The nervous system has emerged as a critical regulator of tumor biology. Over the past 2 decades, accumulating evidence has given rise to the rapidly expanding field of cancer neuroscience, revealing that neural circuits actively shape tumor initiation, progression, metastasis, prognosis, and therapeutic response. While the nervous system comprises both central and peripheral components, increasing attention has focused on the peripheral nervous system (PNS) as a key mediator of tumor–host interactions within the tumor microenvironment (TME). Autonomic (sympathetic, parasympathetic, and enteric) and sensory neural pathways interact dynamically with tumor cells, immune cells, glial cells, and other stromal components, influencing tumor growth, invasion, metastasis, and immune regulation through diverse cellular and molecular mechanisms. In addition, environmental and patient pathophysiological factors—including environmental stress, psychological states, pain, microbiota, aging, metabolic status, and lifestyle behaviors—can further modulate nerve–cancer interactions and reshape the tumor ecosystem. In this review, we systematically organize PNS–cancer interactions within the TME across 3 integrative dimensions: pathological phenotypes, cellular components, and modes of communication, thereby providing a conceptual framework for understanding the mechanistic landscape of cancer neuroscience. This structured perspective highlights the diverse modalities of nerve–tumor communication, identifies key modulatory factors influencing these interactions, and discusses emerging therapeutic strategies targeting nerve–cancer signaling.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of childbearing age. Infertility caused by ovulatory disorders and low follicle quality is an urgent problem. Abnormal fatty acid oxidation (FAO) contributes critically to the etiology and progression in PCOS. However, the potential mechanism by which FAO affects follicular development in PCOS patients is unclear. Here, we demonstrate that increased expression of tripartite motif-containing protein 21 (TRIM21) (an E3 ubiquitin ligase) in the prenatal anti-Müllerian hormone PCOS mouse model leads to abnormal FAO in ovarian granulosa cells. Functionally, knocking down TRIM21 increased mitochondrial membrane potential homeostasis and improved fatty acid-dependent aerobic respiration and oxidative phosphorylation functions. TRIM21 regulated the ubiquitination and degradation of carnitine palmitoyltransferase 1A (CPT1A), a key enzyme for FAO, at the K161 site. TRIM21 is regulated by the E2 ubiquitin ligase ubiquitin conjugating enzyme E2 M (UBE2M), which enhances its protein expression and ubiquitination by TRIM21 neddylation. MLN4924 (a neddylation inhibitor) reversed the ubiquitination degradation of CPT1A by inhibiting TRIM21 neddylation. The phenotype of PCOS mice treated with MLN4924 was alleviated, and the maturation of oocytes and embryonic development improved. Together, these findings indicate that TRIM21-CPT1A plays an indispensable role in FAO of granulosa cells, and inhibiting TRIM21 neddylation may be a therapeutic strategy to improve abnormal follicular development in PCOS.

Traditional Chinese medicine (TCM), rooted in holistic philosophy, features a “multicomponent, multitarget, multipathway” therapeutic model that has long posed challenges for modern scientific interpretation due to its inherent complexity. Studies elucidating its biological mechanisms have historically relied on correlation-based analytical paradigms. Although artificial intelligence (AI) has been increasingly introduced into TCM research, most current applications remain confined to disease classification, outcome prediction, or herb–target association mining, with limited capacity to reconstruct the underlying biological logic of Zheng (TCM Syndrome) differentiation and formula compatibility. This review systematically elaborates on how network pharmacology serves as a foundational framework, constructing “herb–compound–target–disease” networks that align with TCM’s holistic nature, while AI addresses network pharmacology’s limitations—machine learning streamlines active component screening and ADME/T (absorption, distribution, metabolism, excretion, and toxicity) property prediction, and deep learning decodes spectroscopic data, complex biological interaction networks, and formula synergies. The integrated “computational prediction-experimental validation” workflow, validated across oncology, metabolic diseases, and infectious diseases, has become the gold standard for mechanistic research. Additionally, AI revolutionizes TCM quality control by linking chemical signatures to stable efficacy, integrates multiomics data to construct holistic regulatory networks, and enables translational progress through precision patient stratification, real-world evidence integration, and TCM knowledge graphs that structure fragmented knowledge. With the advancement of technology, generative AI for drug design, large language models for mining ancient texts, and multimodal “life models” promise to deepen integration. Ultimately, AI transcends being a mere tool, translating TCM’s holistic philosophy into modern scientific language, advancing its modernization and internationalization, and offering insights for multitarget drug development in global healthcare.

Expanding near-field regions in high-frequency 6G systems necessitates precise spatial-field control, yet narrow beamwidths and 3-dimensional tracking complexities create severe alignment hurdles. Here, we present an eye-tracking-driven programmable metasurface that bridges human visual intent with real-time electromagnetic responses via gaze-contingent beam steering. The system integrates a polarization-agile metasurface featuring independent 1-bit phase control for both copolarized and cross-polarized reflections. By engineering a 90° phase offset between these channels, the eye-tracking-driven programmable metasurface enables high-gain beam focusing and efficient linear-to-circular polarization conversion. Experimental results confirm that the system dynamically maps 3-dimensional gaze coordinates to metasurface coding patterns with millisecond-level responsiveness, facilitating robust near-field focusing and far-field scanning. This work establishes a “service-follows-vision” communication scenarios for intelligent wireless systems, offering distinct advantages in signal enhancement and interference mitigation.

The global pulp industry discards over 50 million tons of lignin annually, with conventional valorization strategies hindered by performance and cost barriers. We report an ion-exchange, self-catalytic strategy to upcycle the industrial lignosulfonate into high-performance bio-based adhesives. The facile ion-exchange process transforms sodium lignosulfonate into lignosulfonic acid, which acts as not only a copolymer backbone of adhesive but also an intrinsic macromolecular catalyst, autonomously driving esterification reaction with citric acid and then wood polymers, eliminating the need of fossil-derived cross-linkers and energy-intensive pretreatments. This mechanism endows it performing excellent performance in bonding strength and boiling-water resistance. Crucially, the performance gains are coupled with important economic and environmental benefits; production costs are substantially lower than conventional petrochemical resins, and a life cycle assessment confirms markedly reduced environmental impacts alongside negligible formaldehyde emissions. This work successfully resolves the performance–sustainability–cost trade-off, establishing a waste-to-wealth pathway for circular manufacturing.

Mutations in a specific protein called calcium-activated nucleotidase 1 (Cant1) cause skeletal deformities, but the role of Cant1 in these deformities remains unclear. This study shows how Cant1 acts as a key regulator of bone and cartilage health. We found that Cant1 binds to and stabilizes a protein called Wnt/β-Catenin. Wnt/β-Catenin then enters the cell nucleus to activate specific genes. One of these genes, CHSY1, is turned on to produce building blocks such as collagen and sugars that form the extracellular matrix (ECM), which acts as the scaffolding of cartilage. When Cant1 and Wnt/β-Catenin expression are suppressed, there is a reduction in glycosaminoglycans (GAGs; mucopolysaccharides) and proteoglycans (like ACAN), which create a hydrated, gel-like matrix by binding with hyaluronan and link proteins to make cartilage resistant to compression. Additionally, there is a decrease in the α-1 chain of type II collagen (COL2α1), which forms the structural mesh or framework that gives tissue its tensile strength. In summary, we identified a conserved signaling pathway, the Cant1/β-Catenin/transcription factor 4 (TCF4)–CHSY1 axis, that regulates ECM homeostasis during skeletal development. Dysfunction of this pathway is a core cause of skeletal disorders. These findings not only provide mechanistic insights into human Cant1-related skeletal diseases but also highlight potential new targets for broad-spectrum therapies aimed at correcting deficiencies in ECM biosynthesis.

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide and are hallmarked by profound disturbances in energy metabolism and maladaptive tissue remodeling. Lactate, long dismissed as a metabolic waste product, is now recognized as a context-dependent central carbon source and signaling metabolite. A key recent advance is the discovery of lysine lactylation (Kla), an evolutionarily conserved posttranslational modification that couples lactate abundance to chromatin state and protein function. Here, we synthesize current knowledge on the biogenesis and enzymatic regulation of Kla, and delineate how lactate-driven histone and nonhistone lactylation remodel transcriptional and signaling networks controlling fibrosis, energy metabolism, immune and inflammatory responses, and angiogenesis. We then focus on emerging evidence that Kla is a nodal regulator across major cardiovascular pathologies—including atherosclerosis, myocardial infarction and ischemia/reperfusion injury, heart failure, valvular and arterial calcification, and pulmonary hypertension—where it can act as a context-dependent “accelerator” or “brake” of disease progression. Finally, we outline a translational framework that targets the lactate–lactylation axis at 3 levels: lactate transport, lactate production, and lactylation writers/erasers, highlighting opportunities and challenges for therapeutic intervention. Together, these insights position protein lactylation as a pivotal metabolic–epigenetic interface in the cardiovascular system and a promising entry point for precision therapies in CVDs.

Low-dimensional halides (LDHs) with self-trapped exciton (STE) emission are promising materials for scintillation applications. Nonetheless, for almost all LDHs, the measured scintillation yield is still far below theoretical value due to severe exciton–exciton/exciton–defect interaction under ionizing radiation, despite high photoluminescence quantum yield (PLQY). Here, we reported a substantial enhancement of scintillation yield in zero-dimensional (0D) Cs₃YCl₆ by structural modulation. By copper(I) alloying in Cs₃YCl₆, the delocalized excitons in [YCl₆]³⁻ octahedra convert to strongly localized excitons within [Cu₂(YCl₆)₃]⁷⁻ clusters in (Cs₈Cu)Y₃Cl₁₈, as confirmed by first-principles calculations. Temperature-dependent photoluminescence spectroscopy and kinetic results reveal a higher energy barrier for STE quenching in (Cs₈Cu)Y₃Cl₁₈ than in Cs₃YCl₆. Benefiting from the enhanced exciton confinement effect, (Cs₈Cu)Y₃Cl₁₈ exhibits a 460% enhancement in the STE-related scintillation yield. This work opens up a new strategy to enhance scintillation yield in LDHs under ionizing radiation excitation.

Ischemic stroke remains a major cause of mortality and long-term disability, with few effective neuroprotective treatments currently available. Ferroptosis, an iron-dependent form of regulated cell death marked by lipid peroxidation, is increasingly recognized as a driver of neuronal damage. However, the mitochondrial mechanisms linking ischemia to ferroptosis remain poorly defined. Here, we identify circMTCO2, a mitochondria-encoded circular RNA (circRNA), as a novel endogenous modulator of neuronal ferroptosis. circMTCO2 expression is dynamically down-regulated following cerebral ischemia/reperfusion in vitro and in vivo. Mechanistically, circMTCO2 interacts with adenine nucleotide translocase 1 (ANT1), a key regulator associated with the mitochondrial permeability transition pore (mPTP), thereby inhibiting mPTP opening and suppressing mitochondrial reactive oxygen species release. Disruption of the binding site abolishes circMTCO2–ANT1 interaction and eliminates the protective effects of circMTCO2. To restore and enhance this intrinsic defense mechanism, we developed a dual-targeting extracellular vesicle system (RVG-EV^mt-RNA) capable of delivering circMTCO2 specifically to neuronal mitochondria. Systemic administration of RVG-EV^mt-RNA decreased infarct volume, attenuated ferroptosis-associated injury, and improved neurological function in a mouse model of ischemic stroke, without inducing systemic toxicity. These findings establish circMTCO2 as a previously unrecognized mitochondrial circRNA that regulates ferroptosis by modulating mPTP activity and provide a proof of concept that organ-to-organelle circRNA delivery can be leveraged as a precision neuroprotective strategy for ischemic stroke.

This study aimed to explore the impact of treadmill running at different intensities and durations on hippocampal neurogenesis and cognitive function in mice, with a focus on the interorgan communication mechanism mediated by the extracellular vesicle (EV) cargo cathepsin B (CTSB) via the muscle–brain axis. We define the intensity of treadmill running mice based on measurements of maximum oxygen uptake. The findings from treadmill running studies at varying intensities and durations in C57BL/6J mice revealed that treadmill running improved hippocampal neurogenesis and memory in wild-type (WT) mice in an intensity-dependent manner. Omics and UK Biobank cohort analyses identified muscle-derived CTSB as a key exercise-responsive factor, whose expression may be regulated by O-linked N-acetylglucosaminylation. Overexpression of O-linked N-acetylglucosaminyltransferase (OGT) prolonged the half-life of CTSB and inhibited its ubiquitination-mediated degradation, whereas inhibition of OGT accelerated its degradation. Mechanistically, treadmill running may promote the secretion of muscle-derived CTSB into the bloodstream via EVs and its subsequent delivery to the hippocampus through activation of the OGT/CTSB signaling. In WT mice, knockdown of muscular CTSB partially reversed the treadmill-running-induced improvements in hippocampal neurogenesis and memory, while overexpression of muscular OGT further enhanced the release of muscle-derived CTSB. Moreover, in amyloid precursor protein/presenilin 1 mice, treadmill running potentially improved cognitive function, reduced amyloid-β deposition, neurofibrillary degeneration, and neuroinflammation by up-regulating muscular CTSB. Knockdown of muscular CTSB attenuated the benefits of treadmill running, while overexpression of CTSB further enhanced the exercise-induced effects. Overall, this study demonstrates that treadmill running may activate the muscular OGT/CTSB signaling axis, promoting the secretion of the myokine CTSB protein into the circulatory system via EVs and its transport to the brain, thereby improving hippocampal neurogenesis and cognitive function in both WT and amyloid precursor protein/presenilin 1 mice. These findings highlight the role of myokine CTSB as a pivotal modulator in muscle–brain axis communication mechanism, with its stability regulated by O-linked N-acetylglucosaminylation.