Science Bulletin最新文献

Depression has been closely associated with an elevated risk of myocardial infarction, yet the underlying mechanistic link remains unclear. Adenosine, a neuromodulator implicated in both depression and cardiovascular diseases, is believed to play a critical role in this connection. Here, we present a highly sensitive adenosine-responsive nanosensor capable of in vivo imaging of adenosine levels in the brain. Using this nanosensor, we identified a marked elevation of adenosine levels in the habenula of mouse models exhibiting both depressive-like behavior and myocardial infarction. Mechanistically, we found that accumulated adenosine activates microglia, leading to the release of pro-inflammatory cytokines and subsequent neuroinflammation. This neuroinflammatory response appears to trigger peripheral inflammation, ultimately activating the JAK1-STAT1-RIPK1-caspase-8 signaling pathway in cardiomyocytes and exacerbating myocardial injury. Importantly, treatment with the antidepressant fluoxetine significantly reduced adenosine accumulation in the brain, as detected by the nanosensor, and simultaneously alleviated myocardial damage. This innovative approach to imaging adenosine in the brain offers fresh insights into the relationship between depression and myocardial infarction.

Cu-based catalysts have been considered promising electrocatalysts for converting CO₂ into multi-carbon products (C₂₊ products). However, achieving selectivity toward a specific C₂₊ product remains challenging, necessitating the delicate design of catalytic sites to regulate the energy preference of reaction pathways. Herein, we introduced catalytic sites that evolve active hydrogen atoms (*H) on Cu surfaces to regulate electrocatalytic CO₂ hydrogenation pathways to achieve the selective production of ethylene. Ru single-atom site (Ru₁) was theoretically screened from 17 elements with 51 structures, exhibiting optimal activity in promoting hydrogenation of CO₂ reduction intermediates. The accordingly synthesized Ru₁-doped oxide-derived Cu (Ru₁-ODCu) catalyst delivered an ethylene selectivity of 82% in C₂₊ products with a Faradaic efficiency of 58.9% and a partial current density of 353.4 mA cm^-2 in KHCO₃ electrolyte. Kinetic isotopic and in situ spectroscopic analyses evidenced that the Ru₁ sites effectively promote intermediate hydrogenation by regulating *H transfer to intermediates, facilitating the energy-preferred pathway to ethylene production. These results provide insights into the design of Cu-based catalysts for converting CO₂ into specific products.

The direct-current (DC) Josephson, or superconducting diode effect, i.e., the nonreciprocal behavior of critical current in a superconductor, has been observed in various systems exhibiting both time-reversal and parity symmetry breakings. However, we show that breaking these two types of symmetries is only a necessary but not sufficient condition for the diode effect, for which certain additional symmetries, including particle-hole symmetry and many others, must also be broken. The dependencies of the free energy on the gauge-independent phase difference across the junction and the magnetic field are classified, exhibiting the current-reversion (JR), field-reversion, and field-current reversion conditions, respectively. All symmetries satisfying the JR condition need to be broken for the DC Josephson diode effect. The relations of critical currents with respect to the magnetic field are classified into five classes, and three of them exhibit the diode effect. These symmetry considerations are applied to concrete examples. Our work reveals that the DC Josephson diode effect is a natural consequence of the JR symmetry breaking, and hence provides a guiding principle to understand or design a DC Josephson diode.

The Yan Mountain Region (YMR), a transition zone between the Mongolian Plateau and northern China, played a pivotal yet understudied role in shaping the prehistoric East Asian genetic and cultural landscapes. Analyzing 42 ancient genomes (7700-4300 before present (BP)), focusing on the Early Neolithic Sitaimengguying (STM_EN) and Late Neolithic Jiangjialiang (JJL_LN) sites, we reveal the fine-scaled population history of the Neolithic YMR. We genetically link Early Neolithic YMR groups (Yumin and STM_EN) to the Early Neolithic Lake Baikal groups, in line with similar burial practices in the Lake Baikal region. JJL_LN individuals who belonged to the Late Neolithic Xiaoheyan culture were genetically heterogeneous reflecting an admixture between STM_EN-related groups and Yellow River farmers, and filled in an ancient genome sampling gap between the Hongshan and Lower Xiajiadian cultures. This study consolidates the idea of pre-pastoralist contact between the Eurasian steppe and northern Chinese agricultural societies and highlights the YMR as a key interaction sphere between the Yellow and West Liao River regions.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) messenger RNA (mRNA) delivery has fueled a great hope for tumor immunotherapy via augmenting the immune sensitivity in many human cancers. However, therapeutic efficacy and clinical translation are limited by inadequate mRNA expression, insufficient immune stimulation and stringent storage requirements. Herein, inspired by the intrinsic properties of metal ions and exosomes, we developed a biomimetic delivery system (Mn-NP@PM) with superior stability for precise colorectal cancer immunotherapy. This platform employs adjuvant-metal-ion chelation for PTEN mRNA loading and PD-L1 antibodies (αPD-L1)-modified monocyte-macrophage membrane coating for mRNA protection and tumor targeting. Mn²⁺ was specifically selected due to its capacity for reversible mRNA binding through weak non-electrostatic interactions, facilitating efficient release, while simultaneously activating the stimulator of interferon genes (STING) pathway. Importantly, Mn-NP@PM exhibited membrane fusion for immediate cytosolic mRNA delivery, bypassing endo-lysosomal escape, optimizing transportation efficiency. Clinical-data-driven analyses further demonstrated that Mn-NP@PM-mediated PTEN restoration significantly increased T-cell infiltration and strengthened antitumor immunity in humanized patient derived xenograft (PDX) models. Collectively, this biomimetic, metal-ion-chelating, membrane-coated mRNA delivery system represents a versatile and clinically translatable strategy for personalized cancer immunotherapy.