. Thus, ZBTB21 represents a druggable nexus coordinating pyroptosis resistance and antigen presentation escape, providing a combinatorial strategy to reinvigorate antitumor immunity.

The discovery of near-room-temperature superconductivity in the lanthanum hydride LaH₁₀ has revolutionized this research field. However, the need to use diamond anvils for the synthesis of hydride superconductors severely limits the experimental techniques to study these materials. Nuclear magnetic resonance (NMR) is one of the key methods for probing spin systems of superconductors. Here we show how ¹H NMR can be realized in diamond anvil cells to study lanthanum polyhydrides at pressures up to 165 GPa. In the newly discovered superhydride LaH₁₂, we observed a pronounced suppression of the ¹H NMR signal intensity below T_c ^onset = 260 K in a magnetic field of 7 T, corresponding to the screening of the radio-frequency pulses. Below the critical temperature, all ¹H NMR characteristics, including the nuclear spin-lattice relaxation rate 1/T₁T, exhibit pronounced features that may be associated with superconductivity. In zero field, the radio-frequency signal transmission shows a pronounced drop below T_c ^onset ≈ 267‒279 K, indicating the very beginning of the transition in the most ideal microcrystals. A description of the 1/T₁T data with an exponential form allows the estimation of the superconducting gap Δ(0) = 427‒671 K (corresponding to 36.8‒57.8 meV), and the ratio R_Δ = 2Δ(0)/k_BT_c between 3.76 and 5.16 in the synthesized polyhydride.

While cisplatin is a widely used and effective chemotherapeutic agent in the treatment of head and neck squamous cell carcinoma (HNSCC), the molecular mechanisms underlying its resistance remain poorly understood. In this study, we identify OCIA domain containing 2 (OCIAD2) as a central mediator of chemoresistance and tumor progression in HNSCC. Through transcriptomic analysis and Co-immunoprecipitation coupled with mass spectrometry, we demonstrate that OCIAD2 modulates integrin signaling by directly interacting with integrin β1. Mechanistic investigations reveal that OCIAD2 does not regulate integrin β1 at the transcriptional level, but instead stabilizes its protein expression by preventing lysosomal degradation and enhancing its recycling. Importantly, OCIAD2 binds to SNX17 and enhances its association with integrin β1, promoting its recycling to lipid raft-enriched regions of the plasma membrane. By maintaining integrin β1 in these lipid raft compartments, OCIAD2 sustains the activation of the FAK-PI3K-AKT-mTOR signaling cascade, thereby fostering cellular resilience and resistance to cisplatin. Moreover, targeting OCIAD2, either through genetic silencing or RNA-based therapies, significantly sensitizes tumors to cisplatin treatment in preclinical models. This study uncovers a previously unrecognized trafficking-dependent mechanism of drug resistance, suggesting that OCIAD2 may serve as a novel therapeutic target to overcome chemoresistance in HNSCC.

Zinc-halogen batteries (ZHBs) offer a safer, cost-effective alternative to lithium-ion batteries, leveraging abundant zinc resources and high energy density. Among ZHBs, dual-plating zinc bromine batteries (ZBBs) utilizing ionic liquid (IL)-forming bromine complexing agents (BCAs) exhibit enhanced performance by minimizing halogen crossover and enabling high conductivity via Grotthuss-type halide transport. In this study, the electrochemical impedance of the bromide redox reaction in the presence of 1-ethyl-1-methylpyrrolidinium bromide (MEPBr), an IL-forming BCA, was analyzed. Potentiodynamic operando impedance measurements revealed pronounced asymmetry in mass transport impedance between polybromide ionic liquid (PBIL) formation and dissolution. This asymmetry significantly influenced the potential and impedance trends during galvanostatic cycling of dual-plating ZBBs. During charging, facilitated Br^- transport lowered the positive electrode impedance, resulting in minimal positive electrode overpotential even at high current densities. In contrast, during discharging, PBIL dissolution at the positive electrode exhibited large overpotential at high current densities due to the relatively sluggish internal mass transport of Br_2n+1 ^-. Furthermore, similar asymmetry was observed across various IL-forming BCAs, indicating that the mass transport disparity is an intrinsic property of PBIL rather than limited to MEPBr. These findings provide new insights into PBIL mass transport dynamics and their impact on high-current-density operation in dual-plating ZBBs.