Research最新文献

Autophagy is integral to the rapid proliferation of esophageal squamous cell carcinoma (ESCC), and its regulation presents a promising avenue for therapeutic intervention. Recent studies have elucidated the interplay between autophagy and glucose metabolism, while there is a paucity of anticancer drugs that concurrently target these 2 biological processes. In this study, we identified a natural compound, p-hydroxylcinnamaldehyde (CMSP), originally isolated from Cochinchina momordica seed (CMS) by our research team, which exhibits substantial anticancer activity against ESCC in both in vitro and in vivo models. The study demonstrates that CMSP induces apoptosis in ESCC cell lines and patient-derived organoid (PDO) models by disrupting autophagic flux. Mechanistically, CMSP specifically binds to the glycolytic enzyme LDHA in the cytoplasm, hindering its phosphorylation by blocking its membrane translocation and thereby disrupting its interaction with FGFR1. This inhibition results in decreased lactate production from glycolysis, reduced lysosomal acidity, and suppression of the AMPK/mTOR pathway, ultimately resulting in the blockade of autophagy and the induction of apoptosis. Furthermore, in vivo studies underscore the potential clinical application of CMSP in ESCC by disrupting autophagy. In summary, we propose a novel therapeutic strategy for the precision treatment of ESCC by simultaneously targeting glycolysis-mediated autophagy.

Meniscal injuries are common in the knee joint. Minor meniscal injuries usually respond well to conservative treatment, while severe cases often require complete meniscal replacement. Meniscal injuries cause inflammatory responses that importantly hinder meniscal tissue regeneration. Despite ongoing advances in research, considerable breakthroughs in meniscal regeneration remain out of reach. This study introduces programmable macrophage mimics (PMMs), which enable sequential regulation from anti-inflammatory responses to meniscal fibrocartilage regeneration. PMMs were prepared by encapsulating the transforming growth factor-β3 and insulin-like growth factor-1 growth factors within mesoporous silica nanoparticles modified with branched polyethyleneimine via disulfide bonding. This design allows the initial adsorption of proinflammatory cytokines followed by the controlled release of growth factors that promote adipose-derived stem cell (ADSC) differentiation into fibrochondrocytes. The PMMs were integrated into meniscus-specific acellular matrix hydrogels (mGC), which provided suitable mechanical properties critical for effective regeneration. In rabbit osteoarthritis models, ADSC-loaded PMMs@mGC hydrogels showed marked fibrocartilage regeneration. Additionally, the team developed an advanced biofabrication approach that combines a 3-dimensionally printed polycaprolactone framework designed for total meniscus replacement. This research suggests that PMMs act as a bifunctional "core-shell" nano-delivery system, offering a promising therapeutic strategy for managing inflammatory meniscal conditions.

Zincology, the rigorous cross-disciplinary study of zinc metabolism and its multifaceted biological and applied roles in health and disease, delivers a transformative framework for resolving long-standing uncertainties in biomedical research. As a central regulator of cellular function and a versatile element in applied fields, zinc dyshomeostasis underpins diverse high-burden pathologies, including renal, metabolic, cardiovascular, and neurodegenerative disorders, yet its mechanisms remain fragmented across disciplines. This Perspective marks the first formal definition of Zincology as a distinct cross-disciplinary discipline, clarifying zinc's context-dependent dual role: systemic deficiency exacerbates biological injury through compromised antioxidant defense and inflammation, while local excess drives pathogenesis-exemplified by the Zn-protein kinase B (AKT)-forkhead box protein O1 (FOXO1)-glucose-6-phosphatase catalytic subunit (G6PC) axis in kidney disease. We synthesize Zincology's core principles to integrate systemic and local zinc metabolism, dissect its pathogenic role in the aforementioned disorders, and outline cross-disciplinary research directions with implications extending beyond biomedicine. Leveraging Zincology's multidisciplinary rigor, we establish zinc homeostasis as a unifying framework for deciphering disease mechanisms, with kidney disease serving as a paradigmatic model to validate its core tenets, bridging fragmented basic, clinical, industrial, and environmental research to address global critical unmet medical and societal needs. Notably, Zincology extends beyond biomedicine to encompass engineering, ecology, and other frontier fields, representing a comprehensive cross-disciplinary system that links basic science with diverse applied domains.

The growing imperative to ensure food safety, preserve ecological integrity, and mitigate public health risks associated with pesticide residues has driven a critical demand for highly sensitive optical sensors. In this regard, optical biosensors, including fluorescence (FL), colorimetry (CL), surface-enhanced Raman scattering (SERS), surface plasmon resonance (SPR), and chemiluminescence strategies, have been developed for pesticide detection. This review aims to provide a comprehensive summary of both fundamental knowledge and advancements in the field of optical biosensors for pesticide detection. The advantages of these biosensors are highlighted, such as excellent sensitivity, high specificity, and on-site application. Subsequently, a detailed overview of the sensing mechanism of optical biosensors based on different molecular recognition elements [e.g., enzymes, antibodies, aptamers, molecularly imprinted polymers (MIPs), and supramolecular host-guest complexes] is provided. Finally, perspectives are offered on the current challenges and future directions of pesticide biosensors. This review is expected to serve as a fundamental guide for researchers in the field of optical biosensors for pesticide detection and to provide insights and avenues to enhance the performance of existing sensing mechanisms in applications across diverse fields.

Lunar far-side samples returned by the Chang'e-6 mission offer unprecedented insights into regolith properties within the South Pole-Aitken basin, essential for advancing lunar exploration and in situ resource utilization. This paper presents an integrated characterization framework combining high-resolution x-ray micro-computed tomography with semisupervised machine learning to reconstruct and analyze 349,740 individual particles at high throughput. Morphological analysis demonstrates that far-side regolith exhibits greater irregularity than previously characterized near-side samples, with a median particle diameter of 60.51 μm and a mean 3-dimensional sphericity of 0.74-values distinct from those reported for Apollo and Chang'e-5 materials. Discrete element method simulations incorporating these high-fidelity morphologies under representative lunar surface confining pressures (5 to 15 kPa) reveal a high internal friction angle of 47.96° and a cohesion of 1.08 kPa. These parameters exceed Surveyor mission estimates and align with the upper range of Apollo program values, indicating enhanced mechanical strength and cohesion in far-side regolith. The superior mechanical properties arise primarily from pronounced particle irregularity promoting strong mechanical interlocking, potentially augmented by cementation from abundant glassy agglutinate phases. These findings establish critical geotechnical benchmarks for lunar far-side materials, providing essential design parameters for future robotic and crewed missions, landing site selection, and infrastructure development.

Precise diagnosis and management of lower extremity dysfunction disorders hinge on continuous gait monitoring. Nevertheless, the existing wearable devices fall short as they grapple with insufficient sensing precision, inadequate energy endurance, and ineffective intelligent data analysis. Here, we report a fully integrated, biomimetic smart insole that incorporates 3 synergistic innovations to overcome these challenges. First, inspired by the hierarchical mechanosensory apparatus of mantis legs, we design dual-microstructure capacitive sensors with a detection limit of 0.10 Pa and a maximum detection range of 1.4 MPa. This sensor can distinguish pressures across a wide range from subtle to substantial and exhibits robust mechanical stability over 12,000 cycles, making it highly suitable for insole applications and outperforming current flexible pressure sensors. Second, we realize energy-autonomous operation by integrating nano-perovskite solar cells with high-capacity lithium-sulfur nanobatteries, achieving an average photocharging efficiency of 11.21% and energy storage efficiency of 72.15%. Third, embedded artificial intelligence algorithms interpret the spatiotemporal pressure data transmitted via a 16-channel wireless module. These models achieve 96.0% accuracy in detecting foot arch abnormalities and 97.6% accuracy in classifying 12 pathological gait patterns. Collectively, these 3 advances, including bioinspired high-resolution sensing, sustainable energy interfacing, and intelligent mechanodiagnosis, establish a closed-loop wearable platform validated in clinical studies. This system offers promising applications in early disease screening, personalized rehabilitation, and remote healthcare.

Drug-associated reward memory underlies both the development and relapse of addiction, yet its molecular basis remains poorly understood. Here, transcriptomic profiling and functional validation identified a novel long non-coding RNA (lncRNA), Gm44763, as a critical regulator of morphine-induced reward memory specifically in neurons of the medial prefrontal cortex (mPFC). Behavioral and molecular analyses demonstrated that Gm44763 functions as a sponge for miR-298-5p, thereby relieving the repression of the downstream target gene, eukaryotic translation initiation factor 4E (eIF4E), and modulating both the acquisition and retrieval of reward memory. Golgi staining and fiber photometry further revealed that Gm44763 normalized morphine-induced alterations in synaptic structure and neuronal excitability. miR-298-5p bidirectionally regulated morphine-induced reward memory and reversed both behavioral and neuronal effects mediated by Gm44763. Mechanistically, the downstream effector eIF4E modulates translation via its interaction with eIF4G, thereby contributing to morphine-induced memory regulation. This process can be effectively modulated by 4EGI-1, a selective inhibitor of the eIF4E/eIF4G interaction. In summary, this study characterized lncRNA expression profiles in the mPFC of mice with morphine-induced conditioned place preference. We identified and validated Gm44763 as a novel lncRNA regulator of morphine-induced reward memory and synaptic plasticity. We further delineate a previously uncharacterized Gm44763/miR-298-5p/eIF4E axis that may represent a novel regulatory pathway linking transcriptional and translational control to drug-associated memory formation.

Boron neutron capture therapy (BNCT) is a targeted radiotherapy technique that enables dual targeting at the physico-biological level. Efficient neutron sources and specific boron carriers are essential for successful treatment. By exploiting the ¹⁰B(n,α)⁷Li nuclear reaction, the BNCT enables precise eradication of ¹⁰B-loaded tumor malignant cells while sparing adjacent healthy tissues, rendering it particularly advantageous for treating invasive or radioresistant recurrent tumors. Numerous clinical trials related to BNCT have focus on evaluating the safety and efficacy of treating glioblastoma, head and neck carcinoma, meningioma, malignant melanoma, and liver cancer. Preliminary studies have shown that BNCT treatment may extend the overall survival (OS) and improve the quality of life for patients with these cancers. Additionally, the scope of BNCT clinical trials has expanded to other tumor types, such as lung cancer, breast cancer, extramammary Paget's disease, osteosarcoma, clear cell sarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, thyroid cancer, recurrent chordoma, and gastrointestinal malignancies. This review provides a comprehensive overview of BNCT clinical trials, covering the therapeutic principles of BNCT and the current status and outcomes of clinical trials for various types of tumors. With advancements in neutron beam quality and the development of efficient, specific boron carriers, the therapeutic efficacy of BNCT is expected to be further enhanced, and its scope of application is anticipated to expand. Looking ahead, the BNCT is expected to be integrated with other tumor treatment modalities to augment local tumor control, thereby improving patients' OS and quality of life.

Small inspection robots are highly desirable for inspecting complex machinery and detecting damage in confined spaces. However, common climbing robots that rely on vacuum suction or bioinspired dry adhesion often suffer from bulky sizes or slow locomotion speeds. Developing compact yet intelligent wall-climbing robots that mimic the agility and payload capacity of geckos remains an important challenge. In this work, we design a 20-g, 10-cm artificial intelligence (AI)-integrated robot capable of carrying a 70-g payload while climbing on vertical and inverted surfaces at a speed of 70 mm/s. Acoustic adhesion is generated by vibrating a flexible annular disk on smooth surfaces, where air is periodically absorbed and expelled, resulting in negative pressure. The thin air layer with negative pressure indicates anisotropic performance, characterized by strong normal adhesion and negligible tangential resistance, making it highly suitable for designing small, yet strong, climbing robots. The theoretical model and laser surface morphology measurements reveal the thickness-dependent adhesion of a thin air layer beneath the disk. A servo-spring system is designed to meet the stringent requirements of a thin air layer thickness, yielding robust normal adhesion. Resonance analysis and the use of proper spring material stiffness further enhance adhesion performance. Therefore, combining this innovative acoustic adhesion with optimized structural design, our robot achieves gecko-like mobility and payload capacity. Additionally, integrated AI techniques simplify robot control, allowing voice-commanded operation and autonomous task execution. We demonstrate the functions of these climbing robots through agile inspections in a 3-dimensional maze and retired aircraft engines. This work presents the design of small, strong, and agile climbing robots that utilize anisotropic acoustic adhesions, demonstrating agile mobility across gaps, right corners, and discontinuous curved surfaces. It offers potential solutions for in situ damage detection in aero-engines and other complex equipment cavities.

Aerosol viral transmission monitoring enables early, noninvasive detection of infectious disease spread by identifying airborne viral particles in shared environments. Integrating sampling, sensing, and data analysis, this perspective outlines an integrated framework for transforming epidemic responses from reactive testing to proactive surveillance. It synthesizes current technological advances and deployment experiences to identify key challenges in detection efficiency, data management, and societal trust. This marks a shift from clinical diagnosis to environmental surveillance, transforming epidemic responses from testing individuals to monitoring shared air. By enabling earlier interventions, these systems help reduce transmission, protect vulnerable groups, and limit disruptions to daily life and the economy.