The extreme climatic conditions of the Tibetan Plateau foster unique microbial communities, especially in the sediment ecosystem. A thorough understanding of these communities could facilitate revealing their microbial diversity, biological resources, and response to climate change. Here, we have constructed the Tibetan Plateau Microbial Catalog of Sediment (TPMC-S) based on 248 metagenomic sediment samples from the Tibetan Plateau. We identified 511,056,752 nonredundant genes and recovered 13,696 metagenome-assembled genomes with enormous phylogenetic novelty (over 90% novel species), far exceeding other contemporary Tibetan microbial catalogs and expanding the microbial functional diversity. We also revealed that similarities of sediment microbial communities followed the distance–decay relationship. Furthermore, sediments contained a high proportion of evolutionarily “possible ancient species (PAS)” compared with paired aquatic samples, especially ancient archaeal lineages, suggesting a microbial “sedimentary archive” in sediment. Finally and most importantly, Asgardarchaeota, including 2 potentially novel genera, were identified from the sediments, and their latest divergence predated the uplift of the Tibetan Plateau, while they still gained functions to adapt to extreme environments. Our findings positioned the Tibetan Plateau as both a genomic repository of microbial antiquity, especially Asgardarchaeota, and an active arena for modern extremophile innovation, providing insights for deciphering microbial resilience strategies in climate-sensitive ecosystems and informing novel bioprospecting efforts.

With the continuous advancement of micro-light-emitting diode (Micro-LED) manufacturing technology, Micro-LED displays are poised to emerge as the next-generation display technology, making important strides in areas such as near-eye displays, large-scale high-definition devices, and flexible screens. Among the various technical challenges associated with Micro-LED displays, detection plays a crucial role in identifying defective pixels, improving yield, and reducing overall production costs. Given that Micro-LED chip arrays often consist of millions of tiny chips (<50 μm), existing electrical detection methods face limitations such as low efficiency and high costs. As a result, enhancing detection efficiency, improving accuracy, and reducing costs have become the key trends in the development of Micro-LED detection technology. This review first outlines the key indicators to be monitored during Micro-LED chip detection. It then provides an in-depth analysis of the various detection methods available at different stages of the manufacturing process. Finally, it concludes with a summary of the current state of Micro-LED detection technology and offers a forward-looking perspective on future technological advancements.

Cuproptosis, a newly identified form of copper-dependent programmed cell death, has emerged as a potential therapeutic strategy for cancer treatment. However, its antitumor efficacy was strictly limited by dysregulated glycolytic metabolism of tumor cells. Herein, we proposed multifunctional copper-based nano-PROTACs (CHNDs) to degrade hexokinase 2 (HK-2) and amplify cuproptosis for cancer therapy via dual mitochondrial energy depletion. Our initial evaluation indicated that polyethyleneimine (PEI)-based nano-PROTACs (PHDs) triggered HK-2 degradation via the ubiquitin–proteasome system (UPS). PHDs reduced HK-2 expression to 43.7% in 4T1 cells and 42.1% in CT26 cells, which consequently impaired glycolysis in tumor cells. Furthermore, copper ion release from CHNDs in a controlled manner and the glucose metabolism homeostasis interference by PHDs orchestrally induced effective cuproptosis and glycolysis inhibition for suppressing development and metastasis of tumor cells. Notably, CHNDs markedly inhibited the growth of murine colon and breast tumors by simultaneously disrupting mitochondrial respiration and glycolysis, resulting in tumor inhibition rates of 76.6% and 55.3%, respectively, and extending the median survival of CT26 tumor-bearing mice from 21 to 29 d. Our designed multifunctional engineered nanoparticle-based targeted protein degraders facilitated a new paradigm for precise oncology and proteolysis-targeting chimera (PROTAC) development.

Determining platelet-derived growth factor receptor β (PDGFRβ) expression in biological specimens is pivotal for cancer diagnosis, drug development, and therapeutic monitoring. After tyrosine kinase inhibitor (TKI) therapy, altered PDGFRβ expression may correlate with treatment resistance mechanisms. Real-time, accurate detection of PDGFRβ levels pre- and post-TKI treatment holds substantial clinical value, as it enables therapeutic efficacy evaluation, resistance prediction, and timely regimen adjustment. However, the current repertoire of real-time technologies for precise PDGFRβ monitoring remains highly limited. Herein, we present a novel nanoprobe (Cy3-Gint4.T@BPNSs) for PDGFRβ detection based on a fluorescence quenching–recovery mechanism. Cy3-Gint4.T is a cyanine 3 (Cy3)-labeled aptamer with high specificity and strong selective binding affinity for PDGFRβ. Black phosphorus nanosheets (BPNSs) adsorb Cy3-Gint4.T via van der Waals forces to quench its fluorescence. Upon targeting PDGFRβ on cancer cells, the aptamer–receptor interaction outcompetes Cy3-Gint4.T’s binding to BPNSs, triggering its release and subsequent fluorescence restoration. Notably, the restored fluorescence intensity shows a direct correlation with cellular PDGFRβ expression, highlighting the nanoprobe’s potential for guiding tumor diagnosis and treatment. Critically, our data confirm that dynamic PDGFRβ expression changes induced by specific TKI therapies exhibit a proportional relationship with corresponding fluorescence intensity variations. This finding further supports an association between PDGFRβ expression dynamics and TKI resistance mechanisms, facilitating precise PDGFRβ monitoring and individualized therapeutic guidance.

In the tumor microenvironment, both tumor cells and tumor-associated macrophages (TAMs) frequently impede the effective treatment of glioblastoma (GBM). Herein, a co-extracellular vesicles (EVs) delivery system composed of M0 RAW264.7 macrophage-derived extracellular vesicles (MEVs) and doxorubicin (DOX)-loaded lemon-derived EVs (LEVDs) is demonstrated, enabling a significant enhancement of immunochemotherapy for GBM. This system facilitates the penetration of both EV types across the blood–brain barrier and blood–brain tumor barrier, enabling precise modulation of TAMs and tumor cells within the GBM microenvironment. During this process, MEVs exhibit a remarkable homing capacity toward TAMs, and meanwhile, they are enriched in microRNA let-7f-5p, which targets the 3′ untranslated region of A20 mRNA in M2 macrophages, leading to the activation of nuclear factor κB signaling pathway. This cascade drives the repolarization of M2 macrophages toward an M1 phenotype, effectively reversing the immunosuppressive tumor microenvironment. Concurrently, LEVDs exhibit exceptional targeting of GBM cells through receptor–ligand interactions, facilitating efficient chemotherapy. As expected, the co-EVs delivery system significantly enhances immunochemotherapy for GBM through MEVs-mediated TAM repolarization and LEVDs-driven chemotherapy.

The regeneration of large bone defects remains a major clinical challenge due to the lack of stable and effective osteoinductive signals. Although extracellular vesicles have shown promising potential for cell-free bone regeneration, their application is largely constrained by complex purification and embedding into scaffolds. Migrasomes, newly identified organelles with the extracellular matrix affinity, represent a promising yet underexplored avenue for cell-free tissue engineering. Here, we report a migrasome-enriched bioactive layer as a functional osteoinductive interface for cell-free bone regeneration. We demonstrated that osteoprogenitor stem cells (OPSCs) derived from human cortical bone exhibit robust osteogenic capacity and, upon osteogenic induction, promote the release and deposition of migrasomes together with calcium on culture surfaces. Utilizing these characteristics, we developed an in situ deposition strategy where OPSCs are preseeded on biphasic calcium phosphate (BCP) scaffolds, induced to mineralize, followed by decellularization. This process robustly preserves a native, osteogenic migrasome layer on the scaffold without the need for vesicle isolation or chemical conjugation. The resulting migrasome-functionalized scaffolds markedly up-regulated osteogenic gene expression and promoted bone regeneration in a murine calvarial defect model. Altogether, these findings validate migrasomes as a potent, endogenous signaling platform for bone tissue engineering. Moreover, our new paradigm for cell-free biomaterials employing cellular secretomes opens a new frontier in regenerative medicine, where the transient activity of cells is permanently captured to direct tissue repair.

Effective management of plant pathogenic bacteria faces major challenges, including rapidly evolving bacterial resistance, environmental risks associated with traditional copper-based agrochemicals, and the scarcity of new antibacterial targets. Recently, liquid–liquid phase separation (LLPS) has been extensively demonstrated to play crucial roles in microbial biology. However, the use of phase-separating proteins as targets for bactericide development remains unexplored. Herein, we report the first syringic acid derivative, C₃₁, that targets the alpha subunit of RNA polymerase (RpoA) in Xanthomonas oryzae pv. oryzae (Xoo). C₃₁ exhibits exceptional inhibitory activity against Xoo (EC₅₀ = 0.86 μg/ml, half maximal effective concentration) and maintains a low resistance risk throughout 12 successive passages. Pot experiments show that C₃₁ provides superior control efficacy (59.37%) against rice bacterial leaf blight compared with syringic acid (24.65%) and thiodiazole copper (42.41%), showing sustained efficacy and high crop safety. Mechanistic studies reveal that RpoA and σ⁷⁰ factor undergo LLPS to generate biomolecular condensates that function as “transcriptional hubs”, thereby regulating the expression efficiency of global virulence genes and consequently strengthening Xoo pathogenicity. C₃₁ binds to the C-terminal domain of RpoA and prevents LLPS initiation and subsequent condensate formation, resulting in antibacterial effects. This study establishes an LLPS-based strategy to control phytopathogenic bacteria.

Stretchable conductive hydrogel composites with infrared stealth and electromagnetic interference (EMI) shielding are in high demand for aerospace, military, and soft robotics. However, realizing stable and efficient performance with low conductive filler content under harsh conditions remains a substantial challenge. Herein, a flexible multifunctional double network hydrogels with high performance and environmental stability was constructed via transition metal carbide/nitride (MXene)/(NH₄)₂SO₄-treated strategy-assisted ultrasonic dispersion and thermal polymerization method. The synergistic effect of MXene and (NH₄)₂SO₄ within the hydrogel system led to a 3-fold enhancement in mechanical properties, 20-dB improvement in EMI shielding effectiveness, and 40% enhancement in the gauge factor with only 0.12 wt % conductive filler. Benefiting from its high conductivity, efficient thermal insulation, and composite network structure, the double network hydrogels maintain stable EMI shielding and infrared stealth performance under various harsh conditions including repeated stretching, prolonged water evaporation, low-temperature freezing, high-temperature heating, alcohol lamp flame exposure, and high-strain stretching. These findings demonstrate that the hydrogels combine ultra-low filler efficiency, environmental robustness, and multifunctional adaptability, making it a promising candidate for next-generation aerospace, military, and wearable electronic applications.

Facing challenges such as limited annotated data and insufficient model generalization in medical deep learning, foundation models (FMs) are reshaping the paradigm of medical image interpretation through large-scale pretraining and efficient fine-tuning. Unlike traditional models focused on single modality and task, FMs enable multi-modal representation and task-agnostic transfer, adapting to various downstream applications without extensive annotation or retraining. This paper systematically reviews the research progress on medical FMs, focusing on medical tasks, datasets, and evaluation metrics. It covers key interpretation tasks such as classification, segmentation, generation, and prognosis prediction. At the data level, it integrates multi-source data including 2-dimensional (2D)/3D medical imaging, vision-language data, electronic health records (EHRs), physiological signals, and bioinformatics data, and summarizes the evaluation metrics for each task. On this basis, the paper categorizes and analyzes mainstream medical FMs, including pretrained models, vision FMs, vision-language FMs, and extended multi-modal FMs, providing a systematic comparison of their performance and characteristics. Furthermore, we innovatively proposes the IPIU medical FM platform, which integrates large-scale medical data, universal vision models, medical vision-language models, and medical large language models, and verifies its effectiveness in typical clinical tasks. In addition, this work is the first to systematically analyze the key challenges and emerging trends of medical FMs across 12 critical dimensions, including data, modeling, security, and computational resources, filling the gaps in the existing reviews in systematic sorting and forward-looking analysis. Our aim is to provide theoretical support and practical reference for the sustainable development of medical FMs. Related resources and literature lists will be open sourced on https://github.com/JYAOii/Foundation-Models-meet-Medical-Image-Interpretation.

Intervertebral discs have long been considered to lack neural innervation. However, recent studies have revealed that intervertebral disc degeneration is accompanied by marked pathological nerve invasion. In addition, the transmission mechanism of degeneration and related pain is exacerbated through the neural intervertebral disc microenvironment interaction network. Despite advances in this field, comprehensive reviews remain limited, and systematic analyses are lacking. In this review, we aimed to systematically analyze the potential application of “neural intervertebral disc microenvironment interaction” in the repair of intervertebral disc degeneration. First, in this article, we discussed the neural innervation and functional characteristics of healthy intervertebral discs, elaborated on the mechanism of abnormal nerve growth in the microenvironment of degenerated intervertebral discs, and explained how nerve invasion exacerbates intervertebral disc degeneration and its clinical symptoms by activating pain transmission pathways. Subsequently, we reviewed bioengineering strategies that provided new pathways for the innovative treatment of intervertebral disc degeneration through the synergistic effects of neural regulation and microenvironment interactions. Finally, we explored application prospects of neural-regulated biomaterials in precision medicine, clinical translation, and interdisciplinary fusion, providing a theoretical basis and technical guidance for neural-based intervertebral disc regeneration therapy.