In adult mammals, programmed cell death (PCD) facilitates tissue remodeling and regeneration in spinal cord injury (SCI), but excessive activation impedes SCI repair. However, no comprehensive pan-PCD atlas exists that encompasses diverse cell death patterns to fully elucidate PCD in adult SCI and develop strategies for modulating the excessive PCD response. Here, we identified neonatal mice with balanced PCD post-SCI as an ideal model for adult SCI. Accordingly, we developed “Thanatoset”, an SCI-specific gene panel to map tissue and cellular pan-PCD dynamics across neonatal and adult mice. Microglia were identified as pivotal mediators of pan-PCD, showing greater vulnerability in adults than in neonates. According to computational drug screening, withaferin A can revert microglial pan-PCD in adults to a neonatal-like regenerative state. Histological, functional, and molecular analyses corroborated that withaferin A enhances SCI recovery in adults by modulating microglial pan-PCD. These findings highlight the therapeutic potential of the pan-PCD framework for developing strategies to restore regeneration and improve SCI outcomes.

Temperature measurement in confined environments has long been a substantial challenge. Due to poor accessibility to constrained space, and low visibility, conventional thermometry and existing nanoscale thermometers struggle to achieve efficient and accurate temperature detection. As an emerging technology, microrobots offer great potential for temperature sensing in such challenging conditions. Here, we propose a temperature-responsive microrobot (TRM) that integrates artificial neural networks into microscale thermal sensing, enabling quantitative temperature measurement in complex and constrained environments. The TRM undergoes irreversible color changes in a high-temperature range of 160 to 240 °C. It features a Janus structure composed of a Cu(NH₃)₄SO₄-based thermochromic material and a nickel-coated magnetic actuation layer, allowing reliable operation in nontransparent and geometrically confined environments such as porous geological structures and constrained microspaces. The thermochromic mechanism and motion dynamics of the TRM under elevated temperatures were systematically investigated. The microrobot exhibits distinct chromatic responses at different temperatures. Based on the correlation between chromaticity and temperature, a multilayer perceptron neural network was developed. By inputting the observed color features into the trained model, the surrounding temperature can be quantitatively determined. Experimental results in a simulated porous microchannel model confirmed the feasibility and effectiveness of the TRM for localized high-temperature detection. This work provides a new solution for temperature sensing in restricted environments and lays a solid foundation for the application of microrobots in industrial high-temperature monitoring, highlighting their potential for real-world deployment in complex conditions.

Safe and effective veterinary vaccines prevent infectious diseases and reduce morbidity. In this field, nanovaccines based on nanomaterials are emerging, showing great potential as innovative alternatives to conventional vaccines. This paper highlights the advantages, disadvantages, and mechanisms of nanomaterials, including biomimetic, polymeric, lipid nanoparticles, self-assembling proteins, and other materials used in veterinary vaccine development. We also describe the progress of their research in developing vaccines against common and serious veterinary infectious diseases, such as foot-and-mouth illness, porcine epidemic diarrhea, pseudorabies, and bordetellosis. We aim to provide a scientific basis and practical guidance for the research and development of new veterinary vaccines, thereby contributing to scientific and technological progress in the field of veterinary medicine and the protection of animal health.

Polymetallic nanomaterials have important development potential by integrating the properties and advantages of their components. However, their preparation paradigm urgently needs to be updated to make full use of their characteristics to realize their multifaceted applications. In this study, multifunctional trimetallic gold–silver–chromium nanocomposites (Au–Ag–Cr NCs) were successfully synthesized, and their polymetallic plasmonic absorption properties were used in a variety of applications, from multimode and multianalyte sensing, advanced arithmetic, and reversible logic to long-text information protection. Au–Ag–Cr NCs with Au or Ag nanoparticles anchored on Cr nanobelts were synthesized using Au–Cr nanoseeds, Ag⁺, ascorbic acid as the reductant, and sodium dodecylbenzenesulfonate as the stabilizer. The resulting Au–Ag–Cr NCs exhibited multichannel sensing ability for 2 analytes (Hg²⁺ and hypochlorite), with remarkably improved selectivity and sensitivity when analyzing combined channels. Multiresponsiveness of Au–Ag–Cr NCs to diverse substance combinations underpins input–output mapping relationships, enabling advanced molecular logic computations (such as arithmetic and reversible logic). By digitizing its intrinsic sensing and response mechanisms, advanced molecular information protection (including encoding, encryption, and information concealment) for extended text were successfully implemented. This work not only offers novel insights into the design and multifunctionality of multicomponent nanocomposites but also paves the way for a new paradigm in molecular information technology that integrates sensing, logic processing, and information security.

A promising therapeutic approach in oncology involves immune checkpoint blockade (ICB), which stimulates anti-tumor immune responses. Nevertheless, the effectiveness of this treatment in clinical settings remains limited, underscoring the need for complementary strategies. Recent studies highlight the potential of type I interferon (IFN-I) inducers to reprogram the tumor microenvironment and enhance ICB outcomes. Herein, through high-content screening of a natural compound library, we identified daurisoline (DS), a bioactive alkaloid extracted from the Chinese herbal medicine Rhizoma Menispermi, as a potent inducer of IFN-I signaling. Our findings indicated that DS up-regulates interferon responses and pro-inflammatory cytokine expression in a TANK-binding kinase 1 (TBK1)-dependent manner. In vivo, DS exhibited marked tumor growth inhibition by activating dendritic cells, macrophages, and CD8⁺ T cells, thereby enhancing anti-tumor immunity. Utilizing the LiP-SMap approach, we identified low-density lipoprotein receptor-related protein 1 (LRP1) as the direct target of DS. Mechanistically, the binding of DS to LRP1 substantially disrupted lysosomal function, which subsequently triggered 5′-azacytidine-induced protein 2-mediated TBK1 activation and IFN-I production. Furthermore, DS demonstrated synergistic effects with anti-programmed death 1 therapy and a stimulator of interferon genes agonist by remodeling the immunosuppressive microenvironment. Collectively, our findings establish LRP1 as a novel therapeutic target for cancer immunotherapy and highlight DS-driven immune reprogramming as a translatable strategy to potentiate ICB efficacy.

Recent studies have revealed that polyclonality—where multiple distinct subclones cooperate during early tumor development—is a critical feature of tumor evolution, as demonstrated by Sadien et al. and Lu et al. in Nature (October 2024). These findings show that early polyclonal interactions can overcome fitness barriers, ultimately transitioning to monoclonality as dominant clones emerge. Understanding and targeting these interclonal dynamics offers new therapeutic opportunities. In this perspective, we outline how computational modeling and artificial intelligence (AI) tools can provide deeper insights into tumor polyclonality and identify actionable therapeutic strategies. By applying ligand–receptor interaction analysis, clonal trajectory reconstruction, network and pathway modeling, and spatial analysis, researchers can prioritize communication hubs, evolutionary bottlenecks, and microenvironmental niches that sustain tumor progression. These approaches, when integrated with experimental validation, offer a translational pathway from foundational discoveries to personalized cancer treatments aimed at disrupting cooperative subclonal ecosystems and preventing malignant progression.We commend the recent Nature publications, “Polyclonality overcomes fitness barriers in Apc-driven tumorigenesis” by Sadien et al. [1] and “Polyclonal-to-monoclonal transition in colorectal precancerous evolution” by Lu et al. [2], both featured on 2024 October 30. These groundbreaking studies employed distinct lineage tracing methods to investigate the origins and evolutionary dynamics of colorectal and intestinal tumorigenesis. Despite their different approaches, both studies reached convergent conclusions: Polyclonality plays a pivotal role in the early stages of tumor development, providing critical insights into how diverse cellular populations collaborate to overcome fitness barriers and drive tumor progression.

G protein-coupled receptor 120 (GPR120) plays a pivotal role in regulating lactation, yet its underlying mechanisms remain unclear. In mouse models, GPR120 expression in the mammary gland increases markedly during lactation. Under inflammatory conditions, both n-3 polyunsaturated fatty acids (n-3 PUFAs) and GPR120 agonists markedly reduced inflammatory responses and enhanced lipogenesis and migration in HC11 mammary epithelial cells. These benefits were also observed under non-inflammatory conditions and were diminished when GPR120 was knocked down. Furthermore, the regulatory function of GPR120 under non-inflammatory conditions in in vivo and in vitro models is explored. We discovered that the GPR120–Gα_s–cyclic adenosine monophosphate (cAMP)–exchange protein directly activated by cAMP (EPAC) signaling axis is critical for lipogenesis and migration in mammary epithelial cells. Through transcriptomic analyses, the EPAC–CCCTC-binding factor (CTCF)–peroxisome proliferator-activated receptor γ (PPARγ)/CCAAT enhancer-binding protein α (C/EBPα) pathway was identified to primarily govern lipogenesis, while the EPAC–C-X-C motif chemokine ligand 14 (CXCL14)/C-X-C chemokine receptor type 4 (CXCR4) autocrine loop regulates migration of mammary epithelial cells. Overall, these findings suggest that GPR120, which can be activated by n-3 PUFAs, improves mammary gland performance by alleviating inflammation and directly modulating mammary lipogenesis and mammary gland development through the CTCF–PPARγ/C/EBPα and CXCL14–CXCR4 pathways. Thus, GPR120 and its downstream signaling targets may represent an important clinical target for enhancing maternal lactation.

Neurogenic bone regeneration is essential for the effective restoration of bone tissue functionality, with exosomes derived from Schwann cells regionalized in bone injury tissue playing a crucial role in this process. However, precisely regulating the secretion of Schwann cells localized in bone injury tissue to enhance neurogenic bone regeneration remains a considerable challenge. In this study, an injectable, ultrasound-responsive piezoelectric conductive short fiber network (US@SFG) was innovatively developed using uniform short fiber homogenization techniques and multifunctional chemical modifications, enabling precise acoustic–electrical conversion that regionally activated the secretion of miRNAs from Schwann cell-derived exosomes, thereby promoting neurogenic bone regeneration. The incorporation of the piezoelectric polymer glycine imparts superior piezoelectric characteristics to the fiber network, while the conjugated π-electron motion within the conductive graphene network enhances internal electron transfer efficiency, thereby facilitating electrical conductivity. Compared with traditional piezoelectric fiber networks, acousto-electric conversion fiber networks demonstrated a 1.7-fold increase in piezoelectric performance and a 30-fold increase in conductivity, facilitating precise electrochemical regulation under ultrasound stimulation. In vitro studies revealed that acousto-electric conversion fiber networks precisely modulate the secretion of localized Schwann cell exosomal miRNAs (miRNA-494-3p, miRNA-381-3p, and miRNA-369-3p), activating the phosphatidylinositol 3-kinase/protein kinase B and Wnt signaling pathways in bone marrow mesenchymal stem cells, and thereby promoting osteogenic differentiation. Furthermore, in vivo experiments confirmed that under ultrasound imaging guidance, acousto–electric conversion fiber networks could be directed precisely to bone defects, where precise control of ultrasound parameters facilitated acoustic–electrical conversion and electrical signal modulation, markedly promoting the formation of neural networks and bone tissue regeneration. In this study, for the first time, an injectable acousto-electric conversion fiber network was constructed to activate Schwann cell exosomes in bone injury tissue regionally, providing a novel therapeutic strategy and potential molecular targets for neurogenic bone regeneration.

Recently developed base editing (BE), prime editing (PE), and click editing (CE) technologies enable precise and efficient genome editing with minimal risk of double-strand breaks and associated toxicity. However, their effectiveness in correcting real disease-causing mutations has not been systematically compared. Here, we aim to evaluate the potential of BE, PE, and CE technologies in rescuing the retinal degeneration-causing Pde6b (c.1976T>C, p.L659P) mutation. This site is prone to bystander effects, making it an ideal model for comparing the editing outcomes of these 3 novel technologies, particularly their editing precision. We optimized BE, PE, and CE systems in vitro using Pde6b-L659P cell models and compared their editing via deep sequencing. BE and PE had similar efficiency, but PE was the most precise, minimizing bystander edits. CE had lower efficiency and higher indel rates, needing further optimization. Using the optimal PE system for in vivo electroporation in Pde6b-L659P mice, we achieved 12.4% targeted repair with high precision, partially rescuing retinal degeneration. This study demonstrates proof of concept for the precise correction of the Pde6b-L659P mutation causing retinal degeneration using BE, PE, and CE tools. The findings offer valuable insights into the future optimization of precision gene editing techniques and their potential translational applications.

We aimed to develop a voiding cystourethrography (VCUG) diagnostic artificial intelligence model (VCUG-DAM), which relies on a novel architecture to automatically segment and diagnose the bladder, urethra, and ureters using a single VCUG image, while dynamically assessing the relative importance of each image. A total of 7,899 VCUG images from 1,660 patients across 15 Chinese hospitals were collected between 2021 and 2023. In stage 1, we assessed the performances of the VCUG-DAM model. The patient-level area under the curve (AUC) of VCUG-DAM was 0.8772, 0.7752, 0.9443, and 0.9342 for bladder, urethral, left, and right vesicoureteral reflux (VUR), respectively. In stage 2, we explored whether the VCUG-DAM model could improve the diagnostic ability of clinicians. VCUG-DAM improved the clinician’s diagnostic performance, with mean AUCs increasing from 0.8185 to 0.9456 for the bladder, 0.6507 to 0.7943 for the urethra, 0.6288 to 0.9641 for the left VUR, and 0.7305 to 0.9506 for the right VUR (all P < 0.0001). In stage 3, the consistency of the VCUG-DAM for VUR grading was validated. VCUG-DAM improved inter-clinician agreement for VUR grading. The fully automated VCUG-DAM demonstrated high accuracy, reliability, and robustness in multitask diagnoses of urinary tract abnormalities across multiple VCUG images, while improving the diagnostic ability of clinicians as an auxiliary tool.