Lightweight structural materials that combine high strength, machinability, and sustainability are essential for next-generation construction. Wood, a renewable and low-carbon resource, offers excellent mechanical performance but remains limited by fastener stability and reliance on metals and adhesives. Here, we report a superstrong engineered wood produced through synergistic cell-wall engineering across cellular and molecular scales, enabling metal-free and adhesive-free cross-laminated timber. Pressure-controlled densification induces near-complete closure of open cells in natural beech wood, generating a dense, smooth architecture with a 3-dimensional mechanical interlocking network analogous to micro-mortise-and-tenon joints. The resulting material preserves the intrinsic anisotropic architecture of wood while forming a 3-dimensional mechanical interlocking network resembling micro-mortise-and-tenon joints. Wooden structural material exhibits substantially improved dimensional stability and mechanical performance, including a density of 1.33 g cm⁻³, a flexural strength of 150.89 MPa, a compressive strength of 88.48 MPa, and an exceptional Janka hardness of 18.84 kN. Wood-derived nails fabricated from this material function comparably to steel fasteners, providing high strength-to-weight ratios while eliminating corrosion and adhesive contamination. This approach advances timber construction toward higher performance, reduced environmental impact, and improved sustainability, offering a scalable pathway for green building applications.

Milk is an essential nutritional source for human health, yet developing efficient and sustainable indoor dairy production systems to produce milk-associated components remains a major challenge. Here, we propose a biomimetic mammary gland-on-a-chip system that recapitulates both the structural features and lactation mechanism of the mammary gland for producing milk-associated bioactive components. The chip is designed with a medium channel providing circulation, an intermediate porous hydrogel layer for substance diffusion, and highly specialized microchambers for culturing mammary epithelial cells. The mammary gland-on-a-chip enables tight-junction formation and active secretion of milk bioactive components such as lactotransferrin and triglycerides. More importantly, by expanding the microchambers and parallelizing the chips, increased collection of partial milklike secretions containing selected bioactive components was achieved. Our work represents the successful development of a robust microphysiological system as a potential in vitro platform for mammary gland research and is promising in addressing future food and environmental crises.

Gastric cancer (GC) remains a lethal malignancy with limited therapeutic options and poor prognosis. In this study, we employed integrated RNA sequencing and ribosome nascent-chain complex sequencing analyses to identify a coding circular RNA (circRNA), circRAD23B, which is markedly up-regulated in GC tissues. Its expression correlates strongly with advanced tumor stage, lymph node metastasis, and reduced overall survival. We further demonstrate that the splicing factor U2AF65 facilitates circRAD23B biogenesis through direct binding to intron 1 of the RAD23B pre-mRNA. Functionally, circRAD23B encodes a novel 208-amino acid protein via an internal ribosome entry site-dependent mechanism. This protein promotes GC proliferation, invasion, and lung metastasis in vivo. Mechanistically, circRAD23B-208aa recruits the E2 ligase UBC9 to catalyze SUMOylation of PDIA5 at lysine 25, thereby attenuating its ubiquitination and enhancing protein stability. Stabilized PDIA5 facilitates ATF6 activation by promoting its proteolytic processing, nuclear translocation, and transcriptional induction of key unfolded protein response (UPR) effectors—TXNRD1 and HERPUD1—thereby alleviating endoplasmic reticulum stress and promoting tumor survival. Our findings reveal circRAD23B-208aa as the first circRNA-encoded activator of the UPR pathway via posttranslational regulation of PDIA5, highlighting the therapeutic potential of targeting the SUMOylation-dependent PDIA5/ATF6 axis in GC.

Natural biomaterials achieve exceptional mechanical performance through multi-level hierarchical architectures, yet replicating or surpassing such topological control and multiscale synergy in synthetic hydrogels remains challenging. A key obstacle is the often-overlooked macro–microscale competition mechanism, where macroscopic reinforcement can conflict with finer-scale energy-dissipation pathways. Here, we overcome this limitation by embedding a 3-dimensionally printed gradient-twisted plywood (GT) framework into a hierarchically anisotropic (HA) hydrogel matrix, creating a topologically controllable supra-biomimetic composite (GT-HA composite). A supra-biomimetic design strategy is employed to regulate the macro–microscale competition, wherein the GT framework is expressly designed to coordinate macroscale stress guidance and crack deflection with micrometer-, nanometer-, and molecular-scale dissipation pathways. This coordinated multiscale dissipation endows composites with superior impact resistance. The GT-HA composite attenuates up to 88% of impact force at a low velocity and achieves a compressive strength of 183.57 MPa at a large strain rate of around 4,000 s⁻¹ while maintaining long-term stability (<5% decay over 35 d). Notably, the fabrication process is compatible with integrated circuit/microelectromechanical system technologies, allowing wafer-level integration that effectively protects high-value devices such as processor dies and flexible circuits under high-speed impact. This work establishes a scalable strategy for designing ultra-impact-resistant materials by actively harnessing macro–micro competition, with promising applications in embodied intelligence, aerospace, and advanced electronics protection.

There is a lack of high-frequency electronics based on 2-dimensional p-type transitional metal dichalcogenides, which originates from channel defects during device fabrication and non-optimized metal–semiconductor–insulator interface. Direct metal deposition inevitably induces n-type dominant carrier transport, and high-k dielectric layers cause an elevated carrier concentration enhancing carrier–carrier scattering. Herein, taking tungsten diselenide (WSe₂) as an example, we employ a polyvinyl alcohol (PVA)-assisted transfer of electrodes to realize WSe₂ devices with a high carrier mobility and low hole concentration at the same time. This approach circumvents the interfacial defects and lattice distortions caused by atomic bombardment, cluster dynamics, and localized heating of the contact region during direct metal deposition. Compared to polymethyl methacrylate (PMMA) and other transfer media, the water-soluble PVA layer can be removed without organic solvents, leading to high-quality channel and ideal dielectric interface effectively, which suppress Coulomb impurity scattering and carrier–carrier scattering at low hole concentration (~3.5 × 10¹² cm⁻²). This enables a carrier mobility exceeding 140 cm² V⁻¹ s⁻¹ at room temperature, superior to other heavily doped counterparts. Radio-frequency switches fabricated by transferring a top electrode exhibit a cutoff frequency of 57.5 GHz with a low series resistance of 25 Ω. This realizes the path loss and signal integrity required by 6G communications, rendering WSe₂ a highly promising candidate for millimeter-wave applications.

The perithyroidal adipose tissue (PAT), given its direct anatomical proximity to the thyroid gland, has long been postulated as a modulator of the thyroid tumor microenvironment. However, its cellular composition, functional heterogeneity, and specific roles in thyroid cancer progression remain unknown. To address these knowledge gap, we performed single-nucleus RNA sequencing of PAT from patients with papillary thyroid carcinoma (PTC) and multinodular goiter (MNG), combined with machine learning, proteomics, immunofluorescence, ex vivo assays, and human serum analysis. We constructed the first high-resolution atlas of human PAT, revealing an immune-rich niche and previously unrecognized adipocyte heterogeneity, including thermogenic subpopulations (BL-Ad1, BL-Ad2, OXPHOS-Ad) from distinct progenitors. Functionally, the PAT secretome from PTC substantially enhanced thyroid cancer cell proliferation compared to MNG. Integrated analyses identified a pathogenic adipokine triad characterized by loss of ADIPOQ and gain of NAMPT and IGF1. Restoring ADIPOQ signaling or inhibiting NAMPT/IGF1 suppressed tumor growth in vitro and in vivo. Additionally, we identified CCL14, down-regulated in PTC-derived OXPHOS-Ad, as a key immune regulator. Reduced CCL14–CCR1 signaling impaired CD80 expression in M1-like macrophages, disrupting CD80–CD28 costimulation and consequently diminishing T cell proliferation and recruitment. Consistently, circulating CCL14 levels were reduced in PTC patients. In conclusion, PAT acts as a dynamic endocrine and immunomodulatory component of the tumor microenvironment that promotes thyroid tumor growth through adipokine-mediated and immune-dependent mechanisms.

Spinal cord injury triggers a profound, spatiotemporally dynamic remodeling of the local mechanical microenvironment. Acute tissue softening and extracellular matrix degradation give way progressively to chronic fibrotic stiffening and dense matrix cross-linking. This pathological transformation establishes a formidable physical barrier to axonal regeneration while simultaneously disrupting the biomechanical signals that normally guide cellular behavior and maintain tissue homeostasis. Within this evolving niche, diverse cell populations decode altered stiffness and matrix composition through an array of specialized mechanosensitive receptors. The resulting intracellular signaling cascades orchestrate lineage-specific transcriptional and cytoskeletal programs that ultimately govern the delicate equilibrium between endogenous repair and irreversible fibrotic scar consolidation. This review examines the temporal progression and spatial heterogeneity of postinjury mechanical alterations across the spinal parenchyma, delineates the principal mechanotransduction pathways engaged, and critically evaluates emerging therapeutic strategies designed to modulate this aberrant physical landscape and restore a permissive regenerative milieu. We highlight translational advances spanning surgical decompression, mechanically responsive biomaterials engineered for dynamic niche reprogramming, and mechanoprimed cellular therapies. By framing spinal cord injury as a disorder of aberrant mechanobiology, this work advances a conceptual foundation for precision interventions aimed at overcoming regenerative failure through active remodeling of the tissue microenvironment.

Paclitaxel resistance and poor tumor selectivity remain significant challenges in epithelial ovarian cancer therapy. To overcome these challenges, we engineered PSaA360, a structurally constrained aptamer–drug conjugate with a dual-functional molecular lock that simultaneously rigidifies the AS1411 aptamer and delivers potent telomerase inhibition. Unlike the conformational flexibility of conventional aptamer–drug conjugates, PSaA360 employs the G-quadruplex stabilizer 360A to simultaneously rigidify the AS1411 aptamer into a high-affinity conformation and deliver potent telomerase inhibition. This structure-constrained and therapy-integrated strategy improved nucleolin binding, enhanced cellular internalization, and counteracted paclitaxel chemoresistance. In vivo, PSaA360 exhibited marked tumor inhibition with minimal systemic toxicity. By transforming a therapeutic agent into a structural stabilizer, PSaA360 establishes a new paradigm for mechanism-guided aptamer engineering in chemotherapy-resistant malignancies.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characteristics, structure–activity relationships, anticancer effects, and mechanisms of G4-targeting molecules in cancer treatment. Additionally, it summarizes novel nucleic acid-based drugs targeting G4 structures, providing valuable insights for the future development of more specific and effective G4-targeted therapeutic agents.