Calcium oxalate (CaOx) kidney stones are common and recur frequently, yet effective pharmacological prevention is limited. Randall’s plaques (RPs), calcium deposits on renal papillae, act as anchoring sites for CaOx crystal growth, but the cellular origin and immunoregulatory mechanism underlying early calcium deposition remain unclear. Here, we found that early calcium deposition was partially localized to the renal interstitium surrounding aquaporin 2 (AQP2)-labeled collecting duct cells with apoptotic phenotype, and inhibiting high calcium-induced apoptosis of AQP2⁺ cells markedly reduced cell layer calcium deposition. Given the regulatory role of macrophages in renal stone formation, we revealed that M2 macrophages protected AQP2⁺ cells by delivering TRAF2 via exosomes. Mechanistically, exosomal TRAF2 interacted with intracellular TRAF1 to form a stable complex, which mutually inhibited their ubiquitin-mediated degradation by excluding the shared E3 ubiquitin ligase CBLC. This complex activated downstream nuclear factor κB1 (NF-κB1) and NF-κB2 signaling. NF-κB1 enhanced TRAF1 transcription, whereas NF-κB2 increased BCL2 expression while suppressing BAX and cleaved-PARP1, thereby limiting apoptosis and subsequent calcium deposition. Based on these findings, we developed M2 exosome-loaded, AQP2⁺ cell membrane-coated poly (lactic-co-glycolic acid) nanoparticles (Exo@A-P) for renal-targeted delivery. Exo@A-P treatment reduced collecting duct apoptosis and calcium deposition in hypercalciuria and renal calcified mice (Umod^−/−) without detectable toxicity, potentially supporting a targeted nanotherapeutic strategy to prevent early RP formation by utilizing TRAF2-rich exosome from M2 macrophages.

Lignocellulosic structural boards are often regarded as sustainable materials, yet most still depend on fossil-derived thermoset resins that generate volatile emissions, form weak and irreversible bonded interfaces, and complicate circular end-of-life management. Here, we introduce deep eutectic solvent (DES) ignition-triggered interfacial fusion, a closed-loop strategy that replaces external adhesives through a 2-stage sequence. In the ignition stage, a minimal amount of recyclable DES selectively activates lignocellulosic cell walls and mobilizes native lignin/hemicellulose toward particle contact zones, creating an interface-ready state. In the subsequent fusion stage, hot pressing reconstructs and locks these redistributed components into a continuous, lignin-rich bonding interphase, yielding an adhesive-free BioFuse-Board. The resulting BioFuse-Board delivers an internal bond strength up to 2.53 MPa (vs. the 0.45 MPa commercial requirement) and a 24-h thickness swelling of 10.05%. Mechanistically, ignition promotes β–O–4 bond cleavage, lowers lignin molecular weight, and enriches phenolic and carboxyl sites, whereas fusion promotes condensation while depleting reactive sites, consistent with a locked interfacial network involving oxygen-bridged environments, lignin-rich C–C connectivity, and strengthened hydrogen bonding with cellulose. Beyond performance, the same ignition–fusion architecture embeds circularity via reagent reuse, stream valorization into wood adhesives, and mechanical remanufacturing of end-of-life boards. Technoeconomic and cradle-to-gate life-cycle analyses further demonstrate that DES ignition-triggered interfacial fusion is economically viable and substantially reduces environmental impacts. Collectively, this strategy provides a generalizable route to circular manufacturing of structural-grade, adhesive-free lignocellulosic structural materials.

Neuropathic pain, resulting from somatosensory nervous system damage or disease, is a debilitating condition marked by spontaneous pain, hypersensitivity, and sensory abnormalities. Neuropathic pain involves spinal neuronal hyperexcitability, yet its molecular basis remains poorly defined. We utilized a comprehensive multi-omics approach, incorporating proteomics, phosphoproteomics, concatenated tandem array of consensus transcription response elements, and both single-cell and spatial transcriptomics, to chart time-resolved adaptations in the L4 to L6 spinal cord of a chronic constriction injury rat model. Multi-omics revealed remodeling of glutamatergic synapse pathways and identified non-POU (Pit-Oct-Unc) domain-containing octamer binding (Nono) as a down-regulated transcription factor associated with reduced potassium voltage-gated channel subfamily Q member 2 (Kcnq2) expression. Nono and Kcnq2 were co-enriched in neurexin 3-positive and peripherin-positive spinal neurons. Restoring Nono expression up-regulated Kcnq2, enhanced K⁺ outward currents (an effect largely abolished by the Kcnq2/3 blocker XE991), and alleviated pain hypersensitivity. Mechanistically, Nono was enriched at a conserved Kcnq2 promoter region in vivo and enhanced Kcnq2 promoter activity in reporter assays. Together, these findings established a Nono–Kcnq2 transcriptional axis that constrained spinal excitability and suggested a therapeutic entry point for neuropathic pain.

Nanozymes are emerging as versatile antimicrobial agents to tackle drug-resistant infections and biofilm-associated persistence. In this review, we present an integrated framework that links natural enzyme-mediated host defense to the rational development of antimicrobial nanozymes, and summarize recent advances through a mechanism-materials-engineering-application pipeline. We first summarize representative bactericidal principles of natural enzymes to highlight bioinspired catalytic motifs relevant to nanozyme design. We then classify antibacterial nanozymes by catalytic reaction types, including oxidoreductase- and hydrolase-like activities, and by material platforms, highlighting structure–activity relationships that govern catalytic behavior and antimicrobial performance. Building on these mechanistic and structural insights, we summarize engineering-enhanced bactericidal modalities, including photothermal and photodynamic assistance, metal ion release, immune modulation, cascade catalysis, microenvironment-responsive regulation, and targeting, that help overcome constraints imposed by infectious microenvironments, such as hypoxia, limited hydrogen peroxide availability, elevated antioxidant levels, and biofilm barriers. Finally, we translate these principles into application-oriented guidance across interfaces ranging from abiotic surface protection, including antifouling and device coatings, to superficial and deep-seated infections, and we briefly discuss emerging nanozyme strategies for antifungal and antiviral interventions. Throughout, we emphasize translational considerations, such as activity benchmarking, biosafety evaluation, and scalable manufacturing, to support the development of clinically relevant antimicrobial nanozymes.

Precision surgery in soft tissues is currently hindered by the lack of real-time, depth-resolved visualization. Conventional navigation relies on preoperative images that fail to account for intraoperative deformation, while existing intraoperative tools often lack intuitive spatial correspondence. Here, we propose Surgical Anatomical Structure Transparentization (SAST), an emerging framework anchored by second near-infrared fluorescence imaging. Unlike augmented reality, which merely displays static preoperative models, SAST represents a sensing paradigm that utilizes direct photon scattering suppression to visualize deep anatomy in situ. We delineate the critical technological trajectory—from monocular 2-dimensional fluorescence to 3-dimensional volumetric perception via stereoscopic vision and computational imaging—required to bridge the dimensional gap. By transforming navigation from “referencing a map” to “seeing through tissue”, SAST promises to redefine surgical perception through continuous, real-time anatomical transparency.

Intrahepatic metastasis in multifocal hepatocellular carcinoma is associated with poor prognosis and therapeutic resistance, yet the immune mechanisms driving disease progression remain unclear. Here, we analyzed genetic and immune differences between primary tumors and intrahepatic metastatic lesions using sequencing approaches and spatial validation methods. We found that metastatic lesions shared key genomic features with primary tumors but exhibited a distinct immunosuppressive environment enriched in myeloid and T cell populations. In particular, a subset of macrophages expressing glycoprotein nonmetastatic melanoma protein B (GPNMB) was consistently enriched in metastatic niches across multiple independent cohorts. These macrophages were spatially colocalized with CD8⁺ T cells exhibiting features of terminal exhaustion. Mechanistically, integrated multiomics and functional analyses revealed that GPNMB overexpression triggers lipid metabolic rewiring via the phosphatidylinositol 3-kinase/AKT-cyclooxygenase-2 cascade, leading to elevated prostaglandin E2 secretion, which directly suppresses CD8⁺ T cell cytotoxicity. Specific silencing of this subset using a dual-targeted, lipid-polymer nanoparticle (APL_siGpnmb) effectively reversed T cell exhaustion, inhibited metastasis, and synergized with anti-programmed death 1 immunotherapy in mouse models without inducing systemic toxicity. These findings identify GPNMB-positive macrophages as key metabolic and immune regulatory hubs, suggesting that targeting the GPNMB–prostaglandin E2 axis provides a promising precision therapeutic strategy for intrahepatic metastasis in multifocal hepatocellular carcinoma.

Epidemiological and clinical evidence increasingly highlights a close association between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). The transition from nonalcoholic fatty liver disease (NAFLD) to MASLD represents a conceptual shift toward a metabolism-centered framework with important implications for cardiovascular risk assessment. As the global burden of both conditions continues to rise, clarifying their bidirectional relationship has become increasingly important. This review summarizes current epidemiological and clinical evidence linking MASLD to adverse cardiovascular outcomes and discusses the potential value of liver-specific markers, particularly fibrosis indices, in cardiovascular risk stratification beyond traditional risk factors. Mechanistically, we examine shared upstream metabolic mechanisms linking MASLD and CVD, as well as the bidirectional liver–heart axis involving liver-to-heart effects and cardiovascular feedback to the liver. We further summarize key molecular mediators involved in these processes and their potential relevance to both cardiovascular and hepatic injury. Finally, we discuss the clinical and therapeutic implications of this integrated framework, including the potential to achieve dual hepatic and cardiovascular benefit. A clearer understanding of the MASLD–CVD interplay may support earlier detection, more precise risk stratification, and multidisciplinary management.

Health research is shifting from isolated risk snapshots toward longitudinal, multimodal representations of disease. In type 2 diabetes, patients with comparable glycemic control may follow sharply divergent renal, cardiovascular, hepatic, and neurocognitive courses—heterogeneity that single-endpoint, single-window risk models cannot resolve. Here, we propose the Health Galaxy, a state-space framework that represents each individual by multi-organ position and direction of motion over time, integrating organ-aging clocks, cross-organ coupling, and trajectory-aware generative modeling. We operationalize this framework through 3 falsifiable structural units—clusters, channels, and hubs—that can be tested for reproducibility across cohorts and modalities. The framework reframes intervention as trajectory rerouting rather than marker reduction, with type 2 diabetes as a tractable first test case.

Cigarette butts are common yet overlooked pollutants in urban environments. How this anthropogenic niche shapes microbial life-history strategies and evolutionary mechanisms remains poorly understood, limiting assessments of microbial adaption and urban ecosystem health. However, systematic and multiscale evidence on the ecological effects of cigarette butts on microbial communities remains scarce. Here, we collected cigarette butts, litter, and soil samples from urban parks in 35 Chinese cities and integrated third-generation 16S ribosomal RNA sequencing, metagenomics, and transcriptomics to resolve microbial community composition, functional potential, and evolutionary patterns. The results revealed that microbial communities in cigarette butts were shaped by strong deterministic processes, showed low spatial heterogeneity, and were taxonomically distinct from those in natural niche (i.e., litter) and surrounding soil, with notable enrichment of Proteobacteria, particularly the family Pseudomonadaceae. Functional trait analysis showed that butt-associated communities favored environmental responsiveness and fast-growth strategies, contrasting with metabolism- and resource acquisition-oriented strategies in the litter. Population genomic analysis suggested stronger positive selection in cigarette butt-associated Pseudomonadaceae, while the pure culture experiment provided strain-level evidence that cigarette butt exposure induced the up-regulation of key functional genes in Pseudomonas aeruginosa PAO1. This study demonstrates that cigarette butts, as an emerging ecological niche, reshape microbial community assembly, life-history strategies, and adaptive evolution, offering new insights into microbe-driven evolution on artificial surfaces.